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0 | PMID-10190553 | [
{
"id": "PMID-10190553__text",
"type": "abstract",
"text": [
"Regulation of connexin32 and connexin43 gene expression by DNA methylation in rat liver cells. \nGap junction proteins (connexins) are expressed in a cell-specific manner and expression is often reduced in neoplastic cells. We investigated the mechanisms of connexin32 (Cx32) and connexin43 (Cx43) expression in hepatic cells using MH1C1 rat hepatoma cells and freshly isolated, adult rat hepatocytes that express Cx32 but not Cx43 and WB-F344 rat liver epithelial cells that express Cx43 but not Cx32. Southern blotting after DNA restriction with MspI and HpaII indicated that two MspI/HpaII restriction sites in the Cx32 promoter (positions -147 and -847) were methylated in WB-F344 cells, but not in MH1C1 cells or hepatocytes. In contrast, an MspI/HpaII restriction site in the Cx43 promoter (position -38) was methylated in MH1C1 cells, but not in WB-F344 cells or hepatocytes. Transient transfection of the cell lines with connexin promoter-luciferase constructs indicated that the Cx32 promoter was 7-fold more active in MH1C1 cells and the Cx43 promoter was 5-fold more active in WB-F344 cells. These results suggest that transcription of Cx32 and Cx43 in hepatic cells is controlled by promoter methylation and by cell-specific transcription factors. Similar mechanisms may be involved in the reduced expression of these genes frequently observed in neoplastic cells.\n"
],
"offsets": [
[
0,
1376
]
]
}
] | [
{
"id": "PMID-10190553_T1",
"type": "Protein",
"text": [
"connexin32"
],
"offsets": [
[
14,
24
]
],
"normalized": []
},
{
"id": "PMID-10190553_T2",
"type": "Protein",
"text": [
"connexin43"
],
"offsets": [
[
29,
39
]
],
"normalized": []
},
{
"id": "PMID-10190553_T3",
"type": "Protein",
"text": [
"connexin32"
],
"offsets": [
[
257,
267
]
],
"normalized": []
},
{
"id": "PMID-10190553_T4",
"type": "Protein",
"text": [
"Cx32"
],
"offsets": [
[
269,
273
]
],
"normalized": []
},
{
"id": "PMID-10190553_T5",
"type": "Protein",
"text": [
"connexin43"
],
"offsets": [
[
279,
289
]
],
"normalized": []
},
{
"id": "PMID-10190553_T6",
"type": "Protein",
"text": [
"Cx43"
],
"offsets": [
[
291,
295
]
],
"normalized": []
},
{
"id": "PMID-10190553_T7",
"type": "Protein",
"text": [
"Cx32"
],
"offsets": [
[
413,
417
]
],
"normalized": []
},
{
"id": "PMID-10190553_T8",
"type": "Protein",
"text": [
"Cx43"
],
"offsets": [
[
426,
430
]
],
"normalized": []
},
{
"id": "PMID-10190553_T9",
"type": "Protein",
"text": [
"Cx43"
],
"offsets": [
[
483,
487
]
],
"normalized": []
},
{
"id": "PMID-10190553_T10",
"type": "Protein",
"text": [
"Cx32"
],
"offsets": [
[
496,
500
]
],
"normalized": []
},
{
"id": "PMID-10190553_T11",
"type": "Protein",
"text": [
"MspI"
],
"offsets": [
[
547,
551
]
],
"normalized": []
},
{
"id": "PMID-10190553_T12",
"type": "Protein",
"text": [
"HpaII"
],
"offsets": [
[
556,
561
]
],
"normalized": []
},
{
"id": "PMID-10190553_T13",
"type": "Protein",
"text": [
"MspI"
],
"offsets": [
[
581,
585
]
],
"normalized": []
},
{
"id": "PMID-10190553_T14",
"type": "Protein",
"text": [
"HpaII"
],
"offsets": [
[
586,
591
]
],
"normalized": []
},
{
"id": "PMID-10190553_T15",
"type": "Protein",
"text": [
"Cx32"
],
"offsets": [
[
617,
621
]
],
"normalized": []
},
{
"id": "PMID-10190553_T16",
"type": "Protein",
"text": [
"MspI"
],
"offsets": [
[
746,
750
]
],
"normalized": []
},
{
"id": "PMID-10190553_T17",
"type": "Protein",
"text": [
"HpaII"
],
"offsets": [
[
751,
756
]
],
"normalized": []
},
{
"id": "PMID-10190553_T18",
"type": "Protein",
"text": [
"Cx43"
],
"offsets": [
[
781,
785
]
],
"normalized": []
},
{
"id": "PMID-10190553_T19",
"type": "Protein",
"text": [
"luciferase"
],
"offsets": [
[
946,
956
]
],
"normalized": []
},
{
"id": "PMID-10190553_T20",
"type": "Protein",
"text": [
"Cx32"
],
"offsets": [
[
987,
991
]
],
"normalized": []
},
{
"id": "PMID-10190553_T21",
"type": "Protein",
"text": [
"Cx43"
],
"offsets": [
[
1047,
1051
]
],
"normalized": []
},
{
"id": "PMID-10190553_T22",
"type": "Protein",
"text": [
"Cx32"
],
"offsets": [
[
1146,
1150
]
],
"normalized": []
},
{
"id": "PMID-10190553_T23",
"type": "Protein",
"text": [
"Cx43"
],
"offsets": [
[
1155,
1159
]
],
"normalized": []
},
{
"id": "PMID-10190553_T24",
"type": "Entity",
"text": [
"positions -147"
],
"offsets": [
[
632,
646
]
],
"normalized": []
},
{
"id": "PMID-10190553_T25",
"type": "Entity",
"text": [
"-847"
],
"offsets": [
[
651,
655
]
],
"normalized": []
},
{
"id": "PMID-10190553_T27",
"type": "Entity",
"text": [
"position -38"
],
"offsets": [
[
796,
808
]
],
"normalized": []
},
{
"id": "PMID-10190553_T29",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1194,
1202
]
],
"normalized": []
}
] | [
{
"id": "PMID-10190553_E1",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
662,
672
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10190553_T15"
},
{
"role": "Site",
"ref_id": "PMID-10190553_T24"
}
]
},
{
"id": "PMID-10190553_E2",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
662,
672
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10190553_T15"
},
{
"role": "Site",
"ref_id": "PMID-10190553_T25"
}
]
},
{
"id": "PMID-10190553_E3",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
662,
672
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10190553_T15"
},
{
"role": "Site",
"ref_id": "PMID-10190553_T24"
}
]
},
{
"id": "PMID-10190553_E4",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
662,
672
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10190553_T15"
},
{
"role": "Site",
"ref_id": "PMID-10190553_T25"
}
]
},
{
"id": "PMID-10190553_E5",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
814,
824
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10190553_T18"
},
{
"role": "Site",
"ref_id": "PMID-10190553_T27"
}
]
},
{
"id": "PMID-10190553_E6",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
814,
824
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10190553_T18"
},
{
"role": "Site",
"ref_id": "PMID-10190553_T27"
}
]
},
{
"id": "PMID-10190553_E7",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1203,
1214
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10190553_T22"
},
{
"role": "Site",
"ref_id": "PMID-10190553_T29"
}
]
},
{
"id": "PMID-10190553_E8",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1203,
1214
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10190553_T23"
},
{
"role": "Site",
"ref_id": "PMID-10190553_T29"
}
]
}
] | [
{
"id": "PMID-10190553_1",
"entity_ids": [
"PMID-10190553_T3",
"PMID-10190553_T4"
]
},
{
"id": "PMID-10190553_2",
"entity_ids": [
"PMID-10190553_T5",
"PMID-10190553_T6"
]
}
] | [] |
1 | PMID-10196193 | [
{
"id": "PMID-10196193__text",
"type": "abstract",
"text": [
"CheY-dependent methylation of the asparagine receptor, McpB, during chemotaxis in Bacillus subtilis. \nFor the Gram-positive organism Bacillus subtilis, chemotaxis to the attractant asparagine is mediated by the chemoreceptor McpB. In this study, we show that rapid net demethylation of B. subtilis McpB results in the immediate production of methanol, presumably due to the action of CheB. We also show that net demethylation of McpB occurs upon both addition and removal of asparagine. After each demethylation event, McpB is remethylated to nearly prestimulus levels. Both remethylation events are attributable to CheR using S-adenosylmethionine as a substrate. Therefore, no methyl transfer to an intermediate carrier need be postulated to occur during chemotaxis in B. subtilis as was previously suggested. Furthermore, we show that the remethylation of asparagine-bound McpB requires the response regulator, CheY-P, suggesting that CheY-P acts in a feedback mechanism to facilitate adaptation to positive stimuli during chemotaxis in B. subtilis. This hypothesis is supported by two observations: a cheRBCD mutant is capable of transient excitation and subsequent oscillations that bring the flagellar rotational bias below the prestimulus value in the tethered cell assay, and the cheRBCD mutant is capable of swarming in a Tryptone swarm plate.\n"
],
"offsets": [
[
0,
1352
]
]
}
] | [
{
"id": "PMID-10196193_T1",
"type": "Protein",
"text": [
"CheY"
],
"offsets": [
[
0,
4
]
],
"normalized": []
},
{
"id": "PMID-10196193_T2",
"type": "Protein",
"text": [
"McpB"
],
"offsets": [
[
55,
59
]
],
"normalized": []
},
{
"id": "PMID-10196193_T3",
"type": "Protein",
"text": [
"McpB"
],
"offsets": [
[
225,
229
]
],
"normalized": []
},
{
"id": "PMID-10196193_T4",
"type": "Protein",
"text": [
"McpB"
],
"offsets": [
[
298,
302
]
],
"normalized": []
},
{
"id": "PMID-10196193_T5",
"type": "Protein",
"text": [
"CheB"
],
"offsets": [
[
384,
388
]
],
"normalized": []
},
{
"id": "PMID-10196193_T6",
"type": "Protein",
"text": [
"McpB"
],
"offsets": [
[
429,
433
]
],
"normalized": []
},
{
"id": "PMID-10196193_T7",
"type": "Protein",
"text": [
"McpB"
],
"offsets": [
[
519,
523
]
],
"normalized": []
},
{
"id": "PMID-10196193_T8",
"type": "Protein",
"text": [
"CheR"
],
"offsets": [
[
616,
620
]
],
"normalized": []
},
{
"id": "PMID-10196193_T9",
"type": "Protein",
"text": [
"McpB"
],
"offsets": [
[
875,
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]
],
"normalized": []
},
{
"id": "PMID-10196193_T10",
"type": "Protein",
"text": [
"CheY"
],
"offsets": [
[
913,
917
]
],
"normalized": []
},
{
"id": "PMID-10196193_T11",
"type": "Protein",
"text": [
"CheY"
],
"offsets": [
[
937,
941
]
],
"normalized": []
},
{
"id": "PMID-10196193_T12",
"type": "Protein",
"text": [
"cheR"
],
"offsets": [
[
1104,
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]
],
"normalized": []
},
{
"id": "PMID-10196193_T13",
"type": "Protein",
"text": [
"B"
],
"offsets": [
[
1108,
1109
]
],
"normalized": []
},
{
"id": "PMID-10196193_T14",
"type": "Protein",
"text": [
"C"
],
"offsets": [
[
1109,
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]
],
"normalized": []
},
{
"id": "PMID-10196193_T15",
"type": "Protein",
"text": [
"D"
],
"offsets": [
[
1110,
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]
],
"normalized": []
},
{
"id": "PMID-10196193_T16",
"type": "Protein",
"text": [
"cheR"
],
"offsets": [
[
1287,
1291
]
],
"normalized": []
},
{
"id": "PMID-10196193_T17",
"type": "Protein",
"text": [
"B"
],
"offsets": [
[
1291,
1292
]
],
"normalized": []
},
{
"id": "PMID-10196193_T18",
"type": "Protein",
"text": [
"C"
],
"offsets": [
[
1292,
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]
],
"normalized": []
},
{
"id": "PMID-10196193_T19",
"type": "Protein",
"text": [
"D"
],
"offsets": [
[
1293,
1294
]
],
"normalized": []
}
] | [
{
"id": "PMID-10196193_E1",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
15,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10196193_T2"
}
]
},
{
"id": "PMID-10196193_E2",
"type": "Demethylation",
"trigger": {
"text": [
"demethylation"
],
"offsets": [
[
269,
282
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10196193_T4"
}
]
},
{
"id": "PMID-10196193_E3",
"type": "Demethylation",
"trigger": {
"text": [
"demethylation"
],
"offsets": [
[
412,
425
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10196193_T6"
}
]
},
{
"id": "PMID-10196193_E4",
"type": "Methylation",
"trigger": {
"text": [
"remethylated"
],
"offsets": [
[
527,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10196193_T7"
}
]
},
{
"id": "PMID-10196193_E5",
"type": "Methylation",
"trigger": {
"text": [
"remethylation"
],
"offsets": [
[
575,
588
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10196193_T7"
}
]
},
{
"id": "PMID-10196193_E6",
"type": "Catalysis",
"trigger": {
"text": [
"remethylation"
],
"offsets": [
[
575,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10196193_E5"
},
{
"role": "Cause",
"ref_id": "PMID-10196193_T8"
}
]
},
{
"id": "PMID-10196193_E7",
"type": "Methylation",
"trigger": {
"text": [
"remethylation"
],
"offsets": [
[
841,
854
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10196193_T9"
}
]
}
] | [] | [] |
2 | PMID-10209866 | [
{
"id": "PMID-10209866__text",
"type": "abstract",
"text": [
"Transglycosylation reactions of Bacillus stearothermophilus maltogenic amylase with acarbose and various acceptors. \nIt was observed that Bacillus stearothermophilus maltogenic amylase cleaved the first glycosidic bond of acarbose to produce glucose and a pseudotrisaccharide (PTS) that was transferred to C-6 of the glucose to give an alpha-(1-->6) glycosidic linkage and the formation of isoacarbose. The addition of a number of different carbohydrates to the digest gave transfer products in which PTS was primarily attached alpha-(1-->6) to D-glucose, D-mannose, D-galactose, and methyl alpha-D-glucopyranoside. With D-fructopyranose and D-xylopyranose, PTS was linked alpha-(1-->5) and alpha-(1-->4), respectively. PTS was primarily transferred to C-6 of the nonreducing residue of maltose, cellobiose, lactose, and gentiobiose. Lesser amounts of alpha-(1-->3) and/or alpha-(1-->4) transfer products were also observed for these carbohydrate acceptors. The major transfer product to sucrose gave PTS linked alpha-(1-->4) to the glucose residue. alpha,alpha-Trehalose gave two major products with PTS linked alpha-(1-->6) and alpha-(1-->4). Maltitol gave two major products with PTS linked alpha-(1-->6) and alpha-(1-->4) to the glucopyranose residue. Raffinose gave two major products with PTS linked alpha-(1-->6) and alpha-(1-->4) to the D-galactopyranose residue. Maltotriose gave two major products with PTS linked alpha-(1-->6) and alpha-(1-->4) to the nonreducing end glucopyranose residue. Xylitol gave PTS linked alpha-(1-->5) as the major product and D-glucitol gave PTS linked alpha-(1-->6) as the only product. The structures of the transfer products were determined using thin-layer chromatography, high-performance ion chromatography, enzyme hydrolysis, methylation analysis and 13C NMR spectroscopy. The best acceptor was gentiobiose, followed closely by maltose and cellobiose, and the weakest acceptor was D-glucitol.\n"
],
"offsets": [
[
0,
1939
]
]
}
] | [
{
"id": "PMID-10209866_T1",
"type": "Protein",
"text": [
"maltogenic amylase"
],
"offsets": [
[
60,
78
]
],
"normalized": []
},
{
"id": "PMID-10209866_T2",
"type": "Protein",
"text": [
"maltogenic amylase"
],
"offsets": [
[
166,
184
]
],
"normalized": []
}
] | [] | [] | [] |
3 | PMID-10219568 | [
{
"id": "PMID-10219568__text",
"type": "abstract",
"text": [
"A Plasmodium chabaudi chabaudi high molecular mass glycoprotein translocated to the host cell membrane by a non-classical secretory pathway. \nWe have purified and characterized a novel high molecular mass glycoprotein of P. chabaudi chabaudi (Pc550gp) that is transported to the erythrocyte membrane during the intraerythrocytic cycle. Immuno fluorescence assays with polyclonal monospecific antibodies against Pc550gp show that the protein to be localized in the periphery of young trophozoite stages i.e., on the plasma membrane or parasitophorous vacuole membrane. However, in late trophozoites and schizonts the antigen is distributed in both parasite and host cell membranes. These results were confirmed by immunoblotting of isolated parasites and infected host cell membranes at different stages of parasite development. Moreover, alkali extraction of purified infected erythrocyte membranes at mature stages of parasite development does not solubilize Pc550gp, suggesting that it is an integral membrane protein. In addition proteinase K digestion of intact infected host cells induced the disappearance of Pc550gp. Further indicating its transmembrane nature and that it presents extracellular domains susceptible to proteolysis. Brefeldin A or low temperature (15 degrees C) treatment did not affect the translocation of Pc550gp from the parasite compartments to the erythrocyte membrane, indicating that the secretion of Pc550gp does not follow the classical transport pathway described in most eukaryotic cells.\n"
],
"offsets": [
[
0,
1524
]
]
}
] | [
{
"id": "PMID-10219568_T1",
"type": "Protein",
"text": [
"Pc550gp"
],
"offsets": [
[
243,
250
]
],
"normalized": []
},
{
"id": "PMID-10219568_T2",
"type": "Protein",
"text": [
"Pc550gp"
],
"offsets": [
[
411,
418
]
],
"normalized": []
},
{
"id": "PMID-10219568_T3",
"type": "Protein",
"text": [
"Pc550gp"
],
"offsets": [
[
960,
967
]
],
"normalized": []
},
{
"id": "PMID-10219568_T4",
"type": "Protein",
"text": [
"Pc550gp"
],
"offsets": [
[
1115,
1122
]
],
"normalized": []
},
{
"id": "PMID-10219568_T5",
"type": "Protein",
"text": [
"Pc550gp"
],
"offsets": [
[
1331,
1338
]
],
"normalized": []
},
{
"id": "PMID-10219568_T6",
"type": "Protein",
"text": [
"Pc550gp"
],
"offsets": [
[
1432,
1439
]
],
"normalized": []
}
] | [] | [] | [] |
4 | PMID-10360176 | [
{
"id": "PMID-10360176__text",
"type": "abstract",
"text": [
"Novel roles for classical factors at the interface between translation termination and initiation. \nThe pathway of bacterial ribosome recycling following translation termination has remained obscure. Here, we elucidate two essential steps and describe the roles played by the three translation factors EF-G, RRF, and IF3. Release factor RF3 is known to catalyze the dissociation of RF1 or RF2 from ribosomes after polypeptide release. We show that the next step is dissociation of 50S subunits from the 70S posttermination complex and that it is catalyzed by RRF and EF-G and requires GTP hydrolysis. Removal of deacylated tRNA from the resulting 30S:mRNA:tRNA posttermination complex is then necessary to permit rapid 30S subunit recycling. We show that this step requires initiation factor IF3, whose role was previously thought to be restricted to promoting specific 30S initiation complex formation from free 30S subunits.\n"
],
"offsets": [
[
0,
927
]
]
}
] | [
{
"id": "PMID-10360176_T1",
"type": "Protein",
"text": [
"EF-G"
],
"offsets": [
[
302,
306
]
],
"normalized": []
},
{
"id": "PMID-10360176_T2",
"type": "Protein",
"text": [
"RRF"
],
"offsets": [
[
308,
311
]
],
"normalized": []
},
{
"id": "PMID-10360176_T3",
"type": "Protein",
"text": [
"IF3"
],
"offsets": [
[
317,
320
]
],
"normalized": []
},
{
"id": "PMID-10360176_T4",
"type": "Protein",
"text": [
"RF3"
],
"offsets": [
[
337,
340
]
],
"normalized": []
},
{
"id": "PMID-10360176_T5",
"type": "Protein",
"text": [
"RF1"
],
"offsets": [
[
382,
385
]
],
"normalized": []
},
{
"id": "PMID-10360176_T6",
"type": "Protein",
"text": [
"RF2"
],
"offsets": [
[
389,
392
]
],
"normalized": []
},
{
"id": "PMID-10360176_T7",
"type": "Protein",
"text": [
"RRF"
],
"offsets": [
[
559,
562
]
],
"normalized": []
},
{
"id": "PMID-10360176_T8",
"type": "Protein",
"text": [
"EF-G"
],
"offsets": [
[
567,
571
]
],
"normalized": []
},
{
"id": "PMID-10360176_T9",
"type": "Protein",
"text": [
"IF3"
],
"offsets": [
[
792,
795
]
],
"normalized": []
}
] | [] | [] | [] |
5 | PMID-10428866 | [
{
"id": "PMID-10428866__text",
"type": "abstract",
"text": [
"Effect of alternative glycosylation on insulin receptor processing. \nThe mature insulin receptor is a cell surface heterotetrameric glycoprotein composed of two alpha- and two beta-subunits. In 3T3-L1 adipocytes as in other cell types, the receptor is synthesized as a single polypeptide consisting of uncleaved alpha- and beta-subunits, migrating as a 190-kDa glycoprotein. To examine the importance of N-linked glycosylation on insulin receptor processing, we have used glucose deprivation as a tool to alter protein glycosylation. Western blot analysis shows that glucose deprivation led to a time-dependent accumulation of an alternative proreceptor of 170 kDa in a subcellular fraction consistent with endoplasmic reticulum localization. Co-precipitation assays provide evidence that the alternative proreceptor bound GRP78, an endoplasmic reticulum molecular chaperone. N-Glycosidase F treatment shows that the alternative proreceptor contained N-linked oligosaccharides. Yet, endoglycosidase H insensitivity indicates an aberrant oligosaccharide structure. Using pulse-chase methodology, we show that the synthetic rate was similar between the normal and alternative proreceptor. However, the normal proreceptor was processed into alpha- and beta-subunits (t((1)/(2)) = 1.3 +/- 0.6 h), while the alternative proreceptor was degraded (t((1)/(2)) = 5.1 +/- 0.6 h). Upon refeeding cells that were initially deprived of glucose, the alternative proreceptor was processed to a higher molecular weight form and gained sensitivity to endoglycosidase H. This \"intermediate\" form of the proreceptor was also degraded, although a small fraction escaped degradation, resulting in cleavage to the alpha- and beta-subunits. These data provide evidence for the first time that glucose deprivation leads to the accumulation of an alternative proreceptor, which can be post-translationally glycosylated with the readdition of glucose inducing both accelerated degradation and maturation.\n"
],
"offsets": [
[
0,
1979
]
]
}
] | [
{
"id": "PMID-10428866_T1",
"type": "Protein",
"text": [
"insulin receptor"
],
"offsets": [
[
39,
55
]
],
"normalized": []
},
{
"id": "PMID-10428866_T2",
"type": "Protein",
"text": [
"insulin receptor"
],
"offsets": [
[
80,
96
]
],
"normalized": []
},
{
"id": "PMID-10428866_T3",
"type": "Protein",
"text": [
"insulin receptor"
],
"offsets": [
[
430,
446
]
],
"normalized": []
},
{
"id": "PMID-10428866_T4",
"type": "Protein",
"text": [
"GRP78"
],
"offsets": [
[
823,
828
]
],
"normalized": []
},
{
"id": "PMID-10428866_T5",
"type": "Protein",
"text": [
"N-Glycosidase F"
],
"offsets": [
[
876,
891
]
],
"normalized": []
},
{
"id": "PMID-10428866_T6",
"type": "Protein",
"text": [
"endoglycosidase H"
],
"offsets": [
[
983,
1000
]
],
"normalized": []
},
{
"id": "PMID-10428866_T7",
"type": "Protein",
"text": [
"endoglycosidase H"
],
"offsets": [
[
1534,
1551
]
],
"normalized": []
},
{
"id": "PMID-10428866_T11",
"type": "Entity",
"text": [
"oligosaccharides"
],
"offsets": [
[
960,
976
]
],
"normalized": []
}
] | [
{
"id": "PMID-10428866_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"glycosylation"
],
"offsets": [
[
22,
35
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10428866_T1"
}
]
},
{
"id": "PMID-10428866_E2",
"type": "Glycosylation",
"trigger": {
"text": [
"N-linked glycosylation"
],
"offsets": [
[
404,
426
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10428866_T3"
}
]
},
{
"id": "PMID-10428866_E3",
"type": "Glycosylation",
"trigger": {
"text": [
"N-linked"
],
"offsets": [
[
951,
959
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10428866_T3"
},
{
"role": "Sidechain",
"ref_id": "PMID-10428866_T11"
}
]
}
] | [] | [] |
6 | PMID-10443949 | [
{
"id": "PMID-10443949__text",
"type": "abstract",
"text": [
"Meat, metabolic genotypes and risk for colorectal cancer. \nPersuasive data exist as to the importance of environmental factors in the pathogenesis of sporadic colorectal cancer. One possibility is that the effect of environmental factors varies between individuals, perhaps on the basis of inherited variation (polymorphism) in genes which influence the activation or inactivation of dietary carcinogens. Thus far, the focus has been on acetylator genes (NAT1, NAT2) and the activation of heterocyclic amines, carcinogens generated by cooking meat for prolonged periods at high temperature. Three case-control studies and one prospective study have shown a consistent trend towards higher risks for cancer with higher intakes of meat in rapid acetylators for NAT1, NAT2 or both genotypes. Other links between meat, cooking methods, metabolic genotypes and risk for cancer might include enhanced activation of polycyclic aromatic hydrocarbons and N-nitroso compounds by variant genotypes of CYP1A1 and CYP2E1, respectively, and modulation by meat of the protective effect of the E4 allele of apolipoprotein E on risk for cancer of the proximal colon.\n"
],
"offsets": [
[
0,
1150
]
]
}
] | [
{
"id": "PMID-10443949_T1",
"type": "Protein",
"text": [
"NAT1"
],
"offsets": [
[
455,
459
]
],
"normalized": []
},
{
"id": "PMID-10443949_T2",
"type": "Protein",
"text": [
"NAT2"
],
"offsets": [
[
461,
465
]
],
"normalized": []
},
{
"id": "PMID-10443949_T3",
"type": "Protein",
"text": [
"NAT1"
],
"offsets": [
[
759,
763
]
],
"normalized": []
},
{
"id": "PMID-10443949_T4",
"type": "Protein",
"text": [
"NAT2"
],
"offsets": [
[
765,
769
]
],
"normalized": []
},
{
"id": "PMID-10443949_T5",
"type": "Protein",
"text": [
"CYP1A1"
],
"offsets": [
[
990,
996
]
],
"normalized": []
},
{
"id": "PMID-10443949_T6",
"type": "Protein",
"text": [
"CYP2E1"
],
"offsets": [
[
1001,
1007
]
],
"normalized": []
},
{
"id": "PMID-10443949_T7",
"type": "Protein",
"text": [
"E4"
],
"offsets": [
[
1078,
1080
]
],
"normalized": []
},
{
"id": "PMID-10443949_T8",
"type": "Protein",
"text": [
"apolipoprotein E"
],
"offsets": [
[
1091,
1107
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-10443949_1",
"entity_ids": [
"PMID-10443949_T7",
"PMID-10443949_T8"
]
}
] | [] |
7 | PMID-10457259 | [
{
"id": "PMID-10457259__text",
"type": "abstract",
"text": [
"Differential expression of human lysyl hydroxylase genes, lysine hydroxylation, and cross-linking of type I collagen during osteoblastic differentiation in vitro. \nThe pattern of lysyl hydroxylation in the nontriple helical domains of collagen is critical in determining the cross-linking pathways that are tissue specific. We hypothesized that the tissue specificity of type I collagen cross-linking is, in part, due to the differential expression of lysyl hydroxylase genes (Procollagen-lysine,2-oxyglutarate,5-dioxygenase 1, 2, and 3 [PLOD1, PLOD2, and PLOD3]). In this study, we have examined the expression patterns of these three genes during the course of in vitro differentiation of human osteoprogenitor cells (bone marrow stromal cells [BMSCs]) and normal skin fibroblasts (NSFs). In addition, using the medium and cell layer/matrix fractions in these cultures, lysine hydroxylation of type I collagen alpha chains and collagen cross-linking chemistries have been characterized. High levels of PLOD1 and PLOD3 genes were expressed in both BMSCs and NSFs, and the expression levels did not change in the course of differentiation. In contrast to the PLOD1 and PLOD3 genes, both cell types showed low PLOD2 gene expression in undifferentiated and early differentiated conditions. However, fully differentiated BMSCs, but not NSFs, exhibited a significantly elevated level (6-fold increase) of PLOD2 mRNA. This increase coincided with the onset of matrix mineralization and with the increase in lysyl hydroxylation in the nontriple helical domains of alpha chains of type I collagen molecule. Furthermore, the collagen cross-links that are derived from the nontriple helical hydroxylysine-aldehyde were found only in fully differentiated BMSC cultures. The data suggests that PLOD2 expression is associated with lysine hydroxylation in the nontriple helical domains of collagen and, thus, could be partially responsible for the tissue-specific collagen cross-linking pattern.\n"
],
"offsets": [
[
0,
1983
]
]
}
] | [
{
"id": "PMID-10457259_T1",
"type": "Protein",
"text": [
"Procollagen-lysine,2-oxyglutarate,5-dioxygenase 1"
],
"offsets": [
[
477,
526
]
],
"normalized": []
},
{
"id": "PMID-10457259_T2",
"type": "Protein",
"text": [
"2"
],
"offsets": [
[
528,
529
]
],
"normalized": []
},
{
"id": "PMID-10457259_T3",
"type": "Protein",
"text": [
"3"
],
"offsets": [
[
535,
536
]
],
"normalized": []
},
{
"id": "PMID-10457259_T4",
"type": "Protein",
"text": [
"PLOD1"
],
"offsets": [
[
538,
543
]
],
"normalized": []
},
{
"id": "PMID-10457259_T5",
"type": "Protein",
"text": [
"PLOD2"
],
"offsets": [
[
545,
550
]
],
"normalized": []
},
{
"id": "PMID-10457259_T6",
"type": "Protein",
"text": [
"PLOD3"
],
"offsets": [
[
556,
561
]
],
"normalized": []
},
{
"id": "PMID-10457259_T7",
"type": "Protein",
"text": [
"PLOD1"
],
"offsets": [
[
1004,
1009
]
],
"normalized": []
},
{
"id": "PMID-10457259_T8",
"type": "Protein",
"text": [
"PLOD3"
],
"offsets": [
[
1014,
1019
]
],
"normalized": []
},
{
"id": "PMID-10457259_T9",
"type": "Protein",
"text": [
"PLOD1"
],
"offsets": [
[
1159,
1164
]
],
"normalized": []
},
{
"id": "PMID-10457259_T10",
"type": "Protein",
"text": [
"PLOD3"
],
"offsets": [
[
1169,
1174
]
],
"normalized": []
},
{
"id": "PMID-10457259_T11",
"type": "Protein",
"text": [
"PLOD2"
],
"offsets": [
[
1209,
1214
]
],
"normalized": []
},
{
"id": "PMID-10457259_T12",
"type": "Protein",
"text": [
"PLOD2"
],
"offsets": [
[
1401,
1406
]
],
"normalized": []
},
{
"id": "PMID-10457259_T13",
"type": "Protein",
"text": [
"PLOD2"
],
"offsets": [
[
1783,
1788
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-10457259_1",
"entity_ids": [
"PMID-10457259_T1",
"PMID-10457259_T4"
]
},
{
"id": "PMID-10457259_2",
"entity_ids": [
"PMID-10457259_T2",
"PMID-10457259_T5"
]
},
{
"id": "PMID-10457259_3",
"entity_ids": [
"PMID-10457259_T3",
"PMID-10457259_T6"
]
}
] | [] |
8 | PMID-10460145 | [
{
"id": "PMID-10460145__text",
"type": "abstract",
"text": [
"Phenylalanine residues in the active site of tyrosine hydroxylase: mutagenesis of Phe300 and Phe309 to alanine and metal ion-catalyzed hydroxylation of Phe300. \nResidues Phe300 and Phe309 of tyrosine hydroxylase are located in the active site in the recently described three-dimensional structure of the enzyme, where they have been proposed to play roles in substrate binding. Also based on the structure, Phe300 has been reported to be hydroxylated due to a naturally occurring posttranslational modification [Goodwill, K. E., Sabatier, C., and Stevens, R. C. (1998) Biochemistry 37, 13437-13445]. Mutants of tyrosine hydroxylase with alanine substituted for Phe300 or Phe309 have now been purified and characterized. The F309A protein possesses 40% less activity than wild-type tyrosine hydroxylase in the production of DOPA, but full activity in the production of dihydropterin. The F300A protein shows a 2.5-fold decrease in activity in the production of both DOPA and dihydropterin. The K(6-MPH4) value for F300A tyrosine hydroxylase is twice the wild-type value. These results are consistent with Phe309 having a role in maintaining the integrity of the active site, while Phe300 contributes less than 1 kcal/mol to binding tetrahydropterin. Characterization of Phe300 by MALDI-TOF mass spectrometry and amino acid sequencing showed that hydroxylation only occurs in the isolated catalytic domain after incubation with a large excess of 7, 8-dihydropterin, DTT, and Fe(2+). The modification is not observed in the untreated catalytic domain or in the full-length protein, even in the presence of excess iron. These results establish that hydroxylation of Phe300 is an artifact of the crystallography conditions and is not relevant to catalysis.\n"
],
"offsets": [
[
0,
1752
]
]
}
] | [
{
"id": "PMID-10460145_T1",
"type": "Protein",
"text": [
"tyrosine hydroxylase"
],
"offsets": [
[
45,
65
]
],
"normalized": []
},
{
"id": "PMID-10460145_T2",
"type": "Protein",
"text": [
"tyrosine hydroxylase"
],
"offsets": [
[
191,
211
]
],
"normalized": []
},
{
"id": "PMID-10460145_T3",
"type": "Protein",
"text": [
"tyrosine hydroxylase"
],
"offsets": [
[
611,
631
]
],
"normalized": []
},
{
"id": "PMID-10460145_T4",
"type": "Protein",
"text": [
"tyrosine hydroxylase"
],
"offsets": [
[
781,
801
]
],
"normalized": []
},
{
"id": "PMID-10460145_T5",
"type": "Protein",
"text": [
"tyrosine hydroxylase"
],
"offsets": [
[
1019,
1039
]
],
"normalized": []
}
] | [] | [] | [] |
9 | PMID-10463816 | [
{
"id": "PMID-10463816__text",
"type": "abstract",
"text": [
"Development of an enzyme-linked immunosorbent assay, using a monoclonal antibody against alpha2-macroglobulin, for the diagnosis of systemic lupus erythematosus. \nOBJECTIVES: To develop an enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody (mab) directed against abnormally glycosylated serum alpha2-macroglobulin (alpha2-M) from patients with systemic lupus erythematosus (SLE). DESIGN AND METHODS: Serum alpha2-M purified by HPLC from patients with SLE was injected in a Balb/c, CB6 F1 female mouse and hybrid cell lines were screened using alpha2-M Glu-C fragments derived from SLE and normal donors (NHS). A mab was selected and used to develop an ELISA by which sera from NHS (n = 14), SLE (n = 34), rheumatoid arthritis (n = 15), Sjogren's syndrome (n = 11), mixed connective tissue diseases (n = 12), and liver diseases (n = 11) were analyzed. RESULTS: The affinity of the mab for alpha2-M from SLE, but not from the other diseases, was higher compared to NHS, as demonstrated by immunoblotting and ELISA. CONCLUSIONS: The ELISA was capable of recognizing changes of glycosylation of alpha2-M in SLE and may be useful for its differential diagnosis.\n"
],
"offsets": [
[
0,
1176
]
]
}
] | [
{
"id": "PMID-10463816_T1",
"type": "Protein",
"text": [
"alpha2-macroglobulin"
],
"offsets": [
[
89,
109
]
],
"normalized": []
},
{
"id": "PMID-10463816_T2",
"type": "Protein",
"text": [
"alpha2-macroglobulin"
],
"offsets": [
[
312,
332
]
],
"normalized": []
},
{
"id": "PMID-10463816_T3",
"type": "Protein",
"text": [
"alpha2-M"
],
"offsets": [
[
334,
342
]
],
"normalized": []
},
{
"id": "PMID-10463816_T4",
"type": "Protein",
"text": [
"alpha2-M"
],
"offsets": [
[
425,
433
]
],
"normalized": []
},
{
"id": "PMID-10463816_T5",
"type": "Protein",
"text": [
"alpha2-M"
],
"offsets": [
[
562,
570
]
],
"normalized": []
},
{
"id": "PMID-10463816_T6",
"type": "Protein",
"text": [
"alpha2-M"
],
"offsets": [
[
907,
915
]
],
"normalized": []
},
{
"id": "PMID-10463816_T7",
"type": "Protein",
"text": [
"alpha2-M"
],
"offsets": [
[
1110,
1118
]
],
"normalized": []
}
] | [
{
"id": "PMID-10463816_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"glycosylated"
],
"offsets": [
[
293,
305
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10463816_T2"
}
]
},
{
"id": "PMID-10463816_E2",
"type": "Glycosylation",
"trigger": {
"text": [
"glycosylation"
],
"offsets": [
[
1093,
1106
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10463816_T7"
}
]
}
] | [
{
"id": "PMID-10463816_1",
"entity_ids": [
"PMID-10463816_T2",
"PMID-10463816_T3"
]
}
] | [] |
10 | PMID-10485883 | [
{
"id": "PMID-10485883__text",
"type": "abstract",
"text": [
"Efficient adaptational demethylation of chemoreceptors requires the same enzyme-docking site as efficient methylation. \nThe mechanistic basis of sensory adaptation and gradient sensing in bacterial chemotaxis is reversible covalent modification of transmembrane chemoreceptors, methylation, and demethylation at specific glutamyl residues in their cytoplasmic domains. These reactions are catalyzed by a dedicated methyltransferase CheR and a dedicated methylesterase CheB. The esterase is also a deamidase that creates certain methyl-accepting glutamyls by hydrolysis of glutamine side chains. We investigated the action of CheB and its activated form, phospho-CheB, on a truncated form of the aspartate receptor of Escherichia coli that was missing the last 5 aa of the intact receptor. The deleted pentapeptide is conserved in several chemoreceptors in enteric and related bacteria. The truncated receptor was much less efficiently demethylated and deamidated than intact receptor, but essentially was unperturbed for kinase activation or transmembrane signaling. CheB bound specifically to an affinity column carrying the isolated pentapeptide, implying that in the intact receptor the pentapeptide serves as a docking site for the methylesterase/deamidase and that the truncated receptor was inefficiently modified because the enzyme could not dock. It is striking that the same pentapeptide serves as an activity-enhancing docking site for the methyltransferase CheR, the other enzyme involved in adaptational covalent modification of chemoreceptors. A shared docking site raises the tantalizing possibility that relative rates of methylation and demethylation could be influenced by competition between the two enzymes at that site.\n"
],
"offsets": [
[
0,
1740
]
]
}
] | [
{
"id": "PMID-10485883_T1",
"type": "Protein",
"text": [
"CheR"
],
"offsets": [
[
432,
436
]
],
"normalized": []
},
{
"id": "PMID-10485883_T2",
"type": "Protein",
"text": [
"CheB"
],
"offsets": [
[
468,
472
]
],
"normalized": []
},
{
"id": "PMID-10485883_T3",
"type": "Protein",
"text": [
"CheB"
],
"offsets": [
[
625,
629
]
],
"normalized": []
},
{
"id": "PMID-10485883_T4",
"type": "Protein",
"text": [
"CheB"
],
"offsets": [
[
662,
666
]
],
"normalized": []
},
{
"id": "PMID-10485883_T5",
"type": "Protein",
"text": [
"CheB"
],
"offsets": [
[
1067,
1071
]
],
"normalized": []
},
{
"id": "PMID-10485883_T6",
"type": "Protein",
"text": [
"CheR"
],
"offsets": [
[
1468,
1472
]
],
"normalized": []
}
] | [] | [] | [] |
11 | PMID-10490608 | [
{
"id": "PMID-10490608__text",
"type": "abstract",
"text": [
"Roles of cell division and gene transcription in the methylation of CpG islands. \nDe novo methylation of CpG islands within the promoters of eukaryotic genes is often associated with their transcriptional repression, yet the methylation of CpG islands located downstream of promoters does not block transcription. We investigated the kinetics of mRNA induction, demethylation, and remethylation of the p16 promoter and second-exon CpG islands in T24 cells after 5-aza-2'-deoxycytidine (5-Aza-CdR) treatment to explore the relationship between CpG island methylation and gene transcription. The rates of remethylation of both CpG islands were associated with time but not with the rate of cell division, and remethylation of the p16 exon 2 CpG island occurred at a higher rate than that of the p16 promoter. We also examined the relationship between the remethylation of coding sequence CpG islands and gene transcription. The kinetics of remethylation of the p16 exon 2, PAX-6 exon 5, c-ABL exon 11, and MYF-3 exon 3 loci were examined following 5-Aza-CdR treatment because these genes contain exonic CpG islands which are hypermethylated in T24 cells. Remethylation occurred most rapidly in the p16, PAX-6, and c-ABL genes, shown to be transcribed prior to drug treatment. These regions also exhibited higher levels of remethylation in single-cell clones and subclones derived from 5-Aza-CdR-treated T24 cells. Our data suggest that de novo methylation is not restricted to the S phase of the cell cycle and that transcription through CpG islands does not inhibit their remethylation.\n"
],
"offsets": [
[
0,
1586
]
]
}
] | [
{
"id": "PMID-10490608_T1",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
402,
405
]
],
"normalized": []
},
{
"id": "PMID-10490608_T2",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
728,
731
]
],
"normalized": []
},
{
"id": "PMID-10490608_T3",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
793,
796
]
],
"normalized": []
},
{
"id": "PMID-10490608_T4",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
959,
962
]
],
"normalized": []
},
{
"id": "PMID-10490608_T5",
"type": "Protein",
"text": [
"PAX-6"
],
"offsets": [
[
971,
976
]
],
"normalized": []
},
{
"id": "PMID-10490608_T6",
"type": "Protein",
"text": [
"c-ABL"
],
"offsets": [
[
985,
990
]
],
"normalized": []
},
{
"id": "PMID-10490608_T7",
"type": "Protein",
"text": [
"MYF-3"
],
"offsets": [
[
1004,
1009
]
],
"normalized": []
},
{
"id": "PMID-10490608_T8",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
1196,
1199
]
],
"normalized": []
},
{
"id": "PMID-10490608_T9",
"type": "Protein",
"text": [
"PAX-6"
],
"offsets": [
[
1201,
1206
]
],
"normalized": []
},
{
"id": "PMID-10490608_T10",
"type": "Protein",
"text": [
"c-ABL"
],
"offsets": [
[
1212,
1217
]
],
"normalized": []
},
{
"id": "PMID-10490608_T13",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
406,
414
]
],
"normalized": []
},
{
"id": "PMID-10490608_T14",
"type": "Entity",
"text": [
"second-exon CpG islands"
],
"offsets": [
[
419,
442
]
],
"normalized": []
},
{
"id": "PMID-10490608_T15",
"type": "Entity",
"text": [
"CpG island"
],
"offsets": [
[
543,
553
]
],
"normalized": []
},
{
"id": "PMID-10490608_T18",
"type": "Entity",
"text": [
"exon 2 CpG island"
],
"offsets": [
[
732,
749
]
],
"normalized": []
},
{
"id": "PMID-10490608_T19",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
797,
805
]
],
"normalized": []
},
{
"id": "PMID-10490608_T21",
"type": "Entity",
"text": [
"exon 2"
],
"offsets": [
[
963,
969
]
],
"normalized": []
},
{
"id": "PMID-10490608_T22",
"type": "Entity",
"text": [
"exon 5"
],
"offsets": [
[
977,
983
]
],
"normalized": []
},
{
"id": "PMID-10490608_T23",
"type": "Entity",
"text": [
"exon 11"
],
"offsets": [
[
991,
998
]
],
"normalized": []
},
{
"id": "PMID-10490608_T24",
"type": "Entity",
"text": [
"exon 3"
],
"offsets": [
[
1010,
1016
]
],
"normalized": []
}
] | [
{
"id": "PMID-10490608_E1",
"type": "DNA_demethylation",
"trigger": {
"text": [
"demethylation"
],
"offsets": [
[
362,
375
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T1"
},
{
"role": "Site",
"ref_id": "PMID-10490608_T13"
}
]
},
{
"id": "PMID-10490608_E2",
"type": "DNA_demethylation",
"trigger": {
"text": [
"demethylation"
],
"offsets": [
[
362,
375
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T1"
},
{
"role": "Site",
"ref_id": "PMID-10490608_T14"
}
]
},
{
"id": "PMID-10490608_E3",
"type": "DNA_methylation",
"trigger": {
"text": [
"remethylation"
],
"offsets": [
[
381,
394
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T1"
},
{
"role": "Site",
"ref_id": "PMID-10490608_T13"
}
]
},
{
"id": "PMID-10490608_E4",
"type": "DNA_methylation",
"trigger": {
"text": [
"remethylation"
],
"offsets": [
[
381,
394
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T1"
},
{
"role": "Site",
"ref_id": "PMID-10490608_T14"
}
]
},
{
"id": "PMID-10490608_E5",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
554,
565
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T1"
},
{
"role": "Site",
"ref_id": "PMID-10490608_T15"
}
]
},
{
"id": "PMID-10490608_E6",
"type": "DNA_methylation",
"trigger": {
"text": [
"remethylation"
],
"offsets": [
[
707,
720
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T2"
},
{
"role": "Site",
"ref_id": "PMID-10490608_T18"
}
]
},
{
"id": "PMID-10490608_E7",
"type": "DNA_methylation",
"trigger": {
"text": [
"remethylation"
],
"offsets": [
[
707,
720
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T3"
},
{
"role": "Site",
"ref_id": "PMID-10490608_T19"
}
]
},
{
"id": "PMID-10490608_E8",
"type": "DNA_methylation",
"trigger": {
"text": [
"remethylation"
],
"offsets": [
[
938,
951
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T6"
},
{
"role": "Site",
"ref_id": "PMID-10490608_T23"
}
]
},
{
"id": "PMID-10490608_E9",
"type": "DNA_methylation",
"trigger": {
"text": [
"remethylation"
],
"offsets": [
[
938,
951
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T7"
},
{
"role": "Site",
"ref_id": "PMID-10490608_T24"
}
]
},
{
"id": "PMID-10490608_E10",
"type": "DNA_methylation",
"trigger": {
"text": [
"remethylation"
],
"offsets": [
[
938,
951
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T4"
},
{
"role": "Site",
"ref_id": "PMID-10490608_T21"
}
]
},
{
"id": "PMID-10490608_E11",
"type": "DNA_methylation",
"trigger": {
"text": [
"remethylation"
],
"offsets": [
[
938,
951
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T5"
},
{
"role": "Site",
"ref_id": "PMID-10490608_T22"
}
]
},
{
"id": "PMID-10490608_E12",
"type": "DNA_methylation",
"trigger": {
"text": [
"hypermethylated"
],
"offsets": [
[
1123,
1138
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T4"
},
{
"role": "Site",
"ref_id": "PMID-10490608_T21"
}
]
},
{
"id": "PMID-10490608_E13",
"type": "DNA_methylation",
"trigger": {
"text": [
"hypermethylated"
],
"offsets": [
[
1123,
1138
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T5"
},
{
"role": "Site",
"ref_id": "PMID-10490608_T22"
}
]
},
{
"id": "PMID-10490608_E14",
"type": "DNA_methylation",
"trigger": {
"text": [
"hypermethylated"
],
"offsets": [
[
1123,
1138
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T6"
},
{
"role": "Site",
"ref_id": "PMID-10490608_T23"
}
]
},
{
"id": "PMID-10490608_E15",
"type": "DNA_methylation",
"trigger": {
"text": [
"hypermethylated"
],
"offsets": [
[
1123,
1138
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T7"
},
{
"role": "Site",
"ref_id": "PMID-10490608_T24"
}
]
},
{
"id": "PMID-10490608_E16",
"type": "DNA_methylation",
"trigger": {
"text": [
"Remethylation"
],
"offsets": [
[
1153,
1166
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T8"
}
]
},
{
"id": "PMID-10490608_E17",
"type": "DNA_methylation",
"trigger": {
"text": [
"Remethylation"
],
"offsets": [
[
1153,
1166
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T9"
}
]
},
{
"id": "PMID-10490608_E18",
"type": "DNA_methylation",
"trigger": {
"text": [
"Remethylation"
],
"offsets": [
[
1153,
1166
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T10"
}
]
},
{
"id": "PMID-10490608_E19",
"type": "DNA_methylation",
"trigger": {
"text": [
"remethylation"
],
"offsets": [
[
1320,
1333
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T8"
}
]
},
{
"id": "PMID-10490608_E20",
"type": "DNA_methylation",
"trigger": {
"text": [
"remethylation"
],
"offsets": [
[
1320,
1333
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T9"
}
]
},
{
"id": "PMID-10490608_E21",
"type": "DNA_methylation",
"trigger": {
"text": [
"remethylation"
],
"offsets": [
[
1320,
1333
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10490608_T10"
}
]
}
] | [] | [] |
12 | PMID-10495421 | [
{
"id": "PMID-10495421__text",
"type": "abstract",
"text": [
"Distinct methylation pattern and microsatellite instability in sporadic gastric cancer. \nAberrant 5' CpG island methylation is an alternative mechanism of gene inactivation during the development of cancer as demonstrated for several tumor-suppressor genes. Also, marked relationship of microsatellite instability (MSI) and DNA methylation has been reported in sporadic colorectal cancer, which is a result of epigenetic inactivation of hMLH1 in association of promoter hypermethylation. In the present study, we investigated the 5' CpG island hypermethylation of hMLH1, E-cadherin and p16 in 61 primary gastric cancers (GCs) by using combined bisulfite restriction analysis (COBRA) and methylation-specific PCR (MSP), and their MSI status. Of 61 GCs investigated, 5 (8.1%) tumors presented hMLH1 methylation, 16 (26.2%) and 25 (40.9%) showed E-cadherin and p16 methylation respectively, and 8 (13.1%) presented high-frequency MSI (MSI-H). Of the 8 MSI-H patients, 5 presented hMLH1 methylation, whereas no low-frequency MSI (MSI-L) and microsatellite stable (MSS) cases exhibited hMLH1 methylation (5/8 vs. 0/43, p < 0.00001). Furthermore, these patients also presented E-cadherin and p16 hypermethylation. Our data showed a significant correlation between hMLH1 methylation and MSI in GC, and suggested that a common mechanism of aberrant de novo methylation can be postulated in these cancers.\n"
],
"offsets": [
[
0,
1397
]
]
}
] | [
{
"id": "PMID-10495421_T1",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
438,
442
]
],
"normalized": []
},
{
"id": "PMID-10495421_T2",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
565,
569
]
],
"normalized": []
},
{
"id": "PMID-10495421_T3",
"type": "Protein",
"text": [
"E-cadherin"
],
"offsets": [
[
571,
581
]
],
"normalized": []
},
{
"id": "PMID-10495421_T4",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
586,
589
]
],
"normalized": []
},
{
"id": "PMID-10495421_T5",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
792,
796
]
],
"normalized": []
},
{
"id": "PMID-10495421_T6",
"type": "Protein",
"text": [
"E-cadherin"
],
"offsets": [
[
843,
853
]
],
"normalized": []
},
{
"id": "PMID-10495421_T7",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
858,
861
]
],
"normalized": []
},
{
"id": "PMID-10495421_T8",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
978,
982
]
],
"normalized": []
},
{
"id": "PMID-10495421_T9",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
1082,
1086
]
],
"normalized": []
},
{
"id": "PMID-10495421_T10",
"type": "Protein",
"text": [
"E-cadherin"
],
"offsets": [
[
1171,
1181
]
],
"normalized": []
},
{
"id": "PMID-10495421_T11",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
1186,
1189
]
],
"normalized": []
},
{
"id": "PMID-10495421_T12",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
1259,
1263
]
],
"normalized": []
},
{
"id": "PMID-10495421_T13",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
461,
469
]
],
"normalized": []
},
{
"id": "PMID-10495421_T15",
"type": "Entity",
"text": [
"5' CpG island"
],
"offsets": [
[
530,
543
]
],
"normalized": []
}
] | [
{
"id": "PMID-10495421_E1",
"type": "DNA_methylation",
"trigger": {
"text": [
"hypermethylation"
],
"offsets": [
[
470,
486
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10495421_T1"
},
{
"role": "Site",
"ref_id": "PMID-10495421_T13"
}
]
},
{
"id": "PMID-10495421_E2",
"type": "DNA_methylation",
"trigger": {
"text": [
"hypermethylation"
],
"offsets": [
[
544,
560
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10495421_T2"
},
{
"role": "Site",
"ref_id": "PMID-10495421_T15"
}
]
},
{
"id": "PMID-10495421_E3",
"type": "DNA_methylation",
"trigger": {
"text": [
"hypermethylation"
],
"offsets": [
[
544,
560
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10495421_T3"
},
{
"role": "Site",
"ref_id": "PMID-10495421_T15"
}
]
},
{
"id": "PMID-10495421_E4",
"type": "DNA_methylation",
"trigger": {
"text": [
"hypermethylation"
],
"offsets": [
[
544,
560
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10495421_T4"
},
{
"role": "Site",
"ref_id": "PMID-10495421_T15"
}
]
},
{
"id": "PMID-10495421_E5",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
797,
808
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10495421_T5"
}
]
},
{
"id": "PMID-10495421_E6",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
862,
873
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10495421_T6"
}
]
},
{
"id": "PMID-10495421_E7",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
862,
873
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10495421_T7"
}
]
},
{
