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0
PMID-10025957
[ { "id": "PMID-10025957__text", "type": "abstract", "text": [ "UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells. Uncoupling proteins (UCPs) are a family of mitochondrial transporter proteins that have been implicated in thermoregulatory heat production and maintenance of the basal metabolic rate. We have identified and partially characterized a novel member of the human uncoupling protein family, termed uncoupling protein-4 (UCP4). Protein sequence analyses showed that UCP4 is most related to UCP3 and possesses features characteristic of mitochondrial transporter proteins. Unlike other known UCPs, UCP4 transcripts are exclusively expressed in both fetal and adult brain tissues. UCP4 maps to human chromosome 6p11.2-q12. Consistent with its potential role as an uncoupling protein, UCP4 is localized to the mitochondria and its ectopic expression in mammalian cells reduces mitochondrial membrane potential. These findings suggest that UCP4 may be involved in thermoregulatory heat production and metabolism in the brain.\n" ], "offsets": [ [ 0, 1020 ] ] } ]
[ { "id": "PMID-10025957_T1", "type": "Protein", "offsets": [ [ 0, 4 ] ], "text": [ "UCP4" ], "normalized": [] }, { "id": "PMID-10025957_T2", "type": "Tissue", "offsets": [ [ 14, 19 ] ], "text": [ "brain" ], "normalized": [] }, { "id": "PMID-10025957_T3", "type": "CellComponent", "offsets": [ [ 29, 42 ] ], "text": [ "mitochondrial" ], "normalized": [] }, { "id": "PMID-10025957_T4", "type": "Protein", "offsets": [ [ 43, 50 ] ], "text": [ "protein" ], "normalized": [] }, { "id": "PMID-10025957_T5", "type": "Eukaryote", "offsets": [ [ 86, 95 ] ], "text": [ "mammalian" ], "normalized": [] }, { "id": "PMID-10025957_T6", "type": "Cell", "offsets": [ [ 96, 101 ] ], "text": [ "cells" ], "normalized": [] }, { "id": "PMID-10025957_T7", "type": "Protein", "offsets": [ [ 103, 122 ] ], "text": [ "Uncoupling proteins" ], "normalized": [] }, { "id": "PMID-10025957_T8", "type": "Protein", "offsets": [ [ 124, 128 ] ], "text": [ "UCPs" ], "normalized": [] }, { "id": "PMID-10025957_T9", "type": "CellComponent", "offsets": [ [ 146, 159 ] ], "text": [ "mitochondrial" ], "normalized": [] }, { "id": "PMID-10025957_T10", "type": "Protein", "offsets": [ [ 160, 180 ] ], "text": [ "transporter proteins" ], "normalized": [] }, { "id": "PMID-10025957_T13", "type": "Eukaryote", "offsets": [ [ 357, 362 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10025957_T14", "type": "Protein", "offsets": [ [ 363, 381 ] ], "text": [ "uncoupling protein" ], "normalized": [] }, { "id": "PMID-10025957_T15", "type": "Protein", "offsets": [ [ 397, 417 ] ], "text": [ "uncoupling protein-4" ], "normalized": [] }, { "id": "PMID-10025957_T16", "type": "Protein", "offsets": [ [ 419, 423 ] ], "text": [ "UCP4" ], "normalized": [] }, { "id": "PMID-10025957_T17", "type": "Protein", "offsets": [ [ 426, 433 ] ], "text": [ "Protein" ], "normalized": [] }, { "id": "PMID-10025957_T18", "type": "Protein", "offsets": [ [ 464, 468 ] ], "text": [ "UCP4" ], "normalized": [] }, { "id": "PMID-10025957_T19", "type": "Protein", "offsets": [ [ 488, 492 ] ], "text": [ "UCP3" ], "normalized": [] }, { "id": "PMID-10025957_T20", "type": "CellComponent", "offsets": [ [ 534, 547 ] ], "text": [ "mitochondrial" ], "normalized": [] }, { "id": "PMID-10025957_T21", "type": "Protein", "offsets": [ [ 548, 568 ] ], "text": [ "transporter proteins" ], "normalized": [] }, { "id": "PMID-10025957_T22", "type": "Protein", "offsets": [ [ 589, 593 ] ], "text": [ "UCPs" ], "normalized": [] }, { "id": "PMID-10025957_T23", "type": "Protein", "offsets": [ [ 595, 599 ] ], "text": [ "UCP4" ], "normalized": [] }, { "id": "PMID-10025957_T24", "type": "Transcript", "offsets": [ [ 600, 611 ] ], "text": [ "transcripts" ], "normalized": [] }, { "id": "PMID-10025957_T26", "type": "Tissue", "offsets": [ [ 646, 651 ] ], "text": [ "fetal" ], "normalized": [] }, { "id": "PMID-10025957_T28", "type": "Protein", "offsets": [ [ 677, 681 ] ], "text": [ "UCP4" ], "normalized": [] }, { "id": "PMID-10025957_T29", "type": "Eukaryote", "offsets": [ [ 690, 695 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10025957_T30", "type": "Chromosome", "offsets": [ [ 696, 706 ] ], "text": [ "chromosome" ], "normalized": [] }, { "id": "PMID-10025957_T31", "type": "Protein", "offsets": [ [ 760, 778 ] ], "text": [ "uncoupling protein" ], "normalized": [] }, { "id": "PMID-10025957_T32", "type": "Protein", "offsets": [ [ 780, 784 ] ], "text": [ "UCP4" ], "normalized": [] }, { "id": "PMID-10025957_T33", "type": "CellComponent", "offsets": [ [ 805, 817 ] ], "text": [ "mitochondria" ], "normalized": [] }, { "id": "PMID-10025957_T35", "type": "Eukaryote", "offsets": [ [ 848, 857 ] ], "text": [ "mammalian" ], "normalized": [] }, { "id": "PMID-10025957_T36", "type": "Cell", "offsets": [ [ 858, 863 ] ], "text": [ "cells" ], "normalized": [] }, { "id": "PMID-10025957_T37", "type": "CellComponent", "offsets": [ [ 872, 885 ] ], "text": [ "mitochondrial" ], "normalized": [] }, { "id": "PMID-10025957_T38", "type": "Protein", "offsets": [ [ 934, 938 ] ], "text": [ "UCP4" ], "normalized": [] }, { "id": "PMID-10025957_T41", "type": "Tissue", "offsets": [ [ 1013, 1018 ] ], "text": [ "brain" ], "normalized": [] }, { "id": "PMID-10025957_T45", "type": "ProteinIdentification", "offsets": [ [ 296, 306 ] ], "text": [ "identified" ], "normalized": [] }, { "id": "PMID-10025957_T27", "type": "Tissue", "offsets": [ [ 656, 675 ] ], "text": [ "adult brain tissues" ], "normalized": [] } ]