"id": "PMID-10495421_E8",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
983,
994
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10495421_T8"
}
]
},
{
"id": "PMID-10495421_E9",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1087,
1098
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10495421_T9"
}
]
},
{
"id": "PMID-10495421_E10",
"type": "DNA_methylation",
"trigger": {
"text": [
"hypermethylation"
],
"offsets": [
[
1190,
1206
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10495421_T10"
}
]
},
{
"id": "PMID-10495421_E11",
"type": "DNA_methylation",
"trigger": {
"text": [
"hypermethylation"
],
"offsets": [
[
1190,
1206
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10495421_T11"
}
]
},
{
"id": "PMID-10495421_E12",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1264,
1275
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10495421_T12"
}
]
}
] | [] | [] |
13 | PMID-10532353 | [
{
"id": "PMID-10532353__text",
"type": "abstract",
"text": [
"Effect of HSP47 on prolyl 4-hydroxylation of collagen model peptides. \nProlyl 4-hydroxylation, the most important post-translational modification in collagen biosynthesis, is catalyzed by prolyl 4-hydroxylase, an endoplasmic reticulum-resident enzyme. HSP47 is a collagen-binding stress protein which also resides in the endoplasmic reticulum (Nagata, K. and Yamada, K.M. (1986) J. Biol. Chem., 261, 7531-7536). Both prolyl 4-hydroxylase and HSP47 interact with procollagen alpha-chains during their folding and/or modification in the endoplasmic reticulum. Recent study has revealed that a simple collagen model peptide, (Pro-Pro-Gly)n, is recognized by HSP47 as well as by prolyl 4-hydroxylase in vitro (Koide et al., manuscript submitted). In the present study, we investigated the effect of HSP47 on the prolyl 4-hydroxylation of such collagen model peptides. To monitor the enzymatic hydroxylation of the peptides, we developed a non-RI assay system based on reversed-phase HPLC. When HSP47 was added to the reaction mixture, substrate and less-hydroxylated materials accumulated. This effect depended on the peptide-binding activity of HSP47, because a mutant HSP47 without collagen-binding activity did not show any inhibitory effect on prolyl 4-hydroxylation. Kinetic analysis and other biochemical analyses suggest that HSP47 retards the enzymatic reaction competing for the substrate peptide.\n"
],
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0,
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] | [] | [] | [] |
14 | PMID-10564083 | [
{
"id": "PMID-10564083__text",
"type": "abstract",
"text": [
"Mouse K-Cl cotransporter KCC1: cloning, mapping, pathological expression, and functional regulation. \nAlthough K-Cl cotransporter (KCC1) mRNA is expressed in many tissues, K-Cl cotransport activity has been measured in few cell types, and detection of endogenous KCC1 polypeptide has not yet been reported. We have cloned the mouse erythroid KCC1 (mKCC1) cDNA and its flanking genomic regions and mapped the mKCC1 gene to chromosome 8. Three anti-peptide antibodies raised against recombinant mKCC1 function as immunoblot and immunoprecipitation reagents. The tissue distributions of mKCC1 mRNA and protein are widespread, and mKCC1 RNA is constitutively expressed during erythroid differentiation of ES cells. KCC1 polypeptide or related antigen is present in erythrocytes of multiple species in which K-Cl cotransport activity has been documented. Erythroid KCC1 polypeptide abundance is elevated in proportion to reticulocyte counts in density-fractionated cells, in bleeding-induced reticulocytosis, in mouse models of sickle cell disease and thalassemia, and in the corresponding human disorders. mKCC1-mediated uptake of (86)Rb into Xenopus oocytes requires extracellular Cl(-), is blocked by the diuretic R(+)-[2-n-butyl-6,7-dichloro-2-cyclopentyl-2, 3-dihydro-1-oxo-1H-indenyl-5-yl-)oxy]acetic acid, and exhibits an erythroid pattern of acute regulation, with activation by hypotonic swelling, N-ethylmaleimide, and staurosporine and inhibition by calyculin and okadaic acid. These reagents and findings will expedite studies of KCC1 structure-function relationships and of the pathobiology of KCC1-mediated K-Cl cotransport.\n"
],
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[
0,
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}
] | [] | [] | [] |
15 | PMID-10566667 | [
{
"id": "PMID-10566667__text",
"type": "abstract",
"text": [
"Progesterone metabolism in the human kidney and inhibition of 11beta-hydroxysteroid dehydrogenase type 2 by progesterone and its metabolites. \nProgesterone binds with high affinity to the mineralocorticoid (MC) receptor, but confers only very low agonistic MC activity. Therefore, progesterone is a potent MC antagonist in vitro. Although progesterone reaches up to 100 times higher plasma levels in late pregnancy than aldosterone, the in vivo MC antagonistic effect of progesterone seems to be relatively weak. One explanation for this phenomenon could be local metabolism of progesterone in the human kidney, similar to the inactivation of cortisol to cortisone by the 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 2. We studied the metabolism of progesterone in the human kidney in vitro and found reduction to 20alpha-dihydro (DH)-progesterone as the main metabolite. Ring-A reduction to 5alpha-DH-progesterone, 20alpha-DH-5alpha-DH-progesterone, and 3beta,5alpha-tetrahydro (TH)-progesterone was also documented. We further showed for the first time that 17-hydroxylation of progesterone (17alpha-OH-progesterone, 17alpha-OH, 20alpha-DH-progesterone), normally localized in the adrenals and the gonads, occurs in the human adult kidney. We found no formation of deoxycorticosterone from progesterone in the human adult kidney. Using human kidney cortex microsomes, we tested the inhibitory potency of progesterone and its metabolites on the 11beta-HSD type 2. The most potent inhibitor was progesterone itself (IC50 = 4.8 x 10(-8) mol/L), followed by 5alpha-DH-progesterone (IC50 = 2.4 x 10(-7) mol/L), 20alpha-DH-progesterone, 3beta,5alpha-TH-progesterone, 17alpha-OH-progesterone, and 20alpha-DH-5alpha-DH-progesterone (IC50 between 7.7 x 10(-7) mol/L and 1.3 x 10(-6) mol/L). The least potent inhibitor was 17alpha-OH,20alpha-DH-progesterone. In addition to progesterone metabolism by the kidney, the inhibition of 11beta-HSD type 2 by progesterone and its metabolites could be a second explanation for the weak MC-antagonist activity of progesterone in vivo. Inhibition of 11beta-HSD type 2 leads to an increase of intracellular cortisol in a way that the local equilibrium between the MC agonist cortisol and the antagonist progesterone is shifted to the agonist side.\n"
],
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[
0,
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"id": "PMID-10566667_T1",
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],
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"id": "PMID-10566667_T2",
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],
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}
] | [] | [] | [] |
16 | PMID-10593387 | [
{
"id": "PMID-10593387__text",
"type": "abstract",
"text": [
"Deglycosylation of a bifunctional lutropin-follitropin agonist reduced its follitropin activity more than its lutropin activity. \nOBJECTIVE: To design a drug that blocks the gonadal actions of lutropins and follitropins. DESIGN: Controlled in vitro study. SETTING: Academic laboratory. PATIENT(S): None. INTERVENTION(S): We removed three glycosylation signals from an hCG-hFSH chimera known to have high affinity for LH and FSH receptors, expecting this would create a bifunctional antagonist (dgCFC). To offset the inhibition of subunit combination caused by deglycosylation of alpha-subunit loop 2, we prepared dgCFC as a single-chain fusion protein containing the alpha-subunit downstream of the chimeric beta-subunit. MAIN OUTCOME MEASURE(S): Receptor binding, cyclic adenosine monophosphate accumulation. RESULT(S): dgCFC bound LH or FSH receptors similar to hCG or hFSH. It was a partial agonist and had one tenth the efficacy of hFSH and two thirds the efficacy of hCG. CONCLUSION(S): The surprising high residual lutropin activity of dgCFC indicated that its FSH residues offset the effects of deglycosylation, suggesting this approach to preparing a bifunctional antagonist is unlikely to lead to a useful drug. The increased lutropin efficacy of dgCFC relative to deglycosylated hCG supports the idea that oligosaccharides modulate glycoprotein hormone efficacy through an influence on hormone conformation.\n"
],
"offsets": [
[
0,
1418
]
]
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] | [
{
"id": "PMID-10593387_T1",
"type": "Protein",
"text": [
"LH"
],
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[
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},
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"id": "PMID-10593387_T2",
"type": "Protein",
"text": [
"FSH receptors"
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"id": "PMID-10593387_T3",
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"id": "PMID-10593387_T4",
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"FSH receptors"
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] | [] | [] | [] |
17 | PMID-10601977 | [
{
"id": "PMID-10601977__text",
"type": "abstract",
"text": [
"Regulation of thyrotropin receptor protein expression in insect cells. \nExpression of large quantities of conformationally intact thyrotropin receptor (TSHR) is essential to understand the structure-function relationship of the receptor. We expressed three different constructs of full-length human TSHR in insect cells: (a) a TSHR cDNA lacking signal sequence (TSHR-ns), (b) a TSHR cDNA containing human TSHR signal sequence (TSHR-hs) and (c) a TSHR cDNA with baculovirus envelope protein encoded signal sequence gp-67 (TSHR-gp). No unique protein band, corresponding to any of these recombinant proteins, was visible upon Coomassie Blue staining after SDS-PAGE. However, Western blot using TSHR specific monoclonal antibody showed unique bands around 80, 100 and 100 kDa in TSHR-ns, TSHR-hs and TSHR-gp virus infected insect cells respectively. All three full-length TSHR proteins could neutralize the TSH binding inhibitory immunoglobulin (TBII) activity from sera of experimental animals. However, only glycosylated proteins (TSHR-hs and TSHR-gp) neutralized the TBII activity of sera from autoimmune thyroid patients, confirming the importance of glycosylation for patient autoantibody reactivity. Expression levels of full-length TSHR proteins were much lower than the levels of similarly produced corresponding ectodomains of TSHR proteins. Southern blot and Northern blot analyses showed that DNA and RNA levels in full-length TSHR virus infected insect cells were comparable to the levels found in cells infected with viruses encoding only the ectodomain of TSHR. These data suggest that full-length TSHR expression is very low and is regulated at the translational level.\n"
],
"offsets": [
[
0,
1682
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]
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] | [
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"id": "PMID-10601977_T1",
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"id": "PMID-10601977_T2",
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"id": "PMID-10601977_T3",
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"id": "PMID-10601977_T4",
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] | [
{
"id": "PMID-10601977_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"glycosylated"
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"arguments": [
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"role": "Theme",
"ref_id": "PMID-10601977_T17"
}
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"id": "PMID-10601977_E2",
"type": "Glycosylation",
"trigger": {
"text": [
"glycosylated"
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10601977_T18"
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] | [
{
"id": "PMID-10601977_1",
"entity_ids": [
"PMID-10601977_T2",
"PMID-10601977_T3"
]
}
] | [] |
18 | PMID-10672186 | [
{
"id": "PMID-10672186__text",
"type": "abstract",
"text": [
"BasT, a membrane-bound transducer protein for amino acid detection in Halobacterium salinarum. \nHalophilic archaea, such as eubacteria, use methyl-accepting chemotaxis proteins (MCPs) to sense their environment. We show here that BasT is a halobacterial transducer protein (Htp) responsible for chemotaxis towards five attractant amino acids. The C-terminus of the protein exhibits the highly conserved regions that are diagnostic for MCPs: the signalling domain for communication with the histidine kinase and the methylation sites that interact with the methylation/demethylation enzymes for adaptation. Hydropathy analysis predicts an enterobacterial-type transducer protein topology for BasT, with an extracellular putative ligand-binding domain flanked by two transmembrane helices and a cytoplasmic domain. BasT-inactivated mutant cells are missing a membrane protein radiolabelled with L-[methyl-3H]-methionine in wild-type cells, confirming that BasT is methylatable and membrane bound. Behavioural analysis of the basT mutant cells by capillary and chemical-in-plug assays demonstrates complete loss of chemotactic responses towards five (leucine, isoleucine, valine, methionine and cysteine) of the six attractant amino acids for Halobacterium salinarum, whereas they still respond to arginine. The volatile methyl group production assays also corroborate these findings and confirm that BasT signalling induces methyl group turnover. Our data identify BasT as the chemotaxis transducer protein for the branched chain amino acids leucine, isoleucine and valine as well as for methionine and cysteine. Thus, BasT and the arginine sensor Car cover the entire spectrum of chemotactic responses towards attractant amino acids in H. salinarum.\n"
],
"offsets": [
[
0,
1749
]
]
}
] | [
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"id": "PMID-10672186_T1",
"type": "Protein",
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0,
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},
{
"id": "PMID-10672186_T2",
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"text": [
"BasT"
],
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230,
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]
],
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},
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"id": "PMID-10672186_T3",
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"BasT"
],
"offsets": [
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691,
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]
],
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},
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"id": "PMID-10672186_T4",
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"id": "PMID-10672186_T5",
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"id": "PMID-10672186_T6",
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"id": "PMID-10672186_T7",
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"id": "PMID-10672186_T8",
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"id": "PMID-10672186_T9",
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"id": "PMID-10672186_T10",
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"Car"
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[
1646,
1649
]
],
"normalized": []
}
] | [
{
"id": "PMID-10672186_E1",
"type": "Methylation",
"trigger": {
"text": [
"methylatable"
],
"offsets": [
[
962,
974
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10672186_T5"
}
]
}
] | [] | [] |
19 | PMID-10715549 | [
{
"id": "PMID-10715549__text",
"type": "abstract",
"text": [
"Additional N-glycosylation at Asn(13) rescues the human LHbeta-subunit from disulfide-linked aggregation. \nCG, LH, FSH, and TSH are a family of heterodimeric glycoprotein hormones that contain a common alpha-subunit, but differ in their hormone-specific beta-subunits. Despite the considerable homology between LHbeta and CGbeta, we previously demonstrated that, when expressed in GH(3) cells, the secreted form of LHbeta showed mispaired disulfide-linked aggregation in addition to monomer, whereas no aggregation was observed in CGbeta. To determine the domains which are associated with the LHbeta-aggregation and which prevent CGbeta-aggregation, mutant beta-subunits in glycosylation and carboxy-terminus were expressed in GH(3) cells, and the occurrence of aggregation was assessed by continuous labeling with [35S]methionine/cysteine, immunoprecipitation with anti-hCGbeta serum, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis in a non-reducing condition. No aggregation was seen when N-linked oligosaccharides were attached to the Asn(13) of LHbeta. Removal of the carbohydrate unit at the Asn(13) of CGbeta caused aggregation, although the amount was less than 10% of monomer. The carboxy-terminal regions of neither LHbeta nor CGbeta were associated with their aggregation. Both CGbeta wild-type (WT) and CGbeta lacking N-glycosylation at Asn(13) (CGbeta-N13) showed aggregates in lysate. However, in contrast to CGbeta-N13, CGbetaWT revealed no aggregation in medium. These results indicate that the backbone structure consisting of 114 amino acids and N-linked glycosylation at Asn(30) is involved in the aggregation of LHbeta. Moreover, N-glycosylation at Asn(13) does not prevent such aggregation, but instead plays an important role in correct folding for both LHbeta- and CGbeta-subunits to be secreted as monomer.\n"
],
"offsets": [
[
0,
1846
]
]
}
] | [
{
"id": "PMID-10715549_T1",
"type": "Protein",
"text": [
"LHbeta"
],
"offsets": [
[
56,
62
]
],
"normalized": []
},
{
"id": "PMID-10715549_T2",
"type": "Protein",
"text": [
"LHbeta"
],
"offsets": [
[
311,
317
]
],
"normalized": []
},
{
"id": "PMID-10715549_T3",
"type": "Protein",
"text": [
"CGbeta"
],
"offsets": [
[
322,
328
]
],
"normalized": []
},
{
"id": "PMID-10715549_T4",
"type": "Protein",
"text": [
"LHbeta"
],
"offsets": [
[
415,
421
]
],
"normalized": []
},
{
"id": "PMID-10715549_T5",
"type": "Protein",
"text": [
"CGbeta"
],
"offsets": [
[
531,
537
]
],
"normalized": []
},
{
"id": "PMID-10715549_T6",
"type": "Protein",
"text": [
"LHbeta"
],
"offsets": [
[
594,
600
]
],
"normalized": []
},
{
"id": "PMID-10715549_T7",
"type": "Protein",
"text": [
"CGbeta"
],
"offsets": [
[
631,
637
]
],
"normalized": []
},
{
"id": "PMID-10715549_T8",
"type": "Protein",
"text": [
"CGbeta"
],
"offsets": [
[
873,
879
]
],
"normalized": []
},
{
"id": "PMID-10715549_T9",
"type": "Protein",
"text": [
"LHbeta"
],
"offsets": [
[
1065,
1071
]
],
"normalized": []
},
{
"id": "PMID-10715549_T10",
"type": "Protein",
"text": [
"CGbeta"
],
"offsets": [
[
1124,
1130
]
],
"normalized": []
},
{
"id": "PMID-10715549_T11",
"type": "Protein",
"text": [
"LHbeta"
],
"offsets": [
[
1241,
1247
]
],
"normalized": []
},
{
"id": "PMID-10715549_T12",
"type": "Protein",
"text": [
"CGbeta"
],
"offsets": [
[
1252,
1258
]
],
"normalized": []
},
{
"id": "PMID-10715549_T13",
"type": "Protein",
"text": [
"CGbeta"
],
"offsets": [
[
1304,
1310
]
],
"normalized": []
},
{
"id": "PMID-10715549_T14",
"type": "Protein",
"text": [
"CGbeta"
],
"offsets": [
[
1330,
1336
]
],
"normalized": []
},
{
"id": "PMID-10715549_T15",
"type": "Protein",
"text": [
"CGbeta"
],
"offsets": [
[
1438,
1444
]
],
"normalized": []
},
{
"id": "PMID-10715549_T16",
"type": "Protein",
"text": [
"CGbeta"
],
"offsets": [
[
1450,
1456
]
],
"normalized": []
},
{
"id": "PMID-10715549_T17",
"type": "Protein",
"text": [
"LHbeta"
],
"offsets": [
[
1647,
1653
]
],
"normalized": []
},
{
"id": "PMID-10715549_T18",
"type": "Protein",
"text": [
"LHbeta"
],
"offsets": [
[
1791,
1797
]
],
"normalized": []
},
{
"id": "PMID-10715549_T19",
"type": "Protein",
"text": [
"CGbeta"
],
"offsets": [
[
1803,
1809
]
],
"normalized": []
},
{
"id": "PMID-10715549_T21",
"type": "Entity",
"text": [
"Asn(13)"
],
"offsets": [
[
30,
37
]
],
"normalized": []
},
{
"id": "PMID-10715549_T22",
"type": "Entity",
"text": [
"oligosaccharides"
],
"offsets": [
[
1016,
1032
]
],
"normalized": []
},
{
"id": "PMID-10715549_T24",
"type": "Entity",
"text": [
"Asn(13)"
],
"offsets": [
[
1054,
1061
]
],
"normalized": []
},
{
"id": "PMID-10715549_T26",
"type": "Entity",
"text": [
"carbohydrate"
],
"offsets": [
[
1088,
1100
]
],
"normalized": []
},
{
"id": "PMID-10715549_T27",
"type": "Entity",
"text": [
"Asn(13)"
],
"offsets": [
[
1113,
1120
]
],
"normalized": []
},
{
"id": "PMID-10715549_T29",
"type": "Entity",
"text": [
"Asn(13)"
],
"offsets": [
[
1364,
1371
]
],
"normalized": []
},
{
"id": "PMID-10715549_T31",
"type": "Entity",
"text": [
"Asn(30)"
],
"offsets": [
[
1605,
1612
]
],
"normalized": []
},
{
"id": "PMID-10715549_T33",
"type": "Entity",
"text": [
"Asn(13)"
],
"offsets": [
[
1684,
1691
]
],
"normalized": []
}
] | [
{
"id": "PMID-10715549_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"N-glycosylation"
],
"offsets": [
[
11,
26
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10715549_T1"
},
{
"role": "Site",
"ref_id": "PMID-10715549_T21"
}
]
},
{
"id": "PMID-10715549_E2",
"type": "Glycosylation",
"trigger": {
"text": [
"attached"
],
"offsets": [
[
1038,
1046
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10715549_T9"
},
{
"role": "Site",
"ref_id": "PMID-10715549_T24"
},
{
"role": "Sidechain",
"ref_id": "PMID-10715549_T22"
}
]
},
{
"id": "PMID-10715549_E3",
"type": "Deglycosylation",
"trigger": {
"text": [
"Removal"
],
"offsets": [
[
1073,
1080
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10715549_T10"
},
{
"role": "Site",
"ref_id": "PMID-10715549_T27"
},
{
"role": "Sidechain",
"ref_id": "PMID-10715549_T26"
}
]
},
{
"id": "PMID-10715549_E4",
"type": "Glycosylation",
"trigger": {
"text": [
"N-glycosylation"
],
"offsets": [
[
1345,
1360
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10715549_T14"
},
{
"role": "Site",
"ref_id": "PMID-10715549_T29"
}
]
},
{
"id": "PMID-10715549_E5",
"type": "Glycosylation",
"trigger": {
"text": [
"N-linked glycosylation"
],
"offsets": [
[
1579,
1601
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10715549_T17"
},
{
"role": "Site",
"ref_id": "PMID-10715549_T31"
}
]
},
{
"id": "PMID-10715549_E6",
"type": "Glycosylation",
"trigger": {
"text": [
"N-glycosylation"
],
"offsets": [
[
1665,
1680
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10715549_T17"
},
{
"role": "Site",
"ref_id": "PMID-10715549_T33"
}
]
}
] | [] | [] |
20 | PMID-10722741 | [
{
"id": "PMID-10722741__text",
"type": "abstract",
"text": [
"Type XIII collagen forms homotrimers with three triple helical collagenous domains and its association into disulfide-bonded trimers is enhanced by prolyl 4-hydroxylase. \nType XIII collagen is a type II transmembrane protein predicted to consist of a short cytosolic domain, a single transmembrane domain, and three collagenous domains flanked by noncollagenous sequences. Previous studies on mRNAs indicate that the structures of the collagenous domain closest to the cell membrane, COL1, the adjacent noncollagenous domain, NC2, and the C-terminal domains COL3 and NC4 are subject to alternative splicing. In order to extend studies of type XIII collagen from cDNAs to the protein level we have produced it in insect cells by means of baculoviruses. Type XIII collagen alpha chains were found to associate into disulfide-bonded trimers, and hydroxylation of proline residues dramatically enhanced this association. This protein contains altogether eight cysteine residues, and interchain disulfide bonds could be located in the NC1 domain and possibly at the junction of COL1 and NC2, while the two cysteine residues in NC4 are likely to form intrachain bonds. Pepsin and trypsin/chymotrypsin digestions indicated that the type XIII collagen alpha chains form homotrimers whose three collagenous domains are in triple helical conformation. The thermal stabilities (T(m)) of the COL1, COL2, and COL3 domains were 38, 49 and 40 degrees C, respectively. The T(m) of the central collagenous domain is unusually high, which in the light of this domain being invariant in terms of alternative splicing suggests that the central portion of the molecule may have an important role in the stability of the molecule. All in all, most of the type XIII collagen ectodomain appears to be present in triple helical conformation, which is in clear contrast to the short or highly interrupted triple helical domains of the other known collagenous transmembrane proteins.\n"
],
"offsets": [
[
0,
1957
]
]
}
] | [
{
"id": "PMID-10722741_T1",
"type": "Protein",
"text": [
"Type XIII collagen"
],
"offsets": [
[
0,
18
]
],
"normalized": []
},
{
"id": "PMID-10722741_T2",
"type": "Protein",
"text": [
"Type XIII collagen"
],
"offsets": [
[
171,
189
]
],
"normalized": []
},
{
"id": "PMID-10722741_T3",
"type": "Protein",
"text": [
"type XIII collagen"
],
"offsets": [
[
638,
656
]
],
"normalized": []
},
{
"id": "PMID-10722741_T4",
"type": "Protein",
"text": [
"Type XIII collagen alpha chains"
],
"offsets": [
[
752,
783
]
],
"normalized": []
},
{
"id": "PMID-10722741_T5",
"type": "Protein",
"text": [
"Pepsin"
],
"offsets": [
[
1163,
1169
]
],
"normalized": []
},
{
"id": "PMID-10722741_T6",
"type": "Protein",
"text": [
"type XIII collagen alpha chains"
],
"offsets": [
[
1225,
1256
]
],
"normalized": []
},
{
"id": "PMID-10722741_T7",
"type": "Protein",
"text": [
"type XIII collagen"
],
"offsets": [
[
1733,
1751
]
],
"normalized": []
},
{
"id": "PMID-10722741_T9",
"type": "Entity",
"text": [
"proline residues"
],
"offsets": [
[
860,
876
]
],
"normalized": []
}
] | [
{
"id": "PMID-10722741_E1",
"type": "Hydroxylation",
"trigger": {
"text": [
"hydroxylation"
],
"offsets": [
[
843,
856
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10722741_T4"
},
{
"role": "Site",
"ref_id": "PMID-10722741_T9"
}
]
}
] | [] | [] |
21 | PMID-10729220 | [
{
"id": "PMID-10729220__text",
"type": "abstract",
"text": [
"Symmetric and asymmetric DNA methylation in the human IGF2-H19 imprinted region. \nThe two contiguous IGF2 (human insulin-like growth factor II) and H19 genes are reciprocally imprinted in both human and mouse. In most tissues, IGF2 is transcribed only from the paternal chromosome while H19 is transcribed only from the maternal allele. The presence of a differential methylation region (DMR) on the two parental alleles at the 5' flanking region of H19 has been proposed to constitute the gametic imprint, which controls the reciprocal allelic expression of the two genes. Using bisulfite genomic sequencing, we have assessed the methylation status of cytosine (including 154 CpG sites) in six CpG-rich regions of the human IGF2-H19 genes. In a CpG island near promoter P3 of the IGF2 gene, more than 99.8% of all cytosines were converted to thymidine by sodium bisulfite mutagenesis, indicating that none of the CpGs was methylated. In the IGF2 exon 8-9 region, mosaic methylation of 56 CpG sites was observed in fetal tissues and in adult blood DNA. In contrast to the mosaic methylation of IGF2, the allelic methylation of the human H19 DMR was uniform. In the CpG region located 2 kb upstream (-2362 to -1911) of the H19 transcription site, all 25 CpG sites were completely methylated on only one parental allele. Uniform allele-specific methylation was also observed in the CpG island proximal to the H19 promoter (-711 to -290) with complete methylation of all 25 CpG sites in one parental allele. In contrast, the CpG region in the H19 promoter (-292 to +15) was mosaically methylated in all tissues. In addition, cytosine was methylated at three CpNpG and GpNpC sites on the top DNA strand and one CpNpG site on the bottom DNA strand from the fetal brain. The cytosines at CpG sites were methylated on both DNA strands (symmetric methylation) while cytosines at the CpNpG and GpNpC sites were methylated on only one DNA strand (asymmetric methylation). The asymmetric methylation was associated with tissue-specific disruption of H19 genomic imprinting in fetal brain.\n"
],
"offsets": [
[
0,
2078
]
]
}
] | [
{
"id": "PMID-10729220_T1",
"type": "Protein",
"text": [
"IGF2"
],
"offsets": [
[
54,
58
]
],
"normalized": []
},
{
"id": "PMID-10729220_T2",
"type": "Protein",
"text": [
"H19"
],
"offsets": [
[
59,
62
]
],
"normalized": []
},
{
"id": "PMID-10729220_T3",
"type": "Protein",
"text": [
"IGF2"
],
"offsets": [
[
101,
105
]
],
"normalized": []
},
{
"id": "PMID-10729220_T4",
"type": "Protein",
"text": [
"insulin-like growth factor II"
],
"offsets": [
[
113,
142
]
],
"normalized": []
},
{
"id": "PMID-10729220_T5",
"type": "Protein",
"text": [
"H19"
],
"offsets": [
[
148,
151
]
],
"normalized": []
},
{
"id": "PMID-10729220_T6",
"type": "Protein",
"text": [
"IGF2"
],
"offsets": [
[
227,
231
]
],
"normalized": []
},
{
"id": "PMID-10729220_T7",
"type": "Protein",
"text": [
"H19"
],
"offsets": [
[
287,
290
]
],
"normalized": []
},
{
"id": "PMID-10729220_T8",
"type": "Protein",
"text": [
"H19"
],
"offsets": [
[
450,
453
]
],
"normalized": []
},
{
"id": "PMID-10729220_T9",
"type": "Protein",
"text": [
"IGF2"
],
"offsets": [
[
725,
729
]
],
"normalized": []
},
{
"id": "PMID-10729220_T10",
"type": "Protein",
"text": [
"H19"
],
"offsets": [
[
730,
733
]
],
"normalized": []
},
{
"id": "PMID-10729220_T11",
"type": "Protein",
"text": [
"IGF2"
],
"offsets": [
[
781,
785
]
],
"normalized": []
},
{
"id": "PMID-10729220_T12",
"type": "Protein",
"text": [
"IGF2"
],
"offsets": [
[
942,
946
]
],
"normalized": []
},
{
"id": "PMID-10729220_T13",
"type": "Protein",
"text": [
"IGF2"
],
"offsets": [
[
1094,
1098
]
],
"normalized": []
},
{
"id": "PMID-10729220_T14",
"type": "Protein",
"text": [
"H19"
],
"offsets": [
[
1137,
1140
]
],
"normalized": []
},
{
"id": "PMID-10729220_T15",
"type": "Protein",
"text": [
"H19"
],
"offsets": [
[
1222,
1225
]
],
"normalized": []
},
{
"id": "PMID-10729220_T16",
"type": "Protein",
"text": [
"H19"
],
"offsets": [
[
1407,
1410
]
],
"normalized": []
},
{
"id": "PMID-10729220_T17",
"type": "Protein",
"text": [
"H19"
],
"offsets": [
[
1540,
1543
]
],
"normalized": []
},
{
"id": "PMID-10729220_T18",
"type": "Protein",
"text": [
"H19"
],
"offsets": [
[
2039,
2042
]
],
"normalized": []
},
{
"id": "PMID-10729220_T20",
"type": "Entity",
"text": [
"imprinted region"
],
"offsets": [
[
63,
79
]
],
"normalized": []
},
{
"id": "PMID-10729220_T22",
"type": "Entity",
"text": [
"5' flanking region"
],
"offsets": [
[
428,
446
]
],
"normalized": []
},
{
"id": "PMID-10729220_T24",
"type": "Entity",
"text": [
"cytosine"
],
"offsets": [
[
653,
661
]
],
"normalized": []
},
{
"id": "PMID-10729220_T25",
"type": "Entity",
"text": [
"CpG island"
],
"offsets": [
[
746,
756
]
],
"normalized": []
},
{
"id": "PMID-10729220_T28",
"type": "Entity",
"text": [
"CpG sites"
],
"offsets": [
[
989,
998
]
],
"normalized": []
},
{
"id": "PMID-10729220_T31",
"type": "Entity",
"text": [
"DMR"
],
"offsets": [
[
1141,
1144
]
],
"normalized": []
},
{
"id": "PMID-10729220_T32",
"type": "Entity",
"text": [
"25 CpG sites"
],
"offsets": [
[
1250,
1262
]
],
"normalized": []
},
{
"id": "PMID-10729220_T35",
"type": "Entity",
"text": [
"CpG island"
],
"offsets": [
[
1380,
1390
]
],
"normalized": []
},
{
"id": "PMID-10729220_T37",
"type": "Entity",
"text": [
"25 CpG sites"
],
"offsets": [
[
1468,
1480
]
],
"normalized": []
},
{
"id": "PMID-10729220_T38",
"type": "Entity",
"text": [
"CpG region"
],
"offsets": [
[
1522,
1532
]
],
"normalized": []
},
{
"id": "PMID-10729220_T41",
"type": "Entity",
"text": [
"CpNpG"
],
"offsets": [
[
1655,
1660
]
],
"normalized": []
},
{
"id": "PMID-10729220_T42",
"type": "Entity",
"text": [
"GpNpC"
],
"offsets": [
[
1665,
1670
]
],
"normalized": []
},
{
"id": "PMID-10729220_T43",
"type": "Entity",
"text": [
"CpNpG"
],
"offsets": [
[
1707,
1712
]
],
"normalized": []
},
{
"id": "PMID-10729220_T44",
"type": "Entity",
"text": [
"cytosines"
],
"offsets": [
[
1769,
1778
]
],
"normalized": []
},
{
"id": "PMID-10729220_T46",
"type": "Entity",
"text": [
"cytosines"
],
"offsets": [
[
1858,
1867
]
],
"normalized": []
}
] | [
{
"id": "PMID-10729220_E1",
"type": "DNA_methylation",
"trigger": {
"text": [
"DNA methylation"
],
"offsets": [
[
25,
40
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10729220_T1"
},
{
"role": "Site",
"ref_id": "PMID-10729220_T20"
}
]
},
{
"id": "PMID-10729220_E2",
"type": "DNA_methylation",
"trigger": {
"text": [
"DNA methylation"
],
"offsets": [
[
25,
40
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10729220_T2"
},
{
"role": "Site",
"ref_id": "PMID-10729220_T20"
}
]
},
{
"id": "PMID-10729220_E3",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
368,
379
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10729220_T8"
},
{
"role": "Site",
"ref_id": "PMID-10729220_T22"
}
]
},
{
"id": "PMID-10729220_E4",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
631,
642
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10729220_T9"
},
{
"role": "Site",
"ref_id": "PMID-10729220_T24"
}
]
},
{
"id": "PMID-10729220_E5",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
631,
642
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10729220_T10"
},
{
"role": "Site",
"ref_id": "PMID-10729220_T24"
}
]
},
{
"id": "PMID-10729220_E6",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
923,
933
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10729220_T11"
},
{
"role": "Site",
"ref_id": "PMID-10729220_T25"
}
]
},
{
"id": "PMID-10729220_E7",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
971,
982
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10729220_T12"
},
{
"role": "Site",
"ref_id": "PMID-10729220_T28"
}
]
},
{
"id": "PMID-10729220_E8",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1079,
1090
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10729220_T13"
}
]
},
{
"id": "PMID-10729220_E9",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1112,
1123
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10729220_T14"
},
{
"role": "Site",
"ref_id": "PMID-10729220_T31"
}
]
},
{
"id": "PMID-10729220_E10",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
1279,
1289
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10729220_T15"
},
{
"role": "Site",
"ref_id": "PMID-10729220_T32"
}
]
},
{
"id": "PMID-10729220_E11",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1343,
1354
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10729220_T16"
},
{
"role": "Site",
"ref_id": "PMID-10729220_T35"
}
]
},
{
"id": "PMID-10729220_E12",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1449,
1460
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10729220_T16"
},
{
"role": "Site",
"ref_id": "PMID-10729220_T37"
}
]
},
{
"id": "PMID-10729220_E13",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
1582,
1592
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10729220_T17"
},
{
"role": "Site",
"ref_id": "PMID-10729220_T38"
}
]
},
{
"id": "PMID-10729220_E14",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
1635,
1645
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10729220_T17"
},
{
"role": "Site",
"ref_id": "PMID-10729220_T41"
}
]
},
{
"id": "PMID-10729220_E15",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
1635,
1645
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10729220_T17"
},
{
"role": "Site",
"ref_id": "PMID-10729220_T42"
}
]
},
{
"id": "PMID-10729220_E16",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
1635,
1645
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10729220_T17"
},
{
"role": "Site",
"ref_id": "PMID-10729220_T43"
}
]
},
{
"id": "PMID-10729220_E17",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
1797,
1807
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10729220_T17"
},
{
"role": "Site",
"ref_id": "PMID-10729220_T44"
}
]
},
{
"id": "PMID-10729220_E18",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
1902,
1912
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10729220_T17"
},
{
"role": "Site",
"ref_id": "PMID-10729220_T46"
}
]
},
{
"id": "PMID-10729220_E19",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1977,
1988
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10729220_T18"
}
]
}
] | [
{
"id": "PMID-10729220_1",
"entity_ids": [
"PMID-10729220_T3",
"PMID-10729220_T4"
]
}
] | [] |
22 | PMID-10746157 | [
{
"id": "PMID-10746157__text",
"type": "abstract",
"text": [
"An increase in histone acetylation and IL-2 antagonizing the immunoinhibitory effect are necessary for augmentation by butyrate of in vitro anti-TNP antibody production. \nWe investigated the role of histone acetylation in the promotion of antigen-specific antibody production in murine B cells induced by sodium butyrate (NaBu) plus interleukin 2 (IL-2). NaBu dose dependently increased the acetylation levels of histone H4 at concentrations which effectively enhanced anti-trinitrophenyl (TNP) antibody production in the presence of IL-2. Among other short-chain fatty acids and NaBu analogs, propionate, valerate and vinylacetate were effective in the presence of IL-2 in increasing both antibody production and the histone H4 acetylation level, but acetate, alpha-, beta- and gamma-hydroxybutyrates and alpha-, beta- and gamma-aminobutyrates were not effective, even in the presence of IL-2. The effect of the specific histone deacetylase inhibitor trichostatin A (TSA), which enhances anti-TNP antibody production without IL-2, was markedly inhibited by adding NaBu simultaneously. However, the effect of TSA was neither inhibited nor potentiated by NaBu in the presence of IL-2. Splenic B cells treated with NaBu, TSA and both together in the presence or absence of IL-2 showed almost the same increased acetylation level of histone H4. These results suggest that the NaBu-induced enhancement of anti-TNP antibody production in the presence of IL-2 is mediated through a moderate increase in the level of histone acetylation and that NaBu has both stimulating and inhibiting activities for anti-TNP antibody production, the latter of which is overcome by IL-2.\n"
],
"offsets": [
[
0,
1666
]
]
}
] | [
{
"id": "PMID-10746157_T1",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
15,
22
]
],
"normalized": []
},
{
"id": "PMID-10746157_T2",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
39,
43
]
],
"normalized": []
},
{
"id": "PMID-10746157_T3",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
199,
206
]
],
"normalized": []
},
{
"id": "PMID-10746157_T4",
"type": "Protein",
"text": [
"interleukin 2"
],
"offsets": [
[
333,
346
]
],
"normalized": []
},
{
"id": "PMID-10746157_T5",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
348,
352
]
],
"normalized": []
},
{
"id": "PMID-10746157_T6",
"type": "Protein",
"text": [
"histone H4"
],
"offsets": [
[
413,
423
]
],
"normalized": []
},
{
"id": "PMID-10746157_T7",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
534,
538
]
],
"normalized": []
},
{
"id": "PMID-10746157_T8",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
666,
670
]
],
"normalized": []
},
{
"id": "PMID-10746157_T9",
"type": "Protein",
"text": [
"histone H4"
],
"offsets": [
[
718,
728
]
],
"normalized": []
},
{
"id": "PMID-10746157_T10",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
889,
893
]
],
"normalized": []
},
{
"id": "PMID-10746157_T11",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
922,
929
]
],
"normalized": []
},
{
"id": "PMID-10746157_T12",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1026,
1030
]
],
"normalized": []
},
{
"id": "PMID-10746157_T13",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1178,
1182
]
],
"normalized": []
},
{
"id": "PMID-10746157_T14",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1271,
1275
]
],
"normalized": []
},
{
"id": "PMID-10746157_T15",
"type": "Protein",
"text": [
"histone H4"
],
"offsets": [
[
1330,
1340
]
],
"normalized": []
},
{
"id": "PMID-10746157_T16",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1449,
1453
]
],
"normalized": []
},
{
"id": "PMID-10746157_T17",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
1510,
1517
]
],
"normalized": []
},
{
"id": "PMID-10746157_T18",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1660,
1664
]
],
"normalized": []
}
] | [
{
"id": "PMID-10746157_E1",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
23,
34
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10746157_T1"
}
]
},
{
"id": "PMID-10746157_E2",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
207,
218
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10746157_T3"
}
]
},
{
"id": "PMID-10746157_E3",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
391,
402
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10746157_T6"
}
]
},
{
"id": "PMID-10746157_E4",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
729,
740
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10746157_T9"
}
]
},
{
"id": "PMID-10746157_E5",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
1309,
1320
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10746157_T15"
}
]
},
{
"id": "PMID-10746157_E6",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
1518,
1529
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10746157_T17"
}
]
}
] | [
{
"id": "PMID-10746157_1",
"entity_ids": [
"PMID-10746157_T4",
"PMID-10746157_T5"
]
}
] | [] |
23 | PMID-10799457 | [
{
"id": "PMID-10799457__text",
"type": "abstract",
"text": [
"New immunofluorescence assays for detection of Human herpesvirus 8-specific antibodies. \nSeveral assays have been developed for detection of immunoglobulin G antibodies to Human herpesvirus 8 (HHV-8), including immunofluorescence assays (IFAs) and enzyme-linked immunosorbent assays (ELISAs). However, the specificity and sensitivity of these assays are not completely defined due to the lack of a \"gold standard.\" Although IFAs based on primary effusion lymphoma (PEL) cell lines are used widely, the assays can be confounded by nonspecific reactions against cellular components and potential cross-reaction with antibodies against other herpesviruses. To provide more reliable IFAs, we established recombinant Semliki Forest viruses (rSFVs) expressing the HHV-8-specific proteins ORF73 and K8.1 and used BHK-21 cells infected with these rSFVs for IFA (ORF73-IFA and K8.1-IFA). Expression of the HHV-8-specific proteins at very high levels by the rSFV system allowed easy scoring for IFA and thereby increased specificity. The rSFV system also allowed detection of antibodies against glycosylation-dependent epitopes of K8.1. Titers measured by rSFV-based IFAs and PEL-based IFAs correlated well (correlation coefficients of >0.9), and concordances of seroreactivities between rSFV-based and PEL-based IFAs were >97% (kappa > 0.93). K8.1-IFA was more sensitive than either ORF73-IFA or peptide ELISAs. Using PEL-based lytic IFA as a reference assay, the sensitivity and specificity of K8.1-IFA were estimated to be 94 and 100%, respectively. HHV-8 prevalences determined by K8.1-IFA among the human immunodeficiency virus (HIV)-positive (HIV(+)) Kaposi's sarcoma (KS) patients, HIV(+) KS(-) patients, and healthy controls were 100, 65, and 6.7%, respectively, which were consistent with prior reports. Therefore, our rSFV-based IFAs may provide a specific and sensitive method for use in epidemiology studies. In addition, they will provide a basis for further development of diagnostic tests for HHV-8 infection.\n"
],
"offsets": [
[
0,
2016
]
]
}
] | [
{
"id": "PMID-10799457_T1",
"type": "Protein",
"text": [
"ORF73"
],
"offsets": [
[
783,
788
]
],
"normalized": []
},
{
"id": "PMID-10799457_T2",
"type": "Protein",
"text": [
"K8.1"
],
"offsets": [
[
793,
797
]
],
"normalized": []
},
{
"id": "PMID-10799457_T3",
"type": "Protein",
"text": [
"ORF73"
],
"offsets": [
[
855,
860
]
],
"normalized": []
},
{
"id": "PMID-10799457_T4",
"type": "Protein",
"text": [
"K8.1"
],
"offsets": [
[
869,
873
]
],
"normalized": []
},
{
"id": "PMID-10799457_T5",
"type": "Protein",
"text": [
"K8.1"
],
"offsets": [
[
1122,
1126
]
],
"normalized": []
},
{
"id": "PMID-10799457_T6",
"type": "Protein",
"text": [
"ORF73"
],
"offsets": [
[
1375,
1380
]
],
"normalized": []
},
{
"id": "PMID-10799457_T7",
"type": "Protein",
"text": [
"K8.1"
],
"offsets": [
[
1487,
1491
]
],
"normalized": []
},
{
"id": "PMID-10799457_T8",
"type": "Protein",
"text": [
"K8.1"
],
"offsets": [
[
1576,
1580
]
],
"normalized": []
}
] | [] | [] | [] |
24 | PMID-10880980 | [
{
"id": "PMID-10880980__text",
"type": "abstract",
"text": [
"Evidence that the lizard helospectin peptides are O-glycosylated. \nSix forms of helospectin (a vasoactive intestinal peptide analogue) were purified from the venom of the Heloderma horridum lizard. Their identification was performed by combining sequencing by automated Edman degradation and electrospray mass spectrometry analysis on the complete peptides and their tryptic fragments. The products resulting from the action of an O-glycosidase were also analysed. Two forms were identified as the previously named Hs1 and Hs2 of 38 and 37 amino-acid residues, respectively. Two forms corresponded to Hs1 and Hs2 O-glycosylated by a N-acetylhexosamine-hexose motif attached to the Ser32 residue. Two other forms were not completely characterized but might correspond to the O-glycosylated forms bearing a phosphate or a sulfate group. The glycosylation did not affect the capacity of the helospectins to recognize and to activate the human and the rat VPAC1 and VPAC2 receptors.\n"
],
"offsets": [
[
0,
979
]
]
}
] | [
{
"id": "PMID-10880980_T1",
"type": "Protein",
"text": [
"helospectin"
],
"offsets": [
[
25,
36
]
],
"normalized": []
},
{
"id": "PMID-10880980_T2",
"type": "Protein",
"text": [
"helospectin"
],
"offsets": [
[
80,
91
]
],
"normalized": []
},
{
"id": "PMID-10880980_T3",
"type": "Protein",
"text": [
"Hs1"
],
"offsets": [
[
515,
518
]
],
"normalized": []
},
{
"id": "PMID-10880980_T4",
"type": "Protein",
"text": [
"Hs2"
],
"offsets": [
[
523,
526
]
],
"normalized": []
},
{
"id": "PMID-10880980_T5",
"type": "Protein",
"text": [
"Hs1"
],
"offsets": [
[
601,
604
]
],
"normalized": []
},
{
"id": "PMID-10880980_T6",
"type": "Protein",
"text": [
"Hs2"
],
"offsets": [
[
609,
612
]
],
"normalized": []
},
{
"id": "PMID-10880980_T7",
"type": "Protein",
"text": [
"helospectins"
],
"offsets": [
[
888,
900
]
],
"normalized": []
},
{
"id": "PMID-10880980_T8",
"type": "Protein",
"text": [
"VPAC1"
],
"offsets": [
[
952,
957
]
],
"normalized": []
},
{
"id": "PMID-10880980_T9",
"type": "Protein",
"text": [
"VPAC2"
],
"offsets": [
[
962,
967
]
],
"normalized": []
},
{
"id": "PMID-10880980_T12",
"type": "Entity",
"text": [
"N-acetylhexosamine-hexose"
],
"offsets": [
[
633,
658
]
],
"normalized": []
},
{
"id": "PMID-10880980_T13",
"type": "Entity",
"text": [
"Ser32"
],
"offsets": [
[
681,
686
]
],
"normalized": []
}
] | [
{
"id": "PMID-10880980_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"O-glycosylated"
],
"offsets": [
[
50,
64
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10880980_T1"
}
]
},
{
"id": "PMID-10880980_E2",
"type": "Glycosylation",
"trigger": {
"text": [
"O-glycosylated"
],
"offsets": [
[
613,
627
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10880980_T5"
},
{
"role": "Site",
"ref_id": "PMID-10880980_T13"
},
{
"role": "Sidechain",
"ref_id": "PMID-10880980_T12"
}
]
},
{
"id": "PMID-10880980_E3",
"type": "Glycosylation",
"trigger": {
"text": [
"O-glycosylated"
],
"offsets": [
[
613,
627
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10880980_T6"
},
{
"role": "Site",
"ref_id": "PMID-10880980_T13"
},
{
"role": "Sidechain",
"ref_id": "PMID-10880980_T12"
}
]
}
] | [] | [] |
25 | PMID-10898761 | [
{
"id": "PMID-10898761__text",
"type": "abstract",
"text": [
"Changes in methionine adenosyltransferase and S-adenosylmethionine homeostasis in alcoholic rat liver. \nLiver-specific and non-liver-specific methionine adenosyltransferase (MAT) are products of two genes, MAT1A and MAT2A, respectively, that catalyze the formation of S-adenosylmethionine (SAM). We previously showed that MAT2A expression was associated with more rapid cell growth. Changes in MAT expression have not been examined in animal models of alcoholic liver injury, which is the focus of the current study. After rats were fed intragastrically with ethanol and high fat for 9 wk, the mRNA level of both MAT forms doubled but only the protein level of MAT2A increased. Although liver-specific MAT activity did not change, it was 32% lower after one and 68% lower after eight weekly enteral doses of lipopolysaccharide. Hepatic levels of methionine, SAM, and DNA methylation fell by approximately 40%. c-myc was hypomethylated, and its mRNA level increased. Genome-wide DNA strand break increased. Thus in the prefibrotic stage of alcoholic liver injury, there is already a switch in MAT expression, global DNA hypomethylation, increased c-myc expression, and genome-wide DNA strand break. These changes may be important in predisposing this liver disease to malignant degeneration.\n"
],
"offsets": [
[
0,
1291
]
]
}
] | [
{
"id": "PMID-10898761_T1",
"type": "Protein",
"text": [
"MAT1A"
],
"offsets": [
[
206,
211
]
],
"normalized": []
},
{
"id": "PMID-10898761_T2",
"type": "Protein",
"text": [
"MAT2A"
],
"offsets": [
[
216,
221
]
],
"normalized": []
},
{
"id": "PMID-10898761_T3",
"type": "Protein",
"text": [
"MAT2A"
],
"offsets": [
[
322,
327
]
],
"normalized": []
},
{
"id": "PMID-10898761_T4",
"type": "Protein",
"text": [
"MAT2A"
],
"offsets": [
[
661,
666
]
],
"normalized": []
},
{
"id": "PMID-10898761_T5",
"type": "Protein",
"text": [
"c-myc"
],
"offsets": [
[
910,
915
]
],
"normalized": []
},
{
"id": "PMID-10898761_T6",
"type": "Protein",
"text": [
"c-myc"
],
"offsets": [
[
1146,
1151
]
],
"normalized": []
}
] | [
{
"id": "PMID-10898761_E1",
"type": "DNA_methylation",
"trigger": {
"text": [
"hypomethylated"
],
"offsets": [
[
920,
934
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10898761_T5"
}
]
}
] | [] | [] |
26 | PMID-10903903 | [
{
"id": "PMID-10903903__text",
"type": "abstract",
"text": [
"Hsl7p, the yeast homologue of human JBP1, is a protein methyltransferase. \nThe yeast protein Hsl7p is a homologue of Janus kinase binding protein 1, JBP1, a newly characterized protein methyltransferase. In this report, Hsl7p also is shown to be a methyltransferase. It can be crosslinked to [(3)H]S-adenosylmethionine and exhibits in vitro protein methylation activity. Calf histones H2A and H4 and bovine myelin basic protein were methylated by Hsl7p, whereas histones H1, H2B, and H3 and bovine cytochrome c were not. We demonstrated that JBP1 can complement Saccharomyces cerevisiae with a disrupted HSL7 gene as judged by a reduction of the elongated bud phenotype, and a point mutation in the JBP1 S-adenosylmethionine consensus binding sequence eliminated all complementation by JBP1. Therefore, we conclude the yeast protein Hsl7p is a sequence and functional homologue of JBP1. These data provide evidence for an intricate link between protein methylation and macroscopic changes in yeast morphology.\n"
],
"offsets": [
[
0,
1010
]
]
}
] | [
{
"id": "PMID-10903903_T1",
"type": "Protein",
"text": [
"Hsl7p"
],
"offsets": [
[
0,
5
]
],
"normalized": []
},
{
"id": "PMID-10903903_T2",
"type": "Protein",
"text": [
"JBP1"
],
"offsets": [
[
36,
40
]
],
"normalized": []
},
{
"id": "PMID-10903903_T3",
"type": "Protein",
"text": [
"Hsl7p"
],
"offsets": [
[
93,
98
]
],
"normalized": []
},
{
"id": "PMID-10903903_T4",
"type": "Protein",
"text": [
"Janus kinase binding protein 1"
],
"offsets": [
[
117,
147
]
],
"normalized": []
},
{
"id": "PMID-10903903_T5",
"type": "Protein",
"text": [
"JBP1"
],
"offsets": [
[
149,
153
]
],
"normalized": []
},
{
"id": "PMID-10903903_T6",
"type": "Protein",
"text": [
"Hsl7p"
],
"offsets": [
[
220,
225
]
],
"normalized": []
},
{
"id": "PMID-10903903_T7",
"type": "Protein",
"text": [
"histones H2A"
],
"offsets": [
[
376,
388
]
],
"normalized": []
},
{
"id": "PMID-10903903_T8",
"type": "Protein",
"text": [
"H4"
],
"offsets": [
[
393,
395
]
],
"normalized": []
},
{
"id": "PMID-10903903_T9",
"type": "Protein",
"text": [
"myelin basic protein"
],
"offsets": [
[
407,
427
]
],
"normalized": []
},
{
"id": "PMID-10903903_T10",
"type": "Protein",
"text": [
"Hsl7p"
],
"offsets": [
[
447,
452
]
],
"normalized": []
},
{
"id": "PMID-10903903_T11",
"type": "Protein",
"text": [
"histones H1"
],
"offsets": [
[
462,
473
]
],
"normalized": []
},
{
"id": "PMID-10903903_T12",
"type": "Protein",
"text": [
"H2B"
],
"offsets": [
[
475,
478
]
],
"normalized": []
},
{
"id": "PMID-10903903_T13",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
484,
486
]
],
"normalized": []
},
{
"id": "PMID-10903903_T14",
"type": "Protein",
"text": [
"cytochrome c"
],
"offsets": [
[
498,
510
]
],
"normalized": []
},
{
"id": "PMID-10903903_T15",
"type": "Protein",
"text": [
"JBP1"
],
"offsets": [
[
542,
546
]
],
"normalized": []
},
{
"id": "PMID-10903903_T16",
"type": "Protein",
"text": [
"HSL7"
],
"offsets": [
[
604,
608
]
],
"normalized": []
},
{
"id": "PMID-10903903_T17",
"type": "Protein",
"text": [
"JBP1"
],
"offsets": [
[
699,
703
]
],
"normalized": []
},
{
"id": "PMID-10903903_T18",
"type": "Protein",
"text": [
"JBP1"
],
"offsets": [
[
786,
790
]
],
"normalized": []
},
{
"id": "PMID-10903903_T19",
"type": "Protein",
"text": [
"Hsl7p"
],
"offsets": [
[
833,
838
]
],
"normalized": []
},
{
"id": "PMID-10903903_T20",
"type": "Protein",
"text": [
"JBP1"
],
"offsets": [
[
881,
885
]
],
"normalized": []
}
] | [
{
"id": "PMID-10903903_E1",
"type": "Methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
433,
443
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10903903_T7"
}
]
},
{
"id": "PMID-10903903_E2",
"type": "Methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
433,
443
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10903903_T14"
}
]
},
{
"id": "PMID-10903903_E3",
"type": "Catalysis",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
433,
443
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10903903_E1"
},
{
"role": "Cause",
"ref_id": "PMID-10903903_T10"
}
]
},
{
"id": "PMID-10903903_E4",
"type": "Methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
433,
443
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10903903_T8"
}
]
},
{
"id": "PMID-10903903_E5",
"type": "Catalysis",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
433,
443
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10903903_E4"
},
{
"role": "Cause",
"ref_id": "PMID-10903903_T10"
}
]
},
{
"id": "PMID-10903903_E6",
"type": "Methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
433,
443
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10903903_T9"
}
]
},
{
"id": "PMID-10903903_E7",
"type": "Catalysis",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
433,
443
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10903903_E6"
},
{
"role": "Cause",
"ref_id": "PMID-10903903_T10"
}
]
},
{
"id": "PMID-10903903_E8",
"type": "Methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
433,
443
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10903903_T11"
}
]
},
{
"id": "PMID-10903903_E9",
"type": "Methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
433,
443
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10903903_T12"
}
]
},
{
"id": "PMID-10903903_E10",
"type": "Methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
433,
443
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10903903_T13"
}
]
}
] | [
{
"id": "PMID-10903903_1",
"entity_ids": [
"PMID-10903903_T4",
"PMID-10903903_T5"
]
}
] | [] |
27 | PMID-10938272 | [
{
"id": "PMID-10938272__text",
"type": "abstract",
"text": [
"Rapid induction of histone hyperacetylation and cellular differentiation in human breast tumor cell lines following degradation of histone deacetylase-1. \nQuinidine inhibits proliferation and promotes cellular differentiation in human breast tumor epithelial cells. Previously we showed quinidine arrested MCF-7 cells in G(1) phase of the cell cycle and led to a G(1) to G(0) transition followed by apoptotic cell death. The present experiments demonstrated that MCF-7, MCF-7ras, T47D, MDA-MB-231, and MDA-MB-435 cells transiently differentiate before undergoing apoptosis in response to quinidine. The cells accumulated lipid droplets, and the cytokeratin 18 cytoskeleton was reorganized. Hyperacetylated histone H4 appeared within 2 h of the addition of quinidine to the medium, and levels were maximal by 24 h. Quinidine-treated MCF-7 cells showed elevated p21(WAF1), hypophosphorylation and suppression of retinoblastoma protein, and down-regulation of cyclin D1, similar to the cell cycle response observed with cells induced to differentiate by histone deacetylase inhibitors, trichostatin A, and trapoxin. Quinidine did not show evidence for direct inhibition of histone deacetylase enzymatic activity in vitro. HDAC1 was undetectable in MCF-7 cells 30 min after addition of quinidine to the growth medium. The proteasome inhibitors MG-132 and lactacystin completely protected HDAC1 from the action of quinidine. We conclude that quinidine is a breast tumor cell differentiating agent that causes the loss of HDAC1 via a proteasomal sensitive mechanism.\n"
],
"offsets": [
[
0,
1561
]
]
}
] | [
{
"id": "PMID-10938272_T1",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
19,
26
]
],
"normalized": []
},
{
"id": "PMID-10938272_T2",
"type": "Protein",
"text": [
"histone deacetylase-1"
],
"offsets": [
[
131,
152
]
],
"normalized": []
},
{
"id": "PMID-10938272_T3",
"type": "Protein",
"text": [
"cytokeratin 18"
],
"offsets": [
[
645,
659
]
],
"normalized": []
},
{
"id": "PMID-10938272_T4",
"type": "Protein",
"text": [
"histone H4"
],
"offsets": [
[
706,
716
]
],
"normalized": []
},
{
"id": "PMID-10938272_T5",
"type": "Protein",
"text": [
"p21"
],
"offsets": [
[
860,
863
]
],
"normalized": []
},
{
"id": "PMID-10938272_T6",
"type": "Protein",
"text": [
"WAF1"
],
"offsets": [
[
864,
868
]
],
"normalized": []
},
{
"id": "PMID-10938272_T7",
"type": "Protein",
"text": [
"retinoblastoma"
],
"offsets": [
[
910,
924
]
],
"normalized": []
},
{
"id": "PMID-10938272_T8",
"type": "Protein",
"text": [
"cyclin D1"
],
"offsets": [
[
957,
966
]
],
"normalized": []
},
{
"id": "PMID-10938272_T9",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
1051,
1058
]
],
"normalized": []
},
{
"id": "PMID-10938272_T10",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
1170,
1177
]
],
"normalized": []
},
{
"id": "PMID-10938272_T11",
"type": "Protein",
"text": [
"HDAC1"
],
"offsets": [
[
1219,
1224
]
],
"normalized": []
},
{
"id": "PMID-10938272_T12",
"type": "Protein",
"text": [
"HDAC1"
],
"offsets": [
[
1384,
1389
]
],
"normalized": []
},
{
"id": "PMID-10938272_T13",
"type": "Protein",
"text": [
"HDAC1"
],
"offsets": [
[
1516,
1521
]
],
"normalized": []
}
] | [
{
"id": "PMID-10938272_E1",
"type": "Acetylation",
"trigger": {
"text": [
"hyperacetylation"
],
"offsets": [
[
27,
43
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10938272_T1"
}
]
},
{
"id": "PMID-10938272_E2",
"type": "Acetylation",
"trigger": {
"text": [
"Hyperacetylated"
],
"offsets": [
[
690,
705
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10938272_T4"
}
]
},
{
"id": "PMID-10938272_E3",
"type": "Phosphorylation",
"trigger": {
"text": [
"hypophosphorylation"
],
"offsets": [
[
871,
890
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10938272_T5"
}
]
}
] | [
{
"id": "PMID-10938272_1",
"entity_ids": [
"PMID-10938272_T5",
"PMID-10938272_T6"
]
}
] | [] |
28 | PMID-10960154 | [
{
"id": "PMID-10960154__text",
"type": "abstract",
"text": [
"Glycosylation influences gating and pH sensitivity of I(sK). \nThe KvLQT1 and minK subunits that coassemble to form I(sK) channels, contain potential N-glycosylation sites. To examine the role of glycosylation in channel function, a Chinese hamster ovary cell line deficient in glycosylation (Lec-1) and its parental cell line (Pro-5) were transiently transfected with human KvLQT1 (hKvLQT1) cDNA, alone and in combination with the rat (rminK) or human minK (hminK) cDNA. Functional KvLQT1 and I(sK) currents were expressed in both cell lines, although amplitudes were larger in Pro-5 than Lec-1 cells transfected with hKvLQT1 and hKvLQT1/hminK. For I(sK), but not KvLQT1, the voltage-dependence of activation was shifted to more positive voltages and the activation kinetics were slower in the Lec-1 compared to the Pro-5 cells. The effect of extracellular acidification on recombinant KvLQT1 and I(sK) currents was investigated in Pro-5 and Lec-1 cells. Changing external pH (pH(o)) from 7.4 to 6.0 significantly decreased the amplitude and increased the half-activation voltage (V(1/2)) of KvLQT1 currents in Pro-5 and Lec-1 cells. In Pro-5 cells, decreasing pH(o) reduced I(sK) amplitude without increasing V(1/2), whether rminK or hminK was coexpressed with hKvLQT. In contrast, changing pH(o) from 7.4 to 6.0 did not significantly change I(sK) amplitude in Lec-1 cells. Thus, oligosaccharides attached to the minK subunit affect not only the gating properties, but also the pH sensitivity of I(sK).\n"
],
"offsets": [
[
0,
1504
]
]
}
] | [
{
"id": "PMID-10960154_T1",
"type": "Protein",
"text": [
"KvLQT1"
],
"offsets": [
[
66,
72
]
],
"normalized": []
},
{
"id": "PMID-10960154_T2",
"type": "Protein",
"text": [
"minK"
],
"offsets": [
[
77,
81
]
],
"normalized": []
},
{
"id": "PMID-10960154_T3",
"type": "Protein",
"text": [
"KvLQT1"
],
"offsets": [
[
374,
380
]
],
"normalized": []
},
{
"id": "PMID-10960154_T4",
"type": "Protein",
"text": [
"KvLQT1"
],
"offsets": [
[
383,
389
]
],
"normalized": []
},
{
"id": "PMID-10960154_T5",
"type": "Protein",
"text": [
"minK"
],
"offsets": [
[
437,
441
]
],
"normalized": []
},
{
"id": "PMID-10960154_T6",
"type": "Protein",
"text": [
"minK"
],
"offsets": [
[
452,
456
]
],
"normalized": []
},
{
"id": "PMID-10960154_T7",
"type": "Protein",
"text": [
"minK"
],
"offsets": [
[
459,
463
]
],
"normalized": []
},
{
"id": "PMID-10960154_T8",
"type": "Protein",
"text": [
"KvLQT1"
],
"offsets": [
[
482,
488
]
],
"normalized": []
},
{
"id": "PMID-10960154_T9",
"type": "Protein",
"text": [
"KvLQT1"
],
"offsets": [
[
619,
625
]
],
"normalized": []
},
{
"id": "PMID-10960154_T10",
"type": "Protein",
"text": [
"KvLQT1"
],
"offsets": [
[
631,
637
]
],
"normalized": []
},
{
"id": "PMID-10960154_T11",
"type": "Protein",
"text": [
"minK"
],
"offsets": [
[
639,
643
]
],
"normalized": []
},
{
"id": "PMID-10960154_T12",
"type": "Protein",
"text": [
"KvLQT1"
],
"offsets": [
[
664,
670
]
],
"normalized": []
},
{
"id": "PMID-10960154_T13",
"type": "Protein",
"text": [
"KvLQT1"
],
"offsets": [
[
886,
892
]
],
"normalized": []
},
{
"id": "PMID-10960154_T14",
"type": "Protein",
"text": [
"KvLQT1"
],
"offsets": [
[
1092,
1098
]
],
"normalized": []
},
{
"id": "PMID-10960154_T15",
"type": "Protein",
"text": [
"minK"
],
"offsets": [
[
1227,
1231
]
],
"normalized": []
},
{
"id": "PMID-10960154_T16",
"type": "Protein",
"text": [
"minK"
],
"offsets": [
[
1236,
1240
]
],
"normalized": []
},
{
"id": "PMID-10960154_T17",
"type": "Protein",
"text": [
"KvLQT"
],
"offsets": [
[
1263,
1268
]
],
"normalized": []
},
{
"id": "PMID-10960154_T18",
"type": "Protein",
"text": [
"minK"
],
"offsets": [
[
1414,
1418
]
],
"normalized": []
},
{
"id": "PMID-10960154_T19",
"type": "Entity",
"text": [
"oligosaccharides"
],
"offsets": [
[
1381,
1397
]
],
"normalized": []
}
] | [
{
"id": "PMID-10960154_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"attached"
],
"offsets": [
[
1398,
1406
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10960154_T18"
},
{
"role": "Sidechain",
"ref_id": "PMID-10960154_T19"
}
]
}
] | [] | [] |
29 | PMID-10973948 | [
{
"id": "PMID-10973948__text",
"type": "abstract",
"text": [
"A novel post-translational modification of yeast elongation factor 1A. Methylesterification at the C terminus. \nProtein methylation reactions can play important roles in cell physiology. After labeling intact Saccharomyces cerevisiae cells with S-adenosyl-l-[methyl-(3)H]methionine, we identified a major methylated 49-kDa polypeptide containing [(3)H]methyl groups in two distinct types of linkages. Peptide sequence analysis of the purified methylated protein revealed that it is eukaryotic elongation factor 1A (eEF1A, formerly EF-1alpha), the protein that forms a complex with GTP and aminoacyl-tRNAs for binding to the ribosomal A site during protein translation. Previous studies have shown that eEF1A is methylated on several internal lysine residues to give mono-, di-, and tri-N-epsilon-methyl-lysine derivatives. We confirm this finding but also detect methylation that is released as volatile methyl groups after base hydrolysis, characteristic of ester linkages. In cycloheximide-treated cells, methyl esterified eEF1A was detected largely in the ribosome and polysome fractions; little or no methylated protein was found in the soluble fraction. Because the base-labile, volatile [methyl-(3)H]radioactivity of eEF1A could be released by trypsin treatment but not by carboxypeptidase Y or chymotrypsin treatment, we suggest that the methyl ester is present on the alpha-carboxyl group of its C-terminal lysine residue. From the results of pulse-chase experiments using radiolabeled intact yeast cells, we find that the N-methylated lysine residues of eEF1A are stable over 4 h, whereas the eEF1A carboxyl methyl ester has a half-life of less than 10 min. The rapid turnover of the methyl ester suggests that the methylation/demethylation of eEF1A at the C-terminal carboxyl group may represent a novel mode of regulation of the activity of this protein in yeast.\n"
],
"offsets": [
[
0,
1876
]
]
}
] | [
{
"id": "PMID-10973948_T1",
"type": "Protein",
"text": [
"elongation factor 1A"
],
"offsets": [
[
49,
69
]
],
"normalized": []
},
{
"id": "PMID-10973948_T2",
"type": "Protein",
"text": [
"elongation factor 1A"
],
"offsets": [
[
494,
514
]
],
"normalized": []
},
{
"id": "PMID-10973948_T3",
"type": "Protein",
"text": [
"eEF1A"
],
"offsets": [
[
516,
521
]
],
"normalized": []
},
{
"id": "PMID-10973948_T4",
"type": "Protein",
"text": [
"EF-1alpha"
],
"offsets": [
[
532,
541
]
],
"normalized": []
},
{
"id": "PMID-10973948_T5",
"type": "Protein",
"text": [
"eEF1A"
],
"offsets": [
[
703,
708
]
],
"normalized": []
},
{
"id": "PMID-10973948_T6",
"type": "Protein",
"text": [
"eEF1A"
],
"offsets": [
[
1026,
1031
]
],
"normalized": []
},
{
"id": "PMID-10973948_T7",
"type": "Protein",
"text": [
"eEF1A"
],
"offsets": [
[
1224,
1229
]
],
"normalized": []
},
{
"id": "PMID-10973948_T8",
"type": "Protein",
"text": [
"carboxypeptidase Y"
],
"offsets": [
[
1280,
1298
]
],
"normalized": []
},
{
"id": "PMID-10973948_T9",
"type": "Protein",
"text": [
"chymotrypsin"
],
"offsets": [
[
1302,
1314
]
],
"normalized": []
},
{
"id": "PMID-10973948_T10",
"type": "Protein",
"text": [
"eEF1A"
],
"offsets": [
[
1564,
1569
]
],
"normalized": []
},
{
"id": "PMID-10973948_T11",
"type": "Protein",
"text": [
"eEF1A"
],
"offsets": [
[
1603,
1608
]
],
"normalized": []
},
{
"id": "PMID-10973948_T12",
"type": "Protein",
"text": [
"eEF1A"
],
"offsets": [
[
1754,
1759
]
],
"normalized": []
},
{
"id": "PMID-10973948_T14",
"type": "Entity",
"text": [
"C terminus"
],
"offsets": [
[
100,
110
]
],
"normalized": []
},
{
"id": "PMID-10973948_T16",
"type": "Entity",
"text": [
"lysine residues"
],
"offsets": [
[
743,
758
]
],
"normalized": []
},
{
"id": "PMID-10973948_T21",
"type": "Entity",
"text": [
"lysine residues"
],
"offsets": [
[
1545,
1560
]
],
"normalized": []
},
{
"id": "PMID-10973948_T24",
"type": "Entity",
"text": [
"C-terminal"
],
"offsets": [
[
1767,
1777
]
],
"normalized": []
}
] | [
{
"id": "PMID-10973948_E1",
"type": "Methylation",
"trigger": {
"text": [
"Methylesterification"
],
"offsets": [
[
72,
92
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10973948_T1"
},
{
"role": "Site",
"ref_id": "PMID-10973948_T14"
}
]
},
{
"id": "PMID-10973948_E2",
"type": "Methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
712,
722
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10973948_T5"
},
{
"role": "Site",
"ref_id": "PMID-10973948_T16"
}
]
},
{
"id": "PMID-10973948_E3",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
864,
875
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10973948_T5"
}
]
},
{
"id": "PMID-10973948_E4",
"type": "Methylation",
"trigger": {
"text": [
"methyl esterified"
],
"offsets": [
[
1008,
1025
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10973948_T6"
}
]
},
{
"id": "PMID-10973948_E5",
"type": "Methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
1106,
1116
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10973948_T6"
}
]
},
{
"id": "PMID-10973948_E6",
"type": "Methylation",
"trigger": {
"text": [
"N-methylated"
],
"offsets": [
[
1532,
1544
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10973948_T10"
},
{
"role": "Site",
"ref_id": "PMID-10973948_T21"
}
]
},
{
"id": "PMID-10973948_E7",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1725,
1736
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10973948_T12"
},
{
"role": "Site",
"ref_id": "PMID-10973948_T24"
}
]
},
{
"id": "PMID-10973948_E8",
"type": "Demethylation",
"trigger": {
"text": [
"demethylation"
],
"offsets": [
[
1737,
1750
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10973948_T12"
},
{
"role": "Site",
"ref_id": "PMID-10973948_T24"
}
]
}
] | [
{
"id": "PMID-10973948_1",
"entity_ids": [
"PMID-10973948_T2",
"PMID-10973948_T3",
"PMID-10973948_T4"
]
}
] | [] |
30 | PMID-11013212 | [
{
"id": "PMID-11013212__text",
"type": "abstract",
"text": [
"Decreased UDP-GlcNAc levels abrogate proliferation control in EMeg32-deficient cells. \nThe hexosamine pathway provides UDP-N:-acetylhexosamine donor substrates used in cytosolic and Golgi-mediated glycosylation of proteins and for formation of glycosylphosphatidylinositol (GPI) anchors, which tether proteins to the outer plasma membrane. We have recently identified the murine glucosamine-6-phosphate (GlcN6P) acetyltransferase, EMeg32, as a developmentally regulated enzyme on the route to UDP-N:-acetylglucosamine (UDP-GlcNAc). Here we describe embryos and cells that have the EMeg32 gene inactivated by homologous recombination. Homozygous mutant embryos die at around embryonic day (E) 7.5 with a general proliferative delay of development. In vitro differentiated EMeg32(-/-) ES cells show reduced proliferation. Mouse embryonic fibroblasts (MEFs) deficient for EMeg32 exhibit defects in proliferation and adhesiveness, which could be complemented by stable re-expression of EMeg32 or by nutritional restoration of intracellular UDP-GlcNAc levels. Reduced UDP-GlcNAc levels predominantly translated into decreased O-GlcNAc modifications of cytosolic and nuclear proteins. Interestingly, growth-impaired EMeg32(-/-) MEFs withstand a number of apoptotic stimuli and express activated PKB/AKT. Thus, EMeg32-dependent UDP-GlcNAc levels influence cell cycle progression and susceptibility to apoptotic stimuli.\n"
],
"offsets": [
[
0,
1413
]
]
}
] | [
{
"id": "PMID-11013212_T1",
"type": "Protein",
"text": [
"EMeg32"
],
"offsets": [
[
62,
68
]
],
"normalized": []
},
{
"id": "PMID-11013212_T2",
"type": "Protein",
"text": [
"glucosamine-6-phosphate (GlcN6P) acetyltransferase"
],
"offsets": [
[
379,
429
]
],
"normalized": []
},
{
"id": "PMID-11013212_T3",
"type": "Protein",
"text": [
"EMeg32"
],
"offsets": [
[
431,
437
]
],
"normalized": []
},
{
"id": "PMID-11013212_T4",
"type": "Protein",
"text": [
"EMeg32"
],
"offsets": [
[
581,
587
]
],
"normalized": []
},
{
"id": "PMID-11013212_T5",
"type": "Protein",
"text": [
"EMeg32"
],
"offsets": [
[
771,
777
]
],
"normalized": []
},
{
"id": "PMID-11013212_T6",
"type": "Protein",
"text": [
"EMeg32"
],
"offsets": [
[
869,
875
]
],
"normalized": []
},
{
"id": "PMID-11013212_T7",
"type": "Protein",
"text": [
"EMeg32"
],
"offsets": [
[
982,
988
]
],
"normalized": []
},
{
"id": "PMID-11013212_T8",
"type": "Protein",
"text": [
"EMeg32"
],
"offsets": [
[
1210,
1216
]
],
"normalized": []
},
{
"id": "PMID-11013212_T9",
"type": "Protein",
"text": [
"PKB"
],
"offsets": [
[
1289,
1292
]
],
"normalized": []
},
{
"id": "PMID-11013212_T10",
"type": "Protein",
"text": [
"AKT"
],
"offsets": [
[
1293,
1296
]
],
"normalized": []
},
{
"id": "PMID-11013212_T11",
"type": "Protein",
"text": [
"EMeg32"
],
"offsets": [
[
1304,
1310
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-11013212_1",
"entity_ids": [
"PMID-11013212_T2",
"PMID-11013212_T3"
]
},
{
"id": "PMID-11013212_2",
"entity_ids": [
"PMID-11013212_T9",
"PMID-11013212_T10"
]
}
] | [] |
31 | PMID-11032800 | [
{
"id": "PMID-11032800__text",
"type": "abstract",
"text": [
"Post-translational hydroxylation at the N-terminus of the prion protein reveals presence of PPII structure in vivo. \nThe transmissible spongiform encephalopathies are characterized by conversion of a host protein, PrP(C) (cellular prion protein), to a protease-resistant isoform, PrP(Sc) (prion protein scrapie isoform). The importance of the highly flexible, N-terminal region of PrP has recently become more widely appreciated, particularly the biological activities associated with its metal ion-binding domain and its potential to form a poly(L-proline) II (PPII) helix. Circular dichroism spectroscopy of an N-terminal peptide, PrP(37-53), showed that the PPII helix is formed in aqueous buffer; as it also contains an Xaa-Pro-Gly consensus sequence, it may act as a substrate for the collagen-modifying enzyme prolyl 4-hydroxylase. Direct evidence for this modification was obtained by mass spectrometry and Edman sequencing in recombinant mouse PrP secreted from stably transfected Chinese hamster ovary cells. Almost complete conversion of proline to 4-hydroxyproline occurs specifically at residue Pro44 of this murine protein; the same hydroxylated residue was detected, at lower levels, in PrP(Sc) from the brains of scrapie-infected mice. Cation binding and/or post-translational hydroxylation of this region of PrP may regulate its role in the physiology and pathobiology of the cell.\n"
],
"offsets": [
[
0,
1398
]
]
}
] | [
{
"id": "PMID-11032800_T1",
"type": "Protein",
"text": [
"prion protein"
],
"offsets": [
[
58,
71
]
],
"normalized": []
},
{
"id": "PMID-11032800_T2",
"type": "Protein",
"text": [
"PrP(C)"
],
"offsets": [
[
214,
220
]
],
"normalized": []
},
{
"id": "PMID-11032800_T3",
"type": "Protein",
"text": [
"prion protein"
],
"offsets": [
[
231,
244
]
],
"normalized": []
},
{
"id": "PMID-11032800_T4",
"type": "Protein",
"text": [
"PrP"
],
"offsets": [
[
280,
283
]
],
"normalized": []
},
{
"id": "PMID-11032800_T5",
"type": "Protein",
"text": [
"prion protein"
],
"offsets": [
[
289,
302
]
],
"normalized": []
},
{
"id": "PMID-11032800_T6",
"type": "Protein",
"text": [
"PrP"
],
"offsets": [
[
381,
384
]
],
"normalized": []
},
{
"id": "PMID-11032800_T7",
"type": "Protein",
"text": [
"PrP"
],
"offsets": [
[
633,
636
]
],
"normalized": []
},
{
"id": "PMID-11032800_T8",
"type": "Protein",
"text": [
"PrP"
],
"offsets": [
[
952,
955
]
],
"normalized": []
},
{
"id": "PMID-11032800_T9",
"type": "Protein",
"text": [
"PrP"
],
"offsets": [
[
1201,
1204
]
],
"normalized": []
},
{
"id": "PMID-11032800_T10",
"type": "Protein",
"text": [
"PrP"
],
"offsets": [
[
1324,
1327
]
],
"normalized": []
},
{
"id": "PMID-11032800_T12",
"type": "Entity",
"text": [
"N-terminus"
],
"offsets": [
[
40,
50
]
],
"normalized": []
},
{
"id": "PMID-11032800_T14",
"type": "Entity",
"text": [
"Pro44"
],
"offsets": [
[
1107,
1112
]
],
"normalized": []
}
] | [
{
"id": "PMID-11032800_E1",
"type": "Hydroxylation",
"trigger": {
"text": [
"hydroxylation"
],
"offsets": [
[
19,
32
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11032800_T1"
},
{
"role": "Site",
"ref_id": "PMID-11032800_T12"
}
]
},
{
"id": "PMID-11032800_E2",
"type": "Hydroxylation",
"trigger": {
"text": [
"conversion"
],
"offsets": [
[
1034,
1044
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11032800_T8"
},
{
"role": "Site",
"ref_id": "PMID-11032800_T14"
}
]
},
{
"id": "PMID-11032800_E3",
"type": "Hydroxylation",
"trigger": {
"text": [
"hydroxylated"
],
"offsets": [
[
1146,
1158
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11032800_T9"
},
{
"role": "Site",
"ref_id": "PMID-11032800_T14"
}
]
},
{
"id": "PMID-11032800_E4",
"type": "Hydroxylation",
"trigger": {
"text": [
"hydroxylation"
],
"offsets": [
[
1292,
1305
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11032800_T10"
}
]
}
] | [
{
"id": "PMID-11032800_1",
"entity_ids": [
"PMID-11032800_T2",
"PMID-11032800_T3"
]
},
{
"id": "PMID-11032800_2",
"entity_ids": [
"PMID-11032800_T4",
"PMID-11032800_T5"
]
}
] | [] |
32 | PMID-11038366 | [
{
"id": "PMID-11038366__text",
"type": "abstract",
"text": [
"Carboxymethylation of the PP2A catalytic subunit in Saccharomyces cerevisiae is required for efficient interaction with the B-type subunits Cdc55p and Rts1p. \nProtein phosphatase 2A (PP2A) is an essential eukaryotic serine/threonine phosphatase known to play important roles in cell cycle regulation. Association of different B-type targeting subunits with the heterodimeric core (A/C) enzyme is known to be an important mechanism of regulating PP2A activity, substrate specificity, and localization. However, how the binding of these targeting subunits to the A/C heterodimer might be regulated is unknown. We have used the budding yeast Saccharomyces cerevisiae as a model system to investigate the hypothesis that covalent modification of the C subunit (Pph21p/Pph22p) carboxyl terminus modulates PP2A complex formation. Two approaches were taken. First, S. cerevisiae cells were generated whose survival depended on the expression of different carboxyl-terminal Pph21p mutants. Second, the major S. cerevisiae methyltransferase (Ppm1p) that catalyzes the methylation of the PP2A C subunit carboxyl-terminal leucine was identified, and cells deleted for this methyltransferase were utilized for our studies. Our results demonstrate that binding of the yeast B subunit, Cdc55p, to Pph21p was disrupted by either acidic substitution of potential carboxyl-terminal phosphorylation sites on Pph21p or by deletion of the gene for Ppm1p. Loss of Cdc55p association was accompanied in each case by a large reduction in binding of the yeast A subunit, Tpd3p, to Pph21p. Moreover, decreased Cdc55p and Tpd3p binding invariably resulted in nocodazole sensitivity, a known phenotype of CDC55 or TPD3 deletion. Furthermore, loss of methylation also greatly reduced the association of another yeast B-type subunit, Rts1p. Thus, methylation of Pph21p is important for formation of PP2A trimeric and dimeric complexes, and consequently, for PP2A function. Taken together, our results indicate that methylation and phosphorylation may be mechanisms by which the cell dynamically regulates PP2A complex formation and function.\n"
],
"offsets": [
[
0,
2113
]
]
}
] | [
{
"id": "PMID-11038366_T1",
"type": "Protein",
"text": [
"Cdc55p"
],
"offsets": [
[
140,
146
]
],
"normalized": []
},
{
"id": "PMID-11038366_T2",
"type": "Protein",
"text": [
"Rts1p"
],
"offsets": [
[
151,
156
]
],
"normalized": []
},
{
"id": "PMID-11038366_T3",
"type": "Protein",
"text": [
"Pph21p"
],
"offsets": [
[
757,
763
]
],
"normalized": []
},
{
"id": "PMID-11038366_T4",
"type": "Protein",
"text": [
"Pph22p"
],
"offsets": [
[
764,
770
]
],
"normalized": []
},
{
"id": "PMID-11038366_T5",
"type": "Protein",
"text": [
"Pph21p"
],
"offsets": [
[
966,
972
]
],
"normalized": []
},
{
"id": "PMID-11038366_T6",
"type": "Protein",
"text": [
"Ppm1p"
],
"offsets": [
[
1033,
1038
]
],
"normalized": []
},
{
"id": "PMID-11038366_T7",
"type": "Protein",
"text": [
"Cdc55p"
],
"offsets": [
[
1272,
1278
]
],
"normalized": []
},
{
"id": "PMID-11038366_T8",
"type": "Protein",
"text": [
"Pph21p"
],
"offsets": [
[
1283,
1289
]
],
"normalized": []
},
{
"id": "PMID-11038366_T9",
"type": "Protein",
"text": [
"Pph21p"
],
"offsets": [
[
1390,
1396
]
],
"normalized": []
},
{
"id": "PMID-11038366_T10",
"type": "Protein",
"text": [
"Ppm1p"
],
"offsets": [
[
1428,
1433
]
],
"normalized": []
},
{
"id": "PMID-11038366_T11",
"type": "Protein",
"text": [
"Cdc55p"
],
"offsets": [
[
1443,
1449
]
],
"normalized": []
},
{
"id": "PMID-11038366_T12",
"type": "Protein",
"text": [
"Tpd3p"
],
"offsets": [
[
1547,
1552
]
],
"normalized": []
},
{
"id": "PMID-11038366_T13",
"type": "Protein",
"text": [
"Pph21p"
],
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[
1557,
1563
]
],
"normalized": []
},
{
"id": "PMID-11038366_T14",
"type": "Protein",
"text": [
"Cdc55p"
],
"offsets": [
[
1585,
1591
]
],
"normalized": []
},
{
"id": "PMID-11038366_T15",
"type": "Protein",
"text": [
"Tpd3p"
],
"offsets": [
[
1596,
1601
]
],
"normalized": []
},
{
"id": "PMID-11038366_T16",
"type": "Protein",
"text": [
"CDC55"
],
"offsets": [
[
1678,
1683
]
],
"normalized": []
},
{
"id": "PMID-11038366_T17",
"type": "Protein",
"text": [
"TPD3"
],
"offsets": [
[
1687,
1691
]
],
"normalized": []
},
{
"id": "PMID-11038366_T18",
"type": "Protein",
"text": [
"Rts1p"
],
"offsets": [
[
1805,
1810
]
],
"normalized": []
},
{
"id": "PMID-11038366_T19",
"type": "Protein",
"text": [
"Pph21p"
],
"offsets": [
[
1833,
1839
]
],
"normalized": []
}
] | [
{
"id": "PMID-11038366_E1",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1818,
1829
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11038366_T19"
}
]
}
] | [] | [] |
33 | PMID-11055323 | [
{
"id": "PMID-11055323__text",
"type": "abstract",
"text": [
"Safety and pharmacokinetic study with escalating doses of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy male volunteers. \nOBJECTIVES: To evaluate the safety and pharmacokinetics of 3-acetyl-7-oxo-DHEA (3beta-acetoxyandrost-5-ene-7,17-dione) given orally. DESIGN: A randomized, double blind, placebo-controlled, escalating dose study. SETTING: The Chicago Center for Clinical Research. PARTICIPANTS: Twenty-two healthy men. STUDY METHOD: The participants received placebo (n = 6) or 3-acetyl-7-oxo-DHEA (n = 16) at 50 mg/d for 7 days followed by a 7-day washout; 100 mg/d for 7 days followed by a 7-day washout; and 200 mg/d for 28 days. OUTCOME MEASURES: Safety parameters, evaluated at each dose level, included measurement of total testosterone, free testosterone, dihydrotestosterone, estradiol, cortisol, thyroxin and insulin levels. Analyses for 7-oxo-DHEA-3beta-sulfate (DHEA-S), the only detectable metabolic product of the administered steroid, were conducted on plasma drawn from all subjects at 0.25, 0.5, 1, 2, 4, 6 and 12 hours after the final 100 mg dose of 3beta-acetyl-7-oxo-DHEA. RESULTS: There were no differences in the clinical laboratory values or in reported minor adverse experiences, between treatment and placebo groups. In general, blood hormone concentrations were unaffected by the treatment with 3beta-acetyl-7-oxo-DHEA and remained within the normal range. No changes in vital signs, blood chemistry or urinalysis occurred during treatment with 3beta-acetyl-7-oxo-DHEA compared to placebo. The administered steroid was not detected in the blood but was rapidly converted to 7-oxo-DHEA-S, the concentrations of which were proportional to dose. This steroid sulfate did not accumulate; plasma concentrations 12 hours after the 3beta-acetyl-7-oxo-DHEA dose at 7 and 28 days on the 200 mg/d dose were 15.8 and 16.3 microg/L respectively. The mean time to peak plasma level of 7-oxo-DHEA-S was 2.2 hours; the mean half life was 2.17 hours. The apparent clearance averaged 172 L/h, and the apparent mean volume of distribution was 540 L. CONCLUSION: These results indicate that 3beta-acetyl-7-oxo-DHEA is safe and well tolerated in normal healthy men at doses up to 200 mg/d for 4 weeks.\n"
],
"offsets": [
[
0,
2214
]
]
}
] | [
{
"id": "PMID-11055323_T1",
"type": "Protein",
"text": [
"insulin"
],
"offsets": [
[
825,
832
]
],
"normalized": []
}
] | [] | [] | [] |
34 | PMID-11073455 | [
{
"id": "PMID-11073455__text",
"type": "abstract",
"text": [
"Aureusidin synthase: a polyphenol oxidase homolog responsible for flower coloration. \nAurones are plant flavonoids that provide yellow color to the flowers of some popular ornamental plants, such as snapdragon and cosmos. In this study, we have identified an enzyme responsible for the synthesis of aurone from chalcones in the yellow snapdragon flower. The enzyme (aureusidin synthase) is a 39-kilodalton, copper-containing glycoprotein catalyzing the hydroxylation and/or oxidative cyclization of the precursor chalcones, 2',4',6',4-tetrahydroxychalcone and 2',4',6',3,4-pentahydroxychalcone. The complementary DNA encoding aureusidin synthase is expressed in the petals of aurone-containing varieties. DNA sequence analysis revealed that aureusidin synthase belongs to the plant polyphenol oxidase family, providing an unequivocal example of the function of the polyphenol oxidase homolog in plants, i.e., flower coloration.\n"
],
"offsets": [
[
0,
928
]
]
}
] | [
{
"id": "PMID-11073455_T1",
"type": "Protein",
"text": [
"Aureusidin synthase"
],
"offsets": [
[
0,
19
]
],
"normalized": []
},
{
"id": "PMID-11073455_T2",
"type": "Protein",
"text": [
"aureusidin synthase"
],
"offsets": [
[
366,
385
]
],
"normalized": []
},
{
"id": "PMID-11073455_T3",
"type": "Protein",
"text": [
"aureusidin synthase"
],
"offsets": [
[
626,
645
]
],
"normalized": []
},
{
"id": "PMID-11073455_T4",
"type": "Protein",
"text": [
"aureusidin synthase"
],
"offsets": [
[
741,
760
]
],
"normalized": []
}
] | [] | [] | [] |
35 | PMID-11106238 | [
{
"id": "PMID-11106238__text",
"type": "abstract",
"text": [
"E-cadherin expression is silenced by 5' CpG island methylation in acute leukemia. \nE-Cadherin is a transmembrane glycoprotein that mediates Ca2+-dependent intercellular adhesion in normal epithelium. In tumors of epithelial origin, E-cadherin expression frequently is reduced, an event that contributes to tumor invasion and metastasis. The role of E-cadherin in hematopoietic tissues is less clear. In normal bone marrow, E-cadherin is expressed on erythroid progenitors, CD34+ stem cells, and stromal cells, where it likely contributes to intercellular interactions during hematopoiesis. In this study, we used a nested-PCR approach to examine the methylation status of the E-cadherin 5' CpG island in blood and bone marrow samples from normal donors and in bone marrow from patients with acute leukemia. In normal peripheral blood mononuclear cells and bone marrow, E-cadherin was completely unmethylated. In peripheral blood mononuclear cells, expression was evident by reverse transcription-PCR. Immunoblotting confirmed E-cadherin protein expression in two lymphoblastoid cell lines derived from normal donors. In contrast, E-cadherin was aberrantly methylated in 4 of 4 (100%) leukemia cell lines, 14 of 44 (32%) acute myelogenous leukemias, and 18 of 33 (53%) acute lymphoblastic leukemias. Genomic bisulfite sequencing of primary leukemias confirmed dense methylation across the CpG island. Methylation was associated with loss of E-cadherin RNA and protein in leukemia cell lines and primary leukemias. Following treatment with 5-aza-2'-deoxycytidine, a methylated leukemia cell line expressed both E-cadherin transcript and protein. Our results show that methylation of E-cadherin occurs commonly in acute leukemia and suggests a hypothesis for E-cadherin down-regulation in leukemogenesis.\n"
],
"offsets": [
[
0,
1802
]
]
}
] | [
{
"id": "PMID-11106238_T1",
"type": "Protein",
"text": [
"E-cadherin"
],
"offsets": [
[
0,
10
]
],
"normalized": []
},
{
"id": "PMID-11106238_T2",
"type": "Protein",
"text": [
"E-Cadherin"
],
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[
83,
93
]
],
"normalized": []
},
{
"id": "PMID-11106238_T3",
"type": "Protein",
"text": [
"E-cadherin"
],
"offsets": [
[
232,
242
]
],
"normalized": []
},
{
"id": "PMID-11106238_T4",
"type": "Protein",
"text": [
"E-cadherin"
],
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[
349,
359
]
],
"normalized": []
},
{
"id": "PMID-11106238_T5",
"type": "Protein",
"text": [
"E-cadherin"
],
"offsets": [
[
423,
433
]
],
"normalized": []
},
{
"id": "PMID-11106238_T6",
"type": "Protein",
"text": [
"CD34"
],
"offsets": [
[
473,
477
]
],
"normalized": []
},
{
"id": "PMID-11106238_T7",
"type": "Protein",
"text": [
"E-cadherin"
],
"offsets": [
[
676,
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]
],
"normalized": []
},
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"id": "PMID-11106238_T8",
"type": "Protein",
"text": [
"E-cadherin"
],
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869,
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]
],
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},
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"id": "PMID-11106238_T9",
"type": "Protein",
"text": [
"E-cadherin"
],
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1026,
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],
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},
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"id": "PMID-11106238_T10",
"type": "Protein",
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"E-cadherin"
],
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[
1130,
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],
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},
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"id": "PMID-11106238_T11",
"type": "Protein",
"text": [
"E-cadherin"
],
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1440,
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],
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},
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"id": "PMID-11106238_T12",
"type": "Protein",
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"E-cadherin"
],
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1609,
1619
]
],
"normalized": []
},
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"id": "PMID-11106238_T13",
"type": "Protein",
"text": [
"E-cadherin"
],
"offsets": [
[
1681,
1691
]
],
"normalized": []
},
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"id": "PMID-11106238_T14",
"type": "Protein",
"text": [
"E-cadherin"
],
"offsets": [
[
1756,
1766
]
],
"normalized": []
},
{
"id": "PMID-11106238_T15",
"type": "Entity",
"text": [
"5' CpG island"
],
"offsets": [
[
37,
50
]
],
"normalized": []
},
{
"id": "PMID-11106238_T18",
"type": "Entity",
"text": [
"5' CpG island"
],
"offsets": [
[
687,
700
]
],
"normalized": []
},
{
"id": "PMID-11106238_T22",
"type": "Entity",
"text": [
"CpG island"
],
"offsets": [
[
1388,
1398
]
],
"normalized": []
}
] | [
{
"id": "PMID-11106238_E1",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
51,
62
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11106238_T1"
},
{
"role": "Site",
"ref_id": "PMID-11106238_T15"
}
]
},
{
"id": "PMID-11106238_E2",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
650,
661
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11106238_T7"
},
{
"role": "Site",
"ref_id": "PMID-11106238_T18"
}
]
},
{
"id": "PMID-11106238_E3",
"type": "DNA_methylation",
"trigger": {
"text": [
"unmethylated"
],
"offsets": [
[
895,
907
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11106238_T8"
}
]
},
{
"id": "PMID-11106238_E4",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
1156,
1166
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11106238_T10"
}
]
},
{
"id": "PMID-11106238_E5",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1365,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11106238_T10"
},
{
"role": "Site",
"ref_id": "PMID-11106238_T22"
}
]
},
{
"id": "PMID-11106238_E6",
"type": "DNA_methylation",
"trigger": {
"text": [
"Methylation"
],
"offsets": [
[
1400,
1411
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11106238_T11"
}
]
},
{
"id": "PMID-11106238_E7",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
1564,
1574
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11106238_T12"
}
]
},
{
"id": "PMID-11106238_E8",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1666,
1677
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11106238_T13"
}
]
}
] | [] | [] |
36 | PMID-11159919 | [
{
"id": "PMID-11159919__text",
"type": "abstract",
"text": [
"Defect in N-glycosylation of proteins is tissue-dependent in congenital disorders of glycosylation Ia. \nThe biochemical hallmark of Congenital Disorders of Glycosylation (CDG) including type Ia is a defective N-glycosylation of serum glycoproteins. Hypoglycosylated forms of alpha1-antitrypsin have been detected by Western blot in serum from CDG Ia patients. In contrast we were not able to detect hypoglycosylation in alpha1-antitrypsin synthesized by fibroblasts, keratinocytes, enterocytes, and leukocytes. Similarly no hypoglycosylation was detectable in a membrane-associated N-linked glycoprotein, the facilitative glucose transporter GLUT-1 and also in serum immunoglobulin G isolated from sera of CDG Ia patients. We conclude that the phenotypic expression of CDG Ia is tissue-dependent.\n"
],
"offsets": [
[
0,
797
]
]
}
] | [
{
"id": "PMID-11159919_T1",
"type": "Protein",
"text": [
"alpha1-antitrypsin"
],
"offsets": [
[
275,
293
]
],
"normalized": []
},
{
"id": "PMID-11159919_T2",
"type": "Protein",
"text": [
"alpha1-antitrypsin"
],
"offsets": [
[
420,
438
]
],
"normalized": []
},
{
"id": "PMID-11159919_T3",
"type": "Protein",
"text": [
"GLUT-1"
],
"offsets": [
[
642,
648
]
],
"normalized": []
}
] | [
{
"id": "PMID-11159919_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"Hypoglycosylated"
],
"offsets": [
[
249,
265
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11159919_T1"
}
]
},
{
"id": "PMID-11159919_E2",
"type": "Glycosylation",
"trigger": {
"text": [
"hypoglycosylation"
],
"offsets": [
[
399,
416
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11159919_T2"
}
]
},
{
"id": "PMID-11159919_E3",
"type": "Glycosylation",
"trigger": {
"text": [
"hypoglycosylation"
],
"offsets": [
[
524,
541
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11159919_T3"
}
]
}
] | [] | [] |
37 | PMID-11162640 | [
{
"id": "PMID-11162640__text",
"type": "abstract",
"text": [
"Molecular cloning and characterization of CHM1L, a novel membrane molecule similar to chondromodulin-I. \nChondromodulin-I (ChM-I) is a cartilage-specific glycoprotein that stimulates the growth of chondrocytes and inhibits the tube formation of endothelial cells. In the present study, we identified a novel ChM-I like molecule, designated ChM1L. Cloning of full length cDNAs of human, mouse, and rat ChM1L revealed that ChM1L encodes 317 amino acids novel type II transmembrane protein. ChM1L protein was expressed on the cell surface as N-glycosylated and non-N-glycosylated protein with molecular mass of 45 and 40 kDa, respectively. In adult mouse tissues, ChM1L mRNA was highly expressed in eye, skeletal muscle, and whole rib. The temporal pattern of ChM1L mRNA was examined using whole embryo at day 10 to 19 of gestation. After day 11, ChM1L mRNA was detected and its level was progressively elevated in association with development of mouse embryo. These data suggest that ChM1L is a novel membrane molecule which is similar to ChM-I that plays a regulatory role in eye, skeletal muscle, and development of embryo.\n"
],
"offsets": [
[
0,
1124
]
]
}
] | [
{
"id": "PMID-11162640_T1",
"type": "Protein",
"text": [
"CHM1L"
],
"offsets": [
[
42,
47
]
],
"normalized": []
},
{
"id": "PMID-11162640_T2",
"type": "Protein",
"text": [
"chondromodulin-I"
],
"offsets": [
[
86,
102
]
],
"normalized": []
},
{
"id": "PMID-11162640_T3",
"type": "Protein",
"text": [
"Chondromodulin-I"
],
"offsets": [
[
105,
121
]
],
"normalized": []
},
{
"id": "PMID-11162640_T4",
"type": "Protein",
"text": [
"ChM-I"
],
"offsets": [
[
123,
128
]
],
"normalized": []
},
{
"id": "PMID-11162640_T5",
"type": "Protein",
"text": [
"ChM-I"
],
"offsets": [
[
308,
313
]
],
"normalized": []
},
{
"id": "PMID-11162640_T6",
"type": "Protein",
"text": [
"ChM1L"
],
"offsets": [
[
340,
345
]
],
"normalized": []
},
{
"id": "PMID-11162640_T7",
"type": "Protein",
"text": [
"ChM1L"
],
"offsets": [
[
401,
406
]
],
"normalized": []
},
{
"id": "PMID-11162640_T8",
"type": "Protein",
"text": [
"ChM1L"
],
"offsets": [
[
421,
426
]
],
"normalized": []
},
{
"id": "PMID-11162640_T9",
"type": "Protein",
"text": [
"ChM1L"
],
"offsets": [
[
488,
493
]
],
"normalized": []
},
{
"id": "PMID-11162640_T10",
"type": "Protein",
"text": [
"ChM1L"
],
"offsets": [
[
661,
666
]
],
"normalized": []
},
{
"id": "PMID-11162640_T11",
"type": "Protein",
"text": [
"ChM1L"
],
"offsets": [
[
757,
762
]
],
"normalized": []
},
{
"id": "PMID-11162640_T12",
"type": "Protein",
"text": [
"ChM1L"
],
"offsets": [
[
844,
849
]
],
"normalized": []
},
{
"id": "PMID-11162640_T13",
"type": "Protein",
"text": [
"ChM1L"
],
"offsets": [
[
982,
987
]
],
"normalized": []
},
{
"id": "PMID-11162640_T14",
"type": "Protein",
"text": [
"ChM-I"
],
"offsets": [
[
1037,
1042
]
],
"normalized": []
}
] | [
{
"id": "PMID-11162640_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"N-glycosylated"
],
"offsets": [
[
539,
553
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11162640_T9"
}
]
},
{
"id": "PMID-11162640_E2",
"type": "Glycosylation",
"trigger": {
"text": [
"non-N-glycosylated"
],
"offsets": [
[
558,
576
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11162640_T9"
}
]
}
] | [
{
"id": "PMID-11162640_1",
"entity_ids": [
"PMID-11162640_T3",
"PMID-11162640_T4"
]
}
] | [] |
38 | PMID-11281648 | [
{
"id": "PMID-11281648__text",
"type": "abstract",
"text": [
"Targeting of calsequestrin to the sarcoplasmic reticulum of skeletal muscle upon deletion of its glycosylation site. \nThe glycoprotein calsequestrin (CS) is segregated to the junctional sarcoplasmic reticulum (jSR) and is responsible for intraluminal Ca(2+) binding. A chimeric CS-hemoagglutinin 1 (HA1), obtained by adding the nine amino acid viral epitope hemoagglutinin to the carboxy terminal of CS and shown to be correctly segregated to skeletal muscle jSR [A. Nori, K. A. Nadalini, A. Martini, R. Rizzuto, A. Villa, and P. Volpe (1997). Chimeric calsequestrin and its targeting to the junctional sarcoplasmic reticulum of skeletal muscle. Am. J. Physiol. 272, C1420-C1428] lends itself as a molecular tool to investigate the targeting domains of CS. A putative targeting mechanism of CS to jSR implies glycosylation-dependent steps in the endoplasmic reticulum (ER) and Golgi complex. To test this hypothesis, CS-HA1DeltaGly, a mutant in which the unique N-glycosylation site Asn316 was changed to Ile, was engineered by site-directed mutagenesis. The mutant cDNA was transiently transfected in either HeLa cells, myoblasts of rat skeletal muscle primary cultures, or regenerating soleus muscle fibers of adult rats. The expression and intracellular localization of CS-HA1DeltaGly was studied by double-labeling epifluorescence by means of antibodies against either CS, HA1, or the ryanodine receptor calcium release channel. CS-HA1DeltaGly was expressed and retained to ER and ER/sarcoplasmic reticulum of HeLa cells and myotubes, respectively, and expressed, sorted, and correctly segregated to jSR of regenerating soleus muscle fibers. Thus, the targeting mechanism of CS in vivo appears not to be affected by glycosylation-that is, the sorting, docking, and segregation of CS are independent of cotranslational and posttranslational glycosylation or glycosylations.\n"
],
"offsets": [
[
0,
1877
]
]
}
] | [
{
"id": "PMID-11281648_T1",
"type": "Protein",
"text": [
"hemoagglutinin 1"
],
"offsets": [
[
281,
297
]
],
"normalized": []
},
{
"id": "PMID-11281648_T2",
"type": "Protein",
"text": [
"HA1"
],
"offsets": [
[
299,
302
]
],
"normalized": []
},
{
"id": "PMID-11281648_T3",
"type": "Protein",
"text": [
"hemoagglutinin"
],
"offsets": [
[
358,
372
]
],
"normalized": []
},
{
"id": "PMID-11281648_T4",
"type": "Protein",
"text": [
"HA1"
],
"offsets": [
[
920,
923
]
],
"normalized": []
},
{
"id": "PMID-11281648_T5",
"type": "Protein",
"text": [
"HA1"