[ { "id": "PMID-10025957_E1", "type": "CellularProcess", "trigger": { "text": [ "thermoregulatory heat production" ], "offsets": [ [ 210, 242 ] ] }, "arguments": [] }, { "id": "PMID-10025957_E2", "type": "MetabolicPathway", "trigger": { "text": [ "metabolic" ], "offsets": [ [ 272, 281 ] ] }, "arguments": [] }, { "id": "PMID-10025957_E3", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 628, 637 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10025957_T24" } ] }, { "id": "PMID-10025957_E4", "type": "GeneExpression", "trigger": { "text": [ "ectopic expression" ], "offsets": [ [ 826, 844 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10025957_T32" } ] }, { "id": "PMID-10025957_E5", "type": "CellularProcess", "trigger": { "text": [ "thermoregulatory heat production" ], "offsets": [ [ 958, 990 ] ] }, "arguments": [] }, { "id": "PMID-10025957_E6", "type": "MetabolicPathway", "trigger": { "text": [ "metabolism" ], "offsets": [ [ 995, 1005 ] ] }, "arguments": [] }, { "id": "PMID-10025957_E7", "type": "CellHomeostasis", "trigger": { "text": [ "membrane potential" ], "offsets": [ [ 64, 82 ] ] }, "arguments": [] }, { "id": "PMID-10025957_E8", "type": "Affecting", "trigger": { "text": [ "reduces" ], "offsets": [ [ 56, 63 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10025957_T4" }, { "role": "hasPatient", "ref_id": "PMID-10025957_E7" } ] }, { "id": "PMID-10025957_E9", "type": "Maintenance", "trigger": { "text": [ "maintenance" ], "offsets": [ [ 247, 258 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10025957_E2" } ] }, { "id": "PMID-10025957_E10", "type": "CellHomeostasis", "trigger": { "text": [ "membrane potential" ], "offsets": [ [ 886, 904 ] ] }, "arguments": [] }, { "id": "PMID-10025957_E11", "type": "Affecting", "trigger": { "text": [ "reduces" ], "offsets": [ [ 864, 871 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10025957_E4" }, { "role": "hasPatient", "ref_id": "PMID-10025957_E10" } ] } ]
[]
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1
PMID-10025962
[ { "id": "PMID-10025962__text", "type": "abstract", "text": [ "Molecular cloning and characterization of a novel angiopoietin family protein, angiopoietin-3. Using homology-based PCR, we have isolated cDNA encoding a novel member (491 amino acids) of the angiopoietin (Ang) family from human adult heart cDNA and have designated it angiopoietin-3 (Ang3). The NH2-terminal and COOH-terminal portions of Ang-3 contain the characteristic coiled-coil domain and fibrinogen-like domain that are conserved in other known Angs. Ang3 has a highly hydrophobic region at the N-terminus (approximately 21 amino acids) that is typical of a signal sequence for protein secretion. Ang3 mRNA is most abundant in adrenal gland, placenta, thyroid gland, heart and small intestine in human adult tissues. Additionally, Ang3 is a secretory protein, but is not a mitogen in endothelial cells.\n" ], "offsets": [ [ 0, 810 ] ] } ]
[ { "id": "PMID-10025962_T1", "type": "Protein", "offsets": [ [ 50, 77 ] ], "text": [ "angiopoietin family protein" ], "normalized": [] }, { "id": "PMID-10025962_T2", "type": "Protein", "offsets": [ [ 79, 93 ] ], "text": [ "angiopoietin-3" ], "normalized": [] }, { "id": "PMID-10025962_T3", "type": "DNA", "offsets": [ [ 138, 142 ] ], "text": [ "cDNA" ], "normalized": [] }, { "id": "PMID-10025962_T4", "type": "AminoAcid", "offsets": [ [ 172, 183 ] ], "text": [ "amino acids" ], "normalized": [] }, { "id": "PMID-10025962_T5", "type": "Protein", "offsets": [ [ 192, 204 ] ], "text": [ "angiopoietin" ], "normalized": [] }, { "id": "PMID-10025962_T6", "type": "Protein", "offsets": [ [ 206, 209 ] ], "text": [ "Ang" ], "normalized": [] }, { "id": "PMID-10025962_T7", "type": "Eukaryote", "offsets": [ [ 223, 228 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10025962_T8", "type": "Tissue", "offsets": [ [ 235, 240 ] ], "text": [ "heart" ], "normalized": [] }, { "id": "PMID-10025962_T9", "type": "DNA", "offsets": [ [ 241, 245 ] ], "text": [ "cDNA" ], "normalized": [] }, { "id": "PMID-10025962_T11", "type": "Protein", "offsets": [ [ 285, 289 ] ], "text": [ "Ang3" ], "normalized": [] }, { "id": "PMID-10025962_T12", "type": "Protein", "offsets": [ [ 339, 344 ] ], "text": [ "Ang-3" ], "normalized": [] }, { "id": "PMID-10025962_T13", "type": "ProteinDomain", "offsets": [ [ 372, 390 ] ], "text": [ "coiled-coil domain" ], "normalized": [] }, { "id": "PMID-10025962_T14", "type": "ProteinDomain", "offsets": [ [ 395, 417 ] ], "text": [ "fibrinogen-like domain" ], "normalized": [] }, { "id": "PMID-10025962_T15", "type": "Protein", "offsets": [ [ 452, 456 ] ], "text": [ "Angs" ], "normalized": [] }, { "id": "PMID-10025962_T16", "type": "Protein", "offsets": [ [ 458, 462 ] ], "text": [ "Ang3" ], "normalized": [] }, { "id": "PMID-10025962_T18", "type": "Protein", "offsets": [ [ 604, 608 ] ], "text": [ "Ang3" ], "normalized": [] }, { "id": "PMID-10025962_T19", "type": "MessengerRNA", "offsets": [ [ 609, 613 ] ], "text": [ "mRNA" ], "normalized": [] }, { "id": "PMID-10025962_T20", "type": "Tissue", "offsets": [ [ 634, 647 ] ], "text": [ "adrenal gland" ], "normalized": [] }, { "id": "PMID-10025962_T21", "type": "Tissue", "offsets": [ [ 649, 657 ] ], "text": [ "placenta" ], "normalized": [] }, { "id": "PMID-10025962_T22", "type": "Tissue", "offsets": [ [ 659, 672 ] ], "text": [ "thyroid gland" ], "normalized": [] }, { "id": "PMID-10025962_T23", "type": "Tissue", "offsets": [ [ 674, 679 ] ], "text": [ "heart" ], "normalized": [] }, { "id": "PMID-10025962_T24", "type": "Tissue", "offsets": [ [ 684, 699 ] ], "text": [ "small intestine" ], "normalized": [] }, { "id": "PMID-10025962_T25", "type": "Eukaryote", "offsets": [ [ 703, 708 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10025962_T26", "type": "Tissue", "offsets": [ [ 715, 722 ] ], "text": [ "tissues" ], "normalized": [] }, { "id": "PMID-10025962_T27", "type": "Protein", "offsets": [ [ 738, 742 ] ], "text": [ "Ang3" ], "normalized": [] }, { "id": "PMID-10025962_T28", "type": "Protein", "offsets": [ [ 748, 765 ] ], "text": [ "secretory protein" ], "normalized": [] }, { "id": "PMID-10025962_T29", "type": "Protein", "offsets": [ [ 780, 787 ] ], "text": [ "mitogen" ], "normalized": [] }, { "id": "PMID-10025962_T30", "type": "Cell", "offsets": [ [ 791, 808 ] ], "text": [ "endothelial cells" ], "normalized": [] }, { "id": "PMID-10025962_T31", "type": "Sequence", "offsets": [ [ 565, 580 ] ], "text": [ "signal sequence" ], "normalized": [] } ]