],
"offsets": [
[
1276,
1279
]
],
"normalized": []
},
{
"id": "PMID-11281648_T6",
"type": "Protein",
"text": [
"HA1"
],
"offsets": [
[
1377,
1380
]
],
"normalized": []
},
{
"id": "PMID-11281648_T7",
"type": "Protein",
"text": [
"HA1"
],
"offsets": [
[
1436,
1439
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-11281648_1",
"entity_ids": [
"PMID-11281648_T1",
"PMID-11281648_T2"
]
}
] | [] |
39 | PMID-11292861 | [
{
"id": "PMID-11292861__text",
"type": "abstract",
"text": [
"Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. \nHypoxia-inducible factor (HIF) is a transcriptional complex that plays a central role in the regulation of gene expression by oxygen. In oxygenated and iron replete cells, HIF-alpha subunits are rapidly destroyed by a mechanism that involves ubiquitylation by the von Hippel-Lindau tumor suppressor (pVHL) E3 ligase complex. This process is suppressed by hypoxia and iron chelation, allowing transcriptional activation. Here we show that the interaction between human pVHL and a specific domain of the HIF-1alpha subunit is regulated through hydroxylation of a proline residue (HIF-1alpha P564) by an enzyme we have termed HIF-alpha prolyl-hydroxylase (HIF-PH). An absolute requirement for dioxygen as a cosubstrate and iron as cofactor suggests that HIF-PH functions directly as a cellular oxygen sensor.\n"
],
"offsets": [
[
0,
916
]
]
}
] | [
{
"id": "PMID-11292861_T1",
"type": "Protein",
"text": [
"von Hippel-Lindau"
],
"offsets": [
[
30,
47
]
],
"normalized": []
},
{
"id": "PMID-11292861_T2",
"type": "Protein",
"text": [
"von Hippel-Lindau tumor suppressor"
],
"offsets": [
[
374,
408
]
],
"normalized": []
},
{
"id": "PMID-11292861_T3",
"type": "Protein",
"text": [
"pVHL"
],
"offsets": [
[
410,
414
]
],
"normalized": []
},
{
"id": "PMID-11292861_T4",
"type": "Protein",
"text": [
"pVHL"
],
"offsets": [
[
578,
582
]
],
"normalized": []
},
{
"id": "PMID-11292861_T5",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
612,
622
]
],
"normalized": []
},
{
"id": "PMID-11292861_T6",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
688,
698
]
],
"normalized": []
},
{
"id": "PMID-11292861_T8",
"type": "Entity",
"text": [
"P564"
],
"offsets": [
[
699,
703
]
],
"normalized": []
}
] | [
{
"id": "PMID-11292861_E1",
"type": "Hydroxylation",
"trigger": {
"text": [
"hydroxylation"
],
"offsets": [
[
652,
665
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11292861_T5"
},
{
"role": "Site",
"ref_id": "PMID-11292861_T8"
}
]
}
] | [
{
"id": "PMID-11292861_1",
"entity_ids": [
"PMID-11292861_T2",
"PMID-11292861_T3"
]
}
] | [] |
40 | PMID-11292862 | [
{
"id": "PMID-11292862__text",
"type": "abstract",
"text": [
"HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. \nHIF (hypoxia-inducible factor) is a transcription factor that plays a pivotal role in cellular adaptation to changes in oxygen availability. In the presence of oxygen, HIF is targeted for destruction by an E3 ubiquitin ligase containing the von Hippel-Lindau tumor suppressor protein (pVHL). We found that human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated. Because proline hydroxylation requires molecular oxygen and Fe(2+), this protein modification may play a key role in mammalian oxygen sensing.\n"
],
"offsets": [
[
0,
678
]
]
}
] | [
{
"id": "PMID-11292862_T1",
"type": "Protein",
"text": [
"VHL"
],
"offsets": [
[
22,
25
]
],
"normalized": []
},
{
"id": "PMID-11292862_T2",
"type": "Protein",
"text": [
"ubiquitin"
],
"offsets": [
[
312,
321
]
],
"normalized": []
},
{
"id": "PMID-11292862_T3",
"type": "Protein",
"text": [
"von Hippel-Lindau tumor suppressor"
],
"offsets": [
[
344,
378
]
],
"normalized": []
},
{
"id": "PMID-11292862_T4",
"type": "Protein",
"text": [
"pVHL"
],
"offsets": [
[
388,
392
]
],
"normalized": []
},
{
"id": "PMID-11292862_T5",
"type": "Protein",
"text": [
"pVHL"
],
"offsets": [
[
415,
419
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-11292862_1",
"entity_ids": [
"PMID-11292862_T3",
"PMID-11292862_T4"
]
}
] | [] |
41 | PMID-11306499 | [
{
"id": "PMID-11306499__text",
"type": "abstract",
"text": [
"Genetic and clinical features of human pancreatic ductal adenocarcinomas with widespread microsatellite instability. \nThe incidences of microsatellite instability (MSI) and underlying DNA mismatch repair (MMR) defects in pancreatic carcinogenesis have not been well established. We analyzed 100 sporadic and 3 hereditary pancreatic ductal adenocarcinomas for MSI, and high-frequency MSI (MSI-H) and low-frequency MSI (MSI-L) tumors were further analyzed for frameshift mutations of possible target genes and for promoter methylation and mutation of DNA MMR genes, including hMLH1, hMSH2, hMSH3, and hMSH6 genes. Among the 100 sporadic tumors, 13 (13%) were MSI-H, 13 (13%) were MSI-L, and 74 (74%) were microsatellite stable (MSS) tumors. All of the three hereditary tumors from hereditary nonpolyposis colorectal cancer (HNPCC) patients were MSI-H. MSI-H tumors were significantly associated with poor differentiation and the presence of wild-type K-RAS and p53 genes. Patients with MSI-H tumors had a significantly longer overall survival time than did those with MSI-L or MSS tumors (P = 0.0057). Frameshift mutations of hMSH3, hMLH3, BRCA-2, TGF-beta type II receptor, and BAX genes were detected in MSI-H tumors. Hypermethylation of the hMLH1 promoter was observed in 6 (46%) of the 13 sporadic MSI-H tumors but not in any of the 3 hereditary MSI-H tumors or 13 MSI-L tumors. All of the 3 HNPCC cases had germ-line hMLH1 mutation accompanied by loss of heterogeneity or other mutation in the tumor. Our results suggest that pancreatic carcinomas with MSI-H represent a distinctive oncogenic pathway because they exhibit peculiar clinical, pathological, and molecular characteristics. Our results also suggest the principal involvement of epigenetic or genetic inactivation of the hMLH1 gene in the pathogenesis of pancreatic carcinoma with MSI-H.\n"
],
"offsets": [
[
0,
1852
]
]
}
] | [
{
"id": "PMID-11306499_T1",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
575,
579
]
],
"normalized": []
},
{
"id": "PMID-11306499_T2",
"type": "Protein",
"text": [
"MSH2"
],
"offsets": [
[
582,
586
]
],
"normalized": []
},
{
"id": "PMID-11306499_T3",
"type": "Protein",
"text": [
"MSH3"
],
"offsets": [
[
589,
593
]
],
"normalized": []
},
{
"id": "PMID-11306499_T4",
"type": "Protein",
"text": [
"MSH6"
],
"offsets": [
[
600,
604
]
],
"normalized": []
},
{
"id": "PMID-11306499_T5",
"type": "Protein",
"text": [
"K-RAS"
],
"offsets": [
[
949,
954
]
],
"normalized": []
},
{
"id": "PMID-11306499_T6",
"type": "Protein",
"text": [
"p53"
],
"offsets": [
[
959,
962
]
],
"normalized": []
},
{
"id": "PMID-11306499_T7",
"type": "Protein",
"text": [
"MSH3"
],
"offsets": [
[
1125,
1129
]
],
"normalized": []
},
{
"id": "PMID-11306499_T8",
"type": "Protein",
"text": [
"MLH3"
],
"offsets": [
[
1132,
1136
]
],
"normalized": []
},
{
"id": "PMID-11306499_T9",
"type": "Protein",
"text": [
"BRCA-2"
],
"offsets": [
[
1138,
1144
]
],
"normalized": []
},
{
"id": "PMID-11306499_T10",
"type": "Protein",
"text": [
"TGF-beta type II receptor"
],
"offsets": [
[
1146,
1171
]
],
"normalized": []
},
{
"id": "PMID-11306499_T11",
"type": "Protein",
"text": [
"BAX"
],
"offsets": [
[
1177,
1180
]
],
"normalized": []
},
{
"id": "PMID-11306499_T12",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
1243,
1247
]
],
"normalized": []
},
{
"id": "PMID-11306499_T13",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
1421,
1425
]
],
"normalized": []
},
{
"id": "PMID-11306499_T14",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
1786,
1790
]
],
"normalized": []
},
{
"id": "PMID-11306499_T15",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
512,
520
]
],
"normalized": []
},
{
"id": "PMID-11306499_T18",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1248,
1256
]
],
"normalized": []
}
] | [
{
"id": "PMID-11306499_E1",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
521,
532
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11306499_T1"
},
{
"role": "Site",
"ref_id": "PMID-11306499_T15"
}
]
},
{
"id": "PMID-11306499_E2",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
521,
532
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11306499_T2"
},
{
"role": "Site",
"ref_id": "PMID-11306499_T15"
}
]
},
{
"id": "PMID-11306499_E3",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
521,
532
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11306499_T3"
},
{
"role": "Site",
"ref_id": "PMID-11306499_T15"
}
]
},
{
"id": "PMID-11306499_E4",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
521,
532
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11306499_T4"
},
{
"role": "Site",
"ref_id": "PMID-11306499_T15"
}
]
},
{
"id": "PMID-11306499_E5",
"type": "DNA_methylation",
"trigger": {
"text": [
"Hypermethylation"
],
"offsets": [
[
1218,
1234
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11306499_T12"
},
{
"role": "Site",
"ref_id": "PMID-11306499_T18"
}
]
}
] | [] | [] |
42 | PMID-11327822 | [
{
"id": "PMID-11327822__text",
"type": "abstract",
"text": [
"The acetylation state of human fetal hemoglobin modulates the strength of its subunit interactions: long-range effects and implications for histone interactions in the nucleosome. \nThe source of the 70-fold increased tetramer strength of liganded fetal hemoglobin relative to that of adult hemoglobin between pH 6.0 and 7.5 reported earlier [Dumoulin et al. (1997) J. Biol. Chem. 272, 31326] has been identified as the N-terminal Gly residue of the gamma-chain, which is replaced by Val in adult hemoglobin. This was revealed by extending the study of the pH dependence of the tetramer-dimer equilibrium of these hemoglobins into the alkaline range as far as pH 9. From pH 7.5 to 9.0, the 70-fold difference in the association equilibrium constant between hemoglobins F and A lessened progressively. This behavior was attributed to the difference in the pK(a) 8.1 of Gly-1(gamma) compared to the pK(a) 7.1 value of Val-1(beta) of hemoglobins F and A, respectively. Evidence for this conclusion was obtained by demonstrating that natural hemoglobin F(1), which is specifically acetylated at Gly-1(gamma) and hence unable to be protonated, behaves like HbA and not HbF in its tetramer-dimer association properties over the pH range studied. An increased degree of protonation of the gamma-chain N-terminus of hemoglobin F from pH 9.0 to 8.0 is therefore suggested as responsible for its increased tetramer strength representing an example of transmission of a signal from its positively charged N-terminal tail to the distant subunit allosteric interface where the equilibrium constant is measured. An analogy is made between the effects of acetylation of the fetal hemoglobin tetramer on the strength of its subunit interactions and acetylation of some internal Lys residues within the N-terminal segments of the histone octamer around which DNA is wrapped in the nucleosome.\n"
],
"offsets": [
[
0,
1875
]
]
}
] | [
{
"id": "PMID-11327822_T1",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
140,
147
]
],
"normalized": []
}
] | [] | [] | [] |
43 | PMID-11352938 | [
{
"id": "PMID-11352938__text",
"type": "abstract",
"text": [
"Synergism of Xist RNA, DNA methylation, and histone hypoacetylation in maintaining X chromosome inactivation. \nXist RNA expression, methylation of CpG islands, and hypoacetylation of histone H4 are distinguishing features of inactive X chromatin. Here, we show that these silencing mechanisms act synergistically to maintain the inactive state. Xist RNA has been shown to be essential for initiation of X inactivation, but not required for maintenance. We have developed a system in which the reactivation frequency of individual X-linked genes can be assessed quantitatively. Using a conditional mutant Xist allele, we provide direct evidence for that loss of Xist RNA destabilizes the inactive state in somatic cells, leading to an increased reactivation frequency of an X-linked GFP transgene and of the endogenous hypoxanthine phosphoribosyl transferase (Hprt) gene in mouse embryonic fibroblasts. Demethylation of DNA, using 5-azadC or by introducing a mutation in Dnmt1, and inhibition of histone hypoacetylation using trichostatin A further increases reactivation in Xist mutant fibroblasts, indicating a synergistic interaction of X chromosome silencing mechanisms.\n"
],
"offsets": [
[
0,
1174
]
]
}
] | [
{
"id": "PMID-11352938_T1",
"type": "Protein",
"text": [
"Xist"
],
"offsets": [
[
13,
17
]
],
"normalized": []
},
{
"id": "PMID-11352938_T2",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
44,
51
]
],
"normalized": []
},
{
"id": "PMID-11352938_T3",
"type": "Protein",
"text": [
"Xist"
],
"offsets": [
[
111,
115
]
],
"normalized": []
},
{
"id": "PMID-11352938_T4",
"type": "Protein",
"text": [
"histone H4"
],
"offsets": [
[
183,
193
]
],
"normalized": []
},
{
"id": "PMID-11352938_T5",
"type": "Protein",
"text": [
"Xist"
],
"offsets": [
[
345,
349
]
],
"normalized": []
},
{
"id": "PMID-11352938_T6",
"type": "Protein",
"text": [
"Xist"
],
"offsets": [
[
604,
608
]
],
"normalized": []
},
{
"id": "PMID-11352938_T7",
"type": "Protein",
"text": [
"Xist"
],
"offsets": [
[
661,
665
]
],
"normalized": []
},
{
"id": "PMID-11352938_T8",
"type": "Protein",
"text": [
"GFP"
],
"offsets": [
[
782,
785
]
],
"normalized": []
},
{
"id": "PMID-11352938_T9",
"type": "Protein",
"text": [
"hypoxanthine phosphoribosyl transferase"
],
"offsets": [
[
818,
857
]
],
"normalized": []
},
{
"id": "PMID-11352938_T10",
"type": "Protein",
"text": [
"Hprt"
],
"offsets": [
[
859,
863
]
],
"normalized": []
},
{
"id": "PMID-11352938_T11",
"type": "Protein",
"text": [
"Dnmt1"
],
"offsets": [
[
970,
975
]
],
"normalized": []
},
{
"id": "PMID-11352938_T12",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
995,
1002
]
],
"normalized": []
},
{
"id": "PMID-11352938_T13",
"type": "Protein",
"text": [
"Xist"
],
"offsets": [
[
1074,
1078
]
],
"normalized": []
}
] | [
{
"id": "PMID-11352938_E1",
"type": "Acetylation",
"trigger": {
"text": [
"hypoacetylation"
],
"offsets": [
[
52,
67
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11352938_T2"
}
]
},
{
"id": "PMID-11352938_E2",
"type": "Acetylation",
"trigger": {
"text": [
"hypoacetylation"
],
"offsets": [
[
164,
179
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11352938_T4"
}
]
},
{
"id": "PMID-11352938_E3",
"type": "Acetylation",
"trigger": {
"text": [
"hypoacetylation"
],
"offsets": [
[
1003,
1018
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11352938_T12"
}
]
}
] | [
{
"id": "PMID-11352938_1",
"entity_ids": [
"PMID-11352938_T9",
"PMID-11352938_T10"
]
}
] | [] |
44 | PMID-11357511 | [
{
"id": "PMID-11357511__text",
"type": "abstract",
"text": [
"Expression of Pichia anomala INV1 gene in Saccharomyces cerevisiae results in two different active forms of hypoglycosylated invertase. \nThe Pichia anomala invertase gene (INV1) was introduced at different copy numbers into a sucrose-nonfermenting mutant of Saccharomyces cerevisiae and expressed from its own promoter sequences. The level reached in the production of invertase by the transformants (up to 540 units/10(10) cells) was in agreement with the INV1 gene dosage. Two forms of multimeric active and glycosylated invertase displaying different subcellular locations and molecular masses could be detected in the transformants. One was found to be present in the culture medium and in the periplasm, and the other could only be detected inside the cell. Each of the two heterologous forms of invertase was shown to be an oligomer composed of identical subunits. The difference found in the apparent molecular masses of their monomers (81.5 and 78.3 kDa, respectively) seems to be due to the size of their N-linked oligosaccharide chains (on average 2.4 and 1.9 kDa, respectively), since the number of sugar chains (9) and the molecular mass of the protein moiety (60.5 kDa) are identical in both forms. The shorter size of their oligosaccharides must also be the reason for the lower apparent molecular masses of the heterologous invertases when compared with the enzyme purified from P. anomala. The hypoglycosylated invertase accumulated within the cells of the transformants to an unusual level (up to 130 units/10(10) cells). Such accumulation of active enzyme inside the cells, as well as its underglycosylation, could be due to intrinsic properties of the P. anomala invertase that are determined by the particular primary structure of its protein moiety.\n"
],
"offsets": [
[
0,
1771
]
]
}
] | [
{
"id": "PMID-11357511_T1",
"type": "Protein",
"text": [
"INV1"
],
"offsets": [
[
29,
33
]
],
"normalized": []
},
{
"id": "PMID-11357511_T2",
"type": "Protein",
"text": [
"invertase"
],
"offsets": [
[
125,
134
]
],
"normalized": []
},
{
"id": "PMID-11357511_T3",
"type": "Protein",
"text": [
"invertase"
],
"offsets": [
[
156,
165
]
],
"normalized": []
},
{
"id": "PMID-11357511_T4",
"type": "Protein",
"text": [
"INV1"
],
"offsets": [
[
172,
176
]
],
"normalized": []
},
{
"id": "PMID-11357511_T5",
"type": "Protein",
"text": [
"invertase"
],
"offsets": [
[
369,
378
]
],
"normalized": []
},
{
"id": "PMID-11357511_T6",
"type": "Protein",
"text": [
"INV1"
],
"offsets": [
[
457,
461
]
],
"normalized": []
},
{
"id": "PMID-11357511_T7",
"type": "Protein",
"text": [
"invertase"
],
"offsets": [
[
523,
532
]
],
"normalized": []
},
{
"id": "PMID-11357511_T8",
"type": "Protein",
"text": [
"invertase"
],
"offsets": [
[
801,
810
]
],
"normalized": []
},
{
"id": "PMID-11357511_T9",
"type": "Protein",
"text": [
"invertase"
],
"offsets": [
[
1427,
1436
]
],
"normalized": []
},
{
"id": "PMID-11357511_T10",
"type": "Protein",
"text": [
"invertase"
],
"offsets": [
[
1682,
1691
]
],
"normalized": []
},
{
"id": "PMID-11357511_T14",
"type": "Entity",
"text": [
"oligosaccharide chains"
],
"offsets": [
[
1023,
1045
]
],
"normalized": []
}
] | [
{
"id": "PMID-11357511_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"hypoglycosylated"
],
"offsets": [
[
108,
124
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11357511_T1"
}
]
},
{
"id": "PMID-11357511_E2",
"type": "Glycosylation",
"trigger": {
"text": [
"glycosylated"
],
"offsets": [
[
510,
522
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11357511_T7"
}
]
},
{
"id": "PMID-11357511_E3",
"type": "Glycosylation",
"trigger": {
"text": [
"N-linked"
],
"offsets": [
[
1014,
1022
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11357511_T8"
},
{
"role": "Sidechain",
"ref_id": "PMID-11357511_T14"
}
]
},
{
"id": "PMID-11357511_E4",
"type": "Glycosylation",
"trigger": {
"text": [
"hypoglycosylated"
],
"offsets": [
[
1410,
1426
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11357511_T9"
}
]
},
{
"id": "PMID-11357511_E5",
"type": "Glycosylation",
"trigger": {
"text": [
"underglycosylation"
],
"offsets": [
[
1607,
1625
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11357511_T10"
}
]
}
] | [
{
"id": "PMID-11357511_1",
"entity_ids": [
"PMID-11357511_T1",
"PMID-11357511_T2"
]
},
{
"id": "PMID-11357511_2",
"entity_ids": [
"PMID-11357511_T3",
"PMID-11357511_T4"
]
}
] | [] |
45 | PMID-11384967 | [
{
"id": "PMID-11384967__text",
"type": "abstract",
"text": [
"The histone acetyltransferase, hGCN5, interacts with and acetylates the HIV transactivator, Tat. \nFactor acetyltransferase activity associated with several histone acetyltransferases plays a key role in the control of transcription. Here we report that hGCN5, a well known histone acetyltransferase, specifically interacts with and acetylates the human immunodeficiency virus type 1 (HIV-1) transactivator protein, Tat. The interaction between Tat and hGCN5 is direct and involves the acetyltransferase and the bromodomain regions of hGCN5, as well as a limited region of Tat encompassing the cysteine-rich domain of the protein. Tat lysines 50 and 51, target of acetylation by p300/CBP, were also found to be acetylated by hGCN5. The acetylation of these two lysines by p300/CBP has been recently shown to stimulate Tat transcriptional activity and accordingly, we have found that hGCN5 can considerably enhance Tat-dependent transcription of the HIV-1 long terminal repeat. These data highlight the importance of the acetylation of lysines 50 and 51 in the function of Tat, since different histone acetyltransferases involved in distinct signaling pathways, GCN5 and p300/CBP, converge to acetylate Tat on the same site.\n"
],
"offsets": [
[
0,
1223
]
]
}
] | [
{
"id": "PMID-11384967_T1",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
4,
11
]
],
"normalized": []
},
{
"id": "PMID-11384967_T2",
"type": "Protein",
"text": [
"GCN5"
],
"offsets": [
[
32,
36
]
],
"normalized": []
},
{
"id": "PMID-11384967_T3",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
92,
95
]
],
"normalized": []
},
{
"id": "PMID-11384967_T4",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
156,
163
]
],
"normalized": []
},
{
"id": "PMID-11384967_T5",
"type": "Protein",
"text": [
"GCN5"
],
"offsets": [
[
254,
258
]
],
"normalized": []
},
{
"id": "PMID-11384967_T6",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
273,
280
]
],
"normalized": []
},
{
"id": "PMID-11384967_T7",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
415,
418
]
],
"normalized": []
},
{
"id": "PMID-11384967_T8",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
444,
447
]
],
"normalized": []
},
{
"id": "PMID-11384967_T9",
"type": "Protein",
"text": [
"GCN5"
],
"offsets": [
[
453,
457
]
],
"normalized": []
},
{
"id": "PMID-11384967_T10",
"type": "Protein",
"text": [
"GCN5"
],
"offsets": [
[
535,
539
]
],
"normalized": []
},
{
"id": "PMID-11384967_T11",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
572,
575
]
],
"normalized": []
},
{
"id": "PMID-11384967_T12",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
630,
633
]
],
"normalized": []
},
{
"id": "PMID-11384967_T13",
"type": "Protein",
"text": [
"p300"
],
"offsets": [
[
678,
682
]
],
"normalized": []
},
{
"id": "PMID-11384967_T14",
"type": "Protein",
"text": [
"CBP"
],
"offsets": [
[
683,
686
]
],
"normalized": []
},
{
"id": "PMID-11384967_T15",
"type": "Protein",
"text": [
"GCN5"
],
"offsets": [
[
725,
729
]
],
"normalized": []
},
{
"id": "PMID-11384967_T16",
"type": "Protein",
"text": [
"p300"
],
"offsets": [
[
771,
775
]
],
"normalized": []
},
{
"id": "PMID-11384967_T17",
"type": "Protein",
"text": [
"CBP"
],
"offsets": [
[
776,
779
]
],
"normalized": []
},
{
"id": "PMID-11384967_T18",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
817,
820
]
],
"normalized": []
},
{
"id": "PMID-11384967_T19",
"type": "Protein",
"text": [
"GCN5"
],
"offsets": [
[
883,
887
]
],
"normalized": []
},
{
"id": "PMID-11384967_T20",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
913,
916
]
],
"normalized": []
},
{
"id": "PMID-11384967_T21",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
1071,
1074
]
],
"normalized": []
},
{
"id": "PMID-11384967_T22",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
1092,
1099
]
],
"normalized": []
},
{
"id": "PMID-11384967_T23",
"type": "Protein",
"text": [
"GCN5"
],
"offsets": [
[
1160,
1164
]
],
"normalized": []
},
{
"id": "PMID-11384967_T24",
"type": "Protein",
"text": [
"p300"
],
"offsets": [
[
1169,
1173
]
],
"normalized": []
},
{
"id": "PMID-11384967_T25",
"type": "Protein",
"text": [
"CBP"
],
"offsets": [
[
1174,
1177
]
],
"normalized": []
},
{
"id": "PMID-11384967_T26",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
1201,
1204
]
],
"normalized": []
},
{
"id": "PMID-11384967_T31",
"type": "Entity",
"text": [
"lysines 50"
],
"offsets": [
[
634,
644
]
],
"normalized": []
},
{
"id": "PMID-11384967_T32",
"type": "Entity",
"text": [
"51"
],
"offsets": [
[
649,
651
]
],
"normalized": []
},
{
"id": "PMID-11384967_T37",
"type": "Entity",
"text": [
"lysines"
],
"offsets": [
[
760,
767
]
],
"normalized": []
},
{
"id": "PMID-11384967_T39",
"type": "Entity",
"text": [
"lysines 50"
],
"offsets": [
[
1034,
1044
]
],
"normalized": []
},
{
"id": "PMID-11384967_T40",
"type": "Entity",
"text": [
"51"
],
"offsets": [
[
1049,
1051
]
],
"normalized": []
}
] | [
{
"id": "PMID-11384967_E1",
"type": "Acetylation",
"trigger": {
"text": [
"acetylates"
],
"offsets": [
[
57,
67
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11384967_T3"
}
]
},
{
"id": "PMID-11384967_E2",
"type": "Catalysis",
"trigger": {
"text": [
"acetylates"
],
"offsets": [
[
57,
67
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11384967_T3"
},
{
"role": "Cause",
"ref_id": "PMID-11384967_T2"
}
]
},
{
"id": "PMID-11384967_E3",
"type": "Acetylation",
"trigger": {
"text": [
"acetylates"
],
"offsets": [
[
332,
342
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11384967_T7"
}
]
},
{
"id": "PMID-11384967_E4",
"type": "Catalysis",
"trigger": {
"text": [
"acetylates"
],
"offsets": [
[
332,
342
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11384967_E3"
},
{
"role": "Cause",
"ref_id": "PMID-11384967_T5"
}
]
},
{
"id": "PMID-11384967_E5",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
663,
674
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11384967_T12"
},
{
"role": "Site",
"ref_id": "PMID-11384967_T31"
}
]
},
{
"id": "PMID-11384967_E6",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
663,
674
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11384967_T12"
},
{
"role": "Site",
"ref_id": "PMID-11384967_T32"
}
]
},
{
"id": "PMID-11384967_E7",
"type": "Acetylation",
"trigger": {
"text": [
"acetylated"
],
"offsets": [
[
710,
720
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11384967_T12"
},
{
"role": "Site",
"ref_id": "PMID-11384967_T31"
}
]
},
{
"id": "PMID-11384967_E8",
"type": "Catalysis",
"trigger": {
"text": [
"acetylated"
],
"offsets": [
[
710,
720
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11384967_E7"
},
{
"role": "Cause",
"ref_id": "PMID-11384967_T15"
}
]
},
{
"id": "PMID-11384967_E9",
"type": "Acetylation",
"trigger": {
"text": [
"acetylated"
],
"offsets": [
[
710,
720
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11384967_T12"
},
{
"role": "Site",
"ref_id": "PMID-11384967_T32"
}
]
},
{
"id": "PMID-11384967_E10",
"type": "Catalysis",
"trigger": {
"text": [
"acetylated"
],
"offsets": [
[
710,
720
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11384967_E9"
},
{
"role": "Cause",
"ref_id": "PMID-11384967_T15"
}
]
},
{
"id": "PMID-11384967_E11",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
735,
746
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11384967_T12"
},
{
"role": "Site",
"ref_id": "PMID-11384967_T37"
}
]
},
{
"id": "PMID-11384967_E12",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
1019,
1030
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11384967_T21"
},
{
"role": "Site",
"ref_id": "PMID-11384967_T39"
}
]
},
{
"id": "PMID-11384967_E13",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
1019,
1030
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11384967_T21"
},
{
"role": "Site",
"ref_id": "PMID-11384967_T40"
}
]
},
{
"id": "PMID-11384967_E14",
"type": "Acetylation",
"trigger": {
"text": [
"acetylate"
],
"offsets": [
[
1191,
1200
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11384967_T26"
},
{
"role": "Site",
"ref_id": "PMID-11384967_T39"
}
]
},
{
"id": "PMID-11384967_E15",
"type": "Catalysis",
"trigger": {
"text": [
"acetylate"
],
"offsets": [
[
1191,
1200
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11384967_E14"
},
{
"role": "Cause",
"ref_id": "PMID-11384967_T23"
}
]
},
{
"id": "PMID-11384967_E16",
"type": "Acetylation",
"trigger": {
"text": [
"acetylate"
],
"offsets": [
[
1191,
1200
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11384967_T26"
},
{
"role": "Site",
"ref_id": "PMID-11384967_T40"
}
]
},
{
"id": "PMID-11384967_E17",
"type": "Catalysis",
"trigger": {
"text": [
"acetylate"
],
"offsets": [
[
1191,
1200
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11384967_E16"
},
{
"role": "Cause",
"ref_id": "PMID-11384967_T23"
}
]
}
] | [] | [] |
46 | PMID-113854 | [
{
"id": "PMID-113854__text",
"type": "abstract",
"text": [
"Hydroxylating activity of frog epidermis tyrosinase. \nTrypsin activated in a similar way both the tyrosine hydroxylase and the dopa-oxidasa activities of frog epidermis tyrosinase. Several electron donors reduced or eliminated the lag period for the hydroxylating enzyme. 4 x 10(-5) M dopa was particularly effective, but without affecting the stationary activity after lag period. Tyrosine hydroxylase had KM = 2.6 X 10(-3) M for tyrosine and 2 x 10(-3) M dopa was a competitive inhibitor with Ki = 5 x 10(-4) M. The enzyme was inactivated during its actuation. Data on thermal denaturation were similar to other obtained from dopa oxidase. Our results tend to confirm our previous hypothesis that the activatory process of the enzyme is accompanied by a spatial unfolding of the enzyme molecule.\n"
],
"offsets": [
[
0,
798
]
]
}
] | [
{
"id": "PMID-113854_T1",
"type": "Protein",
"text": [
"tyrosinase"
],
"offsets": [
[
41,
51
]
],
"normalized": []
},
{
"id": "PMID-113854_T2",
"type": "Protein",
"text": [
"tyrosine hydroxylase"
],
"offsets": [
[
98,
118
]
],
"normalized": []
},
{
"id": "PMID-113854_T3",
"type": "Protein",
"text": [
"tyrosinase"
],
"offsets": [
[
169,
179
]
],
"normalized": []
},
{
"id": "PMID-113854_T4",
"type": "Protein",
"text": [
"Tyrosine hydroxylase"
],
"offsets": [
[
382,
402
]
],
"normalized": []
}
] | [] | [] | [] |
47 | PMID-11393792 | [
{
"id": "PMID-11393792__text",
"type": "abstract",
"text": [
"Canine COL1A2 mutation resulting in C-terminal truncation of pro-alpha2(I) and severe osteogenesis imperfecta. \nRNA and type I collagen were analyzed from cultured skin fibroblasts of a Beagle puppy with fractures consistent with type III osteogenesis imperfecta (OI). In a nonisotopic RNAse cleavage assay (NIRCA), the proband's RNA had a unique cleavage pattern in the region of COL1A2 encoding the C-propeptide. DNA sequence analyses identified a mutation in which nucleotides 3991-3994 (\"CTAG\") were replaced with \"TGTCATTGG.\" The first seven bases of the inserted sequence were identical to nucleotides 4002-4008 of the normal canine COL1A2 sequence. The resulting frameshift changed 30 amino acids and introduced a premature stop codon. Reverse-transcription polymerase chain reaction (RT-PCR) with primers flanking the mutation site amplified two complementary DNA (cDNA) fragments for the proband and a single product for the control. Restriction enzyme digestions also were consistent with a heterozygous mutation in the proband. Type I procollagen labeled with [3H]proline was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Increased density of pC-alpha2(I) suggested comigration with the similarly sized pro-alpha2(I) derived from the mutant allele. Furthermore, a-chains were overhydroxylated and the ratio of alpha1(I):alpha2(I) was 3.2:1, consistent with the presence of alpha1(I) homotrimers. Analyses of COL1A2 and type I collagen were both consistent with the described heterozygous mutation affecting the pro-alpha2(I) C-propeptide and confirmed a diagnosis of OI.\n"
],
"offsets": [
[
0,
1618
]
]
}
] | [
{
"id": "PMID-11393792_T1",
"type": "Protein",
"text": [
"COL1A2"
],
"offsets": [
[
7,
13
]
],
"normalized": []
},
{
"id": "PMID-11393792_T2",
"type": "Protein",
"text": [
"COL1A2"
],
"offsets": [
[
381,
387
]
],
"normalized": []
},
{
"id": "PMID-11393792_T3",
"type": "Protein",
"text": [
"C-propeptide"
],
"offsets": [
[
401,
413
]
],
"normalized": []
},
{
"id": "PMID-11393792_T4",
"type": "Protein",
"text": [
"COL1A2"
],
"offsets": [
[
639,
645
]
],
"normalized": []
},
{
"id": "PMID-11393792_T5",
"type": "Protein",
"text": [
"pC-alpha2(I)"
],
"offsets": [
[
1190,
1202
]
],
"normalized": []
},
{
"id": "PMID-11393792_T6",
"type": "Protein",
"text": [
"alpha2(I)"
],
"offsets": [
[
1254,
1263
]
],
"normalized": []
},
{
"id": "PMID-11393792_T7",
"type": "Protein",
"text": [
"alpha1(I)"
],
"offsets": [
[
1357,
1366
]
],
"normalized": []
},
{
"id": "PMID-11393792_T8",
"type": "Protein",
"text": [
"alpha2(I)"
],
"offsets": [
[
1367,
1376
]
],
"normalized": []
},
{
"id": "PMID-11393792_T9",
"type": "Protein",
"text": [
"alpha1(I)"
],
"offsets": [
[
1420,
1429
]
],
"normalized": []
},
{
"id": "PMID-11393792_T10",
"type": "Protein",
"text": [
"COL1A2"
],
"offsets": [
[
1455,
1461
]
],
"normalized": []
},
{
"id": "PMID-11393792_T11",
"type": "Protein",
"text": [
"alpha2(I)"
],
"offsets": [
[
1562,
1571
]
],
"normalized": []
}
] | [
{
"id": "PMID-11393792_E1",
"type": "Hydroxylation",
"trigger": {
"text": [
"overhydroxylated"
],
"offsets": [
[
1323,
1339
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11393792_T7"
}
]
},
{
"id": "PMID-11393792_E2",
"type": "Hydroxylation",
"trigger": {
"text": [
"overhydroxylated"
],
"offsets": [
[
1323,
1339
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11393792_T8"
}
]
}
] | [] | [] |
48 | PMID-11445559 | [
{
"id": "PMID-11445559__text",
"type": "abstract",
"text": [
"Linking global histone acetylation to the transcription enhancement of X-chromosomal genes in Drosophila males. \nIt has become well established for several genes that targeting of histone acetylation to promoters is required for the activation of transcription. In contrast, global patterns of acetylation have not been ascribed to any particular regulatory function. In Drosophila, a specific modification of H4, acetylation at lysine 16, is enriched at hundreds of sites on the male X chromosome due to the activity of the male-specific lethal (MSL) dosage compensation complex. Utilizing chromatin immunoprecipitation, we have determined that H4Ac16 is present along the entire length of X-linked genes targeted by the MSL complex with relatively modest levels of acetylation at the promoter regions and high levels in the middle and/or 3' end of the transcription units. We propose that global acetylation by the MSL complex increases the expression of X-linked genes by facilitating transcription elongation rather than by enhancing promoter accessibility. We have also determined that H4Ac16 is absent from a region of the X chromosome that includes a gene known to be dosage-compensated by a MSL-independent mechanism. This study represents the first biochemical interpretation of the very large body of cytological observations on the chromosomal distribution of the MSL complex.\n"
],
"offsets": [
[
0,
1388
]
]
}
] | [
{
"id": "PMID-11445559_T1",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
15,
22
]
],
"normalized": []
},
{
"id": "PMID-11445559_T2",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
180,
187
]
],
"normalized": []
},
{
"id": "PMID-11445559_T3",
"type": "Protein",
"text": [
"H4"
],
"offsets": [
[
410,
412
]
],
"normalized": []
},
{
"id": "PMID-11445559_T4",
"type": "Protein",
"text": [
"H4"
],
"offsets": [
[
646,
648
]
],
"normalized": []
},
{
"id": "PMID-11445559_T5",
"type": "Protein",
"text": [
"H4"
],
"offsets": [
[
1091,
1093
]
],
"normalized": []
},
{
"id": "PMID-11445559_T10",
"type": "Entity",
"text": [
"lysine 16"
],
"offsets": [
[
429,
438
]
],
"normalized": []
},
{
"id": "PMID-11445559_T11",
"type": "Entity",
"text": [
"16"
],
"offsets": [
[
650,
652
]
],
"normalized": []
}
] | [
{
"id": "PMID-11445559_E1",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
23,
34
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11445559_T1"
}
]
},
{
"id": "PMID-11445559_E2",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
188,
199
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11445559_T2"
}
]
},
{
"id": "PMID-11445559_E3",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
294,
305
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11445559_T2"
}
]
},
{
"id": "PMID-11445559_E4",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
414,
425
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11445559_T3"
},
{
"role": "Site",
"ref_id": "PMID-11445559_T10"
}
]
},
{
"id": "PMID-11445559_E5",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
767,
778
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11445559_T4"
},
{
"role": "Site",
"ref_id": "PMID-11445559_T11"
}
]
},
{
"id": "PMID-11445559_E6",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
898,
909
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11445559_T4"
}
]
}
] | [] | [] |
49 | PMID-11498546 | [
{
"id": "PMID-11498546__text",
"type": "abstract",
"text": [
"Correlation between histone lysine methylation and developmental changes at the chicken beta-globin locus. \nMethylation of histones at specific residues plays an important role in transcriptional regulation. Chromatin immunoprecipitation of dimethylated lysine 9 on histone H3 across 53 kilobases of the chicken beta-globin locus during erythropoiesis shows an almost complete anticorrelation between regions of elevated lysine 9 methylation and acetylation. Lysine 9 is methylated most over constitutive condensed chromatin and developmentally inactive globin genes. In contrast, lysine 4 methylation of histone H3 correlates with H3 acetylation. These results lead us to propose a mechanism by which the insulator in the beta-globin locus can protect the globin genes from being silenced by adjacent condensed chromatin.\n"
],
"offsets": [
[
0,
823
]
]
}
] | [
{
"id": "PMID-11498546_T1",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
20,
27
]
],
"normalized": []
},
{
"id": "PMID-11498546_T2",
"type": "Protein",
"text": [
"beta-globin"
],
"offsets": [
[
88,
99
]
],
"normalized": []
},
{
"id": "PMID-11498546_T3",
"type": "Protein",
"text": [
"histones"
],
"offsets": [
[
123,
131
]
],
"normalized": []
},
{
"id": "PMID-11498546_T4",
"type": "Protein",
"text": [
"histone H3"
],
"offsets": [
[
266,
276
]
],
"normalized": []
},
{
"id": "PMID-11498546_T5",
"type": "Protein",
"text": [
"beta-globin"
],
"offsets": [
[
312,
323
]
],
"normalized": []
},
{
"id": "PMID-11498546_T6",
"type": "Protein",
"text": [
"histone H3"
],
"offsets": [
[
605,
615
]
],
"normalized": []
},
{
"id": "PMID-11498546_T7",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
632,
634
]
],
"normalized": []
},
{
"id": "PMID-11498546_T8",
"type": "Protein",
"text": [
"beta-globin"
],
"offsets": [
[
723,
734
]
],
"normalized": []
},
{
"id": "PMID-11498546_T9",
"type": "Entity",
"text": [
"lysine"
],
"offsets": [
[
28,
34
]
],
"normalized": []
},
{
"id": "PMID-11498546_T13",
"type": "Entity",
"text": [
"lysine 9"
],
"offsets": [
[
254,
262
]
],
"normalized": []
},
{
"id": "PMID-11498546_T14",
"type": "Entity",
"text": [
"lysine 9"
],
"offsets": [
[
421,
429
]
],
"normalized": []
},
{
"id": "PMID-11498546_T17",
"type": "Entity",
"text": [
"Lysine 9"
],
"offsets": [
[
459,
467
]
],
"normalized": []
},
{
"id": "PMID-11498546_T19",
"type": "Entity",
"text": [
"lysine 4"
],
"offsets": [
[
581,
589
]
],
"normalized": []
}
] | [
{
"id": "PMID-11498546_E1",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
35,
46
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11498546_T1"
},
{
"role": "Site",
"ref_id": "PMID-11498546_T9"
},
{
"role": "Contextgene",
"ref_id": "PMID-11498546_T2"
}
]
},
{
"id": "PMID-11498546_E2",
"type": "Methylation",
"trigger": {
"text": [
"Methylation"
],
"offsets": [
[
108,
119
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11498546_T3"
}
]
},
{
"id": "PMID-11498546_E3",
"type": "Methylation",
"trigger": {
"text": [
"dimethylated"
],
"offsets": [
[
241,
253
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11498546_T4"
},
{
"role": "Site",
"ref_id": "PMID-11498546_T13"
},
{
"role": "Contextgene",
"ref_id": "PMID-11498546_T5"
}
]
},
{
"id": "PMID-11498546_E4",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
430,
441
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11498546_T4"
},
{
"role": "Site",
"ref_id": "PMID-11498546_T14"
}
]
},
{
"id": "PMID-11498546_E5",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
446,
457
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11498546_T4"
}
]
},
{
"id": "PMID-11498546_E6",
"type": "Methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
471,
481
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11498546_T4"
},
{
"role": "Site",
"ref_id": "PMID-11498546_T17"
},
{
"role": "Contextgene",
"ref_id": "PMID-11498546_T5"
}
]
},
{
"id": "PMID-11498546_E7",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
590,
601
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11498546_T6"
},
{
"role": "Site",
"ref_id": "PMID-11498546_T19"
},
{
"role": "Contextgene",
"ref_id": "PMID-11498546_T5"
}
]
},
{
"id": "PMID-11498546_E8",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
635,
646
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11498546_T7"
},
{
"role": "Contextgene",
"ref_id": "PMID-11498546_T5"
}
]
}
] | [] | [] |
50 | PMID-11502179 | [
{
"id": "PMID-11502179__text",
"type": "abstract",
"text": [
"Purification and characterization of a soluble bioactive amino-terminal extracellular domain of the human thyrotropin receptor. \nThe amino-terminal ectodomain of the human TSH receptor has been expressed at the surface of CHO cells as a glycosylphosphatidylinositol-anchored molecule containing a 10-residue histidine tag close to its C terminus. The soluble ectodomain could be released from the cells by treatment with a glycosylphosphatidylinositol-phospholipase C and purified to apparent homogeneity by cobalt-Sepharose chromatography. Two nanomoles of material was obtained, which was suitable for analysis by mass spectrometry. This allowed the identification of four out of the six potential N-glycosylation sites as being effectively glycosylated. A proportion of the purified soluble ectodomain displayed specific binding of (125)I-labeled TSH, allowing for the first time performance of classical saturation binding experiments. Two classes of high-affinity binding sites were identified: site A, K(d) 0.014 nM; site B, K(d) 0.83 nM. The significance of site A, whose affinity is much higher than for the holoreceptor at the surface of intact cells, remains to be clarified. The purified ectodomain was capable of inhibiting efficiently the thyroid stimulating activity of immunoglobulins from patients with Graves' disease. It allowed computation of the amounts of these immunoglobulins in patient's serum, giving values up to 10 microg/mL. Contrary to all currently available assays, the soluble ectodomain of the TSH receptor purified in a functionally competent conformation allows direct studies of its interactions with TSH and autoantibodies and opens the way to structural studies.\n"
],
"offsets": [
[
0,
1701
]
]
}
] | [
{
"id": "PMID-11502179_T1",
"type": "Protein",
"text": [
"thyrotropin receptor"
],
"offsets": [
[
106,
126
]
],
"normalized": []
},
{
"id": "PMID-11502179_T2",
"type": "Protein",
"text": [
"TSH receptor"
],
"offsets": [
[
172,
184
]
],
"normalized": []
},
{
"id": "PMID-11502179_T3",
"type": "Protein",
"text": [
"glycosylphosphatidylinositol-phospholipase C"
],
"offsets": [
[
423,
467
]
],
"normalized": []
},
{
"id": "PMID-11502179_T4",
"type": "Protein",
"text": [
"TSH"
],
"offsets": [
[
850,
853
]
],
"normalized": []
},
{
"id": "PMID-11502179_T5",
"type": "Protein",
"text": [
"TSH receptor"
],
"offsets": [
[
1527,
1539
]
],
"normalized": []
},
{
"id": "PMID-11502179_T6",
"type": "Protein",
"text": [
"TSH"
],
"offsets": [
[
1637,
1640
]
],
"normalized": []
},
{
"id": "PMID-11502179_T7",
"type": "Entity",
"text": [
"glycosylphosphatidylinositol"
],
"offsets": [
[
237,
265
]
],
"normalized": []
},
{
"id": "PMID-11502179_T9",
"type": "Entity",
"text": [
"N-glycosylation sites"
],
"offsets": [
[
700,
721
]
],
"normalized": []
}
] | [
{
"id": "PMID-11502179_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"anchored"
],
"offsets": [
[
266,
274
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11502179_T2"
},
{
"role": "Sidechain",
"ref_id": "PMID-11502179_T7"
}
]
},
{
"id": "PMID-11502179_E2",
"type": "Glycosylation",
"trigger": {
"text": [
"glycosylated"
],
"offsets": [
[
743,
755
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11502179_T2"
},
{
"role": "Site",
"ref_id": "PMID-11502179_T9"
}
]
}
] | [] | [] |
51 | PMID-11504942 | [
{
"id": "PMID-11504942__text",
"type": "abstract",
"text": [
"HIF-1alpha binding to VHL is regulated by stimulus-sensitive proline hydroxylation. \nHypoxia-inducible factor-1alpha (HIF-1alpha) is a global transcriptional regulator of the hypoxic response. Under normoxic conditions, HIF-1alpha is recognized by the von Hippel-Lindau tumor-suppressor protein (VHL), a component of an E3 ubiquitin ligase complex. This interaction thereby promotes the rapid degradation of HIF-1alpha. Under hypoxic conditions, HIF-1alpha is stabilized. We have previously shown that VHL binds in a hypoxia-sensitive manner to a 27-aa segment of HIF-1alpha, and that this regulation depends on a posttranslational modification of HIF-1alpha. Through a combination of in vivo coimmunoprecipitation assays using VHL and a panel of point mutants of HIF-1alpha in this region, as well as MS and in vitro binding assays, we now provide evidence that this modification, which occurs under normoxic conditions, is hydroxylation of Pro-564 of HIF-1alpha. The data furthermore show that this proline hydroxylation is the primary regulator of VHL binding.\n"
],
"offsets": [
[
0,
1064
]
]
}
] | [
{
"id": "PMID-11504942_T1",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
0,
10
]
],
"normalized": []
},
{
"id": "PMID-11504942_T2",
"type": "Protein",
"text": [
"VHL"
],
"offsets": [
[
22,
25
]
],
"normalized": []
},
{
"id": "PMID-11504942_T3",
"type": "Protein",
"text": [
"Hypoxia-inducible factor-1alpha"
],
"offsets": [
[
85,
116
]
],
"normalized": []
},
{
"id": "PMID-11504942_T4",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
118,
128
]
],
"normalized": []
},
{
"id": "PMID-11504942_T5",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
220,
230
]
],
"normalized": []
},
{
"id": "PMID-11504942_T6",
"type": "Protein",
"text": [
"von Hippel-Lindau tumor-suppressor"
],
"offsets": [
[
252,
286
]
],
"normalized": []
},
{
"id": "PMID-11504942_T7",
"type": "Protein",
"text": [
"VHL"
],
"offsets": [
[
296,
299
]
],
"normalized": []
},
{
"id": "PMID-11504942_T8",
"type": "Protein",
"text": [
"ubiquitin"
],
"offsets": [
[
323,
332
]
],
"normalized": []
},
{
"id": "PMID-11504942_T9",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
408,
418
]
],
"normalized": []
},
{
"id": "PMID-11504942_T10",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
446,
456
]
],
"normalized": []
},
{
"id": "PMID-11504942_T11",
"type": "Protein",
"text": [
"VHL"
],
"offsets": [
[
502,
505
]
],
"normalized": []
},
{
"id": "PMID-11504942_T12",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
564,
574
]
],
"normalized": []
},
{
"id": "PMID-11504942_T13",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
648,
658
]
],
"normalized": []
},
{
"id": "PMID-11504942_T14",
"type": "Protein",
"text": [
"VHL"
],
"offsets": [
[
728,
731
]
],
"normalized": []
},
{
"id": "PMID-11504942_T15",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
764,
774
]
],
"normalized": []
},
{
"id": "PMID-11504942_T16",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
953,
963
]
],
"normalized": []
},
{
"id": "PMID-11504942_T17",
"type": "Protein",
"text": [
"VHL"
],
"offsets": [
[
1051,
1054
]
],
"normalized": []
},
{
"id": "PMID-11504942_T18",
"type": "Entity",
"text": [
"proline"
],
"offsets": [
[
61,
68
]
],
"normalized": []
},
{
"id": "PMID-11504942_T21",
"type": "Entity",
"text": [
"Pro-564"
],
"offsets": [
[
942,
949
]
],
"normalized": []
}
] | [
{
"id": "PMID-11504942_E1",
"type": "Hydroxylation",
"trigger": {
"text": [
"hydroxylation"
],
"offsets": [
[
69,
82
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11504942_T1"
},
{
"role": "Site",
"ref_id": "PMID-11504942_T18"
}
]
},
{
"id": "PMID-11504942_E2",
"type": "Hydroxylation",
"trigger": {
"text": [
"hydroxylation"
],
"offsets": [
[
925,
938
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11504942_T16"
},
{
"role": "Site",
"ref_id": "PMID-11504942_T21"
}
]
}
] | [
{
"id": "PMID-11504942_1",
"entity_ids": [
"PMID-11504942_T3",
"PMID-11504942_T4"
]
},
{
"id": "PMID-11504942_2",
"entity_ids": [
"PMID-11504942_T6",
"PMID-11504942_T7"
]
}
] | [] |
52 | PMID-11513145 | [
{
"id": "PMID-11513145__text",
"type": "abstract",
"text": [
"2B4 (CD244) and CS1: novel members of the CD2 subset of the immunoglobulin superfamily molecules expressed on natural killer cells and other leukocytes. \n2B4 is a member of the CD2 subset of the immunoglobulin superfamily molecules expressed on natural killer (NK) cells and other leukocytes. It is the high affinity ligand for CD48. Engagement of 2B4 on NK-cell surfaces with specific antibodies or CD48 can trigger cell-mediated cytotoxicity, interferon-gamma secretion, phosphoinositol turnover and NK-cell invasiveness. The function of 2B4 in CD8+ T cells and myeloid cells remains unknown. The cytoplasmic domain of 2B4 contains unique tyrosine motifs (TxYxxV/I) that associate with src homology 2 domain-containing protein or signaling lymphocyte activation molecule (SLAM)-associated protein, whose mutation is the underlying genetic defect in the X-linked lymphoproliferative disease (XLPD). Impaired signaling via 2B4 and SLAM is implicated in the immunopathogenesis of XLPD. CS1 is a novel member of the CD2 subset that contains two of the unique tyrosine motifs present in 2B4 and SLAM. Signaling through 2B4, CS1 and other members of the CD2 subset may play a major role in the regulation of NK cells and other leukocyte functions.\n"
],
"offsets": [
[
0,
1244
]
]
}
] | [
{
"id": "PMID-11513145_T1",
"type": "Protein",
"text": [
"2B4"
],
"offsets": [
[
0,
3
]
],
"normalized": []
},
{
"id": "PMID-11513145_T2",
"type": "Protein",
"text": [
"CD244"
],
"offsets": [
[
5,
10
]
],
"normalized": []
},
{
"id": "PMID-11513145_T3",
"type": "Protein",
"text": [
"CS1"
],
"offsets": [
[
16,
19
]
],
"normalized": []
},
{
"id": "PMID-11513145_T4",
"type": "Protein",
"text": [
"CD2"
],
"offsets": [
[
42,
45
]
],
"normalized": []