[ { "id": "PMID-10025962_E1", "type": "ProteinTransport", "trigger": { "text": [ "protein secretion" ], "offsets": [ [ 585, 602 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10025962_T31" } ] } ]
[]
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2
PMID-10026142
[ { "id": "PMID-10026142__text", "type": "abstract", "text": [ "Purification and identification of a novel subunit of protein serine/threonine phosphatase 4. The catalytic subunit of protein serine/threonine phosphatase 4 (PP4C) has greater than 65% amino acid identity to the catalytic subunit of protein phosphatase 2A (PP2AC). Despite this high homology, PP4 does not appear to associate with known PP2A regulatory subunits. As a first step toward characterization of PP4 holoenzymes and identification of putative PP4 regulatory subunits, PP4 was purified from bovine testis soluble extracts. PP4 existed in two complexes of approximately 270-300 and 400-450 kDa as determined by gel filtration chromatography. The smaller PP4 complex was purified by sequential phenyl-Sepharose, Source 15Q, DEAE2, and Superdex 200 gel filtration chromatographies. The final product contained two major proteins: the PP4 catalytic subunit plus a protein that migrated as a doublet of 120-125 kDa on SDS-polyacrylamide gel electrophoresis. The associated protein, termed PP4R1, and PP4C also bound to microcystin-Sepharose. Mass spectrometry analysis of the purified complex revealed two major peaks, at 35 (PP4C) and 105 kDa (PP4R1). Amino acid sequence information of several peptides derived from the 105 kDa protein was utilized to isolate a human cDNA clone. Analysis of the predicted amino acid sequence revealed 13 nonidentical repeats similar to repeats found in the A subunit of PP2A (PP2AA). The PP4R1 cDNA clone engineered with an N-terminal Myc tag was expressed in COS M6 cells and PP4C co-immunoprecipitated with Myc-tagged PP4R1. These data indicate that one form of PP4 is similar to the core complex of PP2A in that it consists of a catalytic subunit and a \"PP2AA-like\" structural subunit.\n" ], "offsets": [ [ 0, 1730 ] ] } ]
[ { "id": "PMID-10026142_T1", "type": "ProteinSubunit", "offsets": [ [ 43, 50 ] ], "text": [ "subunit" ], "normalized": [] }, { "id": "PMID-10026142_T2", "type": "Enzyme", "offsets": [ [ 54, 92 ] ], "text": [ "protein serine/threonine phosphatase 4" ], "normalized": [] }, { "id": "PMID-10026142_T3", "type": "ProteinSubunit", "offsets": [ [ 98, 115 ] ], "text": [ "catalytic subunit" ], "normalized": [] }, { "id": "PMID-10026142_T4", "type": "Enzyme", "offsets": [ [ 119, 157 ] ], "text": [ "protein serine/threonine phosphatase 4" ], "normalized": [] }, { "id": "PMID-10026142_T5", "type": "ProteinSubunit", "offsets": [ [ 159, 163 ] ], "text": [ "PP4C" ], "normalized": [] }, { "id": "PMID-10026142_T6", "type": "AminoAcid", "offsets": [ [ 186, 196 ] ], "text": [ "amino acid" ], "normalized": [] }, { "id": "PMID-10026142_T7", "type": "ProteinSubunit", "offsets": [ [ 213, 230 ] ], "text": [ "catalytic subunit" ], "normalized": [] }, { "id": "PMID-10026142_T8", "type": "Enzyme", "offsets": [ [ 234, 256 ] ], "text": [ "protein phosphatase 2A" ], "normalized": [] }, { "id": "PMID-10026142_T9", "type": "ProteinSubunit", "offsets": [ [ 258, 263 ] ], "text": [ "PP2AC" ], "normalized": [] }, { "id": "PMID-10026142_T10", "type": "Enzyme", "offsets": [ [ 294, 297 ] ], "text": [ "PP4" ], "normalized": [] }, { "id": "PMID-10026142_T11", "type": "Enzyme", "offsets": [ [ 338, 342 ] ], "text": [ "PP2A" ], "normalized": [] }, { "id": "PMID-10026142_T12", "type": "ProteinSubunit", "offsets": [ [ 343, 362 ] ], "text": [ "regulatory subunits" ], "normalized": [] }, { "id": "PMID-10026142_T13", "type": "Holoenzyme", "offsets": [ [ 407, 422 ] ], "text": [ "PP4 holoenzymes" ], "normalized": [] }, { "id": "PMID-10026142_T14", "type": "Enzyme", "offsets": [ [ 445, 457 ] ], "text": [ "putative PP4" ], "normalized": [] }, { "id": "PMID-10026142_T15", "type": "ProteinSubunit", "offsets": [ [ 458, 477 ] ], "text": [ "regulatory subunits" ], "normalized": [] }, { "id": "PMID-10026142_T16", "type": "Enzyme", "offsets": [ [ 479, 482 ] ], "text": [ "PP4" ], "normalized": [] }, { "id": "PMID-10026142_T17", "type": "Eukaryote", "offsets": [ [ 501, 507 ] ], "text": [ "bovine" ], "normalized": [] }, { "id": "PMID-10026142_T18", "type": "Tissue", "offsets": [ [ 508, 514 ] ], "text": [ "testis" ], "normalized": [] }, { "id": "PMID-10026142_T19", "type": "Enzyme", "offsets": [ [ 533, 536 ] ], "text": [ "PP4" ], "normalized": [] }, { "id": "PMID-10026142_T20", "type": "Enzyme", "offsets": [ [ 663, 674 ] ], "text": [ "PP4 complex" ], "normalized": [] }, { "id": "PMID-10026142_T21", "type": "Protein", "offsets": [ [ 827, 835 ] ], "text": [ "proteins" ], "normalized": [] }, { "id": "PMID-10026142_T22", "type": "Enzyme", "offsets": [ [ 841, 844 ] ], "text": [ "PP4" ], "normalized": [] }, { "id": "PMID-10026142_T23", "type": "ProteinSubunit", "offsets": [ [ 845, 862 ] ], "text": [ "catalytic subunit" ], "normalized": [] }, { "id": "PMID-10026142_T24", "type": "Protein", "offsets": [ [ 870, 877 ] ], "text": [ "protein" ], "normalized": [] }, { "id": "PMID-10026142_T25", "type": "Protein", "offsets": [ [ 967, 985 ] ], "text": [ "associated protein" ], "normalized": [] }, { "id": "PMID-10026142_T26", "type": "ProteinSubunit", "offsets": [ [ 994, 999 ] ], "text": [ "PP4R1" ], "normalized": [] }, { "id": "PMID-10026142_T27", "type": "ProteinSubunit", "offsets": [ [ 1005, 1009 ] ], "text": [ "PP4C" ], "normalized": [] }, { "id": "PMID-10026142_T28", "type": "ProteinComplex", "offsets": [ [ 1090, 1097 ] ], "text": [ "complex" ], "normalized": [] }, { "id": "PMID-10026142_T29", "type": "ProteinSubunit", "offsets": [ [ 1131, 1135 ] ], "text": [ "PP4C" ], "normalized": [] }, { "id": "PMID-10026142_T30", "type": "ProteinSubunit", "offsets": [ [ 1150, 1155 ] ], "text": [ "PP4R1" ], "normalized": [] }, { "id": "PMID-10026142_T31", "type": "AminoAcid", "offsets": [ [ 1158, 1168 ] ], "text": [ "Amino acid" ], "normalized": [] }, { "id": "PMID-10026142_T32", "type": "Peptide", "offsets": [ [ 1201, 1209 ] ], "text": [ "peptides" ], "normalized": [] }, { "id": "PMID-10026142_T33", "type": "Protein", "offsets": [ [ 1235, 1242 ] ], "text": [ "protein" ], "normalized": [] }, { "id": "PMID-10026142_T34", "type": "Eukaryote", "offsets": [ [ 1269, 1274 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10026142_T35", "type": "DNA", "offsets": [ [ 1275, 1279 ] ], "text": [ "cDNA" ], "normalized": [] }, { "id": "PMID-10026142_T36", "type": "AminoAcid", "offsets": [ [ 1313, 1323 ] ], "text": [ "amino acid" ], "normalized": [] }, { "id": "PMID-10026142_T38", "type": "Protein", "offsets": [ [ 1411, 1415 ] ], "text": [ "PP2A" ], "normalized": [] }, { "id": "PMID-10026142_T39", "type": "ProteinSubunit", "offsets": [ [ 1417, 1422 ] ], "text": [ "PP2AA" ], "normalized": [] }, { "id": "PMID-10026142_T40", "type": "ProteinSubunit", "offsets": [ [ 1429, 1434 ] ], "text": [ "PP4R1" ], "normalized": [] }, { "id": "PMID-10026142_T41", "type": "DNA", "offsets": [ [ 1435, 1439 ] ], "text": [ "cDNA" ], "normalized": [] }, { "id": "PMID-10026142_T44", "type": "Cell", "offsets": [ [ 1501, 1513 ] ], "text": [ "COS M6 cells" ], "normalized": [] }, { "id": "PMID-10026142_T45", "type": "Protein", "offsets": [ [ 1518, 1522 ] ], "text": [ "PP4C" ], "normalized": [] }, { "id": "PMID-10026142_T47", "type": "Protein", "offsets": [ [ 1561, 1566 ] ], "text": [ "PP4R1" ], "normalized": [] }, { "id": "PMID-10026142_T48", "type": "Enzyme", "offsets": [ [ 1605, 1608 ] ], "text": [ "PP4" ], "normalized": [] }, { "id": "PMID-10026142_T49", "type": "ProteinComplex", "offsets": [ [ 1627, 1639 ] ], "text": [ "core complex" ], "normalized": [] }, { "id": "PMID-10026142_T50", "type": "Enzyme", "offsets": [ [ 1643, 1647 ] ], "text": [ "PP2A" ], "normalized": [] }, { "id": "PMID-10026142_T53", "type": "ProteinComplex", "offsets": [ [ 552, 561 ] ], "text": [ "complexes" ], "normalized": [] }, { "id": "PMID-10026142_T37", "type": "ProteinSubunit", "offsets": [ [ 1398, 1407 ] ], "text": [ "A subunit" ], "normalized": [] }, { "id": "PMID-10026142_T42", "type": "BindingAssay", "offsets": [ [ 1465, 1483 ] ], "text": [ "N-terminal Myc tag" ], "normalized": [] }, { "id": "PMID-10026142_T46", "type": "BindingAssay", "offsets": [ [ 1523, 1544 ] ], "text": [ "co-immunoprecipitated" ], "normalized": [] }, { "id": "PMID-10026142_T54", "type": "ProteinSubunit", "offsets": [ [ 1673, 1690 ] ], "text": [ "catalytic subunit" ], "normalized": [] }, { "id": "PMID-10026142_T51", "type": "ProteinSubunit", "offsets": [ [ 1697, 1728 ] ], "text": [ "\"PP2AA-like\" structural subunit" ], "normalized": [] } ]
[ { "id": "PMID-10026142_E1", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1488, 1497 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026142_T41" } ] } ]
[]
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3
PMID-10026181
[ { "id": "PMID-10026181__text", "type": "abstract", "text": [ "Conserved residues of human XPG protein important for nuclease activity and function in nucleotide excision repair. The human XPG endonuclease cuts on the 3' side of a DNA lesion during nucleotide excision repair. Mutations in XPG can lead to the disorders xeroderma pigmentosum (XP) and Cockayne syndrome. XPG shares sequence similarities in two regions with a family of structure-specific nucleases and exonucleases. To begin defining its catalytic mechanism, we changed highly conserved residues and determined the effects on the endonuclease activity of isolated XPG, its function in open complex formation and dual incision reconstituted with purified proteins, and its ability to restore cellular resistance to UV light. The substitution A792V present in two XP complementation group G (XP-G) individuals reduced but did not abolish endonuclease activity, explaining their mild clinical phenotype. Isolated XPG proteins with Asp-77 or Glu-791 substitutions did not cleave DNA. In the reconstituted repair system, alanine substitutions at these positions permitted open complex formation but were inactive for 3' cleavage, whereas D77E and E791D proteins retained considerable activity. The function of each mutant protein in the reconstituted system was mirrored by its ability to restore UV resistance to XP-G cell lines. Hydrodynamic measurements indicated that XPG exists as a monomer in high salt conditions, but immunoprecipitation of intact and truncated XPG proteins showed that XPG polypeptides can interact with each other, suggesting dimerization as an element of XPG function. The mutation results define critical residues in the catalytic center of XPG and strongly suggest that key features of the strand cleavage mechanism and active site structure are shared by members of the nuclease family.\n" ], "offsets": [ [ 0, 1815 ] ] } ]