},
{
"id": "PMID-11513145_T5",
"type": "Protein",
"text": [
"2B4"
],
"offsets": [
[
154,
157
]
],
"normalized": []
},
{
"id": "PMID-11513145_T6",
"type": "Protein",
"text": [
"CD2"
],
"offsets": [
[
177,
180
]
],
"normalized": []
},
{
"id": "PMID-11513145_T7",
"type": "Protein",
"text": [
"CD48"
],
"offsets": [
[
328,
332
]
],
"normalized": []
},
{
"id": "PMID-11513145_T8",
"type": "Protein",
"text": [
"2B4"
],
"offsets": [
[
348,
351
]
],
"normalized": []
},
{
"id": "PMID-11513145_T9",
"type": "Protein",
"text": [
"CD48"
],
"offsets": [
[
400,
404
]
],
"normalized": []
},
{
"id": "PMID-11513145_T10",
"type": "Protein",
"text": [
"interferon-gamma"
],
"offsets": [
[
445,
461
]
],
"normalized": []
},
{
"id": "PMID-11513145_T11",
"type": "Protein",
"text": [
"2B4"
],
"offsets": [
[
540,
543
]
],
"normalized": []
},
{
"id": "PMID-11513145_T12",
"type": "Protein",
"text": [
"CD8+"
],
"offsets": [
[
547,
551
]
],
"normalized": []
},
{
"id": "PMID-11513145_T13",
"type": "Protein",
"text": [
"2B4"
],
"offsets": [
[
621,
624
]
],
"normalized": []
},
{
"id": "PMID-11513145_T14",
"type": "Protein",
"text": [
"signaling lymphocyte activation molecule (SLAM)-associated protein"
],
"offsets": [
[
732,
798
]
],
"normalized": []
},
{
"id": "PMID-11513145_T15",
"type": "Protein",
"text": [
"2B4"
],
"offsets": [
[
923,
926
]
],
"normalized": []
},
{
"id": "PMID-11513145_T16",
"type": "Protein",
"text": [
"CS1"
],
"offsets": [
[
985,
988
]
],
"normalized": []
},
{
"id": "PMID-11513145_T17",
"type": "Protein",
"text": [
"CD2"
],
"offsets": [
[
1014,
1017
]
],
"normalized": []
},
{
"id": "PMID-11513145_T18",
"type": "Protein",
"text": [
"2B4"
],
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[
1084,
1087
]
],
"normalized": []
},
{
"id": "PMID-11513145_T19",
"type": "Protein",
"text": [
"2B4"
],
"offsets": [
[
1116,
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]
],
"normalized": []
},
{
"id": "PMID-11513145_T20",
"type": "Protein",
"text": [
"CS1"
],
"offsets": [
[
1121,
1124
]
],
"normalized": []
},
{
"id": "PMID-11513145_T21",
"type": "Protein",
"text": [
"CD2"
],
"offsets": [
[
1150,
1153
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-11513145_1",
"entity_ids": [
"PMID-11513145_T1",
"PMID-11513145_T2"
]
}
] | [] |
53 | PMID-11595658 | [
{
"id": "PMID-11595658__text",
"type": "abstract",
"text": [
"N-glycosylation of CRF receptor type 1 is important for its ligand-specific interaction. \nThe corticotropin-releasing factor (CRF) receptor type 1 (CRFR1) contains five potential N-glycosylation sites: N38, N45, N78, N90, and N98. Cells expressing CRFR1 were treated with tunicamycin to block receptor glycosylation. The nonglycosylated receptor did not bind the radioligand and had a decreased cAMP stimulation potency in response to CRF. To determine which of the polysaccharide chain(s) is/are involved in ligand interaction, the polysaccharide chains were deleted using site-directed mutagenesis of the glycosylation consensus, N-X-S/T. Two sets of mutations were performed for each glycosylation site: N to Q and S/T to A, respectively. The single mutants Q38, Q45, Q78, Q90, Q98, A40, A47, A80, A92, and A100 and the double mutants A40/A47 and A80/A100 were well expressed, bound CRF, sauvagine (SVG), and urotensin-I (UTS-I) with a normal affinity, and increased cAMP accumulation with a high efficiency. In contrast, the combined mutations A80/A92/A100, A40/A80/A92/A100, and A40/A47/A80/A92/A100 had low levels of expression, did not bind the radioligand, and had a decreased cAMP stimulation. These data indicate the requirement for three or more polysaccharide chains for normal CRFR1 function.\n"
],
"offsets": [
[
0,
1306
]
]
}
] | [
{
"id": "PMID-11595658_T1",
"type": "Protein",
"text": [
"CRF receptor type 1"
],
"offsets": [
[
19,
38
]
],
"normalized": []
},
{
"id": "PMID-11595658_T2",
"type": "Protein",
"text": [
"corticotropin-releasing factor (CRF) receptor type 1"
],
"offsets": [
[
94,
146
]
],
"normalized": []
},
{
"id": "PMID-11595658_T3",
"type": "Protein",
"text": [
"CRFR1"
],
"offsets": [
[
148,
153
]
],
"normalized": []
},
{
"id": "PMID-11595658_T4",
"type": "Protein",
"text": [
"CRFR1"
],
"offsets": [
[
248,
253
]
],
"normalized": []
},
{
"id": "PMID-11595658_T5",
"type": "Protein",
"text": [
"CRF"
],
"offsets": [
[
435,
438
]
],
"normalized": []
},
{
"id": "PMID-11595658_T6",
"type": "Protein",
"text": [
"CRF"
],
"offsets": [
[
886,
889
]
],
"normalized": []
},
{
"id": "PMID-11595658_T7",
"type": "Protein",
"text": [
"sauvagine"
],
"offsets": [
[
891,
900
]
],
"normalized": []
},
{
"id": "PMID-11595658_T8",
"type": "Protein",
"text": [
"SVG"
],
"offsets": [
[
902,
905
]
],
"normalized": []
},
{
"id": "PMID-11595658_T9",
"type": "Protein",
"text": [
"urotensin-I"
],
"offsets": [
[
912,
923
]
],
"normalized": []
},
{
"id": "PMID-11595658_T10",
"type": "Protein",
"text": [
"UTS-I"
],
"offsets": [
[
925,
930
]
],
"normalized": []
},
{
"id": "PMID-11595658_T11",
"type": "Protein",
"text": [
"CRFR1"
],
"offsets": [
[
1290,
1295
]
],
"normalized": []
}
] | [
{
"id": "PMID-11595658_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"N-glycosylation"
],
"offsets": [
[
0,
15
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11595658_T1"
}
]
}
] | [
{
"id": "PMID-11595658_1",
"entity_ids": [
"PMID-11595658_T2",
"PMID-11595658_T3"
]
},
{
"id": "PMID-11595658_2",
"entity_ids": [
"PMID-11595658_T7",
"PMID-11595658_T8"
]
},
{
"id": "PMID-11595658_3",
"entity_ids": [
"PMID-11595658_T9",
"PMID-11595658_T10"
]
}
] | [] |
54 | PMID-11604495 | [
{
"id": "PMID-11604495__text",
"type": "abstract",
"text": [
"Reduced rates of gene loss, gene silencing, and gene mutation in Dnmt1-deficient embryonic stem cells. \nTumor suppressor gene inactivation is a crucial event in oncogenesis. Gene inactivation mechanisms include events resulting in loss of heterozygosity (LOH), gene mutation, and transcriptional silencing. The contribution of each of these different pathways varies among tumor suppressor genes and by cancer type. The factors that influence the relative utilization of gene inactivation pathways are poorly understood. In this study, we describe a detailed quantitative analysis of the three major gene inactivation mechanisms for a model gene at two different genomic integration sites in mouse embryonic stem (ES) cells. In addition, we targeted the major DNA methyltransferase gene, Dnmt1, to investigate the relative contribution of DNA methylation to these various competing gene inactivation pathways. Our data show that gene loss is the predominant mode of inactivation of a herpes simplex virus thymidine kinase neomycin phosphotransferase reporter gene (HSV-TKNeo) at the two integration sites tested and that this event is significantly reduced in Dnmt1-deficient cells. Gene silencing by promoter methylation requires Dnmt1, suggesting that the expression of Dnmt3a and Dnmt3b alone in ES cells is insufficient to achieve effective gene silencing. We used a novel assay to show that missense mutation rates are also substantially reduced in Dnmt1-deficient cells. This is the first direct demonstration that DNA methylation affects point mutation rates in mammalian cells. Surprisingly, the fraction of CpG transition mutations was not reduced in Dnmt1-deficient cells. Finally, we show that methyl group-deficient growth conditions do not cause an increase in missense mutation rates in Dnmt1-proficient cells, as predicted by methyltransferase-mediated mutagenesis models. We conclude that Dnmt1 deficiency and the accompanying genomic DNA hypomethylation result in a reduction of three major pathways of gene inactivation in our model system.\n"
],
"offsets": [
[
0,
2059
]
]
}
] | [
{
"id": "PMID-11604495_T1",
"type": "Protein",
"text": [
"Dnmt1"
],
"offsets": [
[
65,
70
]
],
"normalized": []
},
{
"id": "PMID-11604495_T2",
"type": "Protein",
"text": [
"Dnmt1"
],
"offsets": [
[
788,
793
]
],
"normalized": []
},
{
"id": "PMID-11604495_T3",
"type": "Protein",
"text": [
"thymidine kinase"
],
"offsets": [
[
1005,
1021
]
],
"normalized": []
},
{
"id": "PMID-11604495_T4",
"type": "Protein",
"text": [
"Dnmt1"
],
"offsets": [
[
1160,
1165
]
],
"normalized": []
},
{
"id": "PMID-11604495_T5",
"type": "Protein",
"text": [
"Dnmt1"
],
"offsets": [
[
1231,
1236
]
],
"normalized": []
},
{
"id": "PMID-11604495_T6",
"type": "Protein",
"text": [
"Dnmt3a"
],
"offsets": [
[
1272,
1278
]
],
"normalized": []
},
{
"id": "PMID-11604495_T7",
"type": "Protein",
"text": [
"Dnmt3b"
],
"offsets": [
[
1283,
1289
]
],
"normalized": []
},
{
"id": "PMID-11604495_T8",
"type": "Protein",
"text": [
"Dnmt1"
],
"offsets": [
[
1454,
1459
]
],
"normalized": []
},
{
"id": "PMID-11604495_T9",
"type": "Protein",
"text": [
"Dnmt1"
],
"offsets": [
[
1660,
1665
]
],
"normalized": []
},
{
"id": "PMID-11604495_T10",
"type": "Protein",
"text": [
"Dnmt1"
],
"offsets": [
[
1801,
1806
]
],
"normalized": []
},
{
"id": "PMID-11604495_T11",
"type": "Protein",
"text": [
"Dnmt1"
],
"offsets": [
[
1905,
1910
]
],
"normalized": []
}
] | [] | [] | [] |
55 | PMID-11711599 | [
{
"id": "PMID-11711599__text",
"type": "abstract",
"text": [
"Induction of hepatitis C virus E1 envelope protein-specific immune response can be enhanced by mutation of N-glycosylation sites. \nDeglycosylation of viral glycoproteins has been shown to influence the number of available epitopes and to modulate immune recognition of antigens. We investigated the role played by N-glycans in the immunogenicity of hepatitis C virus (HCV) E1 envelope glycoprotein, a naturally poor immunogen. Eight plasmids were engineered, encoding E1 protein mutants in which the four N-linked glycosylation sites of the protein were mutated separately or in combination. In vitro expression studies showed an influence of N-linked glycosylation on expression efficiency, instability, and/or secretion of the mutated proteins. Immunogenicity of the E1 mutants was studied in BALB/c mice following intramuscular and intraepidermal injection of the plasmids. Whereas some mutations had no or only minor effects on the antibody titers induced, mutation of the fourth glycosylation site (N4) significantly enhanced the anti-E1 humoral response in terms of both seroconversion rates and antibody titers. Moreover, antibody induced by the N4 mutant was able to recognize HCV-like particles with higher titers than those induced by the wild-type construct. Epitope mapping indicated that the E1 mutant antigens induced antibody directed at two major domains: one, located at amino acids (aa) 313 to 332, which is known to be reactive with sera from HCV patients, and a second one, located in the N-terminal domain of E1 (aa 192 to 226). Analysis of the induced immune cellular response confirmed the induction of gamma interferon-producing cells by all mutants, albeit to different levels. These results show that N-linked glycosylation can limit the antibody response to the HCV E1 protein and reveal a potential vaccine candidate with enhanced immunogenicity.\n"
],
"offsets": [
[
0,
1875
]
]
}
] | [
{
"id": "PMID-11711599_T1",
"type": "Protein",
"text": [
"E1"
],
"offsets": [
[
31,
33
]
],
"normalized": []
},
{
"id": "PMID-11711599_T2",
"type": "Protein",
"text": [
"E1"
],
"offsets": [
[
373,
375
]
],
"normalized": []
},
{
"id": "PMID-11711599_T3",
"type": "Protein",
"text": [
"E1"
],
"offsets": [
[
468,
470
]
],
"normalized": []
},
{
"id": "PMID-11711599_T4",
"type": "Protein",
"text": [
"E1"
],
"offsets": [
[
769,
771
]
],
"normalized": []
},
{
"id": "PMID-11711599_T5",
"type": "Protein",
"text": [
"E1"
],
"offsets": [
[
1040,
1042
]
],
"normalized": []
},
{
"id": "PMID-11711599_T6",
"type": "Protein",
"text": [
"E1"
],
"offsets": [
[
1305,
1307
]
],
"normalized": []
},
{
"id": "PMID-11711599_T7",
"type": "Protein",
"text": [
"E1"
],
"offsets": [
[
1530,
1532
]
],
"normalized": []
},
{
"id": "PMID-11711599_T8",
"type": "Protein",
"text": [
"gamma interferon"
],
"offsets": [
[
1626,
1642
]
],
"normalized": []
},
{
"id": "PMID-11711599_T9",
"type": "Protein",
"text": [
"E1"
],
"offsets": [
[
1793,
1795
]
],
"normalized": []
}
] | [
{
"id": "PMID-11711599_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"N-linked glycosylation"
],
"offsets": [
[
643,
665
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11711599_T3"
}
]
},
{
"id": "PMID-11711599_E2",
"type": "Glycosylation",
"trigger": {
"text": [
"N-linked glycosylation"
],
"offsets": [
[
1727,
1749
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11711599_T9"
}
]
}
] | [] | [] |
56 | PMID-11773073 | [
{
"id": "PMID-11773073__text",
"type": "abstract",
"text": [
"Absence of post-translational aspartyl beta-hydroxylation of epidermal growth factor domains in mice leads to developmental defects and an increased incidence of intestinal neoplasia. \nThe BAH genomic locus encodes three distinct proteins: junctin, humbug, and BAH. All three proteins share common exons, but differ significantly based upon the use of alternative terminal exons. The biological roles of BAH and humbug and their functional relationship to junctin remain unclear. To evaluate the role of BAH in vivo, the catalytic domain of BAH was specifically targeted such that the coding regions of junctin and humbug remained undisturbed. BAH null mice lack measurable BAH protein in several tissues, lack aspartyl beta-hydroxylase activity in liver preparations, and exhibit no hydroxylation of the epidermal growth factor (EGF) domain of clotting Factor X. In addition to reduced fertility in females, BAH null mice display several developmental defects including syndactyly, facial dysmorphology, and a mild defect in hard palate formation. The developmental defects present in BAH null mice are similar to defects observed in knock-outs and hypomorphs of the Notch ligand Serrate-2. In this work, beta-hydroxylation of Asp residues in EGF domains is demonstrated for a soluble form of a Notch ligand, human Jagged-1. These results along with recent reports that another post-translational modification of EGF domains in Notch gene family members (glycosylation by Fringe) alters Notch pathway signaling, lends credence to the suggestion that aspartyl beta-hydroxylation may represent another post-translational modification of EGF domains that can modulate Notch pathway signaling. Previous work has demonstrated increased levels of BAH in certain tumor tissues and a role for BAH in tumorigenesis has been proposed. The role of hydroxylase in tumor formation was tested directly by crossing BAH KO mice with an intestinal tumor model, APCmin mice. Surprisingly, BAH null/APCmin mice show a statistically significant increase in both intestinal polyp size and number when compared with BAH wild-type/APCmin controls. These results suggest that, in contrast to expectations, loss of BAH catalytic activity may promote tumor formation.\n"
],
"offsets": [
[
0,
2243
]
]
}
] | [
{
"id": "PMID-11773073_T1",
"type": "Protein",
"text": [
"BAH"
],
"offsets": [
[
189,
192
]
],
"normalized": []
},
{
"id": "PMID-11773073_T2",
"type": "Protein",
"text": [
"junctin"
],
"offsets": [
[
240,
247
]
],
"normalized": []
},
{
"id": "PMID-11773073_T3",
"type": "Protein",
"text": [
"humbug"
],
"offsets": [
[
249,
255
]
],
"normalized": []
},
{
"id": "PMID-11773073_T4",
"type": "Protein",
"text": [
"BAH"
],
"offsets": [
[
261,
264
]
],
"normalized": []
},
{
"id": "PMID-11773073_T5",
"type": "Protein",
"text": [
"BAH"
],
"offsets": [
[
404,
407
]
],
"normalized": []
},
{
"id": "PMID-11773073_T6",
"type": "Protein",
"text": [
"humbug"
],
"offsets": [
[
412,
418
]
],
"normalized": []
},
{
"id": "PMID-11773073_T7",
"type": "Protein",
"text": [
"junctin"
],
"offsets": [
[
456,
463
]
],
"normalized": []
},
{
"id": "PMID-11773073_T8",
"type": "Protein",
"text": [
"BAH"
],
"offsets": [
[
504,
507
]
],
"normalized": []
},
{
"id": "PMID-11773073_T9",
"type": "Protein",
"text": [
"BAH"
],
"offsets": [
[
541,
544
]
],
"normalized": []
},
{
"id": "PMID-11773073_T10",
"type": "Protein",
"text": [
"junctin"
],
"offsets": [
[
603,
610
]
],
"normalized": []
},
{
"id": "PMID-11773073_T11",
"type": "Protein",
"text": [
"humbug"
],
"offsets": [
[
615,
621
]
],
"normalized": []
},
{
"id": "PMID-11773073_T12",
"type": "Protein",
"text": [
"BAH"
],
"offsets": [
[
644,
647
]
],
"normalized": []
},
{
"id": "PMID-11773073_T13",
"type": "Protein",
"text": [
"BAH"
],
"offsets": [
[
674,
677
]
],
"normalized": []
},
{
"id": "PMID-11773073_T14",
"type": "Protein",
"text": [
"Factor X"
],
"offsets": [
[
854,
862
]
],
"normalized": []
},
{
"id": "PMID-11773073_T15",
"type": "Protein",
"text": [
"BAH"
],
"offsets": [
[
909,
912
]
],
"normalized": []
},
{
"id": "PMID-11773073_T16",
"type": "Protein",
"text": [
"BAH"
],
"offsets": [
[
1086,
1089
]
],
"normalized": []
},
{
"id": "PMID-11773073_T17",
"type": "Protein",
"text": [
"Serrate-2"
],
"offsets": [
[
1181,
1190
]
],
"normalized": []
},
{
"id": "PMID-11773073_T18",
"type": "Protein",
"text": [
"Jagged-1"
],
"offsets": [
[
1316,
1324
]
],
"normalized": []
},
{
"id": "PMID-11773073_T19",
"type": "Protein",
"text": [
"BAH"
],
"offsets": [
[
1742,
1745
]
],
"normalized": []
},
{
"id": "PMID-11773073_T20",
"type": "Protein",
"text": [
"BAH"
],
"offsets": [
[
1786,
1789
]
],
"normalized": []
},
{
"id": "PMID-11773073_T21",
"type": "Protein",
"text": [
"BAH"
],
"offsets": [
[
1901,
1904
]
],
"normalized": []
},
{
"id": "PMID-11773073_T22",
"type": "Protein",
"text": [
"BAH"
],
"offsets": [
[
1972,
1975
]
],
"normalized": []
},
{
"id": "PMID-11773073_T23",
"type": "Protein",
"text": [
"BAH"
],
"offsets": [
[
2095,
2098
]
],
"normalized": []
},
{
"id": "PMID-11773073_T24",
"type": "Protein",
"text": [
"BAH"
],
"offsets": [
[
2191,
2194
]
],
"normalized": []
},
{
"id": "PMID-11773073_T26",
"type": "Entity",
"text": [
"epidermal growth factor (EGF) domain"
],
"offsets": [
[
805,
841
]
],
"normalized": []
},
{
"id": "PMID-11773073_T28",
"type": "Entity",
"text": [
"Asp residues"
],
"offsets": [
[
1228,
1240
]
],
"normalized": []
}
] | [
{
"id": "PMID-11773073_E1",
"type": "Hydroxylation",
"trigger": {
"text": [
"hydroxylation"
],
"offsets": [
[
784,
797
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11773073_T14"
},
{
"role": "Site",
"ref_id": "PMID-11773073_T26"
}
]
},
{
"id": "PMID-11773073_E2",
"type": "Hydroxylation",
"trigger": {
"text": [
"beta-hydroxylation"
],
"offsets": [
[
1206,
1224
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11773073_T18"
},
{
"role": "Site",
"ref_id": "PMID-11773073_T28"
}
]
}
] | [] | [] |
57 | PMID-11791185 | [
{
"id": "PMID-11791185__text",
"type": "abstract",
"text": [
"Molecular cloning of ESET, a novel histone H3-specific methyltransferase that interacts with ERG transcription factor. \nThe ets-related gene erg encodes a transcription factor that is implicated in the control of cell growth and differentiation. To identify interacting partners of ERG, we screened a yeast two-hybrid cDNA library constructed from mouse hematopoietic cells using the N-terminal region of ERG as a bait. We isolated a 4.6 kb full-length mouse cDNA encoding a 1307-amino acid protein migrating as a 180 kD band, which was termed ESET (ERG-associated protein with SET domain). ESET is 92% identical to the human protein SETDB1 (SET domain, bifurcated 1). The interaction between ESET and ERG was supported by in vitro pull-down using glutathione S-transferase (GST) fusion protein, by transfection and co-immunoprecipitation experiments, and by association of endogenous SETDB1 with ERG. Since ESET possesses evolutionarily conserved SET, preSET, and postSET domains implicated in histone methylation, we tested the ability of ESET to methylate core histones. The results of these studies demonstrated that ESET is a histone H3-specific methyltransferase, and that mutations within ESET abolished its methyltransferase activity. Together, these findings raise the possibility that transcription factor ERG may participate in transcriptional regulation through ESET-mediated histone methylation.\n"
],
"offsets": [
[
0,
1409
]
]
}
] | [
{
"id": "PMID-11791185_T1",
"type": "Protein",
"text": [
"ESET"
],
"offsets": [
[
21,
25
]
],
"normalized": []
},
{
"id": "PMID-11791185_T2",
"type": "Protein",
"text": [
"histone H3"
],
"offsets": [
[
35,
45
]
],
"normalized": []
},
{
"id": "PMID-11791185_T3",
"type": "Protein",
"text": [
"ERG"
],
"offsets": [
[
93,
96
]
],
"normalized": []
},
{
"id": "PMID-11791185_T4",
"type": "Protein",
"text": [
"erg"
],
"offsets": [
[
141,
144
]
],
"normalized": []
},
{
"id": "PMID-11791185_T5",
"type": "Protein",
"text": [
"ERG"
],
"offsets": [
[
282,
285
]
],
"normalized": []
},
{
"id": "PMID-11791185_T6",
"type": "Protein",
"text": [
"ERG"
],
"offsets": [
[
405,
408
]
],
"normalized": []
},
{
"id": "PMID-11791185_T7",
"type": "Protein",
"text": [
"ESET"
],
"offsets": [
[
544,
548
]
],
"normalized": []
},
{
"id": "PMID-11791185_T8",
"type": "Protein",
"text": [
"ERG-associated protein with SET domain"
],
"offsets": [
[
550,
588
]
],
"normalized": []
},
{
"id": "PMID-11791185_T9",
"type": "Protein",
"text": [
"ESET"
],
"offsets": [
[
591,
595
]
],
"normalized": []
},
{
"id": "PMID-11791185_T10",
"type": "Protein",
"text": [
"SETDB1"
],
"offsets": [
[
634,
640
]
],
"normalized": []
},
{
"id": "PMID-11791185_T11",
"type": "Protein",
"text": [
"SET domain, bifurcated 1"
],
"offsets": [
[
642,
666
]
],
"normalized": []
},
{
"id": "PMID-11791185_T12",
"type": "Protein",
"text": [
"ESET"
],
"offsets": [
[
693,
697
]
],
"normalized": []
},
{
"id": "PMID-11791185_T13",
"type": "Protein",
"text": [
"ERG"
],
"offsets": [
[
702,
705
]
],
"normalized": []
},
{
"id": "PMID-11791185_T14",
"type": "Protein",
"text": [
"SETDB1"
],
"offsets": [
[
885,
891
]
],
"normalized": []
},
{
"id": "PMID-11791185_T15",
"type": "Protein",
"text": [
"ERG"
],
"offsets": [
[
897,
900
]
],
"normalized": []
},
{
"id": "PMID-11791185_T16",
"type": "Protein",
"text": [
"ESET"
],
"offsets": [
[
908,
912
]
],
"normalized": []
},
{
"id": "PMID-11791185_T17",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
995,
1002
]
],
"normalized": []
},
{
"id": "PMID-11791185_T18",
"type": "Protein",
"text": [
"ESET"
],
"offsets": [
[
1041,
1045
]
],
"normalized": []
},
{
"id": "PMID-11791185_T19",
"type": "Protein",
"text": [
"histones"
],
"offsets": [
[
1064,
1072
]
],
"normalized": []
},
{
"id": "PMID-11791185_T20",
"type": "Protein",
"text": [
"ESET"
],
"offsets": [
[
1121,
1125
]
],
"normalized": []
},
{
"id": "PMID-11791185_T21",
"type": "Protein",
"text": [
"histone H3"
],
"offsets": [
[
1131,
1141
]
],
"normalized": []
},
{
"id": "PMID-11791185_T22",
"type": "Protein",
"text": [
"ESET"
],
"offsets": [
[
1196,
1200
]
],
"normalized": []
},
{
"id": "PMID-11791185_T23",
"type": "Protein",
"text": [
"ERG"
],
"offsets": [
[
1316,
1319
]
],
"normalized": []
},
{
"id": "PMID-11791185_T24",
"type": "Protein",
"text": [
"ESET"
],
"offsets": [
[
1374,
1378
]
],
"normalized": []
},
{
"id": "PMID-11791185_T25",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
1388,
1395
]
],
"normalized": []
}
] | [
{
"id": "PMID-11791185_E1",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1003,
1014
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11791185_T17"
}
]
},
{
"id": "PMID-11791185_E2",
"type": "Catalysis",
"trigger": {
"text": [
"mediated"
],
"offsets": [
[
1379,
1387
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11791185_E3"
},
{
"role": "Cause",
"ref_id": "PMID-11791185_T24"
}
]
},
{
"id": "PMID-11791185_E3",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1396,
1407
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11791185_T25"
}
]
}
] | [
{
"id": "PMID-11791185_1",
"entity_ids": [
"PMID-11791185_T7",
"PMID-11791185_T8"
]
},
{
"id": "PMID-11791185_2",
"entity_ids": [
"PMID-11791185_T10",
"PMID-11791185_T11"
]
}
] | [] |
58 | PMID-11795592 | [
{
"id": "PMID-11795592__text",
"type": "abstract",
"text": [
"Regulation of HIF by the von Hippel-Lindau tumour suppressor: implications for cellular oxygen sensing. \nHypoxia-inducible factor (HIF) is central in coordinating many of the transcriptional adaptations to hypoxia. Composed of a heterodimer of alpha and beta subunits, the alpha subunit is rapidly degraded in normoxia, leading to inactivation of the hypoxic response. Many models for a molecular oxygen sensor regulating this system have been proposed, but an important finding has been the ability to mimic hypoxia by chelation or substitution of iron. A key insight has been the recognition that HIF-alpha is targeted for degradation by the ubiquitin-proteasome pathway through binding to the von Hippel-Lindau tumour suppressor protein (pVHL), which forms the recognition component of an E3 ubiquitin ligase complex leading to ubiquitylation of HIF-alpha. Importantly, the classical features of regulation by iron and oxygen availability are reflected in regulation of the HIF-alpha/pVHL interaction. It has recently been shown that HIF-alpha undergoes an iron- and oxygen-dependent modification before it can interact with pVHL, and that this results in hydroxylation of at least one prolyl residue (HIF-1alpha, Pro 564). This modification is catalysed by an enzyme termed HIF-prolyl hydroxylase (HIF-PH), and compatible with all previously described prolyl-4-hydroxylases HIF-PH also requires 2-oxoglutarate as a cosubstrate. The key position of this hydroxylation in the degradation pathway of HIF-alpha, together with its requirement for molecular dioxygen as a co-substrate, provides the potential for HIF-PH to function directly as a cellular oxygen sensor. However, the ability of these enzyme(s) to account for the full range of physiological regulation displayed by the HIF system remains to be defined.\n"
],
"offsets": [
[
0,
1817
]
]
}
] | [
{
"id": "PMID-11795592_T1",
"type": "Protein",
"text": [
"von Hippel-Lindau tumour suppressor"
],
"offsets": [
[
25,
60
]
],
"normalized": []
},
{
"id": "PMID-11795592_T2",
"type": "Protein",
"text": [
"ubiquitin"
],
"offsets": [
[
644,
653
]
],
"normalized": []
},
{
"id": "PMID-11795592_T3",
"type": "Protein",
"text": [
"von Hippel-Lindau tumour suppressor"
],
"offsets": [
[
696,
731
]
],
"normalized": []
},
{
"id": "PMID-11795592_T4",
"type": "Protein",
"text": [
"pVHL"
],
"offsets": [
[
741,
745
]
],
"normalized": []
},
{
"id": "PMID-11795592_T5",
"type": "Protein",
"text": [
"ubiquitin"
],
"offsets": [
[
795,
804
]
],
"normalized": []
},
{
"id": "PMID-11795592_T6",
"type": "Protein",
"text": [
"pVHL"
],
"offsets": [
[
987,
991
]
],
"normalized": []
},
{
"id": "PMID-11795592_T7",
"type": "Protein",
"text": [
"pVHL"
],
"offsets": [
[
1128,
1132
]
],
"normalized": []
},
{
"id": "PMID-11795592_T8",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
1205,
1215
]
],
"normalized": []
},
{
"id": "PMID-11795592_T10",
"type": "Entity",
"text": [
"prolyl residue"
],
"offsets": [
[
1189,
1203
]
],
"normalized": []
},
{
"id": "PMID-11795592_T11",
"type": "Entity",
"text": [
"Pro 564"
],
"offsets": [
[
1217,
1224
]
],
"normalized": []
}
] | [
{
"id": "PMID-11795592_E1",
"type": "Hydroxylation",
"trigger": {
"text": [
"hydroxylation"
],
"offsets": [
[
1159,
1172
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11795592_T8"
},
{
"role": "Site",
"ref_id": "PMID-11795592_T10"
}
]
}
] | [
{
"id": "PMID-11795592_1",
"entity_ids": [
"PMID-11795592_T3",
"PMID-11795592_T4"
]
},
{
"id": "PMID-11795592_2",
"entity_ids": [
"PMID-11795592_T10",
"PMID-11795592_T11"
]
}
] | [] |
59 | PMID-11872960 | [
{
"id": "PMID-11872960__text",
"type": "abstract",
"text": [
"Promoter methylation status of the DNA repair genes hMLH1 and MGMT in gastric carcinoma and metaplastic mucosa. \nHypermethylation of CpG islands in the promoter region is associated with the silencing of a variety of tumor suppressor genes. DNA repair genes human Mut L homologue 1 (hMLH1) and O(6)-methylguanine-DNA methyltransferase (MGMT) have been shown to be hypermethylated in certain carcinomas. We studied DNA methylation of CpG islands in hMLH1 and MGMT in 50 gastric carcinomas and 10 intestinal metaplastic mucosa samples. We analyzed the methylation status of hMLH1 and MGMT using methylation-specific polymerase chain reaction and DNA sequencing analysis. We measured protein levels of hMLH1 using Western blot and immunohistochemical analysis. CpG island hypermethylation of hMLH1 and MGMT was detected in 11 (22%) and 8 (16%) of the 50 gastric tumors, respectively. Hypermethylation of the promoter was more common in intestinal-type gastric carcinomas than in poorly diffuse-type gastric carcinomas (p = 0.016 and 0.021, respectively; Fisher's exact test). However, hMLH1 promoter hypermethylation did not coincide with MGMT promoter hypermethylation except in 1 patient. Hypermethylation of the hMLH1 promoter but not the MGMT promoter occurred in intestinal metaplastic mucosae. Immunohistochemical analysis revealed a corresponding reduction in hMLH1 protein expression in some of the intestinal metaplastic mucosae. Our results suggest that at least two types of promoter methylation participate in the development of gastric carcinoma. Tumor-specific promoter hypermethylation of hMLH1 may be an early event in carcinogenesis in the stomach.\n"
],
"offsets": [
[
0,
1663
]
]
}
] | [
{
"id": "PMID-11872960_T1",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
53,
57
]
],
"normalized": []
},
{
"id": "PMID-11872960_T2",
"type": "Protein",
"text": [
"MGMT"
],
"offsets": [
[
62,
66
]
],
"normalized": []
},
{
"id": "PMID-11872960_T3",
"type": "Protein",
"text": [
"Mut L homologue 1"
],
"offsets": [
[
264,
281
]
],
"normalized": []
},
{
"id": "PMID-11872960_T4",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
284,
288
]
],
"normalized": []
},
{
"id": "PMID-11872960_T5",
"type": "Protein",
"text": [
"O(6)-methylguanine-DNA methyltransferase"
],
"offsets": [
[
294,
334
]
],
"normalized": []
},
{
"id": "PMID-11872960_T6",
"type": "Protein",
"text": [
"MGMT"
],
"offsets": [
[
336,
340
]
],
"normalized": []
},
{
"id": "PMID-11872960_T7",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
449,
453
]
],
"normalized": []
},
{
"id": "PMID-11872960_T8",
"type": "Protein",
"text": [
"MGMT"
],
"offsets": [
[
458,
462
]
],
"normalized": []
},
{
"id": "PMID-11872960_T9",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
573,
577
]
],
"normalized": []
},
{
"id": "PMID-11872960_T10",
"type": "Protein",
"text": [
"MGMT"
],
"offsets": [
[
582,
586
]
],
"normalized": []
},
{
"id": "PMID-11872960_T11",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
700,
704
]
],
"normalized": []
},
{
"id": "PMID-11872960_T12",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
790,
794
]
],
"normalized": []
},
{
"id": "PMID-11872960_T13",
"type": "Protein",
"text": [
"MGMT"
],
"offsets": [
[
799,
803
]
],
"normalized": []
},
{
"id": "PMID-11872960_T14",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
1083,
1087
]
],
"normalized": []
},
{
"id": "PMID-11872960_T15",
"type": "Protein",
"text": [
"MGMT"
],
"offsets": [
[
1136,
1140
]
],
"normalized": []
},
{
"id": "PMID-11872960_T16",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
1213,
1217
]
],
"normalized": []
},
{
"id": "PMID-11872960_T17",
"type": "Protein",
"text": [
"MGMT"
],
"offsets": [
[
1239,
1243
]
],
"normalized": []
},
{
"id": "PMID-11872960_T18",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
1365,
1369
]
],
"normalized": []
},
{
"id": "PMID-11872960_T19",
"type": "Protein",
"text": [
"MLH1"
],
"offsets": [
[
1602,
1606
]
],
"normalized": []
},
{
"id": "PMID-11872960_T20",
"type": "Entity",
"text": [
"Promoter"
],
"offsets": [
[
0,
8
]
],
"normalized": []
},
{
"id": "PMID-11872960_T24",
"type": "Entity",
"text": [
"CpG islands"
],
"offsets": [
[
433,
444
]
],
"normalized": []
},
{
"id": "PMID-11872960_T26",
"type": "Entity",
"text": [
"CpG island"
],
"offsets": [
[
758,
768
]
],
"normalized": []
},
{
"id": "PMID-11872960_T28",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1088,
1096
]
],
"normalized": []
},
{
"id": "PMID-11872960_T30",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1141,
1149
]
],
"normalized": []
},
{
"id": "PMID-11872960_T33",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1218,
1226
]
],
"normalized": []
},
{
"id": "PMID-11872960_T34",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1244,
1252
]
],
"normalized": []
},
{
"id": "PMID-11872960_T35",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1572,
1580
]
],
"normalized": []
}
] | [
{
"id": "PMID-11872960_E1",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
9,
20
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11872960_T1"
},
{
"role": "Site",
"ref_id": "PMID-11872960_T20"
}
]
},
{
"id": "PMID-11872960_E2",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
9,
20
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11872960_T2"
},
{
"role": "Site",
"ref_id": "PMID-11872960_T20"
}
]
},
{
"id": "PMID-11872960_E3",
"type": "DNA_methylation",
"trigger": {
"text": [
"hypermethylated"
],
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[
364,
379
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11872960_T3"
}
]
},
{
"id": "PMID-11872960_E4",
"type": "DNA_methylation",
"trigger": {
"text": [
"hypermethylated"
],
"offsets": [
[
364,
379
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11872960_T5"
}
]
},
{
"id": "PMID-11872960_E5",
"type": "DNA_methylation",
"trigger": {
"text": [
"DNA methylation"
],
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414,
429
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11872960_T7"
},
{
"role": "Site",
"ref_id": "PMID-11872960_T24"
}
]
},
{
"id": "PMID-11872960_E6",
"type": "DNA_methylation",
"trigger": {
"text": [
"DNA methylation"
],
"offsets": [
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414,
429
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11872960_T8"
},
{
"role": "Site",
"ref_id": "PMID-11872960_T24"
}
]
},
{
"id": "PMID-11872960_E7",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
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550,
561
]
]
},
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{
"role": "Theme",
"ref_id": "PMID-11872960_T9"
}
]
},
{
"id": "PMID-11872960_E8",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
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[
550,
561
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11872960_T10"
}
]
},
{
"id": "PMID-11872960_E9",
"type": "DNA_methylation",
"trigger": {
"text": [
"hypermethylation"
],
"offsets": [
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769,
785
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11872960_T12"
},
{
"role": "Site",
"ref_id": "PMID-11872960_T26"
}
]
},
{
"id": "PMID-11872960_E10",
"type": "DNA_methylation",
"trigger": {
"text": [
"hypermethylation"
],
"offsets": [
[
769,
785
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11872960_T13"
},
{
"role": "Site",
"ref_id": "PMID-11872960_T26"
}
]
},
{
"id": "PMID-11872960_E11",
"type": "DNA_methylation",
"trigger": {
"text": [
"hypermethylation"
],
"offsets": [
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1113
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11872960_T14"
},
{
"role": "Site",
"ref_id": "PMID-11872960_T28"
}
]
},
{
"id": "PMID-11872960_E12",
"type": "DNA_methylation",
"trigger": {
"text": [
"hypermethylation"
],
"offsets": [
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1150,
1166
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11872960_T15"
},
{
"role": "Site",
"ref_id": "PMID-11872960_T30"
}
]
},
{
"id": "PMID-11872960_E13",
"type": "DNA_methylation",
"trigger": {
"text": [
"Hypermethylation"
],
"offsets": [
[
1188,
1204
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11872960_T16"
},
{
"role": "Site",
"ref_id": "PMID-11872960_T33"
}
]
},
{
"id": "PMID-11872960_E14",
"type": "DNA_methylation",
"trigger": {
"text": [
"Hypermethylation"
],
"offsets": [
[
1188,
1204
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11872960_T17"
},
{
"role": "Site",
"ref_id": "PMID-11872960_T34"
}
]
},
{
"id": "PMID-11872960_E15",
"type": "DNA_methylation",
"trigger": {
"text": [
"hypermethylation"
],
"offsets": [
[
1581,
1597
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11872960_T19"
},
{
"role": "Site",
"ref_id": "PMID-11872960_T35"
}
]
}
] | [
{
"id": "PMID-11872960_1",
"entity_ids": [
"PMID-11872960_T3",
"PMID-11872960_T4"
]
},
{
"id": "PMID-11872960_2",
"entity_ids": [
"PMID-11872960_T5",
"PMID-11872960_T6"
]
}
] | [] |
60 | PMID-11902574 | [
{
"id": "PMID-11902574__text",
"type": "abstract",
"text": [
"Histone deacetylases and cancer: causes and therapies. \nTogether, histone acetyltransferases and histone deacetylases (HDACs) determine the acetylation status of histones. This acetylation affects the regulation of gene expression, and inhibitors of HDACs have been found to cause growth arrest, differentiation and/or apoptosis of many tumours cells by altering the transcription of a small number of genes. HDAC inhibitors are proving to be an exciting therapeutic approach to cancer, but how do they exert this effect?\n"
],
"offsets": [
[
0,
522
]
]
}
] | [
{
"id": "PMID-11902574_T1",
"type": "Protein",
"text": [
"Histone"
],
"offsets": [
[
0,
7
]
],
"normalized": []
},
{
"id": "PMID-11902574_T2",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
66,
73
]
],
"normalized": []
},
{
"id": "PMID-11902574_T3",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
97,
104
]
],
"normalized": []
},
{
"id": "PMID-11902574_T4",
"type": "Protein",
"text": [
"histones"
],
"offsets": [
[
162,
170
]
],
"normalized": []
}
] | [
{
"id": "PMID-11902574_E1",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
140,
151
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11902574_T4"
}
]
},
{
"id": "PMID-11902574_E2",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
177,
188
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11902574_T4"
}
]
}
] | [] | [] |
61 | PMID-11914074 | [
{
"id": "PMID-11914074__text",
"type": "abstract",
"text": [
"Co- and posttranslational modification of the alpha(1B)-adrenergic receptor: effects on receptor expression and function. \nWe have characterized the maturation, co- and posttranslational modifications, and functional properties of the alpha(1B)-adrenergic receptor (AR) expressed in different mammalian cells transfected using conventional approaches or the Semliki Forest virus system. We found that the alpha(1B)-AR undergoes N-linked glycosylation as demonstrated by its sensitivity to endoglycosidases and by the effect of tunicamycin on receptor maturation. Pulse-chase labeling experiments in BHK-21 cells demonstrate that the alpha(1B)-AR is synthesized as a 70 kDa core glycosylated precursor that is converted to the 90 kDa mature form of the receptor with a half-time of approximately 2 h. N-Linked glycosylation of the alpha(1B)-AR occurs at four asparagines on the N-terminus of the receptor. Mutations of the N-linked glycosylation sites did not have a significant effect on receptor function or expression. Surprisingly, receptor mutants lacking N-linked glycosylation migrated as heterogeneous bands in SDS-PAGE. Our findings demonstrate that N-linked glycosylation and phosphorylation, but not palmitoylation or O-linked glycosylation, contribute to the structural heterogeneity of the alpha(1B)-AR as it is observed in SDS-PAGE. The modifications found are similar in the different mammalian expression systems explored. Our findings indicate that the Semliki Forest virus system can provide large amounts of functional and fully glycosylated alpha(1B)-AR protein suitable for biochemical and structural studies. The results of this study contribute to elucidate the basic steps involved in the processing of G protein-coupled receptors as well as to optimize strategies for their overexpression.\n"
],
"offsets": [
[
0,
1814
]
]
}
] | [
{
"id": "PMID-11914074_T1",
"type": "Protein",
"text": [
"alpha(1B)-adrenergic receptor"
],
"offsets": [
[
46,
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]
],
"normalized": []
},
{
"id": "PMID-11914074_T2",
"type": "Protein",
"text": [
"alpha(1B)-adrenergic receptor"
],
"offsets": [
[
235,
264
]
],
"normalized": []
},
{
"id": "PMID-11914074_T3",
"type": "Protein",
"text": [
"alpha(1B)-AR"
],
"offsets": [
[
405,
417
]
],
"normalized": []
},
{
"id": "PMID-11914074_T4",
"type": "Protein",
"text": [
"alpha(1B)-AR"
],
"offsets": [
[
633,
645
]
],
"normalized": []
},
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"id": "PMID-11914074_T5",
"type": "Protein",
"text": [
"alpha(1B)-AR"
],
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[
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]
],
"normalized": []
},
{
"id": "PMID-11914074_T6",
"type": "Protein",
"text": [
"alpha(1B)-AR"
],
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[
1302,
1314
]
],
"normalized": []
},
{
"id": "PMID-11914074_T7",
"type": "Protein",
"text": [
"alpha(1B)-AR"
],
"offsets": [
[
1560,
1572
]
],
"normalized": []
},
{
"id": "PMID-11914074_T11",
"type": "Entity",
"text": [
"four asparagines"
],
"offsets": [
[
853,
869
]
],
"normalized": []
}
] | [
{
"id": "PMID-11914074_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"N-linked glycosylation"
],
"offsets": [
[
428,
450
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11914074_T3"
}
]
},
{
"id": "PMID-11914074_E2",
"type": "Glycosylation",
"trigger": {
"text": [
"glycosylated"
],
"offsets": [
[
678,
690
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11914074_T4"
}
]
},
{
"id": "PMID-11914074_E3",
"type": "Glycosylation",
"trigger": {
"text": [
"glycosylation"
],
"offsets": [
[
809,
822
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11914074_T5"
},
{
"role": "Site",
"ref_id": "PMID-11914074_T11"
}
]
},
{
"id": "PMID-11914074_E4",
"type": "Glycosylation",
"trigger": {
"text": [
"N-linked glycosylation"
],
"offsets": [
[
1158,
1180
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11914074_T6"
}
]
},
{
"id": "PMID-11914074_E5",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
1185,
1200
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11914074_T6"
}
]
},
{
"id": "PMID-11914074_E6",
"type": "Glycosylation",
"trigger": {
"text": [
"O-linked glycosylation"
],
"offsets": [
[
1228,
1250
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11914074_T6"
}
]
},
{
"id": "PMID-11914074_E7",
"type": "Glycosylation",
"trigger": {
"text": [
"glycosylated"
],
"offsets": [
[
1547,
1559
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11914074_T7"
}
]
}
] | [] | [] |
62 | PMID-11960489 | [
{
"id": "PMID-11960489__text",
"type": "abstract",
"text": [
"Binding mode analysis of 3-(4-benzoyl-1-methyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamide: a new synthetic histone deacetylase inhibitor inducing histone hyperacetylation, growth inhibition, and terminal cell differentiation. \nThe binding mode of 3-(4-aroyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamides 1a-c, belonging to a recently reported class of synthetic histone deacetylase (HDAC) inhibitors (Massa, S.; et al. J. Med. Chem. 2001, 44, 2069-2072), into the new modeled HDAC1 catalytic core is presented, and enzyme/inhibitor interactions are discussed. HDAC1 X-ray coordinates were obtained by virtual \"mutation\" of those of histone deacetylase-like protein, a bacterial HDAC homologue. In in vitro antimaize HD2 as well as antimouse HDAC1 assay, compounds 1a-c showed inhibitory activities in the low micromolar range. Similarly, 1a-c are endowed with anti-HDAC activity in vivo: on mouse A20 cells, 1a-c induced histone hyperacetylation leading to a highly increased acetylation level of H4 as compared to control histones. Results obtained with acid-urea-triton polyacrylamide gel electrophoresis have been confirmed by Western Blot experiments. Finally, compound 1a, chosen as a representative member of this class of HDAC inhibitors, resulted endowed with antiproliferative (45 and 85% cell growth inhibition at 40 and 80 microM, respectively) and cellular differentiation (18 and 21% of benzidine positive cells at the same concentrations) activities in murine erythroleukemic cells.\n"
],
"offsets": [
[
0,
1487
]
]
}
] | [
{
"id": "PMID-11960489_T1",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
103,
110
]
],
"normalized": []
},
{
"id": "PMID-11960489_T2",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
142,
149
]
],
"normalized": []
},
{
"id": "PMID-11960489_T3",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
352,
359
]
],
"normalized": []
},
{
"id": "PMID-11960489_T4",
"type": "Protein",
"text": [
"HDAC1"
],
"offsets": [
[
466,
471
]
],
"normalized": []
},
{
"id": "PMID-11960489_T5",
"type": "Protein",
"text": [
"HDAC1"
],
"offsets": [
[
550,
555
]
],
"normalized": []
},
{
"id": "PMID-11960489_T6",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
622,
629
]
],
"normalized": []
},
{
"id": "PMID-11960489_T7",
"type": "Protein",
"text": [
"HDAC1"
],
"offsets": [
[
731,
736
]
],
"normalized": []
},
{
"id": "PMID-11960489_T8",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
911,
918
]
],
"normalized": []
},
{
"id": "PMID-11960489_T9",
"type": "Protein",
"text": [
"H4"
],
"offsets": [
[
987,
989
]
],
"normalized": []
},
{
"id": "PMID-11960489_T10",
"type": "Protein",
"text": [
"histones"
],
"offsets": [
[
1013,
1021
]
],
"normalized": []
}
] | [
{
"id": "PMID-11960489_E1",
"type": "Acetylation",
"trigger": {
"text": [
"hyperacetylation"
],
"offsets": [
[
150,
166
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11960489_T2"
}
]
},
{
"id": "PMID-11960489_E2",
"type": "Acetylation",
"trigger": {
"text": [
"hyperacetylation"
],
"offsets": [
[
919,
935
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11960489_T8"
}
]
},
{
"id": "PMID-11960489_E3",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
966,
977
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11960489_T9"
}
]
}
] | [] | [] |
63 | PMID-12042299 | [
{
"id": "PMID-12042299__text",
"type": "abstract",
"text": [
"Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family. \nActivity of the hypoxia-inducible factor (HIF) complex is controlled by oxygen-dependent hydroxylation of prolyl and asparaginyl residues. Hydroxylation of specific prolyl residues by 2-oxoglutarate (2-OG)-dependent oxygenases mediates ubiquitinylation and proteasomal destruction of HIF-alpha. Hydroxylation of an asparagine residue in the C-terminal transactivation domain (CAD) of HIF-alpha abrogates interaction with p300, preventing transcriptional activation. Yeast two-hybrid assays recently identified factor inhibiting HIF (FIH) as a protein that associates with the CAD region of HIF-alpha. Since FIH contains certain motifs present in iron- and 2-OG-dependent oxygenases we investigated whether FIH was the HIF asparaginyl hydroxylase. Assays using recombinant FIH and HIF-alpha fragments revealed that FIH is the enzyme that hydroxylates the CAD asparagine residue, that the activity is directly inhibited by cobalt(II) and limited by hypoxia, and that the oxygen in the alcohol of the hydroxyasparagine residue is directly derived from dioxygen. Sequence analyses involving FIH link the 2-OG oxygenases with members of the cupin superfamily, including Zn(II)-utilizing phosphomannose isomerase, revealing structural and evolutionary links between these metal-binding proteins that share common motifs.\n"
],
"offsets": [
[
0,
1461
]
]
}
] | [
{
"id": "PMID-12042299_T1",
"type": "Protein",
"text": [
"Hypoxia-inducible factor (HIF) asparagine hydroxylase"
],
"offsets": [
[
0,
53
]
],
"normalized": []
},
{
"id": "PMID-12042299_T2",
"type": "Protein",
"text": [
"factor inhibiting HIF"
],
"offsets": [
[
70,
91
]
],
"normalized": []
},
{
"id": "PMID-12042299_T3",
"type": "Protein",
"text": [
"FIH"
],
"offsets": [
[
93,
96
]
],
"normalized": []
},
{
"id": "PMID-12042299_T4",
"type": "Protein",
"text": [
"p300"
],
"offsets": [
[
567,
571
]
],
"normalized": []
},
{
"id": "PMID-12042299_T5",
"type": "Protein",
"text": [
"factor inhibiting HIF"
],
"offsets": [
[
656,
677
]
],
"normalized": []
},
{
"id": "PMID-12042299_T6",
"type": "Protein",
"text": [
"FIH"
],
"offsets": [
[
679,
682
]
],
"normalized": []
},
{
"id": "PMID-12042299_T7",
"type": "Protein",
"text": [
"FIH"
],
"offsets": [
[
753,
756
]
],
"normalized": []
},
{
"id": "PMID-12042299_T8",
"type": "Protein",
"text": [
"FIH"
],
"offsets": [
[
852,
855
]
],
"normalized": []
},
{
"id": "PMID-12042299_T9",
"type": "Protein",
"text": [
"HIF asparaginyl hydroxylase"
],
"offsets": [
[
864,
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]
],
"normalized": []
},
{
"id": "PMID-12042299_T10",
"type": "Protein",
"text": [
"FIH"
],
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[
918,
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]
],
"normalized": []
},
{
"id": "PMID-12042299_T11",
"type": "Protein",
"text": [
"FIH"
],
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[
960,
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]
],
"normalized": []
},
{
"id": "PMID-12042299_T12",
"type": "Protein",
"text": [
"FIH"
],
"offsets": [
[
1233,
1236
]
],
"normalized": []
},
{
"id": "PMID-12042299_T13",
"type": "Protein",
"text": [
"phosphomannose isomerase"
],
"offsets": [
[
1328,
1352
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-12042299_1",
"entity_ids": [
"PMID-12042299_T1",
"PMID-12042299_T2",
"PMID-12042299_T3"
]
},
{
"id": "PMID-12042299_2",
"entity_ids": [
"PMID-12042299_T5",
"PMID-12042299_T6"
]
},
{
"id": "PMID-12042299_3",
"entity_ids": [
"PMID-12042299_T8",
"PMID-12042299_T9"
]
}
] | [] |
64 | PMID-12080085 | [
{
"id": "PMID-12080085__text",
"type": "abstract",
"text": [
"FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. \nMammalian cells adapt to hypoxic conditions through a transcriptional response pathway mediated by the hypoxia-inducible factor, HIF. HIF transcriptional activity is suppressed under normoxic conditions by hydroxylation of an asparagine residue within its C-terminal transactivation domain, blocking association with coactivators. Here we show that the protein FIH-1, previously shown to interact with HIF, is an asparaginyl hydroxylase. Like known hydroxylase enzymes, FIH-1 is an Fe(II)-dependent enzyme that uses molecular O(2) to modify its substrate. Together with the recently discovered prolyl hydroxylases that regulate HIF stability, this class of oxygen-dependent enzymes comprises critical regulatory components of the hypoxic response pathway.\n"
],
"offsets": [
[
0,
873
]
]
}
] | [
{
"id": "PMID-12080085_T1",
"type": "Protein",
"text": [
"FIH-1"
],
"offsets": [
[
0,
5
]
],
"normalized": []
},
{
"id": "PMID-12080085_T2",
"type": "Protein",
"text": [
"FIH-1"
],
"offsets": [
[
478,
483
]
],
"normalized": []
},
{
"id": "PMID-12080085_T3",
"type": "Protein",
"text": [
"FIH-1"
],
"offsets": [
[
587,
592
]
],
"normalized": []
}
] | [] | [] | [] |
65 | PMID-12080182 | [
{
"id": "PMID-12080182__text",
"type": "abstract",
"text": [
"[alpha]-Secretase ADAM10 as well as [alpha]APPs is reduced in platelets and CSF of Alzheimer disease patients. \nBACKGROUND: Members of membrane-bound disintegrin metalloproteinases (ADAMs) were shown to be capable of cleaving amyloid precursor protein (APP) at the alpha-cleavage site in different cell systems. One of the candidate alpha-secretases identified in this family is ADAM10. The present study addresses the following major questions: 1) Are the levels of an alpha-secretase candidate (i.e., ADAM10) reduced in accessible cells of Alzheimer Disease (AD) patients? 2) Are ADAM10 levels in the peripheral cells of AD patients related to a concomitant decrease in alpha APPs? MATERIALS AND METHODS: Western Blot analysis of ADAM10 is performed on platelet homogenates from 33 sporadic AD patients and on 26 age-matched control subjects. Moreover, the levels of alpha-secretase metabolite (alpha APPs) are tested both in platelets and cerebrospinal fluid (CSF) of the same pool of subjects by means of Western blot with a specific antibody. RESULTS: A significant decrease of platelet ADAM10 levels is observed in patients affected by probable AD when compared to control subjects and this is paralleled by a reduced level of alpha APPs released from platelets. Moreover, in the same pool of AD patients, alpha APPs levels were reduced concomitantly in CSF. CONCLUSIONS: ADAM10 is expressed in platelets. A reduced level of ADAM10 is observed in platelets obtained from AD patients compared to age-matched controls. Further, in the same pool of AD patients, a qualitatively and quantitatively similar decrease in alpha APPs is present both in thrombin-activated platelets and CSF, thus suggesting that alterations of APP processing might occur both in the neuronal compartment and peripheral cells.\n"
],
"offsets": [
[
0,
1808
]
]
}
] | [
{
"id": "PMID-12080182_T1",
"type": "Protein",
"text": [
"ADAM10"
],
"offsets": [
[
18,
24
]
],
"normalized": []
},
{
"id": "PMID-12080182_T2",
"type": "Protein",
"text": [
"[alpha]APPs"
],
"offsets": [
[
36,
47
]
],
"normalized": []
},
{
"id": "PMID-12080182_T3",
"type": "Protein",
"text": [
"amyloid precursor protein"
],
"offsets": [
[
226,
251
]
],
"normalized": []
},
{
"id": "PMID-12080182_T4",
"type": "Protein",
"text": [
"APP"
],
"offsets": [
[
253,
256
]
],
"normalized": []
},
{
"id": "PMID-12080182_T5",
"type": "Protein",
"text": [
"ADAM10"
],
"offsets": [
[
379,
385
]
],
"normalized": []
},
{
"id": "PMID-12080182_T6",
"type": "Protein",
"text": [
"ADAM10"
],
"offsets": [
[
503,
509
]
],
"normalized": []
},
{
"id": "PMID-12080182_T7",
"type": "Protein",
"text": [
"ADAM10"
],
"offsets": [
[
583,
589
]
],
"normalized": []
},
{
"id": "PMID-12080182_T8",
"type": "Protein",
"text": [
"alpha APPs"
],
"offsets": [
[
673,
683
]
],
"normalized": []
},
{
"id": "PMID-12080182_T9",
"type": "Protein",
"text": [
"ADAM10"
],
"offsets": [
[
734,
740
]
],
"normalized": []
},
{
"id": "PMID-12080182_T10",
"type": "Protein",
"text": [
"alpha APPs"
],
"offsets": [
[
899,
909
]
],
"normalized": []
},
{
"id": "PMID-12080182_T11",
"type": "Protein",
"text": [
"ADAM10"
],
"offsets": [
[
1094,
1100
]
],
"normalized": []
},
{
"id": "PMID-12080182_T12",
"type": "Protein",
"text": [
"alpha APPs"
],
"offsets": [
[
1235,
1245
]
],
"normalized": []
},
{
"id": "PMID-12080182_T13",
"type": "Protein",
"text": [
"alpha APPs"
],
"offsets": [
[
1314,
1324
]
],
"normalized": []
},
{
"id": "PMID-12080182_T14",
"type": "Protein",
"text": [
"ADAM10"
],
"offsets": [
[
1380,
1386
]
],
"normalized": []
},
{
"id": "PMID-12080182_T15",
"type": "Protein",
"text": [
"ADAM10"
],
"offsets": [
[
1433,
1439
]
],
"normalized": []
},
{
"id": "PMID-12080182_T16",
"type": "Protein",
"text": [
"alpha APPs"
],
"offsets": [
[
1622,
1632
]
],
"normalized": []
},
{
"id": "PMID-12080182_T17",
"type": "Protein",
"text": [
"thrombin"
],
"offsets": [
[
1652,
1660
]
],
"normalized": []
},
{
"id": "PMID-12080182_T18",
"type": "Protein",
"text": [
"APP"
],
"offsets": [
[
1726,
1729
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-12080182_1",
"entity_ids": [
"PMID-12080182_T3",
"PMID-12080182_T4"
]
}
] | [] |
66 | PMID-12115587 | [
{
"id": "PMID-12115587__text",
"type": "abstract",
"text": [
"Reduced expression of the insulin-induced protein 1 and p41 Arp2/3 complex genes in human gastric cancers. \nAberrantly methylated DNA fragments in a human gastric cancer were searched for by a genome-scanning method, methylation-sensitive-representational difference analysis (MS-RDA). Six DNA fragments flanked by CpG islands (CGIs) and hypermethylated in the cancer were isolated. Four of the 6 fragments possessed genes in their vicinities. Quantitative RT-PCR analysis of the 4 genes showed reduced expression of 2 genes in cancers: Insulin-induced protein 1 (INSIG1/CL-6) and p41 Arp2/3 complex (p41-Arc). As for INSIG1, a DNA fragment was derived from the edge of a CGI in the promoter region. The edge was methylated in 11 of 22 primary gastric cancers, whereas the center was not methylated in any cancer. INSIG1 expression was markedly reduced in 19 cancers, including the 11 cancers with the methylation. By 5-aza-2'-deoxycytidine treatment of 5 cell lines with the methylation of the edge, partial restoration of INSIG1 expression was detected only in 2 of them. These data indicated that, although the reduced INSIG1 expression in cancers was associated with the methylation at the edge of the CGI in the promoter region, the methylation was likely to be a secondary change. As for p41-Arc, a DNA fragment was derived from a CGI overlapping exon 8, and its methylation did not correlate with its expression. However, methylation of a CGI in the promoter region with a marked reduction of its expression was observed in 1 of the 22 primary cancers. INSIG1 and p41-Arc are known to be involved in cellular differentiation and morphology, respectively, and it was suggested that their reduced expressions might be involved in gastric cancer development or progression.\n"
],
"offsets": [
[
0,
1778
]
]
}
] | [
{
"id": "PMID-12115587_T1",
"type": "Protein",
"text": [
"insulin-induced protein 1"
],
"offsets": [
[
26,
51
]
],
"normalized": []
},
{
"id": "PMID-12115587_T2",
"type": "Protein",
"text": [
"p41"
],
"offsets": [
[
56,
59
]
],
"normalized": []
},
{
"id": "PMID-12115587_T3",
"type": "Protein",
"text": [
"Arp2/3 complex genes"
],
"offsets": [
[
60,
80
]
],
"normalized": []
},
{
"id": "PMID-12115587_T4",
"type": "Protein",
"text": [
"Insulin-induced protein 1"
],
"offsets": [
[
537,
562
]
],
"normalized": []
},
{
"id": "PMID-12115587_T5",
"type": "Protein",
"text": [
"INSIG1"
],
"offsets": [
[
564,
570
]
],
"normalized": []
},
{
"id": "PMID-12115587_T6",
"type": "Protein",
"text": [
"CL-6"
],
"offsets": [
[
571,
575
]
],
"normalized": []
},
{
"id": "PMID-12115587_T7",
"type": "Protein",
"text": [
"p41"
],
"offsets": [
[
581,
584
]
],
"normalized": []
},
{
"id": "PMID-12115587_T8",
"type": "Protein",
"text": [
"p41"
],
"offsets": [
[
601,
604
]
],
"normalized": []
},
{
"id": "PMID-12115587_T9",
"type": "Protein",
"text": [
"INSIG1"
],
"offsets": [
[
618,
624
]
],
"normalized": []
},
{
"id": "PMID-12115587_T10",
"type": "Protein",
"text": [
"INSIG1"
],
"offsets": [
[
814,
820
]
],
"normalized": []
},
{
"id": "PMID-12115587_T11",
"type": "Protein",
"text": [
"INSIG1"
],
"offsets": [
[
1024,
1030
]
],
"normalized": []
},
{
"id": "PMID-12115587_T12",
"type": "Protein",
"text": [
"INSIG1"
],
"offsets": [
[
1122,
1128
]
],
"normalized": []
},
{
"id": "PMID-12115587_T13",
"type": "Protein",
"text": [
"p41"
],
"offsets": [
[
1294,
1297
]
],
"normalized": []
},
{
"id": "PMID-12115587_T14",
"type": "Protein",
"text": [
"INSIG1"
],
"offsets": [
[
1560,
1566
]
],
"normalized": []
},
{
"id": "PMID-12115587_T15",
"type": "Protein",
"text": [
"p41"
],
"offsets": [
[
1571,
1574
]
],
"normalized": []
},
{
"id": "PMID-12115587_T16",
"type": "Entity",
"text": [
"edge"
],
"offsets": [
[
704,
708
]
],
"normalized": []
},
{
"id": "PMID-12115587_T18",
"type": "Entity",
"text": [
"center"
],
"offsets": [
[
773,
779
]
],
"normalized": []
},
{
"id": "PMID-12115587_T22",
"type": "Entity",
"text": [
"edge"
],
"offsets": [
[
995,
999
]
],
"normalized": []
},
{
"id": "PMID-12115587_T24",
"type": "Entity",
"text": [
"edge"
],
"offsets": [
[
1194,
1198
]
],
"normalized": []
},
{
"id": "PMID-12115587_T25",
"type": "Entity",
"text": [
"CGI overlapping exon 8"
],
"offsets": [
[
1337,
1359
]
],
"normalized": []
},
{
"id": "PMID-12115587_T28",
"type": "Entity",
"text": [
"CGI"
],
"offsets": [
[
1446,
1449
]
],
"normalized": []
}
] | [
{
"id": "PMID-12115587_E1",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
713,
723
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12115587_T9"
},
{
"role": "Site",
"ref_id": "PMID-12115587_T16"
}
]
},
{
"id": "PMID-12115587_E2",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
788,
798
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12115587_T9"
},
{
"role": "Site",
"ref_id": "PMID-12115587_T18"
}
]
},
{
"id": "PMID-12115587_E3",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
902,
913
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12115587_T10"
}
]
},
{
"id": "PMID-12115587_E4",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
976,
987
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12115587_T11"
},
{
"role": "Site",
"ref_id": "PMID-12115587_T22"
}
]
},
{
"id": "PMID-12115587_E5",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1175,
1186
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12115587_T12"
},
{
"role": "Site",
"ref_id": "PMID-12115587_T24"
}
]
},
{
"id": "PMID-12115587_E6",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1369,
1380
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12115587_T13"
},
{
"role": "Site",
"ref_id": "PMID-12115587_T25"
}
]
},
{
"id": "PMID-12115587_E7",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1429,
1440
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12115587_T13"
},
{
"role": "Site",
"ref_id": "PMID-12115587_T28"
}
]
}
] | [
{
"id": "PMID-12115587_1",
"entity_ids": [
"PMID-12115587_T4",
"PMID-12115587_T5",
"PMID-12115587_T6"
]
}
] | [] |
67 | PMID-12126935 | [
{
"id": "PMID-12126935__text",
"type": "abstract",
"text": [
"The kyphoscoliotic type of Ehlers-Danlos syndrome (type VI): differential effects on the hydroxylation of lysine in collagens I and II revealed by analysis of cross-linked telopeptides from urine. \nThe kyphoscoliotic type of Ehlers-Danlos syndrome (EDS type VIA) (OMIM 225400) is an autosomal recessive connective tissue disorder that results from mutations in the lysyl hydroxylase 1 gene (PLOD1) causing underhydroxylation of lysine residues in tissue collagens, particularly of skin. Previous studies have shown that the pool of collagen cross-linking amino acids, hydroxylysyl pyridinoline (HP) and lysyl pyridinoline (LP) excreted in urine has an abnormally low HP/LP ratio, which is diagnostic of the condition. Here we isolated cross-linked peptides containing these residues from the urine of a child with EDS VIA homozygous for a mutation that results in a stop codon and effective null expression of PLOD1 enzyme activity. Peptides that had originated from bone type I collagen and cartilage type II collagen were identified. A cross-linked N-telopeptide fraction that is derived from bone type I collagen contained only LP, no HP, which means that the helical lysines at residues 930 of alpha 1(I) and 933 of alpha 2(I) of the collagen triple-helix had not been hydroxylated. The equivalent peptide fraction from a normal child's urine gave a ratio of HP to LP of 1.5:1 typical for normal bone collagen. A second cross-linked peptide that is derived from the C-telopeptide domain of cartilage type II collagen showed both HP and LP in a 2:1 ratio, compared with 18:1 for the equivalent peptide from a normal child's urine. The results show that in EDS VIA, bone type I collagen is more markedly underhydroxylated than cartilage type II collagen, at least at those helical sites that form cross-links. The residual fraction of HP found in the urine of EDS VI patients therefore appears to be contributed in significant part by the degradation products of cartilage. Since PLOD1 is null, other PLOD genes must be responsible for the helical hydroxylation activity that results in HP. The presented approach of analyzing urinary cross-linked C-telopeptide fragments of type II collagen may allow the detection of chondrodysplasias due to genetic defects in lysyl hydroxylase isoforms active in cartilage.\n"
],
"offsets": [
[
0,
2313
]
]
}
] | [
{
"id": "PMID-12126935_T1",
"type": "Protein",
"text": [
"II"
],
"offsets": [
[
132,
134
]
],
"normalized": []
},
{
"id": "PMID-12126935_T2",
"type": "Protein",
"text": [
"lysyl hydroxylase 1"
],
"offsets": [
[
365,
384
]
],
"normalized": []
},
{
"id": "PMID-12126935_T3",
"type": "Protein",
"text": [
"PLOD1"
],
"offsets": [
[
391,
396
]
],
"normalized": []
},
{
"id": "PMID-12126935_T4",
"type": "Protein",
"text": [
"PLOD1"
],
"offsets": [
[
910,
915
]
],
"normalized": []
},
{
"id": "PMID-12126935_T5",
"type": "Protein",
"text": [
"type II collagen"
],
"offsets": [
[
1002,
1018
]
],
"normalized": []
},
{
"id": "PMID-12126935_T6",
"type": "Protein",
"text": [
"alpha 1(I)"
],
"offsets": [
[
1198,
1208
]
],
"normalized": []
},
{
"id": "PMID-12126935_T7",
"type": "Protein",
"text": [
"alpha 2(I)"
],
"offsets": [
[
1220,
1230
]
],
"normalized": []
},
{
"id": "PMID-12126935_T8",
"type": "Protein",
"text": [
"type II collagen"
],
"offsets": [
[
1504,
1520
]
],
"normalized": []
},
{
"id": "PMID-12126935_T9",
"type": "Protein",
"text": [
"type II collagen"
],
"offsets": [
[
1739,
1755
]
],
"normalized": []
},
{
"id": "PMID-12126935_T10",
"type": "Protein",
"text": [
"PLOD1"
],
"offsets": [
[
1982,
1987
]
],
"normalized": []
},
{
"id": "PMID-12126935_T11",
"type": "Protein",
"text": [
"type II collagen"
],
"offsets": [
[
2177,
2193
]
],
"normalized": []
},
{
"id": "PMID-12126935_T13",
"type": "Entity",
"text": [
"lysine"
],
"offsets": [
[
106,
112
]
],
"normalized": []
},
{
"id": "PMID-12126935_T14",
"type": "Entity",
"text": [
"residues 930"
],
"offsets": [
[
1182,
1194
]
],
"normalized": []
},
{
"id": "PMID-12126935_T15",
"type": "Entity",
"text": [
"933"
],
"offsets": [
[
1213,
1216
]
],
"normalized": []
}
] | [
{
"id": "PMID-12126935_E1",
"type": "Hydroxylation",
"trigger": {
"text": [
"hydroxylation"
],
"offsets": [
[
89,
102
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12126935_T1"
},
{
"role": "Site",
"ref_id": "PMID-12126935_T13"
}
]
},
{
"id": "PMID-12126935_E2",
"type": "Hydroxylation",
"trigger": {
"text": [
"hydroxylated"
],
"offsets": [
[
1273,
1285
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12126935_T6"
},
{
"role": "Site",
"ref_id": "PMID-12126935_T14"
}
]
},
{
"id": "PMID-12126935_E3",
"type": "Hydroxylation",
"trigger": {
"text": [
"hydroxylated"
],
"offsets": [
[
1273,
1285
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12126935_T7"
},
{
"role": "Site",
"ref_id": "PMID-12126935_T15"
}
]
},
{
"id": "PMID-12126935_E4",
"type": "Hydroxylation",
"trigger": {
"text": [
"underhydroxylated"
],
"offsets": [
[
1706,
1723
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12126935_T9"
}
]
}
] | [
{
"id": "PMID-12126935_1",
"entity_ids": [
"PMID-12126935_T2",
"PMID-12126935_T3"
]
}
] | [] |
68 | PMID-12154089 | [
{
"id": "PMID-12154089__text",
"type": "abstract",
"text": [
"Postsynthetic trimethylation of histone H4 at lysine 20 in mammalian tissues is associated with aging. \nMethylation of the N-terminal region of histones was first described more than 35 years ago, but its biological significance has remained unclear. Proposed functions range from transcriptional regulation to the higher order packing of chromatin in progress of mitotic condensation. Primarily because of the recent discovery of the SET domain-depending H3-specific histone methyltransferases SUV39H1 and Suv39h1, which selectively methylate lysine 9 of the H3 N terminus, this posttranslational modification has regained scientific interest. In the past, investigations concerning the biological significance of histone methylation were largely limited because of a lack of simple and sensitive analytical procedures for detecting this modification. The present work investigated the methylation pattern of histone H4 both in different mammalian organs of various ages and in cell lines by applying mass spectrometric analysis and a newly developed hydrophilic-interaction liquid chromatographic method enabling the simultaneous separation of methylated and acetylated forms, which obviates the need to work with radioactive materials. In rat kidney and liver the dimethylated lysine 20 was found to be the main methylation product, whereas the monomethyl derivative was present in much smaller amounts. In addition, for the first time a trimethylated form of lysine 20 of H4 was found in mammalian tissue. A significant increase in this trimethylated histone H4 was detected in organs of animals older than 30 days, whereas the amounts of mono- and dimethylated forms did not essentially change in organs from young (10 days old) or old animals (30 and 450 days old). Trimethylated H4 was also detected in transformed cells; although it was present in only trace amounts in logarithmically growing cells, we found an increase in trimethylated lysine 20 in cells in the stationary phase.\n"
],
"offsets": [
[
0,
1991
]
]
}
] | [
{
"id": "PMID-12154089_T1",
"type": "Protein",
"text": [
"histone H4"
],
"offsets": [
[
32,
42
]
],
"normalized": []
},
{
"id": "PMID-12154089_T2",
"type": "Protein",
"text": [
"histones"
],
"offsets": [
[
144,
152
]
],
"normalized": []
},
{
"id": "PMID-12154089_T3",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
456,
458
]
],
"normalized": []
},
{
"id": "PMID-12154089_T4",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
468,
475
]
],
"normalized": []
},
{
"id": "PMID-12154089_T5",
"type": "Protein",
"text": [
"SUV39H1"
],
"offsets": [
[
495,
502
]
],
"normalized": []
},
{
"id": "PMID-12154089_T6",
"type": "Protein",
"text": [
"Suv39h1"
],
"offsets": [
[
507,
514
]
],
"normalized": []
},
{
"id": "PMID-12154089_T7",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
560,
562
]
],
"normalized": []
},
{
"id": "PMID-12154089_T8",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
715,
722
]
],
"normalized": []
},
{
"id": "PMID-12154089_T9",
"type": "Protein",
"text": [
"histone H4"
],
"offsets": [
[
910,
920
]
],
"normalized": []
},
{
"id": "PMID-12154089_T10",
"type": "Protein",
"text": [
"H4"
],
"offsets": [
[
1476,
1478
]
],
"normalized": []
},
{
"id": "PMID-12154089_T11",
"type": "Protein",
"text": [
"histone H4"
],
"offsets": [
[
1555,
1565
]
],
"normalized": []
},
{
"id": "PMID-12154089_T12",
"type": "Protein",
"text": [
"H4"
],
"offsets": [
[
1786,
1788
]
],
"normalized": []
},
{
"id": "PMID-12154089_T14",
"type": "Entity",
"text": [
"lysine 20"
],
"offsets": [
[
46,
55
]
],
"normalized": []
},
{
"id": "PMID-12154089_T16",
"type": "Entity",
"text": [
"N-terminal region"
],
"offsets": [
[
123,
140
]
],
"normalized": []
},
{
"id": "PMID-12154089_T19",
"type": "Entity",
"text": [
"lysine 9"
],
"offsets": [
[
544,
552
]
],
"normalized": []
},
{
"id": "PMID-12154089_T23",
"type": "Entity",
"text": [
"lysine 20"
],
"offsets": [
[
1280,
1289
]
],
"normalized": []
},
{
"id": "PMID-12154089_T26",
"type": "Entity",
"text": [
"lysine 20"
],
"offsets": [
[
1463,
1472
]
],
"normalized": []
},
{
"id": "PMID-12154089_T32",
"type": "Entity",
"text": [
"lysine 20"
],
"offsets": [
[
1947,
1956
]
],
"normalized": []
}
] | [
{
"id": "PMID-12154089_E1",
"type": "Methylation",
"trigger": {
"text": [
"trimethylation"
],
"offsets": [
[
14,
28
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12154089_T1"
},
{
"role": "Site",
"ref_id": "PMID-12154089_T14"
}
]
},
{
"id": "PMID-12154089_E2",
"type": "Methylation",
"trigger": {
"text": [
"Methylation"
],
"offsets": [
[
104,
115
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12154089_T2"
},
{
"role": "Site",
"ref_id": "PMID-12154089_T16"
}
]
},
{
"id": "PMID-12154089_E3",
"type": "Methylation",
"trigger": {
"text": [
"methylate"
],
"offsets": [
[
534,
543
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12154089_T7"
},
{
"role": "Site",
"ref_id": "PMID-12154089_T19"
}
]
},
{
"id": "PMID-12154089_E4",
"type": "Catalysis",
"trigger": {
"text": [
"methylate"
],
"offsets": [
[
534,
543
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12154089_E3"
},
{
"role": "Cause",
"ref_id": "PMID-12154089_T5"
}
]
},
{
"id": "PMID-12154089_E5",
"type": "Catalysis",
"trigger": {
"text": [
"methylate"
],
"offsets": [
[
534,
543
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12154089_E3"
},
{
"role": "Cause",
"ref_id": "PMID-12154089_T6"
}
]
},
{
"id": "PMID-12154089_E6",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
723,
734
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12154089_T8"
}
]
},
{
"id": "PMID-12154089_E7",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
887,
898
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12154089_T9"
}
]
},
{
"id": "PMID-12154089_E8",
"type": "Methylation",
"trigger": {
"text": [
"dimethylated"
],
"offsets": [
[
1267,
1279
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12154089_T9"
},
{
"role": "Site",
"ref_id": "PMID-12154089_T23"
}
]
},
{
"id": "PMID-12154089_E9",
"type": "Methylation",
"trigger": {
"text": [
"monomethyl"
],
"offsets": [
[
1348,
1358
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12154089_T9"
},
{
"role": "Site",
"ref_id": "PMID-12154089_T23"
}
]
},
{
"id": "PMID-12154089_E10",
"type": "Methylation",
"trigger": {
"text": [
"trimethylated"
],
"offsets": [
[
1441,
1454
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12154089_T10"
},
{
"role": "Site",
"ref_id": "PMID-12154089_T26"
}
]
},
{
"id": "PMID-12154089_E11",
"type": "Methylation",
"trigger": {
"text": [
"trimethylated"
],
"offsets": [
[
1541,
1554
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12154089_T11"
}
]
},
{
"id": "PMID-12154089_E12",
"type": "Methylation",
"trigger": {
"text": [
"mono-"
],
"offsets": [
[
1643,
1648
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12154089_T11"
}
]
},
{
"id": "PMID-12154089_E13",
"type": "Methylation",
"trigger": {
"text": [
"dimethylated"
],
"offsets": [
[
1653,
1665
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12154089_T11"
}
]
},
{
"id": "PMID-12154089_E14",
"type": "Methylation",
"trigger": {
"text": [
"Trimethylated"
],
"offsets": [
[
1772,
1785
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12154089_T12"
}
]
},
{
"id": "PMID-12154089_E15",
"type": "Methylation",
"trigger": {
"text": [
"trimethylated"
],
"offsets": [
[
1933,
1946
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12154089_T12"
},
{
"role": "Site",
"ref_id": "PMID-12154089_T32"
}
]
}
] | [] | [] |
69 | PMID-12163655 | [
{
"id": "PMID-12163655__text",
"type": "abstract",
"text": [
"In the cystathionine beta-synthase knockout mouse, elevations in total plasma homocysteine increase tissue S-adenosylhomocysteine, but responses of S-adenosylmethionine and DNA methylation are tissue specific. \nThe cystathionine beta-synthase knockout mouse provides a unique opportunity to study biochemical consequences of a defective cystathionine beta-synthase enzyme. The present study was undertaken to assess the effect of elevated plasma total homocysteine caused by cystathionine beta-synthase deficiency on one-carbon metabolism in 10 homozygous mutant mice and 10 age- and sex-matched wild-type mice. Plasma total homocysteine levels, S-adenosylmethionine and S-adenosylhomocysteine concentrations in liver, kidney and brain were measured by HPLC. Tissue DNA methylation status was measured by in vitro DNA methyl acceptance. Plasma total homocysteine concentration in food-deprived homozygous mutant mice (271.1 +/- 61.5 micro mol/L) was markedly higher than in wild-type mice (7.4 +/- 2.9 micro mol/L) (P < 0.001). In liver only, S-adenosylmethionine concentrations were higher in the homozygous mutant mice (35.6 +/- 5.9 nmol/g) than in wild type mice (19.1 +/- 6.1 nmol/g) (P < 0.001) and tended to be lower in kidney (P = 0.07). In contrast, S-adenosylhomocysteine concentrations were significantly higher in homozygous mutant mice compared with wild-type mice in all tissues studied. Genomic DNA methylation status in homozygous mutant compared with wild-type mice was lower in liver (P = 0.037) and tended to be lower in kidney (P = 0.077) but did not differ in brain (P = 0.46). The results of this study are consistent with the predicted role of cystathionine beta-synthase in the regulation of plasma total homocysteine levels and tissue S-adenosylhomocysteine levels. However, the fact that the absence of the enzyme had differential effects on S-adenosylmethionine concentrations and DNA methylation status in different tissues suggests that regulation of biological methylation is a complex tissue-specific phenomenon.\n"
],
"offsets": [
[
0,
2043
]
]
}
] | [
{
"id": "PMID-12163655_T1",
"type": "Protein",
"text": [
"cystathionine beta-synthase"
],
"offsets": [
[
7,
34
]
],
"normalized": []
},
{
"id": "PMID-12163655_T2",
"type": "Protein",
"text": [
"cystathionine beta-synthase"
],
"offsets": [
[
215,
242
]
],
"normalized": []
},
{
"id": "PMID-12163655_T3",
"type": "Protein",
"text": [
"cystathionine beta-synthase"
],
"offsets": [
[
337,
364
]
],
"normalized": []
},
{
"id": "PMID-12163655_T4",
"type": "Protein",
"text": [
"cystathionine beta-synthase"
],
"offsets": [
[
475,
502
]
],
"normalized": []
},
{
"id": "PMID-12163655_T5",
"type": "Protein",
"text": [
"cystathionine beta-synthase"
],
"offsets": [
[
1666,
1693
]
],
"normalized": []
}
] | [] | [] | [] |
70 | PMID-12171601 | [
{
"id": "PMID-12171601__text",
"type": "abstract",
"text": [
"Glycosylation of human proteinase-activated receptor-2 (hPAR2): role in cell surface expression and signalling. \nWe have analysed the role of N-linked glycosylation in regulating human proteinase-activated receptor-2 (hPAR(2)) expression and function. Epitope-tagged wild-type hPAR(2) (wt-hPAR(2)) or hPAR(2) that lacked glycosylation sequons (following site-directed mutagenesis) in either the N-terminus [hPAR(2)N30A (Asn(30)-->Ala)], extracellular loop 2 [ECL2; hPAR(2)N222Q (Asn(222)-->Gln) or hPAR(2)N222A (Asn(222)-->Ala)] or both (hPAR(2)N30A,N222A or hPAR(2)N30A,N222Q) were expressed in the Chinese-hamster ovary (CHO) fibroblast cell line, Pro5. Western blot analysis of wt-hPAR(2) showed mature wt-hPAR(2) to have a molecular mass of 55-100 kDa, and 33-48 kDa following N -glycosidase F deglycosylation. FACS analysis and immunocytochemistry of the wt-hPAR(2) and PAR(2) mutant cell lines revealed that removal of both glycosylation sequons decreases (50% of wt-hPAR(2)) cell surface expression. Western blot analysis indicated that both N-linked sites are glycosylated. In functional studies, hPAR(2)N30A displayed a selective and significant increase in sensitivity towards tryptase. Interestingly, hPAR(2)N222A displayed a loss in sensitivity towards all PAR(2) agonists tested. However, further analysis revealed receptor sensitivity to alanine mutations in this domain, as the more conservative substitution hPAR(2)N222Q displayed no change in response to PAR(2) agonists. hPAR(2)N30A,N222Q displayed increased sensitivity towards tryptase, but a loss in sensitivity towards trypsin and the synthetic peptide SLIGRL-NH(2), although this loss in sensitivity towards trypsin and SLIGRL-NH(2) was secondary to changes in cell-surface expression. Finally, expression of sialic-acid-deficient wt-hPAR(2) in the CHO Lec2 glycosylation-deficient mutant cell line, showed a 40 kDa loss in molecular mass, in addition to a marked and selective increase in sensitivity towards tryptase. We conclude that hPAR(2) N-linked glycosylation and sialylation regulates receptor expression and/or signalling.\n"
],
"offsets": [
[
0,
2106
]
]
}
] | [
{
"id": "PMID-12171601_T1",
"type": "Protein",
"text": [
"proteinase-activated receptor-2"
],
"offsets": [
[
23,
54
]
],
"normalized": []
},
{
"id": "PMID-12171601_T2",
"type": "Protein",
"text": [
"PAR2"
],
"offsets": [
[
57,
61
]
],
"normalized": []
},
{
"id": "PMID-12171601_T3",
"type": "Protein",
"text": [
"proteinase-activated receptor-2"
],
"offsets": [
[
185,
216
]
],
"normalized": []
},
{
"id": "PMID-12171601_T4",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
219,
225
]
],
"normalized": []
},
{
"id": "PMID-12171601_T5",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
278,
284
]
],
"normalized": []
},
{
"id": "PMID-12171601_T6",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
290,
296
]
],
"normalized": []
},
{
"id": "PMID-12171601_T7",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
302,
308
]
],
"normalized": []
},
{
"id": "PMID-12171601_T8",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
408,
414
]
],
"normalized": []
},
{
"id": "PMID-12171601_T9",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
466,
472
]
],
"normalized": []
},
{
"id": "PMID-12171601_T10",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
499,
505
]
],
"normalized": []
},
{
"id": "PMID-12171601_T11",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
539,
545
]
],
"normalized": []
},
{
"id": "PMID-12171601_T12",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
560,
566
]
],
"normalized": []
},
{
"id": "PMID-12171601_T13",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
685,
691
]
],
"normalized": []
},
{
"id": "PMID-12171601_T14",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
710,
716
]
],
"normalized": []
},
{
"id": "PMID-12171601_T15",
"type": "Protein",
"text": [
"N -glycosidase F"
],
"offsets": [
[
781,
797
]
],
"normalized": []
},
{
"id": "PMID-12171601_T16",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
864,
870
]
],
"normalized": []
},
{
"id": "PMID-12171601_T17",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
875,
881
]
],
"normalized": []
},
{
"id": "PMID-12171601_T18",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
974,
980
]
],
"normalized": []
},
{
"id": "PMID-12171601_T19",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
1106,
1112
]
],
"normalized": []
},
{
"id": "PMID-12171601_T20",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
1213,
1219
]
],
"normalized": []
},
{
"id": "PMID-12171601_T21",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
1269,
1275
]
],
"normalized": []
},
{
"id": "PMID-12171601_T22",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
1425,
1431
]
],
"normalized": []
},
{
"id": "PMID-12171601_T23",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
1472,
1478
]
],
"normalized": []
},
{
"id": "PMID-12171601_T24",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
1490,
1496
]
],
"normalized": []
},
{
"id": "PMID-12171601_T25",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
1808,
1814
]
],
"normalized": []
},
{
"id": "PMID-12171601_T26",
"type": "Protein",
"text": [
"PAR(2)"
],
"offsets": [
[
2011,
2017
]
],
"normalized": []
},
{
"id": "PMID-12171601_T31",
"type": "Entity",
"text": [
"N-linked sites"
],
"offsets": [
[
1049,
1063
]
],
"normalized": []
}
] | [
{
"id": "PMID-12171601_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"Glycosylation"
],
"offsets": [
[
0,
13
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12171601_T1"
}
]
},
{
"id": "PMID-12171601_E2",
"type": "Glycosylation",
"trigger": {
"text": [
"N-linked glycosylation"
],
"offsets": [
[
142,
164
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12171601_T3"
}
]
},
{
"id": "PMID-12171601_E3",
"type": "Deglycosylation",
"trigger": {
"text": [
"deglycosylation"
],
"offsets": [
[
798,
813
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12171601_T14"
}
]
},
{
"id": "PMID-12171601_E4",
"type": "Catalysis",
"trigger": {
"text": [
"deglycosylation"
],
"offsets": [
[
798,
813
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12171601_E3"
},
{
"role": "Cause",
"ref_id": "PMID-12171601_T15"
}
]
},
{
"id": "PMID-12171601_E5",
"type": "Glycosylation",
"trigger": {
"text": [
"glycosylated"
],
"offsets": [
[
1068,
1080
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12171601_T16"
},
{
"role": "Site",
"ref_id": "PMID-12171601_T31"
}
]
},
{
"id": "PMID-12171601_E6",
"type": "Glycosylation",
"trigger": {
"text": [
"N-linked glycosylation"
],
"offsets": [
[
2018,
2040
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12171601_T26"
}
]
}
] | [
{
"id": "PMID-12171601_1",
"entity_ids": [
"PMID-12171601_T1",
"PMID-12171601_T2"
]
},
{
"id": "PMID-12171601_2",
"entity_ids": [
"PMID-12171601_T3",
"PMID-12171601_T4"
]
}
] | [] |
71 | PMID-12186410 | [
{
"id": "PMID-12186410__text",
"type": "abstract",
"text": [
"N-acetyltransferase 2 genotype-related sulfapyridine acetylation and its adverse events. \nSulfapyridine (SP), one of the metabolites of sulfasalazine (SASP), is further metabolized into N-acetylsulfapyridine (AcSP) by polymorphic N-acetyltransferase 2 (NAT2). NAT2 activity has been diagnosed by phenotyping, that is, evaluating plasma concentrations or urinary excretions of tentatively administered test drugs for dose individualization and avoidance of serious adverse events. Herein, we investigated the relationship between NAT2 genotypes and the pharmacokinetics of SP in healthy Japanese subjects, as well as the adverse events of SASP in patients with inflammatory bowel disease (IBD). Eight healthy subjects and 13 IBD patients were classified into three groups by NAT2 genotyping; the homozygote for the wild-type allele (Rapid Types), the compound heterozygote for the wild-type and mutant alleles (Intermediate Types), and the homozygote for mutant alleles (Slow Types). A single oral dose of 40 mg/kg SASP was administered to each healthy subject, and plasma and urine samples were taken until 51 and 72 h after administration, respectively. Both the SP and AcSP concentrations in each sample were determined by the HPLC method. The NAT2 genotypes were well-correlated with the plasma concentrations or urinary excretions of SP and AcSP in 8 healthy subjects, except for one Slow Type. In patients with IBD, skin rash was seen in 3 of 6 Rapid Types and 1 of 6 Intermediate Types, consistent with the concept that hypersensitive reactions are independent of serum SP concentrations. In contrast, SASP dosing-related acute pancreatitis was found in the Slow Type patient. In this case, the NAT2 activity was diagnosed by genotyping in advance, and the medical staff could pay scrupulous attention, resulting in no serious subjective symptoms such as abdominal pain, anorexia or fever. Further investigations on the relationship between the NAT2 genotype and adverse events are required, although genotyping appeared to be a promising method to avoid such serious adverse events.\n"
],
"offsets": [
[
0,
2090
]
]
}
] | [
{
"id": "PMID-12186410_T1",
"type": "Protein",
"text": [
"N-acetyltransferase 2"
],
"offsets": [
[
0,
21
]
],
"normalized": []
},
{
"id": "PMID-12186410_T2",
"type": "Protein",
"text": [
"N-acetyltransferase 2"
],
"offsets": [
[
230,
251
]
],
"normalized": []
},
{
"id": "PMID-12186410_T3",
"type": "Protein",
"text": [
"NAT2"
],
"offsets": [
[
253,
257
]
],
"normalized": []
},
{
"id": "PMID-12186410_T4",
"type": "Protein",
"text": [
"NAT2"
],
"offsets": [
[
260,
264
]
],
"normalized": []
},
{
"id": "PMID-12186410_T5",
"type": "Protein",
"text": [
"NAT2"
],
"offsets": [
[
529,
533
]
],
"normalized": []
},
{
"id": "PMID-12186410_T6",
"type": "Protein",
"text": [
"NAT2"
],
"offsets": [
[
774,
778
]
],
"normalized": []
},
{
"id": "PMID-12186410_T7",
"type": "Protein",
"text": [
"NAT2"
],
"offsets": [
[
1246,
1250
]
],
"normalized": []
},
{
"id": "PMID-12186410_T8",
"type": "Protein",
"text": [
"NAT2"
],
"offsets": [
[
1701,
1705
]
],
"normalized": []
},
{
"id": "PMID-12186410_T9",
"type": "Protein",
"text": [
"NAT2"
],
"offsets": [
[
1951,
1955
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-12186410_1",
"entity_ids": [
"PMID-12186410_T2",
"PMID-12186410_T3"
]
}
] | [] |
72 | PMID-12193658 | [
{
"id": "PMID-12193658__text",
"type": "abstract",
"text": [
"Histone H3 lysine 4 methylation is mediated by Set1 and promotes maintenance of active chromatin states in fission yeast. \nMethylation of histone H3 at lysine 4 (H3 Lys-4) or lysine 9 (H3 Lys-9) is known to define active and silent chromosomal domains respectively from fission yeast to humans. However, in budding yeast, H3 Lys-4 methylation is also necessary for silent chromatin assembly at telomeres and ribosomal DNA. Here we demonstrate that deletion of set1, which encodes a protein containing an RNA recognition motif at its amino terminus and a SET domain at the carboxy terminus, abolishes H3 Lys-4 methylation in fission yeast. Unlike in budding yeast, Set1-mediated H3 Lys-4 methylation is not required for heterochromatin assembly at the silent mating-type region and centromeres in fission yeast. Our analysis suggests that H3 Lys-4 methylation is a stable histone modification present throughout the cell cycle, including mitosis. The loss of H3 Lys-4 methylation in set1Delta cells is correlated with a decrease in histone H3 acetylation levels, suggesting a mechanistic link between H3 Lys-4 methylation and acetylation of the H3 tail. We suggest that methylation of H3 Lys-4 primarily acts in the maintenance of transcriptionally poised euchromatic domains, and that this modification is dispensable for heterochromatin formation in fission yeast, which instead utilizes H3 Lys-9 methylation.\n"
],
"offsets": [
[
0,
1411
]
]
}
] | [
{
"id": "PMID-12193658_T1",
"type": "Protein",
"text": [
"Histone H3"
],
"offsets": [
[
0,
10
]
],
"normalized": []
},
{
"id": "PMID-12193658_T2",
"type": "Protein",
"text": [
"Set1"
],
"offsets": [
[
47,
51
]
],
"normalized": []
},
{
"id": "PMID-12193658_T3",
"type": "Protein",
"text": [
"histone H3"
],
"offsets": [
[
138,
148
]
],
"normalized": []
},
{
"id": "PMID-12193658_T4",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
162,
164
]
],
"normalized": []
},
{
"id": "PMID-12193658_T5",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
185,
187
]
],
"normalized": []
},
{
"id": "PMID-12193658_T6",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
322,
324
]
],
"normalized": []
},
{
"id": "PMID-12193658_T7",
"type": "Protein",
"text": [
"set1"
],
"offsets": [
[
460,
464
]
],
"normalized": []
},
{
"id": "PMID-12193658_T8",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
600,
602
]
],
"normalized": []
},
{
"id": "PMID-12193658_T9",
"type": "Protein",
"text": [
"Set1"
],
"offsets": [
[
664,
668
]
],
"normalized": []
},
{
"id": "PMID-12193658_T10",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
678,
680
]
],
"normalized": []
},
{
"id": "PMID-12193658_T11",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
838,
840
]
],
"normalized": []
},
{
"id": "PMID-12193658_T12",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
871,
878
]
],
"normalized": []
},
{
"id": "PMID-12193658_T13",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
958,
960
]
],
"normalized": []
},
{
"id": "PMID-12193658_T14",
"type": "Protein",
"text": [
"set1"
],
"offsets": [
[
982,
986
]
],
"normalized": []
},
{
"id": "PMID-12193658_T15",
"type": "Protein",
"text": [
"histone H3"
],
"offsets": [
[
1031,
1041
]
],
"normalized": []
},
{
"id": "PMID-12193658_T16",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
1100,
1102
]
],
"normalized": []
},
{
"id": "PMID-12193658_T17",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
1144,
1146
]
],
"normalized": []
},
{
"id": "PMID-12193658_T18",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
1184,
1186
]
],
"normalized": []
},
{
"id": "PMID-12193658_T19",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
1389,
1391
]
],
"normalized": []
},
{
"id": "PMID-12193658_T20",
"type": "Entity",
"text": [
"lysine 4"
],
"offsets": [
[
11,
19
]
],
"normalized": []
},
{
"id": "PMID-12193658_T24",
"type": "Entity",
"text": [
"lysine 4"
],
"offsets": [
[
152,
160
]
],
"normalized": []
},
{
"id": "PMID-12193658_T25",
"type": "Entity",
"text": [
"Lys-4"
],
"offsets": [
[
165,
170
]
],
"normalized": []
},
{
"id": "PMID-12193658_T26",
"type": "Entity",
"text": [
"lysine 9"
],
"offsets": [
[
175,
183
]
],
"normalized": []
},
{
"id": "PMID-12193658_T27",
"type": "Entity",
"text": [
"Lys-9"
],
"offsets": [
[
188,
193
]
],
"normalized": []
},
{
"id": "PMID-12193658_T28",
"type": "Entity",
"text": [
"Lys-4"
],
"offsets": [
[
325,
330
]
],
"normalized": []
},
{
"id": "PMID-12193658_T30",
"type": "Entity",
"text": [
"Lys-4"
],
"offsets": [
[
603,
608
]
],
"normalized": []
},
{
"id": "PMID-12193658_T33",
"type": "Entity",
"text": [
"Lys-4"
],
"offsets": [
[
681,
686
]
],
"normalized": []
},
{
"id": "PMID-12193658_T35",
"type": "Entity",
"text": [
"Lys-4"
],
"offsets": [
[
841,
846
]
],
"normalized": []
},
{
"id": "PMID-12193658_T37",
"type": "Entity",
"text": [
"Lys-4"
],
"offsets": [
[
961,
966
]
],
"normalized": []
},
{
"id": "PMID-12193658_T40",
"type": "Entity",
"text": [
"Lys-4"
],
"offsets": [
[
1103,
1108
]
],
"normalized": []
},
{
"id": "PMID-12193658_T43",
"type": "Entity",
"text": [
"tail"
],
"offsets": [
[
1147,
1151
]
],
"normalized": []
},
{
"id": "PMID-12193658_T45",
"type": "Entity",
"text": [
"Lys-4"
],
"offsets": [
[
1187,
1192
]
],
"normalized": []
},
{
"id": "PMID-12193658_T46",
"type": "Entity",
"text": [
"Lys-9"
],
"offsets": [
[
1392,
1397
]
],
"normalized": []
}
] | [
{
"id": "PMID-12193658_E1",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
20,
31
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12193658_T1"
},
{
"role": "Site",
"ref_id": "PMID-12193658_T20"
}
]
},
{
"id": "PMID-12193658_E2",
"type": "Catalysis",
"trigger": {
"text": [
"mediated"
],
"offsets": [
[
35,
43
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12193658_E1"
},
{
"role": "Cause",
"ref_id": "PMID-12193658_T2"
}
]
},
{
"id": "PMID-12193658_E3",
"type": "Methylation",
"trigger": {
"text": [
"Methylation"
],
"offsets": [
[
123,
134
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12193658_T3"
},
{
"role": "Site",
"ref_id": "PMID-12193658_T24"
}
]
},
{
"id": "PMID-12193658_E4",
"type": "Methylation",
"trigger": {
"text": [
"Methylation"
],
"offsets": [
[
123,
134
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12193658_T3"
},
{
"role": "Site",
"ref_id": "PMID-12193658_T26"
}
]
},
{
"id": "PMID-12193658_E5",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
331,
342
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12193658_T6"
},
{
"role": "Site",
"ref_id": "PMID-12193658_T28"
}
]
},
{
"id": "PMID-12193658_E6",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
609,
620
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12193658_T8"
},
{
"role": "Site",
"ref_id": "PMID-12193658_T30"
}
]
},
{
"id": "PMID-12193658_E7",
"type": "Catalysis",
"trigger": {
"text": [
"mediated"
],
"offsets": [
[
669,
677
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12193658_E8"
},
{
"role": "Cause",
"ref_id": "PMID-12193658_T9"
}
]
},
{
"id": "PMID-12193658_E8",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
687,
698
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12193658_T10"
},
{
"role": "Site",
"ref_id": "PMID-12193658_T33"
}
]
},
{
"id": "PMID-12193658_E9",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
847,
858
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12193658_T11"
},
{
"role": "Site",
"ref_id": "PMID-12193658_T35"
}
]
},
{
"id": "PMID-12193658_E10",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
967,
978
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12193658_T13"
},
{
"role": "Site",
"ref_id": "PMID-12193658_T37"
}
]
},
{
"id": "PMID-12193658_E11",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
1042,
1053
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12193658_T15"
}
]
},
{
"id": "PMID-12193658_E12",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1109,
1120
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12193658_T16"
},
{
"role": "Site",
"ref_id": "PMID-12193658_T40"
}
]
},
{
"id": "PMID-12193658_E13",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
1125,
1136
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12193658_T17"
},
{
"role": "Site",
"ref_id": "PMID-12193658_T43"
}
]
},
{
"id": "PMID-12193658_E14",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1169,
1180
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12193658_T18"
},
{
"role": "Site",
"ref_id": "PMID-12193658_T45"
}
]
},
{
"id": "PMID-12193658_E15",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1398,
1409
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12193658_T19"
},
{
"role": "Site",
"ref_id": "PMID-12193658_T46"
}
]
}
] | [
{
"id": "PMID-12193658_1",
"entity_ids": [
"PMID-12193658_T3",
"PMID-12193658_T4"
]
},
{
"id": "PMID-12193658_2",
"entity_ids": [
"PMID-12193658_T24",
"PMID-12193658_T25"
]
},
{
"id": "PMID-12193658_3",
"entity_ids": [
"PMID-12193658_T26",
"PMID-12193658_T27"
]
}
] | [] |
73 | PMID-12215170 | [
{
"id": "PMID-12215170__text",
"type": "abstract",
"text": [
"Hypoxia-inducible factor asparaginyl hydroxylase (FIH-1) catalyses hydroxylation at the beta-carbon of asparagine-803. \nAsparagine-803 in the C-terminal transactivation domain of human hypoxia-inducible factor (HIF)-1 alpha-subunit is hydroxylated by factor inhibiting HIF-1 (FIH-1) under normoxic conditions causing abrogation of the HIF-1alpha/p300 interaction. NMR and other analyses of a hydroxylated HIF fragment produced in vitro demonstrate that hydroxylation occurs at the beta-carbon of Asn-803 and imply production of the threo -isomer, in contrast with other known aspartic acid/asparagine hydroxylases that produce the erythro -isomer.\n"
],
"offsets": [
[
0,
648
]
]
}
] | [
{
"id": "PMID-12215170_T1",
"type": "Protein",
"text": [
"Hypoxia-inducible factor asparaginyl hydroxylase"
],
"offsets": [
[
0,
48
]
],
"normalized": []
},
{
"id": "PMID-12215170_T2",
"type": "Protein",
"text": [
"FIH-1"
],
"offsets": [
[
50,
55
]
],
"normalized": []
},
{
"id": "PMID-12215170_T3",
"type": "Protein",
"text": [
"hypoxia-inducible factor (HIF)-1 alpha-subunit"
],
"offsets": [
[
185,
231
]
],
"normalized": []
},
{
"id": "PMID-12215170_T4",
"type": "Protein",
"text": [
"factor inhibiting HIF-1"
],
"offsets": [
[
251,
274
]
],
"normalized": []
},
{
"id": "PMID-12215170_T5",
"type": "Protein",
"text": [
"FIH-1"
],
"offsets": [
[
276,
281
]
],
"normalized": []
},
{
"id": "PMID-12215170_T6",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
335,
345
]
],
"normalized": []
},
{
"id": "PMID-12215170_T7",
"type": "Protein",
"text": [
"p300"
],
"offsets": [
[
346,
350
]
],
"normalized": []
},
{
"id": "PMID-12215170_T8",
"type": "Entity",
"text": [
"Asparagine-803"
],
"offsets": [
[
120,
134
]
],
"normalized": []
},
{
"id": "PMID-12215170_T12",
"type": "Entity",
"text": [
"Asn-803"
],
"offsets": [
[
496,
503
]
],
"normalized": []
}
] | [
{
"id": "PMID-12215170_E1",
"type": "Hydroxylation",
"trigger": {
"text": [
"hydroxylated"
],
"offsets": [
[
235,
247
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12215170_T3"
},
{
"role": "Site",
"ref_id": "PMID-12215170_T8"
}
]
},
{
"id": "PMID-12215170_E2",
"type": "Catalysis",
"trigger": {
"text": [
"hydroxylated"
],
"offsets": [
[
235,
247
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12215170_E1"
},
{
"role": "Cause",
"ref_id": "PMID-12215170_T4"
}
]
},
{
"id": "PMID-12215170_E3",
"type": "Hydroxylation",
"trigger": {
"text": [
"hydroxylation"
],
"offsets": [
[
453,
466
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12215170_T3"
},
{
"role": "Site",
"ref_id": "PMID-12215170_T12"
}
]
}
] | [
{
"id": "PMID-12215170_1",
"entity_ids": [
"PMID-12215170_T1",
"PMID-12215170_T2"
]
},
{
"id": "PMID-12215170_2",
"entity_ids": [
"PMID-12215170_T4",
"PMID-12215170_T5"
]
}
] | [] |
74 | PMID-12237810 | [
{
"id": "PMID-12237810__text",
"type": "abstract",
"text": [
"Effect of the alcohol extract of the seeds of Mucuna pruriens on free radicals and oxidative stress in albino rats. \nIn vitro and in vivo studies were made with an alcohol extract of the seeds of Mucuna pruriens (Fabaceae) to investigate its antioxidant property. In vitro studies were carried out in rat liver homogenate to investigate the chemical interaction of various phytochemicals with different species of free radicals. The effect was also checked on iron-induced lipid peroxidation, oxidation of GSH content, and its interaction with hydroxyl and superoxide radicals. There was no change on the rate of aerial oxidation of GSH content but it significantly inhibited FeSO(4) induced lipid peroxidation. It also inhibited the specific chemical reactions induced by superoxides and hydroxyl radicals. The removal of these species was through direct chemical interaction. An in vivo study on albino rats for 30 days showed no toxic effect up to a dose of 600 mg/kg body weight, on oral administration. There was no change in the level of TBA-reactive substances, reduced glutathione content and SOD activity in the liver. The activity of serum GOT, GPT and alkaline phosphatase was also unchanged. Thus it could be concluded that the alcohol extract of the seeds of M. pruriens has an antilipid peroxidation property, which is mediated through the removal of superoxides and hydroxyl radicals.\n"