[ { "id": "PMID-10026181_T1", "type": "Eukaryote", "offsets": [ [ 22, 27 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10026181_T2", "type": "Enzyme", "offsets": [ [ 28, 39 ] ], "text": [ "XPG protein" ], "normalized": [] }, { "id": "PMID-10026181_T3", "type": "CatalyticActivity", "offsets": [ [ 54, 71 ] ], "text": [ "nuclease activity" ], "normalized": [] }, { "id": "PMID-10026181_T5", "type": "Eukaryote", "offsets": [ [ 120, 125 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10026181_T6", "type": "Enzyme", "offsets": [ [ 126, 142 ] ], "text": [ "XPG endonuclease" ], "normalized": [] }, { "id": "PMID-10026181_T7", "type": "DNA", "offsets": [ [ 168, 171 ] ], "text": [ "DNA" ], "normalized": [] }, { "id": "PMID-10026181_T10", "type": "Enzyme", "offsets": [ [ 227, 230 ] ], "text": [ "XPG" ], "normalized": [] }, { "id": "PMID-10026181_T13", "type": "Enzyme", "offsets": [ [ 307, 310 ] ], "text": [ "XPG" ], "normalized": [] }, { "id": "PMID-10026181_T14", "type": "Enzyme", "offsets": [ [ 391, 400 ] ], "text": [ "nucleases" ], "normalized": [] }, { "id": "PMID-10026181_T15", "type": "Enzyme", "offsets": [ [ 405, 417 ] ], "text": [ "exonucleases" ], "normalized": [] }, { "id": "PMID-10026181_T16", "type": "CatalyticActivity", "offsets": [ [ 533, 554 ] ], "text": [ "endonuclease activity" ], "normalized": [] }, { "id": "PMID-10026181_T17", "type": "Enzyme", "offsets": [ [ 558, 570 ] ], "text": [ "isolated XPG" ], "normalized": [] }, { "id": "PMID-10026181_T18", "type": "Protein", "offsets": [ [ 657, 665 ] ], "text": [ "proteins" ], "normalized": [] }, { "id": "PMID-10026181_T19", "type": "CatalyticActivity", "offsets": [ [ 839, 860 ] ], "text": [ "endonuclease activity" ], "normalized": [] }, { "id": "PMID-10026181_T20", "type": "Enzyme", "offsets": [ [ 904, 925 ] ], "text": [ "Isolated XPG proteins" ], "normalized": [] }, { "id": "PMID-10026181_T23", "type": "MutantProtein", "offsets": [ [ 1213, 1227 ] ], "text": [ "mutant protein" ], "normalized": [] }, { "id": "PMID-10026181_T24", "type": "Enzyme", "offsets": [ [ 1370, 1373 ] ], "text": [ "XPG" ], "normalized": [] }, { "id": "PMID-10026181_T25", "type": "Enzyme", "offsets": [ [ 1467, 1479 ] ], "text": [ "XPG proteins" ], "normalized": [] }, { "id": "PMID-10026181_T26", "type": "Enzyme", "offsets": [ [ 1492, 1495 ] ], "text": [ "XPG" ], "normalized": [] }, { "id": "PMID-10026181_T27", "type": "Peptide", "offsets": [ [ 1496, 1508 ] ], "text": [ "polypeptides" ], "normalized": [] }, { "id": "PMID-10026181_T29", "type": "Enzyme", "offsets": [ [ 1580, 1583 ] ], "text": [ "XPG" ], "normalized": [] }, { "id": "PMID-10026181_T31", "type": "Enzyme", "offsets": [ [ 1667, 1670 ] ], "text": [ "XPG" ], "normalized": [] }, { "id": "PMID-10026181_T33", "type": "Enzyme", "offsets": [ [ 1798, 1806 ] ], "text": [ "nuclease" ], "normalized": [] }, { "id": "PMID-10026181_T36", "type": "CatalyticActivity", "offsets": [ [ 441, 460 ] ], "text": [ "catalytic mechanism" ], "normalized": [] }, { "id": "PMID-10026181_T39", "type": "Enzyme", "offsets": [ [ 793, 797 ] ], "text": [ "XP-G" ], "normalized": [] }, { "id": "PMID-10026181_T42", "type": "Phenotype", "offsets": [ [ 893, 902 ] ], "text": [ "phenotype" ], "normalized": [] }, { "id": "PMID-10026181_T46", "type": "Cell", "offsets": [ [ 1312, 1327 ] ], "text": [ "XP-G cell lines" ], "normalized": [] }, { "id": "PMID-10026181_T48", "type": "DNA", "offsets": [ [ 1717, 1723 ] ], "text": [ "strand" ], "normalized": [] } ]
[ { "id": "PMID-10026181_E1", "type": "CellularMetabolicProcess", "trigger": { "text": [ "nucleotide excision repair" ], "offsets": [ [ 88, 114 ] ] }, "arguments": [] }, { "id": "PMID-10026181_E2", "type": "CellularMetabolicProcess", "trigger": { "text": [ "nucleotide excision repair" ], "offsets": [ [ 186, 212 ] ] }, "arguments": [] }, { "id": "PMID-10026181_E3", "type": "Mutation", "trigger": { "text": [ "Mutations" ], "offsets": [ [ 214, 223 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026181_T10" } ] }, { "id": "PMID-10026181_E5", "type": "Disease", "trigger": { "text": [ "Cockayne syndrome" ], "offsets": [ [ 288, 305 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026181_E3" } ] }, { "id": "PMID-10026181_E6", "type": "FormationOfProteinDNAComplex", "trigger": { "text": [ "open complex formation" ], "offsets": [ [ 1070, 1092 ] ] }, "arguments": [] }, { "id": "PMID-10026181_E7", "type": "Cleavage", "trigger": { "text": [ "cleavage" ], "offsets": [ [ 1118, 1126 ] ] }, "arguments": [] }, { "id": "PMID-10026181_E8", "type": "BindingToProtein", "trigger": { "text": [ "interact" ], "offsets": [ [ 1513, 1521 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026181_T27" } ] }, { "id": "PMID-10026181_E9", "type": "Mutation", "trigger": { "text": [ "mutation" ], "offsets": [ [ 1598, 1606 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026181_T31" } ] }, { "id": "PMID-10026181_E10", "type": "Cleavage", "trigger": { "text": [ "cleavage" ], "offsets": [ [ 1724, 1732 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026181_T48" } ] }, { "id": "PMID-10026181_E11", "type": "Cleavage", "trigger": { "text": [ "cuts" ], "offsets": [ [ 143, 147 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026181_T6" }, { "role": "hasPatient", "ref_id": "PMID-10026181_T7" } ] }, { "id": "PMID-10026181_E12", "type": "Disease", "trigger": { "text": [ "XP" ], "offsets": [ [ 280, 282 ] ] }, "arguments": [] }, { "id": "PMID-10026181_E13", "type": "ResponseProcess", "trigger": { "text": [ "cellular resistance to UV light" ], "offsets": [ [ 694, 725 ] ] }, "arguments": [] }, { "id": "PMID-10026181_E14", "type": "ActivationOfProcess", "trigger": { "text": [ "restore" ], "offsets": [ [ 686, 693 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026181_E13" } ] }, { "id": "PMID-10026181_E15", "type": "Decrease", "trigger": { "text": [ "reduced" ], "offsets": [ [ 811, 818 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026181_E16" }, { "role": "hasPatient", "ref_id": "PMID-10026181_T19" } ] }, { "id": "PMID-10026181_E16", "type": "Mutation", "trigger": { "text": [ "substitution A792V" ], "offsets": [ [ 731, 749 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026181_T39" } ] }, { "id": "PMID-10026181_E17", "type": "CellularMetabolicProcess", "trigger": { "text": [ "repair system" ], "offsets": [ [ 1004, 1017 ] ] }, "arguments": [] }, { "id": "PMID-10026181_E18", "type": "ActivationOfProcess", "trigger": { "text": [ "restore" ], "offsets": [ [ 1287, 1294 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026181_E19" } ] }, { "id": "PMID-10026181_E19", "type": "ResponseProcess", "trigger": { "text": [ "UV resistance" ], "offsets": [ [ 1295, 1308 ] ] }, "arguments": [] }, { "id": "PMID-10026181_E20", "type": "Dimerization", "trigger": { "text": [ "dimerization" ], "offsets": [ [ 1550, 1562 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026181_T29" } ] } ]
[]
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4
PMID-10026184
[ { "id": "PMID-10026184__text", "type": "abstract", "text": [ "Mapping the functional domains of BRCA1. Interaction of the ring finger domains of BRCA1 and BARD1. Breast cancer 1 (BRCA1) and BRCA1-associated RING domain 1 (BARD1) are multidomain proteins that interact in vivo via their N-terminal RING finger motif regions. To characterize functional aspects of the BRCA1/BARD1 interaction, we have defined the structural domains required for the interaction, as well as their oligomerization state, relative stability, and possible nucleic acid binding activity. We have found that the RING finger motifs do not themselves constitute stable structural domains but are instead part of larger domains comprising residues 1-109 of BRCA1 and residues 26-119 of BARD1. These domains exist as homodimers and preferentially form a stable heterodimer. Shorter BRCA1 RING finger constructs do not interact with BARD1 or with longer BRCA1 constructs, indicating that the heterodimeric and homodimer interactions are mediated by regions outside the canonical RING finger motif. Nucleic acid binding is a generally proposed function of RING finger domains. We show that neither the homodimers nor the heterodimer displays affinity for nucleic acids, indicating that the proposed roles of BRCA1 and BARD1 in DNA repair and/or transcriptional activation must be mediated either by other regions of the proteins or by additional cofactors.\n" ], "offsets": [ [ 0, 1364 ] ] } ]
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[]
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5
PMID-10026192
[ { "id": "PMID-10026192__text", "type": "abstract", "text": [ "Characterization of a mutant pancreatic eIF-2alpha kinase, PEK, and co-localization with somatostatin in islet delta cells. Phosphorylation of eukaryotic translation initiation factor-2alpha (eIF-2alpha) is one of the key steps where protein synthesis is regulated in response to changes in environmental conditions. The phosphorylation is carried out in part by three distinct eIF-2alpha kinases including mammalian double-stranded RNA-dependent eIF-2alpha kinase (PKR) and heme-regulated inhibitor kinase (HRI), and yeast GCN2. We report the identification and characterization of a related kinase, PEK, which shares common features with other eIF-2alpha kinases including phosphorylation of eIF-2alpha in vitro. We show that human PEK is regulated by different mechanisms than PKR or HRI. In contrast to PKR or HRI, which are dependent on autophosphorylation for their kinase activity, a point mutation that replaced the conserved Lys-614 with an alanine completely abolished the eIF-2alpha kinase activity, whereas the mutant PEK was still autophosphorylated when expressed in Sf-9 cells. Northern blot analysis indicates that PEK mRNA was predominantly expressed in pancreas, though low expression was also present in several tissues. Consistent with the high levels of mRNA in pancreas, the PEK protein was only detected in human pancreatic islets, and the kinase co-localized with somatostatin, a pancreatic delta cell-specific hormone. Thus PEK is believed to play an important role in regulating protein synthesis in the pancreatic islet, especially in islet delta cells.\n" ], "offsets": [ [ 0, 1581 ] ] } ]
[ { "id": "PMID-10026192_T2", "type": "Tissue", "offsets": [ [ 29, 39 ] ], "text": [ "pancreatic" ], "normalized": [] }, { "id": "PMID-10026192_T3", "type": "Enzyme", "offsets": [ [ 40, 57 ] ], "text": [ "eIF-2alpha kinase" ], "normalized": [] }, { "id": "PMID-10026192_T4", "type": "Enzyme", "offsets": [ [ 59, 62 ] ], "text": [ "PEK" ], "normalized": [] }, { "id": "PMID-10026192_T5", "type": "Protein", "offsets": [ [ 89, 101 ] ], "text": [ "somatostatin" ], "normalized": [] }, { "id": "PMID-10026192_T6", "type": "Cell", "offsets": [ [ 105, 122 ] ], "text": [ "islet delta cells" ], "normalized": [] }, { "id": "PMID-10026192_T8", "type": "Eukaryote", "offsets": [ [ 143, 153 ] ], "text": [ "eukaryotic" ], "normalized": [] }, { "id": "PMID-10026192_T9", "type": "TranslationFactor", "offsets": [ [ 154, 190 ] ], "text": [ "translation initiation factor-2alpha" ], "normalized": [] }, { "id": "PMID-10026192_T10", "type": "TranslationFactor", "offsets": [ [ 192, 202 ] ], "text": [ "eIF-2alpha" ], "normalized": [] }, { "id": "PMID-10026192_T14", "type": "Enzyme", "offsets": [ [ 378, 396 ] ], "text": [ "eIF-2alpha kinases" ], "normalized": [] }, { "id": "PMID-10026192_T15", "type": "Eukaryote", "offsets": [ [ 407, 416 ] ], "text": [ "mammalian" ], "normalized": [] }, { "id": "PMID-10026192_T16", "type": "RNA", "offsets": [ [ 417, 436 ] ], "text": [ "double-stranded