],
"offsets": [
[
0,
1400
]
]
}
] | [
{
"id": "PMID-12237810_T1",
"type": "Protein",
"text": [
"GOT"
],
"offsets": [
[
1150,
1153
]
],
"normalized": []
},
{
"id": "PMID-12237810_T2",
"type": "Protein",
"text": [
"GPT"
],
"offsets": [
[
1155,
1158
]
],
"normalized": []
}
] | [] | [] | [] |
75 | PMID-12351403 | [
{
"id": "PMID-12351403__text",
"type": "abstract",
"text": [
"Induction of apoptosis of human B-CLL and ALL cells by a novel retinoid and its nonretinoidal analog. \nWe have recently described a novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid (CD437/AHPN) that induces apoptosis in a number of malignant cell types. We now describe our studies examining the effects of CD437 and a nonretinoidal analog (MM002) on the in vitro proliferation of the ALL-REH cell line, the in vitro and in vivo growth of a novel Epstein-Barr virus-negative (EBV(-)) B-cell chronic lymphocytic leukemia (B-CLL) cell line (WSU-CLL), and primary cultures of human B-CLL and acute lymphoblastic leukemia (ALL) cells. CD437 and MM002 induce apoptosis in both cell lines, as indicated by the activation of caspase-2 and caspase-3, cleavage of poly(adenosine diphosphate-ribose) (poly(ADP-ribose)) polymerase, increase in annexin V binding, and subsequent nuclear fragmentation. CD437-mediated apoptosis was not associated with the modulation of Bcl-2, Bax, or Mcl-1 levels, but was associated with the cleavage of the antiapoptotic protein Bcl-X(L) to a proapoptotic 18-kD form. This cleavage of Bcl-X(L) was dependent on caspase-3 activation since Bcl-X(L) cleavage and apoptosis were inhibited by the caspase-3 inhibitor Z-DVED-fmk. CD437 markedly inhibited the growth of WSU-CLL cells in severe combined immunodeficiency (SCID) mice. Tumor growth inhibition, growth delay, and log cell kill were 85.7%, 21 days, and 2.1, respectively, in the treated mice. Moreover, 1 of the 5 treated mice was tumor-free longer than 150 days and thus was considered cured. Exposure of primary cultures of both B-CLL and ALL cells obtained from patients to CD437 and MM002 resulted in their apoptosis. These results suggest that CD437 and MM002 analogs may have a potential role in the treatment of B-CLL and ALL.\n"
],
"offsets": [
[
0,
1843
]
]
}
] | [
{
"id": "PMID-12351403_T1",
"type": "Protein",
"text": [
"caspase-2"
],
"offsets": [
[
749,
758
]
],
"normalized": []
},
{
"id": "PMID-12351403_T2",
"type": "Protein",
"text": [
"caspase-3"
],
"offsets": [
[
763,
772
]
],
"normalized": []
},
{
"id": "PMID-12351403_T3",
"type": "Protein",
"text": [
"annexin V"
],
"offsets": [
[
864,
873
]
],
"normalized": []
},
{
"id": "PMID-12351403_T4",
"type": "Protein",
"text": [
"Bcl-2"
],
"offsets": [
[
988,
993
]
],
"normalized": []
},
{
"id": "PMID-12351403_T5",
"type": "Protein",
"text": [
"Bax"
],
"offsets": [
[
995,
998
]
],
"normalized": []
},
{
"id": "PMID-12351403_T6",
"type": "Protein",
"text": [
"Mcl-1"
],
"offsets": [
[
1003,
1008
]
],
"normalized": []
},
{
"id": "PMID-12351403_T7",
"type": "Protein",
"text": [
"Bcl-X(L)"
],
"offsets": [
[
1083,
1091
]
],
"normalized": []
},
{
"id": "PMID-12351403_T8",
"type": "Protein",
"text": [
"Bcl-X(L)"
],
"offsets": [
[
1139,
1147
]
],
"normalized": []
},
{
"id": "PMID-12351403_T9",
"type": "Protein",
"text": [
"caspase-3"
],
"offsets": [
[
1165,
1174
]
],
"normalized": []
},
{
"id": "PMID-12351403_T10",
"type": "Protein",
"text": [
"Bcl-X(L)"
],
"offsets": [
[
1192,
1200
]
],
"normalized": []
},
{
"id": "PMID-12351403_T11",
"type": "Protein",
"text": [
"caspase-3"
],
"offsets": [
[
1246,
1255
]
],
"normalized": []
}
] | [] | [] | [] |
76 | PMID-12351678 | [
{
"id": "PMID-12351678__text",
"type": "abstract",
"text": [
"Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor. \nThe product of the von Hippel-Lindau gene, pVHL, targets the alpha subunits of the heterodimeric transcription factor hypoxia-inducible factor (HIF) for polyubiquitination in the presence of oxygen. The binding of pVHL to HIF is governed by the enzymatic hydroxylation of conserved prolyl residues within peptidic motifs present in the HIFalpha family members. By using a biochemical purification strategy, we have identified a human homolog of Caenorhabditis elegans Egl9 as a HIF prolyl hydroxylase. In addition, we studied the activity of a structurally diverse collection of low molecular weight inhibitors of procollagen prolyl 4-hydroxylase as potential inhibitors of the HIF hydroxylase. A model compound of this series stabilized HIF in a variety of cells, leading to the increased production of its downstream target, vascular endothelial growth factor.\n"
],
"offsets": [
[
0,
990
]
]
}
] | [
{
"id": "PMID-12351678_T1",
"type": "Protein",
"text": [
"von Hippel-Lindau gene"
],
"offsets": [
[
146,
168
]
],
"normalized": []
},
{
"id": "PMID-12351678_T2",
"type": "Protein",
"text": [
"pVHL"
],
"offsets": [
[
170,
174
]
],
"normalized": []
},
{
"id": "PMID-12351678_T3",
"type": "Protein",
"text": [
"pVHL"
],
"offsets": [
[
341,
345
]
],
"normalized": []
},
{
"id": "PMID-12351678_T4",
"type": "Protein",
"text": [
"Egl9"
],
"offsets": [
[
595,
599
]
],
"normalized": []
},
{
"id": "PMID-12351678_T5",
"type": "Protein",
"text": [
"vascular endothelial growth factor"
],
"offsets": [
[
954,
988
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-12351678_1",
"entity_ids": [
"PMID-12351678_T1",
"PMID-12351678_T2"
]
}
] | [] |
77 | PMID-12374746 | [
{
"id": "PMID-12374746__text",
"type": "abstract",
"text": [
"Control of CBP co-activating activity by arginine methylation. \nThe histone acetyltransferases CREB binding protein (CBP) and the related p300 protein function as key transcriptional co-activators in multiple pathways. In the case of transcriptional activation by nuclear receptors, ligand promotes the recruitment of co-activators of the p160 family, such as GRIP-1. Subsequently, the p160 co-activators recruit other co-activators via two activation domains, AD1 and AD2. AD1 binds CBP or p300, whereas AD2 has been shown to activate transcription through the recruitment of the arginine methyltransferase CARM1. Recently, the KIX domain of CBP has been shown to be methylated by CARM1 in vitro. Here, we report that another domain of CBP is specifically methylated by CARM1 on conserved arginine residues in vitro and in vivo. We also provide functional evidence that arginine residues methylated by CARM1 play a critical role in GRIP-1-dependent transcriptional activation and in hormone-induced gene activation. Altogether, our data provide strong evidence that arginine methylation represents an important mechanism for modulating co-activator transcriptional activity.\n"
],
"offsets": [
[
0,
1176
]
]
}
] | [
{
"id": "PMID-12374746_T1",
"type": "Protein",
"text": [
"CBP"
],
"offsets": [
[
11,
14
]
],
"normalized": []
},
{
"id": "PMID-12374746_T2",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
68,
75
]
],
"normalized": []
},
{
"id": "PMID-12374746_T3",
"type": "Protein",
"text": [
"CREB binding protein"
],
"offsets": [
[
95,
115
]
],
"normalized": []
},
{
"id": "PMID-12374746_T4",
"type": "Protein",
"text": [
"CBP"
],
"offsets": [
[
117,
120
]
],
"normalized": []
},
{
"id": "PMID-12374746_T5",
"type": "Protein",
"text": [
"p300"
],
"offsets": [
[
138,
142
]
],
"normalized": []
},
{
"id": "PMID-12374746_T6",
"type": "Protein",
"text": [
"GRIP-1"
],
"offsets": [
[
360,
366
]
],
"normalized": []
},
{
"id": "PMID-12374746_T7",
"type": "Protein",
"text": [
"CBP"
],
"offsets": [
[
484,
487
]
],
"normalized": []
},
{
"id": "PMID-12374746_T8",
"type": "Protein",
"text": [
"p300"
],
"offsets": [
[
491,
495
]
],
"normalized": []
},
{
"id": "PMID-12374746_T9",
"type": "Protein",
"text": [
"CARM1"
],
"offsets": [
[
608,
613
]
],
"normalized": []
},
{
"id": "PMID-12374746_T10",
"type": "Protein",
"text": [
"CBP"
],
"offsets": [
[
643,
646
]
],
"normalized": []
},
{
"id": "PMID-12374746_T11",
"type": "Protein",
"text": [
"CARM1"
],
"offsets": [
[
682,
687
]
],
"normalized": []
},
{
"id": "PMID-12374746_T12",
"type": "Protein",
"text": [
"CBP"
],
"offsets": [
[
737,
740
]
],
"normalized": []
},
{
"id": "PMID-12374746_T13",
"type": "Protein",
"text": [
"CARM1"
],
"offsets": [
[
771,
776
]
],
"normalized": []
},
{
"id": "PMID-12374746_T14",
"type": "Protein",
"text": [
"CARM1"
],
"offsets": [
[
903,
908
]
],
"normalized": []
},
{
"id": "PMID-12374746_T15",
"type": "Protein",
"text": [
"GRIP-1"
],
"offsets": [
[
933,
939
]
],
"normalized": []
},
{
"id": "PMID-12374746_T16",
"type": "Entity",
"text": [
"arginine"
],
"offsets": [
[
41,
49
]
],
"normalized": []
},
{
"id": "PMID-12374746_T18",
"type": "Entity",
"text": [
"KIX domain"
],
"offsets": [
[
629,
639
]
],
"normalized": []
},
{
"id": "PMID-12374746_T23",
"type": "Entity",
"text": [
"arginine residues"
],
"offsets": [
[
871,
888
]
],
"normalized": []
}
] | [
{
"id": "PMID-12374746_E1",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
50,
61
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12374746_T1"
},
{
"role": "Site",
"ref_id": "PMID-12374746_T16"
}
]
},
{
"id": "PMID-12374746_E2",
"type": "Methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
668,
678
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12374746_T10"
},
{
"role": "Site",
"ref_id": "PMID-12374746_T18"
}
]
},
{
"id": "PMID-12374746_E3",
"type": "Catalysis",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
668,
678
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12374746_E2"
},
{
"role": "Cause",
"ref_id": "PMID-12374746_T11"
}
]
},
{
"id": "PMID-12374746_E4",
"type": "Methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
757,
767
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12374746_T12"
}
]
},
{
"id": "PMID-12374746_E5",
"type": "Catalysis",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
757,
767
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12374746_E4"
},
{
"role": "Cause",
"ref_id": "PMID-12374746_T13"
}
]
},
{
"id": "PMID-12374746_E6",
"type": "Methylation",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
889,
899
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12374746_T12"
},
{
"role": "Site",
"ref_id": "PMID-12374746_T23"
}
]
},
{
"id": "PMID-12374746_E7",
"type": "Catalysis",
"trigger": {
"text": [
"methylated"
],
"offsets": [
[
889,
899
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12374746_E6"
},
{
"role": "Cause",
"ref_id": "PMID-12374746_T14"
}
]
}
] | [
{
"id": "PMID-12374746_1",
"entity_ids": [
"PMID-12374746_T3",
"PMID-12374746_T4"
]
}
] | [] |
78 | PMID-12438637 | [
{
"id": "PMID-12438637__text",
"type": "abstract",
"text": [
"The hepatitis C virus RNA-dependent RNA polymerase membrane insertion sequence is a transmembrane segment. \nThe hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) belongs to a class of membrane proteins termed tail-anchored proteins. Here, we show that the HCV RdRp C-terminal membrane insertion sequence traverses the phospholipid bilayer as a transmembrane segment. Moreover, the HCV RdRp was found to be retained in the endoplasmic reticulum (ER) or an ER-derived modified compartment both following transient transfection and in the context of a subgenomic replicon. An absolutely conserved GVG motif was not essential for membrane insertion but possibly provides a docking site for transmembrane protein-protein interactions. These findings have important implications for the functional architecture of the HCV replication complex.\n"
],
"offsets": [
[
0,
847
]
]
}
] | [
{
"id": "PMID-12438637_T1",
"type": "Protein",
"text": [
"RNA-dependent RNA polymerase"
],
"offsets": [
[
22,
50
]
],
"normalized": []
},
{
"id": "PMID-12438637_T2",
"type": "Protein",
"text": [
"RNA-dependent RNA polymerase"
],
"offsets": [
[
136,
164
]
],
"normalized": []
},
{
"id": "PMID-12438637_T3",
"type": "Protein",
"text": [
"RdRp"
],
"offsets": [
[
166,
170
]
],
"normalized": []
},
{
"id": "PMID-12438637_T4",
"type": "Protein",
"text": [
"RdRp"
],
"offsets": [
[
270,
274
]
],
"normalized": []
},
{
"id": "PMID-12438637_T5",
"type": "Protein",
"text": [
"RdRp"
],
"offsets": [
[
395,
399
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-12438637_1",
"entity_ids": [
"PMID-12438637_T2",
"PMID-12438637_T3"
]
}
] | [] |
79 | PMID-12461688 | [
{
"id": "PMID-12461688__text",
"type": "abstract",
"text": [
"Molecular and biochemical characterisation of a novel sulphatase gene: Arylsulfatase G (ARSG). \nMolecular analysis has provided important insights into the biochemistry and genetics of the sulphatase family of enzymes. Through bioinformatic searches of the EST database, we have identified a novel gene consisting of 11 exons and encoding a 525 aa protein that shares a high degree of sequence similarity with all sulphatases and in particular with arylsulphatases, hence the tentative name Arylsulfatase G (ARSG). The highest homology is shared with Arylsulfatase A, a lysosomal sulphatase which is mutated in metachromatic leukodistrophy, particularly in the amino-terminal region. The 10 amino acids that form the catalytic site are strongly conserved. The murine homologue of Arylsulfatase G gene product shows 87% identity with the human protein. To test the function of this novel gene we transfected the full-length cDNA in Cos7 cells, and detected an Arylsulfatase G precursor protein of 62 kDa. After glycosylation the precursor is maturated in a 70 kDa form, which localises to the endoplasmic reticulum. Northern blot analysis of Arylsulfatase G revealed a ubiquitous expression pattern. We tested the sulphatase activity towards two different artificial substrates 4-methylumbelliferyl (4-MU) sulphate and p-nitrocatechol sulphate, but no arylsulphatase activity was detectable. Further studies are needed to characterise the function of Arylsulfatase G, possibly revealing a novel metabolic pathway.\n"
],
"offsets": [
[
0,
1513
]
]
}
] | [
{
"id": "PMID-12461688_T1",
"type": "Protein",
"text": [
"Arylsulfatase G"
],
"offsets": [
[
71,
86
]
],
"normalized": []
},
{
"id": "PMID-12461688_T2",
"type": "Protein",
"text": [
"ARSG"
],
"offsets": [
[
88,
92
]
],
"normalized": []
},
{
"id": "PMID-12461688_T3",
"type": "Protein",
"text": [
"Arylsulfatase G"
],
"offsets": [
[
491,
506
]
],
"normalized": []
},
{
"id": "PMID-12461688_T4",
"type": "Protein",
"text": [
"ARSG"
],
"offsets": [
[
508,
512
]
],
"normalized": []
},
{
"id": "PMID-12461688_T5",
"type": "Protein",
"text": [
"Arylsulfatase A"
],
"offsets": [
[
551,
566
]
],
"normalized": []
},
{
"id": "PMID-12461688_T6",
"type": "Protein",
"text": [
"Arylsulfatase G"
],
"offsets": [
[
780,
795
]
],
"normalized": []
},
{
"id": "PMID-12461688_T7",
"type": "Protein",
"text": [
"Arylsulfatase G"
],
"offsets": [
[
959,
974
]
],
"normalized": []
},
{
"id": "PMID-12461688_T8",
"type": "Protein",
"text": [
"Arylsulfatase G"
],
"offsets": [
[
1141,
1156
]
],
"normalized": []
},
{
"id": "PMID-12461688_T9",
"type": "Protein",
"text": [
"Arylsulfatase G"
],
"offsets": [
[
1450,
1465
]
],
"normalized": []
}
] | [
{
"id": "PMID-12461688_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"glycosylation"
],
"offsets": [
[
1010,
1023
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12461688_T7"
}
]
}
] | [
{
"id": "PMID-12461688_1",
"entity_ids": [
"PMID-12461688_T1",
"PMID-12461688_T2"
]
},
{
"id": "PMID-12461688_2",
"entity_ids": [
"PMID-12461688_T3",
"PMID-12461688_T4"
]
}
] | [] |
80 | PMID-12498693 | [
{
"id": "PMID-12498693__text",
"type": "abstract",
"text": [
"Gene-specific targeting of H3K9 methylation is sufficient for initiating repression in vivo. \nCovalent modifications of chromatin have emerged as key determinants of the genome's transcriptional competence. Histone H3 lysine 9 (H3K9) methylation is an epigenetic signal that is recognized by HP1 and correlates with gene silencing in a variety of organisms. Discovery of the enzymes that catalyze H3K9 methylation has identified a second gene-specific function for this modification in transcriptional repression. Whether H3K9 methylation is causative in the initiation and establishment of gene repression or is a byproduct of the process leading to the repressed state remains unknown. To investigate the role of HMTs and specifically H3K9 methylation in gene repression, we have employed engineered zinc-finger transcription factors (ZFPs) to target HMT activity to a specific endogenous gene. By utilizing ZFPs that recognize the promoter of the endogenous VEGF-A gene, and thus employing this chromosomal locus as an in vivo reporter, we show that ZFPs linked to a minimal catalytic HMT domain affect local methylation of histone H3K9 and the consequent repression of target gene expression. Furthermore, amino acid substitutions within the HMT that ablate its catalytic activity effectively eliminate the ability of the ZFP fusions to repress transcription. Thus, H3K9 methylation is a primary signal that is sufficient for initiating a gene repression pathway in vivo.\n"
],
"offsets": [
[
0,
1476
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]
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"id": "PMID-12498693_T1",
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"H3"
],
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[
27,
29
]
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"id": "PMID-12498693_T2",
"type": "Protein",
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"Histone H3"
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207,
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"id": "PMID-12498693_T3",
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228,
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"id": "PMID-12498693_T4",
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"id": "PMID-12498693_T5",
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"H3"
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"id": "PMID-12498693_T6",
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"H3"
],
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]
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"id": "PMID-12498693_T7",
"type": "Protein",
"text": [
"VEGF-A"
],
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]
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"normalized": []
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"id": "PMID-12498693_T8",
"type": "Protein",
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"histone H3"
],
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"id": "PMID-12498693_T9",
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"H3"
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"id": "PMID-12498693_T10",
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"id": "PMID-12498693_T12",
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"K9"
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"type": "Entity",
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"K9"
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1372,
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"normalized": []
}
] | [
{
"id": "PMID-12498693_E1",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
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32,
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]
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"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12498693_T1"
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"ref_id": "PMID-12498693_T10"
}
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"type": "Methylation",
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"methylation"
],
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234,
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]
]
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"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12498693_T2"
},
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"role": "Site",
"ref_id": "PMID-12498693_T12"
}
]
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"id": "PMID-12498693_E3",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
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402,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12498693_T4"
},
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"role": "Site",
"ref_id": "PMID-12498693_T15"
}
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"id": "PMID-12498693_E4",
"type": "Methylation",
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"text": [
"methylation"
],
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]
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"role": "Theme",
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}
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"text": [
"methylation"
],
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]
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"arguments": [
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"role": "Theme",
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"role": "Site",
"ref_id": "PMID-12498693_T19"
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"id": "PMID-12498693_E6",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
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"role": "Theme",
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"role": "Site",
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},
{
"role": "Contextgene",
"ref_id": "PMID-12498693_T7"
}
]
},
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"id": "PMID-12498693_E7",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12498693_T9"
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"role": "Site",
"ref_id": "PMID-12498693_T23"
}
]
}
] | [
{
"id": "PMID-12498693_1",
"entity_ids": [
"PMID-12498693_T2",
"PMID-12498693_T3"
]
},
{
"id": "PMID-12498693_2",
"entity_ids": [
"PMID-12498693_T12",
"PMID-12498693_T13"
]
}
] | [] |
81 | PMID-12519694 | [
{
"id": "PMID-12519694__text",
"type": "abstract",
"text": [
"Studies on the inhibition of human cytochromes P450 by selenocysteine Se-conjugates. \n1. To investigate whether cytochrome P450 (P450) inhibition can contribute to the chemopreventive activity of selenocysteine Se-conjugates (SeCys conjugates), 21 SeCys conjugates were screened for their inhibitory potency towards seven of the most important human P450s. 2. The majority of the SeCys conjugates produced near complete inhibition of CYP1A1 at a concentration of 250 microm. The most potent inhibitor, Se-benzyl-L-selenocysteine, displayed an IC50 of 12.8 +/- 1.2 microm. CYP2C9, -2C19 and -2D6 were moderately (50-60%) inhibited by the SeCys conjugates. CYP1A2, -2E1 and -3A4 were least inhibited. 3. Studies on the susceptibility of CYP1A1 to SeCys conjugates implicated a thiol-reactive intermediate, as evidenced by reduced inhibition levels in the presence of glutathione and N-acetyl cysteine. Uncoupling of the P450-catalytic cycle was of no importance as ROS scavengers did not influence inhibition levels. 4. P450 inhibition by two physiologically relevant metabolite classes of SeCys conjugates was also studied. N-acetylation of SeCys conjugates consistently increased the inhibitory potency towards CYP1A2, -2C19, -2E1 and -3A4. Beta-lyase catalysed bioactivation of alkyl-substituted SeCys conjugates or Se-benzyl-L-selenocysteine produced little or no additional inhibition of P450 activity. For Se-phenyl-L-selenocysteine, however, significant increases in P450 inhibition were obtained by beta-lyase pre-incubation. 5. It is concluded that the potent and relatively selective CYP1A1 inhibition exerted by SeCys conjugates may contribute to their chemopreventive activity.\n"
],
"offsets": [
[
0,
1689
]
]
}
] | [
{
"id": "PMID-12519694_T1",
"type": "Protein",
"text": [
"CYP1A1"
],
"offsets": [
[
435,
441
]
],
"normalized": []
},
{
"id": "PMID-12519694_T2",
"type": "Protein",
"text": [
"CYP2C9"
],
"offsets": [
[
573,
579
]
],
"normalized": []
},
{
"id": "PMID-12519694_T3",
"type": "Protein",
"text": [
"-2C19"
],
"offsets": [
[
581,
586
]
],
"normalized": []
},
{
"id": "PMID-12519694_T4",
"type": "Protein",
"text": [
"-2D6"
],
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[
591,
595
]
],
"normalized": []
},
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"id": "PMID-12519694_T5",
"type": "Protein",
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"CYP1A2"
],
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]
],
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},
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"id": "PMID-12519694_T6",
"type": "Protein",
"text": [
"-2E1"
],
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[
664,
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]
],
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},
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"id": "PMID-12519694_T7",
"type": "Protein",
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"-3A4"
],
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[
673,
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]
],
"normalized": []
},
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"id": "PMID-12519694_T8",
"type": "Protein",
"text": [
"CYP1A1"
],
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[
736,
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]
],
"normalized": []
},
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"id": "PMID-12519694_T9",
"type": "Protein",
"text": [
"CYP1A2"
],
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[
1212,
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]
],
"normalized": []
},
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"id": "PMID-12519694_T10",
"type": "Protein",
"text": [
"-2C19"
],
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[
1220,
1225
]
],
"normalized": []
},
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"id": "PMID-12519694_T11",
"type": "Protein",
"text": [
"-2E1"
],
"offsets": [
[
1227,
1231
]
],
"normalized": []
},
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"id": "PMID-12519694_T12",
"type": "Protein",
"text": [
"-3A4"
],
"offsets": [
[
1236,
1240
]
],
"normalized": []
},
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"id": "PMID-12519694_T13",
"type": "Protein",
"text": [
"CYP1A1"
],
"offsets": [
[
1593,
1599
]
],
"normalized": []
}
] | [] | [] | [] |
82 | PMID-12522210 | [
{
"id": "PMID-12522210__text",
"type": "abstract",
"text": [
"Identification of a lactoferrin-derived peptide possessing binding activity to hepatitis C virus E2 envelope protein. \nBovine and human lactoferrins (LF) prevent hepatitis C virus (HCV) infection in cultured human hepatocytes; the preventive mechanism is thought to be the direct interaction between LF and HCV. To clarify this hypothesis, we have characterized the binding activity of LF to HCV E2 envelope protein and have endeavored to determine which region(s) of LF are important for this binding activity. Several regions of human LF have been expressed and purified as thioredoxin-fused proteins in Escherichia coli. Far-Western blot analysis using these LF fragments and the E2 protein, expressed in Chinese hamster ovary cells, revealed that the 93 carboxyl amino acids of LF specifically bound to the E2 protein. The 93 carboxyl amino acids of LFs derived from bovine and horse cells also possessed similar binding activity to the E2 protein. In addition, the amino acid sequences of these carboxyl regions appeared to show partial homology to CD81, a candidate receptor for HCV, and the binding activity of these carboxyl regions was also comparable with that of CD81. Further deletion analysis identified 33 amino acid residues as the minimum binding site in the carboxyl region of LF, and the binding specificity of these 33 amino acids was also confirmed by using 33 maltose-binding protein-fused amino acids. Furthermore, we demonstrated that the 33 maltose-binding protein-fused amino acids prevented HCV infection in cultured human hepatocytes. In addition, the site-directed mutagenesis to an Ala residue in both terminal residues of the 33 amino acids revealed that Cys at amino acid 628 was determined to be critical for binding to the E2 protein. These results led us to consider the development of an effective anti-HCV peptide. This is the first identification of a natural protein-derived peptide that specifically binds to HCV E2 protein and prevents HCV infection.\n"
],
"offsets": [
[
0,
1991
]
]
}
] | [
{
"id": "PMID-12522210_T1",
"type": "Protein",
"text": [
"lactoferrin"
],
"offsets": [
[
20,
31
]
],
"normalized": []
},
{
"id": "PMID-12522210_T2",
"type": "Protein",
"text": [
"E2"
],
"offsets": [
[
97,
99
]
],
"normalized": []
},
{
"id": "PMID-12522210_T3",
"type": "Protein",
"text": [
"lactoferrins"
],
"offsets": [
[
136,
148
]
],
"normalized": []
},
{
"id": "PMID-12522210_T4",
"type": "Protein",
"text": [
"LF"
],
"offsets": [
[
150,
152
]
],
"normalized": []
},
{
"id": "PMID-12522210_T5",
"type": "Protein",
"text": [
"LF"
],
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[
300,
302
]
],
"normalized": []
},
{
"id": "PMID-12522210_T6",
"type": "Protein",
"text": [
"LF"
],
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[
386,
388
]
],
"normalized": []
},
{
"id": "PMID-12522210_T7",
"type": "Protein",
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"E2"
],
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[
396,
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]
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},
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"id": "PMID-12522210_T8",
"type": "Protein",
"text": [
"LF"
],
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[
468,
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]
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},
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"id": "PMID-12522210_T9",
"type": "Protein",
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"LF"
],
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[
537,
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]
],
"normalized": []
},
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"id": "PMID-12522210_T10",
"type": "Protein",
"text": [
"LF"
],
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[
662,
664
]
],
"normalized": []
},
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"id": "PMID-12522210_T11",
"type": "Protein",
"text": [
"E2"
],
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[
683,
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]
],
"normalized": []
},
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"id": "PMID-12522210_T12",
"type": "Protein",
"text": [
"LF"
],
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[
782,
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]
],
"normalized": []
},
{
"id": "PMID-12522210_T13",
"type": "Protein",
"text": [
"E2"
],
"offsets": [
[
811,
813
]
],
"normalized": []
},
{
"id": "PMID-12522210_T14",
"type": "Protein",
"text": [
"LFs"
],
"offsets": [
[
854,
857
]
],
"normalized": []
},
{
"id": "PMID-12522210_T15",
"type": "Protein",
"text": [
"E2"
],
"offsets": [
[
941,
943
]
],
"normalized": []
},
{
"id": "PMID-12522210_T16",
"type": "Protein",
"text": [
"CD81"
],
"offsets": [
[
1054,
1058
]
],
"normalized": []
},
{
"id": "PMID-12522210_T17",
"type": "Protein",
"text": [
"CD81"
],
"offsets": [
[
1174,
1178
]
],
"normalized": []
},
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"id": "PMID-12522210_T18",
"type": "Protein",
"text": [
"LF"
],
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[
1294,
1296
]
],
"normalized": []
},
{
"id": "PMID-12522210_T19",
"type": "Protein",
"text": [
"maltose-binding protein"
],
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[
1465,
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]
],
"normalized": []
},
{
"id": "PMID-12522210_T20",
"type": "Protein",
"text": [
"E2"
],
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[
1756,
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]
],
"normalized": []
},
{
"id": "PMID-12522210_T21",
"type": "Protein",
"text": [
"E2"
],
"offsets": [
[
1952,
1954
]
],
"normalized": []
}
] | [] | [
{
"id": "PMID-12522210_1",
"entity_ids": [
"PMID-12522210_T3",
"PMID-12522210_T4"
]
}
] | [] |
83 | PMID-12546654 | [
{
"id": "PMID-12546654__text",
"type": "abstract",
"text": [
"Glucocorticoid suppression of nuclear factor-kappa B: a role for histone modifications. \nCorticosteroids are by far the most effective treatment for chronic inflammatory diseases such as asthma. Inflammation in asthma is characterized by the increased expression of multiple inflammatory genes, including those that encode cytokines, chemokines, adhesion molecules, and inflammatory enzymes and receptors. Increased expression of inflammatory genes is regulated by pro-inflammatory transcription factors, such as nuclear factor kappa B (NF-kappa B). These bind to, and activate, co-activator molecules that then acetylate core histones resulting in elevated gene transcription. Corticosteroids reverse histone acetylation at the site of inflammatory gene transcription, either by direct binding of the activated glucocorticoid receptor to NF-kappa B-associated co-activators or by recruitment of histone deacetylases to the activated transcription complex. Understanding how corticosteroids work in asthma may help in designing novel corticosteroids with fewer systemic effects, as well as novel anti-inflammatory approaches.\n"
],
"offsets": [
[
0,
1126
]
]
}
] | [
{
"id": "PMID-12546654_T1",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
65,
72
]
],
"normalized": []
},
{
"id": "PMID-12546654_T2",
"type": "Protein",
"text": [
"histones"
],
"offsets": [
[
627,
635
]
],
"normalized": []
},
{
"id": "PMID-12546654_T3",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
702,
709
]
],
"normalized": []
},
{
"id": "PMID-12546654_T4",
"type": "Protein",
"text": [
"glucocorticoid receptor"
],
"offsets": [
[
812,
835
]
],
"normalized": []
},
{
"id": "PMID-12546654_T5",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
896,
903
]
],
"normalized": []
}
] | [
{
"id": "PMID-12546654_E1",
"type": "Acetylation",
"trigger": {
"text": [
"acetylate"
],
"offsets": [
[
612,
621
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12546654_T2"
}
]
},
{
"id": "PMID-12546654_E2",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
710,
721
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12546654_T3"
}
]
}
] | [] | [] |
84 | PMID-12558945 | [
{
"id": "PMID-12558945__text",
"type": "abstract",
"text": [
"Probing the conformational and dynamical effects of O-glycosylation within the immunodominant region of a MUC1 peptide tumor antigen. \nMUC1 mucin is a large transmembrane glycoprotein, the extracellular domain of which is formed by a repeating 20 amino acid sequence, GVTSAPDTRPAPGSTAPPAH. In normal breast epithelial cells, the extracellular domain is densely covered with highly branched complex carbohydrate structures. However, in neoplastic breast tissue, the extracellular domain is under-glycosylated, resulting in the exposure of a highly immunogenic core peptide epitope (PDTRP in bold above), as well as in the exposure of normally cryptic core Tn (GalNAc), STn (sialyl alpha2-6 GalNAc) and TF (Gal beta1-3 GalNAc) carbohydrates. Here, we report the results of 1H NMR structural studies, natural abundance 13C NMR relaxation measurements and distance-restrained MD simulations designed to probe the structural and dynamical effects of Tn-glycosylation within the PDTRP core peptide epitope. Two synthetic peptides were studied: a nine-residue MUC1 peptide of the sequence, Thr1-Ser2-Ala3-Pro4-Asp5-Thr6-Arg7-Pro8-Ala9, and a Tn-glycosylated version of this peptide, Thr1-Ser2-Ala3-Pro4-Asp5-Thr6(alphaGalNAc)-Arg7-Pro8-Ala9. The results of these studies show that a type I beta-turn conformation is adopted by residues PDTR within the PDTRP region of the unglycosylated MUC1 sequence. The existence of a similar beta-turn within the PDTRP core peptide epitope of the under-glycosylated cancer-associated MUC1 mucin protein might explain the immunodominance of this region in vivo, as the presence of defined secondary structure within peptide epitope regions has been correlated with increased immunogenicity in other systems. Our results have also shown that Tn glycosylation at the central threonine within the PDTRP core epitope region shifts the conformational equilibrium away from the type I beta-turn conformation and toward a more rigid and extended state. The significance of these results are discussed in relation to the possible roles that peptide epitope secondary structure and glycosylation state may play in MUC1 tumor immunogenicity.\n"
],
"offsets": [
[
0,
2161
]
]
}
] | [
{
"id": "PMID-12558945_T1",
"type": "Protein",
"text": [
"MUC1"
],
"offsets": [
[
106,
110
]
],
"normalized": []
},
{
"id": "PMID-12558945_T2",
"type": "Protein",
"text": [
"MUC1"
],
"offsets": [
[
135,
139
]
],
"normalized": []
},
{
"id": "PMID-12558945_T3",
"type": "Protein",
"text": [
"MUC1"
],
"offsets": [
[
1053,
1057
]
],
"normalized": []
},
{
"id": "PMID-12558945_T4",
"type": "Protein",
"text": [
"MUC1"
],
"offsets": [
[
1380,
1384
]
],
"normalized": []
},
{
"id": "PMID-12558945_T5",
"type": "Protein",
"text": [
"MUC1"
],
"offsets": [
[
1514,
1518
]
],
"normalized": []
},
{
"id": "PMID-12558945_T6",
"type": "Protein",
"text": [
"MUC1"
],
"offsets": [
[
2134,
2138
]
],
"normalized": []
},
{
"id": "PMID-12558945_T8",
"type": "Entity",
"text": [
"immunodominant region"
],
"offsets": [
[
79,
100
]
],
"normalized": []
},
{
"id": "PMID-12558945_T9",
"type": "Entity",
"text": [
"extracellular domain"
],
"offsets": [
[
465,
485
]
],
"normalized": []
},
{
"id": "PMID-12558945_T11",
"type": "Entity",
"text": [
"Tn"
],
"offsets": [
[
655,
657
]
],
"normalized": []
},
{
"id": "PMID-12558945_T12",
"type": "Entity",
"text": [
"GalNAc"
],
"offsets": [
[
659,
665
]
],
"normalized": []
},
{
"id": "PMID-12558945_T13",
"type": "Entity",
"text": [
"STn"
],
"offsets": [
[
668,
671
]
],
"normalized": []
},
{
"id": "PMID-12558945_T14",
"type": "Entity",
"text": [
"sialyl alpha2-6 GalNAc"
],
"offsets": [
[
673,
695
]
],
"normalized": []
},
{
"id": "PMID-12558945_T15",
"type": "Entity",
"text": [
"TF"
],
"offsets": [
[
701,
703
]
],
"normalized": []
},
{
"id": "PMID-12558945_T16",
"type": "Entity",
"text": [
"Gal beta1-3 GalNAc"
],
"offsets": [
[
705,
723
]
],
"normalized": []
},
{
"id": "PMID-12558945_T18",
"type": "Entity",
"text": [
"PDTRP core peptide epitope"
],
"offsets": [
[
1443,
1469
]
],
"normalized": []
}
] | [
{
"id": "PMID-12558945_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"O-glycosylation"
],
"offsets": [
[
52,
67
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12558945_T1"
},
{
"role": "Site",
"ref_id": "PMID-12558945_T8"
}
]
},
{
"id": "PMID-12558945_E2",
"type": "Glycosylation",
"trigger": {
"text": [
"under-glycosylated"
],
"offsets": [
[
489,
507
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12558945_T2"
},
{
"role": "Site",
"ref_id": "PMID-12558945_T9"
},
{
"role": "Sidechain",
"ref_id": "PMID-12558945_T11"
}
]
},
{
"id": "PMID-12558945_E3",
"type": "Glycosylation",
"trigger": {
"text": [
"under-glycosylated"
],
"offsets": [
[
489,
507
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12558945_T2"
},
{
"role": "Site",
"ref_id": "PMID-12558945_T9"
},
{
"role": "Sidechain",
"ref_id": "PMID-12558945_T13"
}
]
},
{
"id": "PMID-12558945_E4",
"type": "Glycosylation",
"trigger": {
"text": [
"under-glycosylated"
],
"offsets": [
[
489,
507
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12558945_T2"
},
{
"role": "Site",
"ref_id": "PMID-12558945_T9"
},
{
"role": "Sidechain",
"ref_id": "PMID-12558945_T15"
}
]
},
{
"id": "PMID-12558945_E5",
"type": "Glycosylation",
"trigger": {
"text": [
"unglycosylated"
],
"offsets": [
[
1365,
1379
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12558945_T4"
}
]
},
{
"id": "PMID-12558945_E6",
"type": "Glycosylation",
"trigger": {
"text": [
"under-glycosylated"
],
"offsets": [
[
1477,
1495
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12558945_T5"
},
{
"role": "Site",
"ref_id": "PMID-12558945_T18"
}
]
},
{
"id": "PMID-12558945_E7",
"type": "Glycosylation",
"trigger": {
"text": [
"glycosylation"
],
"offsets": [
[
2102,
2115
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12558945_T6"
}
]
}
] | [
{
"id": "PMID-12558945_1",
"entity_ids": [
"PMID-12558945_T11",
"PMID-12558945_T12"
]
},
{
"id": "PMID-12558945_2",
"entity_ids": [
"PMID-12558945_T13",
"PMID-12558945_T14"
]
},
{
"id": "PMID-12558945_3",
"entity_ids": [
"PMID-12558945_T15",
"PMID-12558945_T16"
]
}
] | [] |
85 | PMID-12574507 | [
{
"id": "PMID-12574507__text",
"type": "abstract",
"text": [
"Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: a potential mechanism for position-effect variegation. \nMethylation of lysine-79 (K79) within the globular domain of histone H3 by Dot1 methylase is important for transcriptional silencing and for association of the Sir silencing proteins in yeast. Here, we show that the level of H3-K79 methylation is low at all Sir-dependent silenced loci but not at other transcriptionally repressed regions. Hypomethylation of H3-K79 at the telomeric and silent mating-type loci, but not the ribosomal DNA, requires the Sir proteins. Overexpression of Sir3 concomitantly extends the domain of Sir protein association and H3-K79 hypomethylation at telomeres. In mammalian cells, H3-K79 methylation is found at loci that are active for V(D)J recombination, but not at recombinationally inactive loci that are heterochromatic. These results suggest that H3-K79 methylation is an evolutionarily conserved marker of active chromatin regions, and that silencing proteins block the ability of Dot1 to methylate histone H3. Further, they suggest that Sir proteins preferentially bind chromatin with hypomethylated H3-K79 and then block H3-K79 methylation. This positive feedback loop, and the reverse loop in which H3-K79 methylation weakens Sir protein association and leads to further methylation, suggests a model for position-effect variegation.\n"
],
"offsets": [
[
0,
1419
]
]
}
] | [
{
"id": "PMID-12574507_T1",
"type": "Protein",
"text": [
"histone H3"
],
"offsets": [
[
13,
23
]
],
"normalized": []
},
{
"id": "PMID-12574507_T2",
"type": "Protein",
"text": [
"histone H3"
],
"offsets": [
[
206,
216
]
],
"normalized": []
},
{
"id": "PMID-12574507_T3",
"type": "Protein",
"text": [
"Dot1"
],
"offsets": [
[
220,
224
]
],
"normalized": []
},
{
"id": "PMID-12574507_T4",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
370,
372
]
],
"normalized": []
},
{
"id": "PMID-12574507_T5",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
504,
506
]
],
"normalized": []
},
{
"id": "PMID-12574507_T6",
"type": "Protein",
"text": [
"Sir3"
],
"offsets": [
[
629,
633
]
],
"normalized": []
},
{
"id": "PMID-12574507_T7",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
698,
700
]
],
"normalized": []
},
{
"id": "PMID-12574507_T8",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
755,
757
]
],
"normalized": []
},
{
"id": "PMID-12574507_T9",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
928,
930
]
],
"normalized": []
},
{
"id": "PMID-12574507_T10",
"type": "Protein",
"text": [
"Dot1"
],
"offsets": [
[
1063,
1067
]
],
"normalized": []
},
{
"id": "PMID-12574507_T11",
"type": "Protein",
"text": [
"histone H3"
],
"offsets": [
[
1081,
1091
]
],
"normalized": []
},
{
"id": "PMID-12574507_T12",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
1183,
1185
]
],
"normalized": []
},
{
"id": "PMID-12574507_T13",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
1205,
1207
]
],
"normalized": []
},
{
"id": "PMID-12574507_T14",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
1284,
1286
]
],
"normalized": []
},
{
"id": "PMID-12574507_T15",
"type": "Entity",
"text": [
"Lysine-79"
],
"offsets": [
[
0,
9
]
],
"normalized": []
},
{
"id": "PMID-12574507_T19",
"type": "Entity",
"text": [
"lysine-79"
],
"offsets": [
[
160,
169
]
],
"normalized": []
},
{
"id": "PMID-12574507_T20",
"type": "Entity",
"text": [
"K79"
],
"offsets": [
[
171,
174
]
],
"normalized": []
},
{
"id": "PMID-12574507_T21",
"type": "Entity",
"text": [
"K79"
],
"offsets": [
[
373,
376
]
],
"normalized": []
},
{
"id": "PMID-12574507_T24",
"type": "Entity",
"text": [
"K79"
],
"offsets": [
[
507,
510
]
],
"normalized": []
},
{
"id": "PMID-12574507_T25",
"type": "Entity",
"text": [
"K79"
],
"offsets": [
[
701,
704
]
],
"normalized": []
},
{
"id": "PMID-12574507_T27",
"type": "Entity",
"text": [
"K79"
],
"offsets": [
[
758,
761
]
],
"normalized": []
},
{
"id": "PMID-12574507_T29",
"type": "Entity",
"text": [
"K79"
],
"offsets": [
[
931,
934
]
],
"normalized": []
},
{
"id": "PMID-12574507_T34",
"type": "Entity",
"text": [
"K79"
],
"offsets": [
[
1186,
1189
]
],
"normalized": []
},
{
"id": "PMID-12574507_T35",
"type": "Entity",
"text": [
"K79"
],
"offsets": [
[
1208,
1211
]
],
"normalized": []
},
{
"id": "PMID-12574507_T37",
"type": "Entity",
"text": [
"K79"
],
"offsets": [
[
1287,
1290
]
],
"normalized": []
}
] | [
{
"id": "PMID-12574507_E1",
"type": "Methylation",
"trigger": {
"text": [
"hypomethylated"
],
"offsets": [
[
27,
41
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12574507_T1"
},
{
"role": "Site",
"ref_id": "PMID-12574507_T15"
}
]
},
{
"id": "PMID-12574507_E2",
"type": "Methylation",
"trigger": {
"text": [
"Methylation"
],
"offsets": [
[
145,
156
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12574507_T2"
},
{
"role": "Site",
"ref_id": "PMID-12574507_T19"
}
]
},
{
"id": "PMID-12574507_E3",
"type": "Catalysis",
"trigger": {
"text": [
"Methylation"
],
"offsets": [
[
145,
156
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12574507_E2"
},
{
"role": "Cause",
"ref_id": "PMID-12574507_T3"
}
]
},
{
"id": "PMID-12574507_E4",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
377,
388
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12574507_T4"
},
{
"role": "Site",
"ref_id": "PMID-12574507_T21"
}
]
},
{
"id": "PMID-12574507_E5",
"type": "Methylation",
"trigger": {
"text": [
"Hypomethylation"
],
"offsets": [
[
485,
500
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12574507_T5"
},
{
"role": "Site",
"ref_id": "PMID-12574507_T24"
}
]
},
{
"id": "PMID-12574507_E6",
"type": "Methylation",
"trigger": {
"text": [
"hypomethylation"
],
"offsets": [
[
705,
720
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12574507_T7"
},
{
"role": "Site",
"ref_id": "PMID-12574507_T25"
}
]
},
{
"id": "PMID-12574507_E7",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
762,
773
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12574507_T8"
},
{
"role": "Site",
"ref_id": "PMID-12574507_T27"
}
]
},
{
"id": "PMID-12574507_E8",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
935,
946
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12574507_T9"
},
{
"role": "Site",
"ref_id": "PMID-12574507_T29"
}
]
},
{
"id": "PMID-12574507_E9",
"type": "Catalysis",
"trigger": {
"text": [
"methylate"
],
"offsets": [
[
1071,
1080
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12574507_E10"
},
{
"role": "Cause",
"ref_id": "PMID-12574507_T10"
}
]
},
{
"id": "PMID-12574507_E10",
"type": "Methylation",
"trigger": {
"text": [
"methylate"
],
"offsets": [
[
1071,
1080
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12574507_T11"
}
]
},
{
"id": "PMID-12574507_E11",
"type": "Methylation",
"trigger": {
"text": [
"hypomethylated"
],
"offsets": [
[
1168,
1182
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12574507_T12"
},
{
"role": "Site",
"ref_id": "PMID-12574507_T34"
}
]
},
{
"id": "PMID-12574507_E12",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1212,
1223
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12574507_T13"
},
{
"role": "Site",
"ref_id": "PMID-12574507_T35"
}
]
},
{
"id": "PMID-12574507_E13",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
1291,
1302
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12574507_T14"
},
{
"role": "Site",
"ref_id": "PMID-12574507_T37"
}
]
}
] | [
{
"id": "PMID-12574507_1",
"entity_ids": [
"PMID-12574507_T19",
"PMID-12574507_T20"
]
}
] | [] |
86 | PMID-12586829 | [
{
"id": "PMID-12586829__text",
"type": "abstract",
"text": [
"Cyclosporin A prevents the hypoxic adaptation by activating hypoxia-inducible factor-1alpha Pro-564 hydroxylation. \nThe mechanism by which hypoxia induces gene transcription involves the inhibition of hypoxia-inducible factor (HIF)-1alpha prolyl hydroxylase activity, which prevents von Hippel-Lindau (vHL)-dependent targeting of HIF-1alpha to the ubiquitin-proteasome pathway. HIF-1alpha is stabilized, translocates to the nucleus, interacts with hypoxia-responsive elements, and promotes the activation of target genes. This report shows that cyclosporin A (CsA) interferes with the hypoxic signaling cascade in C6 glioma cells. CsA inhibits hypoxia-dependent gene transcription in a reporter gene assay and prevents the hypoxic accumulation of HIF-1alpha. Addition of the 530-603 C-terminal oxygen-dependent degradation (ODD) domain of HIF-1alpha to the green fluorescent protein (GFP) destabilized the protein in an oxygen-dependent manner. CsA prevented the hypoxic stabilization of an ODD.GFP fusion protein. An assay for 2-oxoglutarate-dependent dioxygenases was developed using a light mitochondrial kidney fraction as a source of enzyme. It uses the capacity of specific peptides to stimulate the degradation of [(14)C]2-oxoglutarate. CsA stimulated the enzymatic activity in the presence of a peptide that mimicked the 557-576 sequence of HIF-1alpha. The enzyme promoted [(35)S]vHL binding to glutathione S-transferase (GST).ODD fusion protein. This association increased in the presence of CsA. CsA effects were not observed when the proline residue corresponding to Pro-564 in the HIF-1alpha sequence was replaced by a hydroxyproline or an alanine residue. Finally, CsA increased vHL-ODD interaction during hypoxia. We conclude that CsA destabilizes HIF-1alpha by promoting hydroxylation of Pro-564 in the ODD domain. Such a mechanism may prevent hypoxic adaptation during CsA-induced nephrotoxicity and contribute to the adverse effects of this drug.\n"