RNA" ], "normalized": [] }, { "id": "PMID-10026192_T17", "type": "Enzyme", "offsets": [ [ 447, 464 ] ], "text": [ "eIF-2alpha kinase" ], "normalized": [] }, { "id": "PMID-10026192_T18", "type": "Enzyme", "offsets": [ [ 466, 469 ] ], "text": [ "PKR" ], "normalized": [] }, { "id": "PMID-10026192_T19", "type": "Enzyme", "offsets": [ [ 475, 506 ] ], "text": [ "heme-regulated inhibitor kinase" ], "normalized": [] }, { "id": "PMID-10026192_T20", "type": "Enzyme", "offsets": [ [ 508, 511 ] ], "text": [ "HRI" ], "normalized": [] }, { "id": "PMID-10026192_T21", "type": "Eukaryote", "offsets": [ [ 518, 523 ] ], "text": [ "yeast" ], "normalized": [] }, { "id": "PMID-10026192_T22", "type": "Enzyme", "offsets": [ [ 524, 528 ] ], "text": [ "GCN2" ], "normalized": [] }, { "id": "PMID-10026192_T23", "type": "Enzyme", "offsets": [ [ 593, 599 ] ], "text": [ "kinase" ], "normalized": [] }, { "id": "PMID-10026192_T24", "type": "Enzyme", "offsets": [ [ 601, 604 ] ], "text": [ "PEK" ], "normalized": [] }, { "id": "PMID-10026192_T25", "type": "Enzyme", "offsets": [ [ 646, 664 ] ], "text": [ "eIF-2alpha kinases" ], "normalized": [] }, { "id": "PMID-10026192_T27", "type": "TranslationFactor", "offsets": [ [ 694, 704 ] ], "text": [ "eIF-2alpha" ], "normalized": [] }, { "id": "PMID-10026192_T28", "type": "Eukaryote", "offsets": [ [ 728, 733 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10026192_T29", "type": "Enzyme", "offsets": [ [ 734, 737 ] ], "text": [ "PEK" ], "normalized": [] }, { "id": "PMID-10026192_T31", "type": "Enzyme", "offsets": [ [ 780, 783 ] ], "text": [ "PKR" ], "normalized": [] }, { "id": "PMID-10026192_T32", "type": "Enzyme", "offsets": [ [ 787, 790 ] ], "text": [ "HRI" ], "normalized": [] }, { "id": "PMID-10026192_T33", "type": "Enzyme", "offsets": [ [ 807, 810 ] ], "text": [ "PKR" ], "normalized": [] }, { "id": "PMID-10026192_T34", "type": "Enzyme", "offsets": [ [ 814, 817 ] ], "text": [ "HRI" ], "normalized": [] }, { "id": "PMID-10026192_T36", "type": "CatalyticActivity", "offsets": [ [ 872, 887 ] ], "text": [ "kinase activity" ], "normalized": [] }, { "id": "PMID-10026192_T39", "type": "TranslationFactor", "offsets": [ [ 983, 993 ] ], "text": [ "eIF-2alpha" ], "normalized": [] }, { "id": "PMID-10026192_T40", "type": "CatalyticActivity", "offsets": [ [ 994, 1009 ] ], "text": [ "kinase activity" ], "normalized": [] }, { "id": "PMID-10026192_T41", "type": "MutantProtein", "offsets": [ [ 1023, 1033 ] ], "text": [ "mutant PEK" ], "normalized": [] }, { "id": "PMID-10026192_T44", "type": "Cell", "offsets": [ [ 1081, 1091 ] ], "text": [ "Sf-9 cells" ], "normalized": [] }, { "id": "PMID-10026192_T45", "type": "Enzyme", "offsets": [ [ 1131, 1134 ] ], "text": [ "PEK" ], "normalized": [] }, { "id": "PMID-10026192_T46", "type": "MessengerRNA", "offsets": [ [ 1135, 1139 ] ], "text": [ "mRNA" ], "normalized": [] }, { "id": "PMID-10026192_T48", "type": "Tissue", "offsets": [ [ 1171, 1179 ] ], "text": [ "pancreas" ], "normalized": [] }, { "id": "PMID-10026192_T50", "type": "Tissue", "offsets": [ [ 1231, 1238 ] ], "text": [ "tissues" ], "normalized": [] }, { "id": "PMID-10026192_T51", "type": "MessengerRNA", "offsets": [ [ 1275, 1279 ] ], "text": [ "mRNA" ], "normalized": [] }, { "id": "PMID-10026192_T52", "type": "Tissue", "offsets": [ [ 1283, 1291 ] ], "text": [ "pancreas" ], "normalized": [] }, { "id": "PMID-10026192_T53", "type": "Enzyme", "offsets": [ [ 1297, 1308 ] ], "text": [ "PEK protein" ], "normalized": [] }, { "id": "PMID-10026192_T54", "type": "Eukaryote", "offsets": [ [ 1330, 1335 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10026192_T55", "type": "Tissue", "offsets": [ [ 1336, 1353 ] ], "text": [ "pancreatic islets" ], "normalized": [] }, { "id": "PMID-10026192_T56", "type": "Enzyme", "offsets": [ [ 1363, 1369 ] ], "text": [ "kinase" ], "normalized": [] }, { "id": "PMID-10026192_T57", "type": "Peptide", "offsets": [ [ 1388, 1400 ] ], "text": [ "somatostatin" ], "normalized": [] }, { "id": "PMID-10026192_T58", "type": "Tissue", "offsets": [ [ 1404, 1414 ] ], "text": [ "pancreatic" ], "normalized": [] }, { "id": "PMID-10026192_T59", "type": "Cell", "offsets": [ [ 1415, 1425 ] ], "text": [ "delta cell" ], "normalized": [] }, { "id": "PMID-10026192_T60", "type": "Chemical", "offsets": [ [ 1435, 1442 ] ], "text": [ "hormone" ], "normalized": [] }, { "id": "PMID-10026192_T61", "type": "Enzyme", "offsets": [ [ 1449, 1452 ] ], "text": [ "PEK" ], "normalized": [] }, { "id": "PMID-10026192_T64", "type": "Tissue", "offsets": [ [ 1530, 1546 ] ], "text": [ "pancreatic islet" ], "normalized": [] }, { "id": "PMID-10026192_T65", "type": "Cell", "offsets": [ [ 1562, 1579 ] ], "text": [ "islet delta cells" ], "normalized": [] }, { "id": "PMID-10026192_T1", "type": "MutantProtein", "offsets": [ [ 22, 28 ] ], "text": [ "mutant" ], "normalized": [] } ]
[ { "id": "PMID-10026192_E2", "type": "Phosphorylation", "trigger": { "text": [ "Phosphorylation" ], "offsets": [ [ 124, 139 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_T9" } ] }, { "id": "PMID-10026192_E3", "type": "ProteinBiosynthesis", "trigger": { "text": [ "protein synthesis" ], "offsets": [ [ 234, 251 ] ] }, "arguments": [] }, { "id": "PMID-10026192_E4", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 255, 264 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_E3" } ] }, { "id": "PMID-10026192_E5", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 321, 336 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026192_T14" } ] }, { "id": "PMID-10026192_E6", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 675, 690 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026192_T24" }, { "role": "hasPatient", "ref_id": "PMID-10026192_T27" } ] }, { "id": "PMID-10026192_E7", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 