],
"offsets": [
[
0,
1964
]
]
}
] | [
{
"id": "PMID-12586829_T1",
"type": "Protein",
"text": [
"hypoxia-inducible factor-1alpha"
],
"offsets": [
[
60,
91
]
],
"normalized": []
},
{
"id": "PMID-12586829_T2",
"type": "Protein",
"text": [
"hypoxia-inducible factor (HIF)-1alpha"
],
"offsets": [
[
201,
238
]
],
"normalized": []
},
{
"id": "PMID-12586829_T3",
"type": "Protein",
"text": [
"von Hippel-Lindau"
],
"offsets": [
[
283,
300
]
],
"normalized": []
},
{
"id": "PMID-12586829_T4",
"type": "Protein",
"text": [
"vHL"
],
"offsets": [
[
302,
305
]
],
"normalized": []
},
{
"id": "PMID-12586829_T5",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
330,
340
]
],
"normalized": []
},
{
"id": "PMID-12586829_T6",
"type": "Protein",
"text": [
"ubiquitin"
],
"offsets": [
[
348,
357
]
],
"normalized": []
},
{
"id": "PMID-12586829_T7",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
378,
388
]
],
"normalized": []
},
{
"id": "PMID-12586829_T8",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
747,
757
]
],
"normalized": []
},
{
"id": "PMID-12586829_T9",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
839,
849
]
],
"normalized": []
},
{
"id": "PMID-12586829_T10",
"type": "Protein",
"text": [
"green fluorescent protein"
],
"offsets": [
[
857,
882
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},
{
"id": "PMID-12586829_T11",
"type": "Protein",
"text": [
"GFP"
],
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[
884,
887
]
],
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},
{
"id": "PMID-12586829_T12",
"type": "Protein",
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"GFP"
],
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995,
998
]
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},
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"id": "PMID-12586829_T13",
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],
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[
1349,
1359
]
],
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},
{
"id": "PMID-12586829_T14",
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"vHL"
],
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1388,
1391
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},
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"id": "PMID-12586829_T15",
"type": "Protein",
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"HIF-1alpha"
],
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1593,
1603
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],
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},
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"id": "PMID-12586829_T16",
"type": "Protein",
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"vHL"
],
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1692,
1695
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],
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},
{
"id": "PMID-12586829_T17",
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"HIF-1alpha"
],
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1762,
1772
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],
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},
{
"id": "PMID-12586829_T18",
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"Pro-564"
],
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92,
99
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},
{
"id": "PMID-12586829_T21",
"type": "Entity",
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"Pro-564"
],
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1803,
1810
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],
"normalized": []
}
] | [
{
"id": "PMID-12586829_E1",
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"text": [
"hydroxylation"
],
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100,
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]
]
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"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12586829_T1"
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"role": "Site",
"ref_id": "PMID-12586829_T18"
}
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"id": "PMID-12586829_E2",
"type": "Hydroxylation",
"trigger": {
"text": [
"hydroxylation"
],
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]
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"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12586829_T17"
},
{
"role": "Site",
"ref_id": "PMID-12586829_T21"
}
]
}
] | [
{
"id": "PMID-12586829_1",
"entity_ids": [
"PMID-12586829_T10",
"PMID-12586829_T11"
]
}
] | [] |
87 | PMID-12606569 | [
{
"id": "PMID-12606569__text",
"type": "abstract",
"text": [
"A role for N-glycanase in the cytosolic turnover of glycoproteins. \nSuccessful maturation determines the intracellular fate of secretory and membrane proteins in the endoplasmic reticulum (ER). Failure of proteins to fold or assemble properly can lead to their retention in the ER and redirects them to the cytosol for degradation by the proteasome. Proteasome inhibitors can yield deglycosylated cytoplasmic intermediates that are the result of an N-glycanase activity, believed to act prior to destruction of these substrates by the proteasome. A gene encoding a yeast peptide:N-glycanase, PNG1, has been cloned, but this N-glycanase and its mammalian homolog were reported to be incapable of deglycosylating full-length glycoproteins. We show that both the yeast PNG1 enzyme and its mammalian homolog display N-glycanase activity towards intact glycoproteins. As substrates, cytosolic PNGase activity prefers proteins containing high-mannose over those bearing complex type oligosaccharides. Importantly, PNG1 discriminates between non-native and folded glycoproteins, consistent with a role for N-glycanase in cytoplasmic turnover of glycoproteins.\n"
],
"offsets": [
[
0,
1153
]
]
}
] | [
{
"id": "PMID-12606569_T1",
"type": "Protein",
"text": [
"PNG1"
],
"offsets": [
[
592,
596
]
],
"normalized": []
},
{
"id": "PMID-12606569_T2",
"type": "Protein",
"text": [
"PNG1"
],
"offsets": [
[
766,
770
]
],
"normalized": []
},
{
"id": "PMID-12606569_T3",
"type": "Protein",
"text": [
"PNGase"
],
"offsets": [
[
888,
894
]
],
"normalized": []
},
{
"id": "PMID-12606569_T4",
"type": "Protein",
"text": [
"PNG1"
],
"offsets": [
[
1008,
1012
]
],
"normalized": []
}
] | [] | [] | [] |
88 | PMID-12620295 | [
{
"id": "PMID-12620295__text",
"type": "abstract",
"text": [
"Preclinical evaluation of antineoplastic activity of inhibitors of DNA methylation (5-aza-2'-deoxycytidine) and histone deacetylation (trichostatin A, depsipeptide) in combination against myeloid leukemic cells. \nDuring the development of leukemia, genes that suppress growth and induce differentiation can be silenced by aberrant DNA methylation and by changes in chromatin structure that involve histone deacetylation. It has been reported that a positive interaction between DNA methylation and histone deacetylation takes place to inhibit transcription. Based on this observation, our working hypothesis was that a combination of inhibitors of these processes should produce an enhancement of their antineoplastic activity on leukemic cells. The cytosine nucleoside analog, 5-aza-2'-deoxycytidine (5AZA), is a potent inhibitor of DNA methylation, which can activate tumor suppressor genes in leukemic cells that have been silenced by aberrant methylation. In clinical trials, 5AZA was demonstrated to be an active antileukemic agent. Histone deacetylase inhibitors (HDI) can also activate gene expression in leukemic cell lines by producing changes in chromatin configuration, and show antineoplastic activity in preclinical studies. In this report, we investigated the in vitro antineoplastic activity of 5AZA, alone and in combination with the HDI, trichostatin A (TSA) and depsipeptide (FR901228, depsi), on the human myeloid leukemic cell lines, HL-60 and KG1a. The results showed that the combination of 5AZA with TSA or depsi produced a greater inhibition of growth and DNA synthesis and a greater loss of clonogenicity than either agent alone. These results suggest that 5AZA used in combination with HDI may be an interesting chemotherapeutic regimen to investigate in patients with acute myeloid leukemia that is resistant to conventional chemotherapy.\n"
],
"offsets": [
[
0,
1866
]
]
}
] | [
{
"id": "PMID-12620295_T1",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
112,
119
]
],
"normalized": []
},
{
"id": "PMID-12620295_T2",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
398,
405
]
],
"normalized": []
},
{
"id": "PMID-12620295_T3",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
498,
505
]
],
"normalized": []
},
{
"id": "PMID-12620295_T4",
"type": "Protein",
"text": [
"Histone"
],
"offsets": [
[
1038,
1045
]
],
"normalized": []
}
] | [
{
"id": "PMID-12620295_E1",
"type": "Deacetylation",
"trigger": {
"text": [
"deacetylation"
],
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[
120,
133
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12620295_T1"
}
]
},
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"id": "PMID-12620295_E2",
"type": "Deacetylation",
"trigger": {
"text": [
"deacetylation"
],
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406,
419
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "PMID-12620295_T2"
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},
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"id": "PMID-12620295_E3",
"type": "Deacetylation",
"trigger": {
"text": [
"deacetylation"
],
"offsets": [
[
506,
519
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12620295_T3"
}
]
}
] | [] | [] |
89 | PMID-12634321 | [
{
"id": "PMID-12634321__text",
"type": "abstract",
"text": [
"Complex-type biantennary N-glycans of recombinant human transferrin from Trichoplusia ni insect cells expressing mammalian [beta]-1,4-galactosyltransferase and [beta]-1,2-N-acetylglucosaminyltransferase II. \nA novel recombinant baculovirus expression vector was used to produce His-tagged human transferrin in a transformed insect cell line (Tn5beta4GalT) that constitutively expresses a mammalian beta-1,4-galactosyltransferase. This virus encoded the His-tagged human transferrin protein in conventional fashion under the control of the very late polyhedrin promoter. In addition, to enhance the synthesis of galactosylated biantennary N-glycans, this virus encoded human beta-1,2- N-acetylglucosaminyltransferase II under the control of an immediate-early (ie1) promoter. Detailed analyses by MALDI-TOF MS, exoglycosidase digestion, and two-dimensional HPLC revealed that the N-glycans on the purified recombinant human transferrin produced by this virus-host system included four different fully galactosylated, biantennary, complex-type glycans. Thus, this study describes a novel baculovirus-host system, which can be used to produce a recombinant glycoprotein with fully galactosylated, biantennary N-glycans.\n"
],
"offsets": [
[
0,
1217
]
]
}
] | [
{
"id": "PMID-12634321_T1",
"type": "Protein",
"text": [
"transferrin"
],
"offsets": [
[
56,
67
]
],
"normalized": []
},
{
"id": "PMID-12634321_T2",
"type": "Protein",
"text": [
"[beta]-1,2-N-acetylglucosaminyltransferase II"
],
"offsets": [
[
160,
205
]
],
"normalized": []
},
{
"id": "PMID-12634321_T3",
"type": "Protein",
"text": [
"transferrin"
],
"offsets": [
[
295,
306
]
],
"normalized": []
},
{
"id": "PMID-12634321_T4",
"type": "Protein",
"text": [
"transferrin"
],
"offsets": [
[
470,
481
]
],
"normalized": []
},
{
"id": "PMID-12634321_T5",
"type": "Protein",
"text": [
"polyhedrin"
],
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[
549,
559
]
],
"normalized": []
},
{
"id": "PMID-12634321_T6",
"type": "Protein",
"text": [
"beta-1,2- N-acetylglucosaminyltransferase II"
],
"offsets": [
[
674,
718
]
],
"normalized": []
},
{
"id": "PMID-12634321_T7",
"type": "Protein",
"text": [
"ie1"
],
"offsets": [
[
760,
763
]
],
"normalized": []
},
{
"id": "PMID-12634321_T8",
"type": "Protein",
"text": [
"transferrin"
],
"offsets": [
[
923,
934
]
],
"normalized": []
}
] | [] | [] | [] |
90 | PMID-12646245 | [
{
"id": "PMID-12646245__text",
"type": "abstract",
"text": [
"Overexpression of the CT GalNAc transferase inhibits muscular dystrophy in a cleavage-resistant dystroglycan mutant mouse. \nTransgenic mice that express dystroglycan containing a serine to alanine point mutation at the normal site of cleavage (DG(S654A)) in their skeletal muscles fail to express endogenously cleaved dystroglycan and have muscular dystrophy [Neuromusc. Disord., in press]. Dystrophic DG(S654A) muscles have reduced binding of antibodies, including VIA4-1, that recognize carbohydrate antigens on alpha dystroglycan, a finding similar to muscles in some forms of congenital muscular dystrophy. Here we describe one DG(S654A) transgenic line where VIA4-1 antibody binding is absent in skeletal muscle. In theory, the absence of this carbohydrate antigen should inhibit later glycosylation events that would occur on the structure or structures this antibody binds to. One such modification is likely to be the CT carbohydrate antigen, which is present on alpha dystroglycan in muscles overexpressing the CT GalNAc transferase [Dev. Biol. 242 (2002) 58]. To test the relationship between the VIA4-1 and CT carbohydrate antigens, we made DG(S654A)/CT GalNAc transferase (DG(S654A)/CT) transgenic mice. Surprisingly, dystroglycan was cleaved, and alpha dystroglycan was glycosylated with the VIA4-1 antigen, in DG(S654A)/CT muscles. In addition, muscles in DG(S654A)/CT transgenic mice had little or no evidence of muscular dystrophy when compared to DG(S654A) littermates. These experiments demonstrate that the CT GalNAc transferase can affect the post-translational processing of dystroglycan and the extent of muscular dystrophy even in muscles where the VIA4-1 antigen is not present.\n"
],
"offsets": [
[
0,
1703
]
]
}
] | [
{
"id": "PMID-12646245_T1",
"type": "Protein",
"text": [
"CT GalNAc transferase"
],
"offsets": [
[
22,
43
]
],
"normalized": []
},
{
"id": "PMID-12646245_T2",
"type": "Protein",
"text": [
"dystroglycan"
],
"offsets": [
[
153,
165
]
],
"normalized": []
},
{
"id": "PMID-12646245_T3",
"type": "Protein",
"text": [
"DG"
],
"offsets": [
[
244,
246
]
],
"normalized": []
},
{
"id": "PMID-12646245_T4",
"type": "Protein",
"text": [
"dystroglycan"
],
"offsets": [
[
318,
330
]
],
"normalized": []
},
{
"id": "PMID-12646245_T5",
"type": "Protein",
"text": [
"DG"
],
"offsets": [
[
402,
404
]
],
"normalized": []
},
{
"id": "PMID-12646245_T6",
"type": "Protein",
"text": [
"alpha dystroglycan"
],
"offsets": [
[
514,
532
]
],
"normalized": []
},
{
"id": "PMID-12646245_T7",
"type": "Protein",
"text": [
"DG"
],
"offsets": [
[
632,
634
]
],
"normalized": []
},
{
"id": "PMID-12646245_T8",
"type": "Protein",
"text": [
"CT GalNAc transferase"
],
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[
1020,
1041
]
],
"normalized": []
},
{
"id": "PMID-12646245_T9",
"type": "Protein",
"text": [
"DG"
],
"offsets": [
[
1152,
1154
]
],
"normalized": []
},
{
"id": "PMID-12646245_T10",
"type": "Protein",
"text": [
"CT GalNAc transferase"
],
"offsets": [
[
1162,
1183
]
],
"normalized": []
},
{
"id": "PMID-12646245_T11",
"type": "Protein",
"text": [
"DG"
],
"offsets": [
[
1185,
1187
]
],
"normalized": []
},
{
"id": "PMID-12646245_T12",
"type": "Protein",
"text": [
"dystroglycan"
],
"offsets": [
[
1230,
1242
]
],
"normalized": []
},
{
"id": "PMID-12646245_T13",
"type": "Protein",
"text": [
"alpha dystroglycan"
],
"offsets": [
[
1260,
1278
]
],
"normalized": []
},
{
"id": "PMID-12646245_T14",
"type": "Protein",
"text": [
"DG"
],
"offsets": [
[
1324,
1326
]
],
"normalized": []
},
{
"id": "PMID-12646245_T15",
"type": "Protein",
"text": [
"DG"
],
"offsets": [
[
1370,
1372
]
],
"normalized": []
},
{
"id": "PMID-12646245_T16",
"type": "Protein",
"text": [
"DG"
],
"offsets": [
[
1464,
1466
]
],
"normalized": []
},
{
"id": "PMID-12646245_T17",
"type": "Protein",
"text": [
"CT GalNAc transferase"
],
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[
1526,
1547
]
],
"normalized": []
},
{
"id": "PMID-12646245_T18",
"type": "Protein",
"text": [
"dystroglycan"
],
"offsets": [
[
1596,
1608
]
],
"normalized": []
}
] | [
{
"id": "PMID-12646245_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"glycosylated"
],
"offsets": [
[
1283,
1295
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12646245_T13"
}
]
}
] | [] | [] |
91 | PMID-12694398 | [
{
"id": "PMID-12694398__text",
"type": "abstract",
"text": [
"Characterization of two novel proteins, NgRH1 and NgRH2, structurally and biochemically homologous to the Nogo-66 receptor. \nNogo-66 receptor (NgR) has recently been identified as the neuronal receptor of the myelin-associated proteins Nogo-A, oligodendrocyte protein (OMgp) and myelin-associated glycoprotein (MAG), and mediates inhibition of axonal regeneration both in vitro and in vivo. Through database searches, we have identified two novel proteins (NgRH1 and NgRH2) that turned out to be homologous in their primary structures, biochemical properties and expression patterns to NgR. Like NgR, the homologues contain eight leucine-rich repeats (LRR) flanked by a leucine-rich repeat C-terminus (LRRCT) and a leucine-rich repeat N-terminus (LRRNT), and also have a C-terminal GPI signal sequence. Northern blot analysis showed predominant expression of NgRH1 and NgRH2 mRNA in the brain. In situ hybridization and immunohistochemistry on rat brain slices revealed neuronal expression of the genes. NgRH1 and NgRH2 were detected on the cell surface of recombinant cell lines as N-glycosylated GPI anchored proteins and, consistent with other GPI anchored proteins, were localized within the lipid rafts of cellular membranes. In addition, an N-terminal proteolytic fragment of NgR comprising the majority of the ectodomain was found to be constitutively secreted from cells. Our data indicate that NgR, NgRH1 and NgRH2 constitute a novel receptor protein family, which may play related roles within the CNS.\n"
],
"offsets": [
[
0,
1513
]
]
}
] | [
{
"id": "PMID-12694398_T1",
"type": "Protein",
"text": [
"NgRH1"
],
"offsets": [
[
40,
45
]
],
"normalized": []
},
{
"id": "PMID-12694398_T2",
"type": "Protein",
"text": [
"NgRH2"
],
"offsets": [
[
50,
55
]
],
"normalized": []
},
{
"id": "PMID-12694398_T3",
"type": "Protein",
"text": [
"Nogo-66 receptor"
],
"offsets": [
[
106,
122
]
],
"normalized": []
},
{
"id": "PMID-12694398_T4",
"type": "Protein",
"text": [
"Nogo-66 receptor"
],
"offsets": [
[
125,
141
]
],
"normalized": []
},
{
"id": "PMID-12694398_T5",
"type": "Protein",
"text": [
"NgR"
],
"offsets": [
[
143,
146
]
],
"normalized": []
},
{
"id": "PMID-12694398_T6",
"type": "Protein",
"text": [
"Nogo-A"
],
"offsets": [
[
236,
242
]
],
"normalized": []
},
{
"id": "PMID-12694398_T7",
"type": "Protein",
"text": [
"oligodendrocyte protein"
],
"offsets": [
[
244,
267
]
],
"normalized": []
},
{
"id": "PMID-12694398_T8",
"type": "Protein",
"text": [
"OMgp"
],
"offsets": [
[
269,
273
]
],
"normalized": []
},
{
"id": "PMID-12694398_T9",
"type": "Protein",
"text": [
"myelin-associated glycoprotein"
],
"offsets": [
[
279,
309
]
],
"normalized": []
},
{
"id": "PMID-12694398_T10",
"type": "Protein",
"text": [
"MAG"
],
"offsets": [
[
311,
314
]
],
"normalized": []
},
{
"id": "PMID-12694398_T11",
"type": "Protein",
"text": [
"NgRH1"
],
"offsets": [
[
457,
462
]
],
"normalized": []
},
{
"id": "PMID-12694398_T12",
"type": "Protein",
"text": [
"NgRH2"
],
"offsets": [
[
467,
472
]
],
"normalized": []
},
{
"id": "PMID-12694398_T13",
"type": "Protein",
"text": [
"NgR"
],
"offsets": [
[
586,
589
]
],
"normalized": []
},
{
"id": "PMID-12694398_T14",
"type": "Protein",
"text": [
"NgR"
],
"offsets": [
[
596,
599
]
],
"normalized": []
},
{
"id": "PMID-12694398_T15",
"type": "Protein",
"text": [
"NgRH1"
],
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[
859,
864
]
],
"normalized": []
},
{
"id": "PMID-12694398_T16",
"type": "Protein",
"text": [
"NgRH2"
],
"offsets": [
[
869,
874
]
],
"normalized": []
},
{
"id": "PMID-12694398_T17",
"type": "Protein",
"text": [
"NgRH1"
],
"offsets": [
[
1004,
1009
]
],
"normalized": []
},
{
"id": "PMID-12694398_T18",
"type": "Protein",
"text": [
"NgRH2"
],
"offsets": [
[
1014,
1019
]
],
"normalized": []
},
{
"id": "PMID-12694398_T19",
"type": "Protein",
"text": [
"NgR"
],
"offsets": [
[
1282,
1285
]
],
"normalized": []
},
{
"id": "PMID-12694398_T20",
"type": "Protein",
"text": [
"NgR"
],
"offsets": [
[
1403,
1406
]
],
"normalized": []
},
{
"id": "PMID-12694398_T21",
"type": "Protein",
"text": [
"NgRH1"
],
"offsets": [
[
1408,
1413
]
],
"normalized": []
},
{
"id": "PMID-12694398_T22",
"type": "Protein",
"text": [
"NgRH2"
],
"offsets": [
[
1418,
1423
]
],
"normalized": []
}
] | [
{
"id": "PMID-12694398_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"N-glycosylated"
],
"offsets": [
[
1083,
1097
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12694398_T17"
}
]
},
{
"id": "PMID-12694398_E2",
"type": "Glycosylation",
"trigger": {
"text": [
"N-glycosylated"
],
"offsets": [
[
1083,
1097
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12694398_T18"
}
]
}
] | [
{
"id": "PMID-12694398_1",
"entity_ids": [
"PMID-12694398_T4",
"PMID-12694398_T5"
]
},
{
"id": "PMID-12694398_2",
"entity_ids": [
"PMID-12694398_T7",
"PMID-12694398_T8"
]
},
{
"id": "PMID-12694398_3",
"entity_ids": [
"PMID-12694398_T9",
"PMID-12694398_T10"
]
}
] | [] |
92 | PMID-12729016 | [
{
"id": "PMID-12729016__text",
"type": "abstract",
"text": [
"Synthesis of hydroxymethylglutathione from glutathione and L-serine catalyzed by carboxypeptidase Y. \nHydroxymethylglutathione (gamma-L-glutamyl-L-cysteinyl-L-serine; hmGSH) occurs in many species belonging to the family Gramineae, but the biosynthetic pathway for hmGSH has not been identified. We found that carboxypeptidase Y (CPY), but not carboxypeptidase A, catalyzed hmGSH synthesis from glutathione and L-serine in vitro at acidic pH. CPY also catalyzed methylglutathione synthesis from glutathione and L-alanine. These findings suggested that a carboxypeptidase-like enzyme may be involved in hmGSH synthesis in vivo.\n"
],
"offsets": [
[
0,
627
]
]
}
] | [
{
"id": "PMID-12729016_T1",
"type": "Protein",
"text": [
"carboxypeptidase Y"
],
"offsets": [
[
81,
99
]
],
"normalized": []
},
{
"id": "PMID-12729016_T2",
"type": "Protein",
"text": [
"carboxypeptidase Y"
],
"offsets": [
[
310,
328
]
],
"normalized": []
},
{
"id": "PMID-12729016_T3",
"type": "Protein",
"text": [
"CPY"
],
"offsets": [
[
330,
333
]
],
"normalized": []
}
] | [] | [] | [] |
93 | PMID-12764140 | [
{
"id": "PMID-12764140__text",
"type": "abstract",
"text": [
"Transcriptional elongation by RNA polymerase II and histone methylation. \nmRNA synthesis in eukaryotic organisms is a key biological process that is regulated at multiple levels. From the covalent modifications of chromatin by a number of chromatin remodeling complexes during the initiation and activation steps of transcription to the processing of mRNA transcripts, a very large consortium of proteins and multiprotein complexes is critical for gene expression by RNA polymerase II. The list of proteins essential for the successful synthesis of mRNA continues to grow at a rapid pace. Recent advances in this area of research have been focused on transcription through chromatin. In this article, we will review the recent literature linking the key biochemical process of transcriptional elongation by RNA polymerase II to histone methylation by COMPASS, Dot1p, and Set2 methyltransferases.\n"
],
"offsets": [
[
0,
896
]
]
}
] | [
{
"id": "PMID-12764140_T1",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
52,
59
]
],
"normalized": []
},
{
"id": "PMID-12764140_T2",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
828,
835
]
],
"normalized": []
},
{
"id": "PMID-12764140_T3",
"type": "Protein",
"text": [
"Dot1p"
],
"offsets": [
[
860,
865
]
],
"normalized": []
},
{
"id": "PMID-12764140_T4",
"type": "Protein",
"text": [
"Set2"
],
"offsets": [
[
871,
875
]
],
"normalized": []
}
] | [
{
"id": "PMID-12764140_E1",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
60,
71
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12764140_T1"
}
]
},
{
"id": "PMID-12764140_E2",
"type": "Methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
836,
847
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12764140_T2"
}
]
},
{
"id": "PMID-12764140_E3",
"type": "Catalysis",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
836,
847
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12764140_E2"
},
{
"role": "Cause",
"ref_id": "PMID-12764140_T3"
}
]
},
{
"id": "PMID-12764140_E4",
"type": "Catalysis",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
836,
847
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12764140_E2"
},
{
"role": "Cause",
"ref_id": "PMID-12764140_T4"
}
]
}
] | [] | [] |
94 | PMID-12771137 | [
{
"id": "PMID-12771137__text",
"type": "abstract",
"text": [
"Prolyl hydroxylation of collagen type I is required for efficient binding to integrin alpha 1 beta 1 and platelet glycoprotein VI but not to alpha 2 beta 1. \nCollagen is a potent adhesive substrate for cells, an event essentially mediated by the integrins alpha 1 beta 1 and alpha 2 beta 1. Collagen fibrils also bind to the integrin alpha 2 beta 1 and the platelet receptor glycoprotein VI to activate and aggregate platelets. The distinct triple helical recognition motifs for these receptors, GXOGER and (GPO)n, respectively, all contain hydroxyproline. Using unhydroxylated collagen I produced in transgenic plants, we investigated the role of hydroxyproline in the receptor-binding properties of collagen. We show that alpha 2 beta 1 but not alpha 1 beta 1 mediates cell adhesion to unhydroxylated collagen. Soluble recombinant alpha 1 beta 1 binding to unhydroxylated collagen is considerably reduced compared with bovine collagens, but binding can be restored by prolyl hydroxylation of recombinant collagen. We also show that platelets use alpha 2 beta 1 to adhere to the unhydroxylated recombinant molecules, but the adhesion is weaker than on fully hydroxylated collagen, and the unhydroxylated collagen fibrils fail to aggregate platelets. Prolyl hydroxylation is thus required for binding of collagen to platelet glycoprotein VI and to cells by alpha 1 beta 1. These observations give new insights into the molecular basis of collagen-receptor interactions and offer new selective applications for the recombinant unhydroxylated collagen I.\n"
],
"offsets": [
[
0,
1553
]
]
}
] | [
{
"id": "PMID-12771137_T1",
"type": "Protein",
"text": [
"integrin alpha 1"
],
"offsets": [
[
77,
93
]
],
"normalized": []
},
{
"id": "PMID-12771137_T2",
"type": "Protein",
"text": [
"beta 1"
],
"offsets": [
[
94,
100
]
],
"normalized": []
},
{
"id": "PMID-12771137_T3",
"type": "Protein",
"text": [
"platelet glycoprotein VI"
],
"offsets": [
[
105,
129
]
],
"normalized": []
},
{
"id": "PMID-12771137_T4",
"type": "Protein",
"text": [
"alpha 2"
],
"offsets": [
[
141,
148
]
],
"normalized": []
},
{
"id": "PMID-12771137_T5",
"type": "Protein",
"text": [
"beta 1"
],
"offsets": [
[
149,
155
]
],
"normalized": []
},
{
"id": "PMID-12771137_T6",
"type": "Protein",
"text": [
"integrins alpha 1"
],
"offsets": [
[
246,
263
]
],
"normalized": []
},
{
"id": "PMID-12771137_T7",
"type": "Protein",
"text": [
"beta 1"
],
"offsets": [
[
264,
270
]
],
"normalized": []
},
{
"id": "PMID-12771137_T8",
"type": "Protein",
"text": [
"alpha 2"
],
"offsets": [
[
275,
282
]
],
"normalized": []
},
{
"id": "PMID-12771137_T9",
"type": "Protein",
"text": [
"beta 1"
],
"offsets": [
[
283,
289
]
],
"normalized": []
},
{
"id": "PMID-12771137_T10",
"type": "Protein",
"text": [
"integrin alpha 2"
],
"offsets": [
[
325,
341
]
],
"normalized": []
},
{
"id": "PMID-12771137_T11",
"type": "Protein",
"text": [
"beta 1"
],
"offsets": [
[
342,
348
]
],
"normalized": []
},
{
"id": "PMID-12771137_T12",
"type": "Protein",
"text": [
"platelet receptor glycoprotein VI"
],
"offsets": [
[
357,
390
]
],
"normalized": []
},
{
"id": "PMID-12771137_T13",
"type": "Protein",
"text": [
"alpha 2"
],
"offsets": [
[
724,
731
]
],
"normalized": []
},
{
"id": "PMID-12771137_T14",
"type": "Protein",
"text": [
"beta 1"
],
"offsets": [
[
732,
738
]
],
"normalized": []
},
{
"id": "PMID-12771137_T15",
"type": "Protein",
"text": [
"alpha 1"
],
"offsets": [
[
747,
754
]
],
"normalized": []
},
{
"id": "PMID-12771137_T16",
"type": "Protein",
"text": [
"beta 1"
],
"offsets": [
[
755,
761
]
],
"normalized": []
},
{
"id": "PMID-12771137_T17",
"type": "Protein",
"text": [
"alpha 1"
],
"offsets": [
[
833,
840
]
],
"normalized": []
},
{
"id": "PMID-12771137_T18",
"type": "Protein",
"text": [
"beta 1"
],
"offsets": [
[
841,
847
]
],
"normalized": []
},
{
"id": "PMID-12771137_T19",
"type": "Protein",
"text": [
"alpha 2"
],
"offsets": [
[
1048,
1055
]
],
"normalized": []
},
{
"id": "PMID-12771137_T20",
"type": "Protein",
"text": [
"beta 1"
],
"offsets": [
[
1056,
1062
]
],
"normalized": []
},
{
"id": "PMID-12771137_T21",
"type": "Protein",
"text": [
"platelet glycoprotein VI"
],
"offsets": [
[
1316,
1340
]
],
"normalized": []
},
{
"id": "PMID-12771137_T22",
"type": "Protein",
"text": [
"alpha 1"
],
"offsets": [
[
1357,
1364
]
],
"normalized": []
},
{
"id": "PMID-12771137_T23",
"type": "Protein",
"text": [
"beta 1"
],
"offsets": [
[
1365,
1371
]
],
"normalized": []
}
] | [] | [] | [] |
95 | PMID-12795616 | [
{
"id": "PMID-12795616__text",
"type": "abstract",
"text": [
"Mechanism, mutagenesis, and chemical rescue of a beta-mannosidase from cellulomonas fimi. \nThe chemical mechanism of a retaining beta-mannosidase from Cellulomonas fimi has been characterized through steady-state kinetic analyses with a range of substrates, coupled with chemical rescue studies on both the wild-type enzyme and mutants in which active site carboxyl groups have been replaced. Studies with a series of aryl beta-mannosides of vastly different reactivities (pK(a)(lg) = 4-10) allowed kinetic isolation of the glycosylation and deglycosylation steps. Substrate inhibition was observed for all but the least reactive of these substrates. Bronsted analysis of k(cat) revealed a downward breaking plot (beta(lg) = -0.54 +/- 0.05) that is consistent with a change in rate-determining step (glycosylation to deglycosylation), and this was confirmed by partitioning studies with ethylene glycol. The pH dependence of k(cat)/K(m) follows an apparent single ionization of a group of pK(a) = 7.65 that must be protonated for catalysis. The tentative assignment of E429 as the acid-base catalyst of Man2A on the basis of sequence alignments with other family 2 glycosidases was confirmed by the increased turnover rate observed for the mutant E429A in the presence of azide and fluoride, leading to the production of beta-mannosyl azide and beta-mannosyl fluoride, respectively. A pH-dependent chemical rescue of E429A activity is also observed with citrate. Substantial oxocarbenium ion character at the transition state was demonstrated by the alpha-deuterium kinetic isotope effect for Man2A E429A of alpha-D(V) = 1.12 +/- 0.01. Surprisingly, this isotope effect was substantially greater in the presence of azide (alpha-D(V) = 1.166 +/- 0.009). Likely involvement of acid/base catalysis was revealed by the pH dependence of k(cat) for Man2A E429A, which follows a bell-shaped profile described by pK(a) values of 6.1 and 8.4, substantially different from that of the wild-type enzyme. The glycosidic bond cleaving activity of Man2A E519A and E519S nucleophile mutants is restored with azide and fluoride and appears to correlate with the corresponding \"glycosynthase\" activities. The contribution of the substrate 2-hydroxyl to stabilization of the Man2A glycosylation transition state (DeltaDeltaG() = 5.1 kcal mol(-1)) was probed using a 2-deoxymannose substrate. This value, surprisingly, is comparable to that found from equivalent studies with beta-glucosidases despite the geometric differences at C-2 and the importance of hydrogen bonding at that position. Modes of stabilizing the mannosidase transition state are discussed.\n"
],
"offsets": [
[
0,
2642
]
]
}
] | [
{
"id": "PMID-12795616_T1",
"type": "Protein",
"text": [
"beta-mannosidase"
],
"offsets": [
[
49,
65
]
],
"normalized": []
},
{
"id": "PMID-12795616_T2",
"type": "Protein",
"text": [
"beta-mannosidase"
],
"offsets": [
[
129,
145
]
],
"normalized": []
},
{
"id": "PMID-12795616_T3",
"type": "Protein",
"text": [
"Man2A"
],
"offsets": [
[
1103,
1108
]
],
"normalized": []
},
{
"id": "PMID-12795616_T4",
"type": "Protein",
"text": [
"Man2A"
],
"offsets": [
[
1593,
1598
]
],
"normalized": []
},
{
"id": "PMID-12795616_T5",
"type": "Protein",
"text": [
"Man2A"
],
"offsets": [
[
1843,
1848
]
],
"normalized": []
},
{
"id": "PMID-12795616_T6",
"type": "Protein",
"text": [
"Man2A"
],
"offsets": [
[
2034,
2039
]
],
"normalized": []
},
{
"id": "PMID-12795616_T7",
"type": "Protein",
"text": [
"Man2A"
],
"offsets": [
[
2257,
2262
]
],
"normalized": []
}
] | [] | [] | [] |
96 | PMID-12871464 | [
{
"id": "PMID-12871464__text",
"type": "abstract",
"text": [
"Occurrence of O-linked Xyl-GlcNAc and Xyl-Glc disaccharides in trocarin, a factor Xa homolog from snake venom. \nTrocarin is a 46515-Da group D prothrombin-activating glycoprotein from the venom of the Australian elapid, Tropidechis carinatus. Amino acid sequencing and functional characterization of trocarin demonstrated that it is a structural and functional homolog of mammalian blood coagulation factor (F)Xa. In this study we show that, in contrast to mammalian Xa, which is not glycosylated, trocarin contains an O-linked carbohydrate moiety in its light chain and an N-linked carbohydrate oligosaccharide in its heavy chain. Mass spectrometry and sugar compositional analysis indicate that the O-linked carbohydrate moiety is a mixture of Xyl-GlcNAc-, GlcNAc-, Xyl-Glc- and Glc- structures linked to Ser 52. The N-linked carbohydrate on Asn 45 of the heavy chain is a sialylated, diantennary oligosaccharide that is located at the lip of the active site of the prothrombin activator.\n"
],
"offsets": [
[
0,
991
]
]
}
] | [
{
"id": "PMID-12871464_T1",
"type": "Protein",
"text": [
"trocarin"
],
"offsets": [
[
63,
71
]
],
"normalized": []
},
{
"id": "PMID-12871464_T2",
"type": "Protein",
"text": [
"factor Xa"
],
"offsets": [
[
75,
84
]
],
"normalized": []
},
{
"id": "PMID-12871464_T3",
"type": "Protein",
"text": [
"Trocarin"
],
"offsets": [
[
112,
120
]
],
"normalized": []
},
{
"id": "PMID-12871464_T4",
"type": "Protein",
"text": [
"prothrombin"
],
"offsets": [
[
143,
154
]
],
"normalized": []
},
{
"id": "PMID-12871464_T5",
"type": "Protein",
"text": [
"trocarin"
],
"offsets": [
[
300,
308
]
],
"normalized": []
},
{
"id": "PMID-12871464_T6",
"type": "Protein",
"text": [
"coagulation factor (F)Xa"
],
"offsets": [
[
388,
412
]
],
"normalized": []
},
{
"id": "PMID-12871464_T7",
"type": "Protein",
"text": [
"Xa"
],
"offsets": [
[
467,
469
]
],
"normalized": []
},
{
"id": "PMID-12871464_T8",
"type": "Protein",
"text": [
"trocarin"
],
"offsets": [
[
498,
506
]
],
"normalized": []
},
{
"id": "PMID-12871464_T9",
"type": "Protein",
"text": [
"prothrombin"
],
"offsets": [
[
968,
979
]
],
"normalized": []
},
{
"id": "PMID-12871464_T11",
"type": "Entity",
"text": [
"Xyl-GlcNAc"
],
"offsets": [
[
23,
33
]
],
"normalized": []
},
{
"id": "PMID-12871464_T12",
"type": "Entity",
"text": [
"Xyl-Glc"
],
"offsets": [
[
38,
45
]
],
"normalized": []
},
{
"id": "PMID-12871464_T15",
"type": "Entity",
"text": [
"carbohydrate moiety"
],
"offsets": [
[
528,
547
]
],
"normalized": []
},
{
"id": "PMID-12871464_T16",
"type": "Entity",
"text": [
"light chain"
],
"offsets": [
[
555,
566
]
],
"normalized": []
},
{
"id": "PMID-12871464_T18",
"type": "Entity",
"text": [
"carbohydrate oligosaccharide"
],
"offsets": [
[
583,
611
]
],
"normalized": []
},
{
"id": "PMID-12871464_T19",
"type": "Entity",
"text": [
"heavy chain"
],
"offsets": [
[
619,
630
]
],
"normalized": []
},
{
"id": "PMID-12871464_T21",
"type": "Entity",
"text": [
"Xyl-GlcNAc-"
],
"offsets": [
[
746,
757
]
],
"normalized": []
},
{
"id": "PMID-12871464_T22",
"type": "Entity",
"text": [
"GlcNAc-"
],
"offsets": [
[
759,
766
]
],
"normalized": []
},
{
"id": "PMID-12871464_T23",
"type": "Entity",
"text": [
"Xyl-Glc-"
],
"offsets": [
[
768,
776
]
],
"normalized": []
},
{
"id": "PMID-12871464_T24",
"type": "Entity",
"text": [
"Glc-"
],
"offsets": [
[
781,
785
]
],
"normalized": []
},
{
"id": "PMID-12871464_T25",
"type": "Entity",
"text": [
"Ser 52"
],
"offsets": [
[
807,
813
]
],
"normalized": []
},
{
"id": "PMID-12871464_T27",
"type": "Entity",
"text": [
"Asn 45"
],
"offsets": [
[
844,
850
]
],
"normalized": []
},
{
"id": "PMID-12871464_T28",
"type": "Entity",
"text": [
"sialylated, diantennary oligosaccharide"
],
"offsets": [
[
875,
914
]
],
"normalized": []
}
] | [
{
"id": "PMID-12871464_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"O-linked"
],
"offsets": [
[
14,
22
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12871464_T1"
},
{
"role": "Sidechain",
"ref_id": "PMID-12871464_T11"
}
]
},
{
"id": "PMID-12871464_E2",
"type": "Glycosylation",
"trigger": {
"text": [
"O-linked"
],
"offsets": [
[
14,
22
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12871464_T1"
},
{
"role": "Sidechain",
"ref_id": "PMID-12871464_T12"
}
]
},
{
"id": "PMID-12871464_E3",
"type": "Glycosylation",
"trigger": {
"text": [
"glycosylated"
],
"offsets": [
[
484,
496
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12871464_T7"
}
]
},
{
"id": "PMID-12871464_E4",
"type": "Glycosylation",
"trigger": {
"text": [
"O-linked"
],
"offsets": [
[
519,
527
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12871464_T8"
},
{
"role": "Site",
"ref_id": "PMID-12871464_T16"
},
{
"role": "Sidechain",
"ref_id": "PMID-12871464_T15"
}
]
},
{
"id": "PMID-12871464_E5",
"type": "Glycosylation",
"trigger": {
"text": [
"N-linked"
],
"offsets": [
[
574,
582
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12871464_T8"
},
{
"role": "Site",
"ref_id": "PMID-12871464_T19"
},
{
"role": "Sidechain",
"ref_id": "PMID-12871464_T18"
}
]
},
{
"id": "PMID-12871464_E6",
"type": "Glycosylation",
"trigger": {
"text": [
"O-linked"
],
"offsets": [
[
701,
709
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12871464_T8"
},
{
"role": "Site",
"ref_id": "PMID-12871464_T25"
},
{
"role": "Sidechain",
"ref_id": "PMID-12871464_T24"
}
]
},
{
"id": "PMID-12871464_E7",
"type": "Glycosylation",
"trigger": {
"text": [
"O-linked"
],
"offsets": [
[
701,
709
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12871464_T8"
},
{
"role": "Site",
"ref_id": "PMID-12871464_T25"
},
{
"role": "Sidechain",
"ref_id": "PMID-12871464_T21"
}
]
},
{
"id": "PMID-12871464_E8",
"type": "Glycosylation",
"trigger": {
"text": [
"O-linked"
],
"offsets": [
[
701,
709
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12871464_T8"
},
{
"role": "Site",
"ref_id": "PMID-12871464_T25"
},
{
"role": "Sidechain",
"ref_id": "PMID-12871464_T22"
}
]
},
{
"id": "PMID-12871464_E9",
"type": "Glycosylation",
"trigger": {
"text": [
"O-linked"
],
"offsets": [
[
701,
709
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12871464_T8"
},
{
"role": "Site",
"ref_id": "PMID-12871464_T25"
},
{
"role": "Sidechain",
"ref_id": "PMID-12871464_T23"
}
]
},
{
"id": "PMID-12871464_E10",
"type": "Glycosylation",
"trigger": {
"text": [
"N-linked"
],
"offsets": [
[
819,
827
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12871464_T8"
},
{
"role": "Site",
"ref_id": "PMID-12871464_T27"
},
{
"role": "Sidechain",
"ref_id": "PMID-12871464_T28"
}
]
}
] | [] | [] |
97 | PMID-12871934 | [
{
"id": "PMID-12871934__text",
"type": "abstract",
"text": [
"Differential glycosylation regulates processing of lipoprotein receptors by gamma-secretase. \nThe low density lipoprotein (LDL) receptor-related protein 1 (LRP1) belongs to a growing number of cell surface proteins that undergo regulated proteolytic processing that culminates in the release of their intracellular domain (ICD) by the intramembranous protease gamma-secretase. Here we show that LRP1 is differentially glycosylated in a tissue-specific manner and that carbohydrate addition reduces proteolytic cleavage of the extracellular domain and, concomitantly, ICD release. The apolipoprotein E (apoE) receptor-2 (apoER2), another member of the LDL receptor family with functions in cellular signal transmission, also undergoes sequential proteolytic processing, resulting in intracellular domain release into the cytoplasm. The penultimate processing step also involves cleavage of the apoER2 extracellular domain. The rate at which this cleavage step occurs is determined by the glycosylation state of the receptor, which in turn is regulated by the alternative splicing of an exon encoding several O-linked sugar attachment sites. These findings suggest a role for differential and tissue-specific glycosylation as a physiological switch that modulates the diverse biological functions of these receptors in a cell-type specific manner.\n"
],
"offsets": [
[
0,
1346
]
]
}
] | [
{
"id": "PMID-12871934_T1",
"type": "Protein",
"text": [
"low density lipoprotein (LDL) receptor-related protein 1"
],
"offsets": [
[
98,
154
]
],
"normalized": []
},
{
"id": "PMID-12871934_T2",
"type": "Protein",
"text": [
"LRP1"
],
"offsets": [
[
156,
160
]
],
"normalized": []
},
{
"id": "PMID-12871934_T3",
"type": "Protein",
"text": [
"LRP1"
],
"offsets": [
[
395,
399
]
],
"normalized": []
},
{
"id": "PMID-12871934_T4",
"type": "Protein",
"text": [
"apolipoprotein E (apoE) receptor-2"
],
"offsets": [
[
584,
618
]
],
"normalized": []
},
{
"id": "PMID-12871934_T5",
"type": "Protein",
"text": [
"apoER2"
],
"offsets": [
[
620,
626
]
],
"normalized": []
},
{
"id": "PMID-12871934_T6",
"type": "Protein",
"text": [
"apoER2"
],
"offsets": [
[
893,
899
]
],
"normalized": []
}
] | [
{
"id": "PMID-12871934_E1",
"type": "Glycosylation",
"trigger": {
"text": [
"glycosylated"
],
"offsets": [
[
418,
430
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12871934_T3"
}
]
},
{
"id": "PMID-12871934_E2",
"type": "Glycosylation",
"trigger": {
"text": [
"glycosylation"
],
"offsets": [
[
987,
1000
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12871934_T6"
}
]
}
] | [
{
"id": "PMID-12871934_1",
"entity_ids": [
"PMID-12871934_T1",
"PMID-12871934_T2"
]
},
{
"id": "PMID-12871934_2",
"entity_ids": [
"PMID-12871934_T4",
"PMID-12871934_T5"
]
}
] | [] |
98 | PMID-12894892 | [
{
"id": "PMID-12894892__text",
"type": "abstract",
"text": [
"Inactivation of p16 gene in leukemia. \nTo determine the frequency of p16 gene inactivation in leukemia cells, and to evaluate their value in the prediction of their clinical outcome. Bone marrow or peripheral blood samples from 48 patients with leukemia were examined by multiplex polymerase chain reaction (MPCR) to detect p16 gene homozygous deletion, and restriction enzyme PCR to detect p16 gene methylation. p16 gene inactivation were detected in 10 of the 48 patients (20.4%). They were five patients with p16 homozygous deletion, and five patients with p16 methylation, respectively. p16 gene inactivation correlates with adverse prognosis features. The patients with p16 inactivation had poor response to chemotherapy, and had significantly shorter survival times than the patients in whom p16 gene was preserved (P<0.001). The inactivation of p16 gene play a key role in the pathogenesis and the progression of some leukemia. The detection of p16 gene is reliable prognostic factor that predict shortened survival times.\n"
],
"offsets": [
[
0,
1030
]
]
}
] | [
{
"id": "PMID-12894892_T1",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
16,
19
]
],
"normalized": []
},
{
"id": "PMID-12894892_T2",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
69,
72
]
],
"normalized": []
},
{
"id": "PMID-12894892_T3",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
324,
327
]
],
"normalized": []
},
{
"id": "PMID-12894892_T4",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
391,
394
]
],
"normalized": []
},
{
"id": "PMID-12894892_T5",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
413,
416
]
],
"normalized": []
},
{
"id": "PMID-12894892_T6",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
512,
515
]
],
"normalized": []
},
{
"id": "PMID-12894892_T7",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
560,
563
]
],
"normalized": []
},
{
"id": "PMID-12894892_T8",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
591,
594
]
],
"normalized": []
},
{
"id": "PMID-12894892_T9",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
675,
678
]
],
"normalized": []
},
{
"id": "PMID-12894892_T10",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
798,
801
]
],
"normalized": []
},
{
"id": "PMID-12894892_T11",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
852,
855
]
],
"normalized": []
},
{
"id": "PMID-12894892_T12",
"type": "Protein",
"text": [
"p16"
],
"offsets": [
[
952,
955
]
],
"normalized": []
}
] | [
{
"id": "PMID-12894892_E1",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
400,
411
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12894892_T4"
}
]
},
{
"id": "PMID-12894892_E2",
"type": "DNA_methylation",
"trigger": {
"text": [
"methylation"
],
"offsets": [
[
564,
575
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12894892_T7"
}
]
}
] | [] | [] |
99 | PMID-12897846 | [
{
"id": "PMID-12897846__text",
"type": "abstract",
"text": [
"A haploid affair: core histone transitions during spermatogenesis. \nThe process of meiosis reduces a diploid cell to four haploid gametes and is accompanied by extensive recombination. Thus, the dynamics of chromatin during meiosis are significantly different than in mitotic cells. As spermatogenesis progresses, there is a widespread reorganization of the haploid genome followed by extensive DNA compaction. It has become increasingly clear that the dynamic composition of chromatin plays a critical role in the activities of enzymes and processes that act upon it. Therefore, an analysis of the role of histone variants and modifications in these processes may shed light upon the mechanisms involved and the control of chromatin structure in general. Histone variants such as histone H3.3, H2AX, and macroH2A appear to play key roles in the various stages of spermiogenesis, in addition to the specifically modulated acetylation of histone H4 (acH4), ubiquitination of histones H2A and H2B (uH2A, uH2B), and phosphorylation of histone H3 (H3p). This review will examine recent discoveries concerning the role of histone modifications and variants during meiosis and spermatogenesis.\n"
],
"offsets": [
[
0,
1188
]
]
}
] | [
{
"id": "PMID-12897846_T1",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
23,
30
]
],
"normalized": []
},
{
"id": "PMID-12897846_T2",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
607,
614
]
],
"normalized": []
},
{
"id": "PMID-12897846_T3",
"type": "Protein",
"text": [
"Histone"
],
"offsets": [
[
756,
763
]
],
"normalized": []
},
{
"id": "PMID-12897846_T4",
"type": "Protein",
"text": [
"histone H3.3"
],
"offsets": [
[
781,
793
]
],
"normalized": []
},
{
"id": "PMID-12897846_T5",
"type": "Protein",
"text": [
"H2AX"
],
"offsets": [
[
795,
799
]
],
"normalized": []
},
{
"id": "PMID-12897846_T6",
"type": "Protein",
"text": [
"macroH2A"
],
"offsets": [
[
805,
813
]
],
"normalized": []
},
{
"id": "PMID-12897846_T7",
"type": "Protein",
"text": [
"histone H4"
],
"offsets": [
[
937,
947
]
],
"normalized": []
},
{
"id": "PMID-12897846_T8",
"type": "Protein",
"text": [
"H4"
],
"offsets": [
[
951,
953
]
],
"normalized": []
},
{
"id": "PMID-12897846_T9",
"type": "Protein",
"text": [
"histones H2A"
],
"offsets": [
[
974,
986
]
],
"normalized": []
},
{
"id": "PMID-12897846_T10",
"type": "Protein",
"text": [
"H2B"
],
"offsets": [
[
991,
994
]
],
"normalized": []
},
{
"id": "PMID-12897846_T11",
"type": "Protein",
"text": [
"H2A"
],
"offsets": [
[
997,
1000
]
],
"normalized": []
},
{
"id": "PMID-12897846_T12",
"type": "Protein",
"text": [
"H2B"
],
"offsets": [
[
1003,
1006
]
],
"normalized": []
},
{
"id": "PMID-12897846_T13",
"type": "Protein",
"text": [
"histone H3"
],
"offsets": [
[
1032,
1042
]
],
"normalized": []
},
{
"id": "PMID-12897846_T14",
"type": "Protein",
"text": [
"H3"
],
"offsets": [
[
1044,
1046
]
],
"normalized": []
},
{
"id": "PMID-12897846_T15",
"type": "Protein",
"text": [
"histone"
],
"offsets": [
[
1117,
1124
]
],
"normalized": []
}
] | [
{
"id": "PMID-12897846_E1",
"type": "Acetylation",
"trigger": {
"text": [
"acetylation"
],
"offsets": [
[
922,
933
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12897846_T7"
}
]
},
{
"id": "PMID-12897846_E2",
"type": "Ubiquitination",
"trigger": {
"text": [
"ubiquitination"
],
"offsets": [
[
956,
970
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12897846_T9"
}
]
},
{
"id": "PMID-12897846_E3",
"type": "Ubiquitination",
"trigger": {
"text": [
"ubiquitination"
],
"offsets": [
[
956,
970
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12897846_T10"
}
]
},
{
"id": "PMID-12897846_E4",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
1013,
1028
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12897846_T13"
}
]
}
] | [
{
"id": "PMID-12897846_1",
"entity_ids": [
"PMID-12897846_T7",
"PMID-12897846_T8"
]
},
{
"id": "PMID-12897846_2",
"entity_ids": [
"PMID-12897846_T9",
"PMID-12897846_T11"
]
},
{
"id": "PMID-12897846_3",
"entity_ids": [
"PMID-12897846_T10",
"PMID-12897846_T12"
]
},
{
"id": "PMID-12897846_4",
"entity_ids": [
"PMID-12897846_T13",
"PMID-12897846_T14"
]
}
] | [] |