741, 750 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_T29" } ] }, { "id": "PMID-10026192_E8", "type": "Phosphorylation", "trigger": { "text": [ "autophosphorylation" ], "offsets": [ [ 842, 861 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_T33" } ] }, { "id": "PMID-10026192_E9", "type": "Mutation", "trigger": { "text": [ "point mutation" ], "offsets": [ [ 891, 905 ] ] }, "arguments": [] }, { "id": "PMID-10026192_E10", "type": "NegativeRegulation", "trigger": { "text": [ "abolished" ], "offsets": [ [ 969, 978 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026192_E9" }, { "role": "hasPatient", "ref_id": "PMID-10026192_T40" } ] }, { "id": "PMID-10026192_E11", "type": "Phosphorylation", "trigger": { "text": [ "autophosphorylated" ], "offsets": [ [ 1044, 1062 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_T41" } ] }, { "id": "PMID-10026192_E12", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1068, 1077 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_T41" } ] }, { "id": "PMID-10026192_E13", "type": "TranscriptionOfGene", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1158, 1167 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_T46" } ] }, { "id": "PMID-10026192_E15", "type": "RegulatoryProcess", "trigger": { "text": [ "regulating" ], "offsets": [ [ 1494, 1504 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026192_T61" }, { "role": "hasPatient", "ref_id": "PMID-10026192_E16" } ] }, { "id": "PMID-10026192_E16", "type": "ProteinBiosynthesis", "trigger": { "text": [ "protein synthesis" ], "offsets": [ [ 1505, 1522 ] ] }, "arguments": [] }, { "id": "PMID-10026192_E1", "type": "ResponseProcess", "trigger": { "text": [ "response" ], "offsets": [ [ 268, 276 ] ] }, "arguments": [] }, { "id": "PMID-10026192_E14", "type": "Decrease", "trigger": { "text": [ "low" ], "offsets": [ [ 1188, 1191 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_E17" } ] }, { "id": "PMID-10026192_E17", "type": "TranscriptionOfGene", "trigger": { "text": [ "expression" ], "offsets": [ [ 1192, 1202 ] ] }, "arguments": [] }, { "id": "PMID-10026192_E18", "type": "Increase", "trigger": { "text": [ "high levels" ], "offsets": [ [ 1260, 1271 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_T51" } ] }, { "id": "PMID-10026192_E19", "type": "Phosphorylation", "trigger": { "text": [ "autophosphorylation" ], "offsets": [ [ 842, 861 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_T34" } ] } ]
[]
[ { "arg1_id": "PMID-10026192_T3", "arg2_id": "PMID-10026192_T2", "id": "PMID-10026192_R1", "type": "locatedIn", "normalized": [] }, { "arg1_id": "PMID-10026192_T3", "arg2_id": "PMID-10026192_T6", "id": "PMID-10026192_R2", "type": "locatedIn", "normalized": [] }, { "arg1_id": "PMID-10026192_T5", "arg2_id": "PMID-10026192_T6", "id": "PMID-10026192_R3", "type": "locatedIn", "normalized": [] }, { "arg1_id": "PMID-10026192_T9", "arg2_id": "PMID-10026192_T8", "id": "PMID-10026192_R4", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10026192_T17", "arg2_id": "PMID-10026192_T15", "id": "PMID-10026192_R5", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10026192_T22", "arg2_id": "PMID-10026192_T21", "id": "PMID-10026192_R6", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10026192_T29", "arg2_id": "PMID-10026192_T28", "id": "PMID-10026192_R7", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10026192_T33", "arg2_id": "PMID-10026192_T36", "id": "PMID-10026192_R8", "type": "hasFunction", "normalized": [] }, { "arg1_id": "PMID-10026192_T34", "arg2_id": "PMID-10026192_T36", "id": "PMID-10026192_R9", "type": "hasFunction", "normalized": [] }, { "arg1_id": "PMID-10026192_T39", "arg2_id": "PMID-10026192_T40", "id": "PMID-10026192_R10", "type": "hasFunction", "normalized": [] }, { "arg1_id": "PMID-10026192_T46", "arg2_id": "PMID-10026192_T45", "id": "PMID-10026192_R12", "type": "encodes", "normalized": [] }, { "arg1_id": "PMID-10026192_T51", "arg2_id": "PMID-10026192_T52", "id": "PMID-10026192_R15", "type": "locatedIn", "normalized": [] }, { "arg1_id": "PMID-10026192_T53", "arg2_id": "PMID-10026192_T55", "id": "PMID-10026192_R16", "type": "locatedIn", "normalized": [] }, { "arg1_id": "PMID-10026192_T55", "arg2_id": "PMID-10026192_T54", "id": "PMID-10026192_R17", "type": "fromSpecies", "normalized": [] } ]
6
PMID-10026197
[ { "id": "PMID-10026197__text", "type": "abstract", "text": [ "Cell adhesion regulates the interaction between the docking protein p130(Cas) and the 14-3-3 proteins. Integrin ligand binding induces a signaling complex formation via the direct association of the docking protein p130(Cas) (Cas) with diverse molecules. We report here that the 14-3-3zeta protein interacts with Cas in the yeast two-hybrid assay. We also found that the two proteins associate in mammalian cells and that this interaction takes place in a phosphoserine-dependent manner, because treatment of Cas with a serine phosphatase greatly reduced its ability to bind 14-3-3zeta. Furthermore, the Cas-14-3-3zeta interaction was found to be regulated by integrin-mediated cell adhesion. Thus, when cells are detached from the extracellular matrix, the binding of Cas to 14-3-3zeta is greatly diminished, whereas replating the cells onto fibronectin rapidly induces the association. Consistent with these results, we found that the subcellular localization of Cas and 14-3-3 is also regulated by integrin ligand binding and that the two proteins display a significant co-localization during cell attachment to the extracellular matrix. In conclusion, our results demonstrate that 14-3-3 proteins participate in integrin-activated signaling pathways through their interaction with Cas, which, in turn, may contribute to important biological responses regulated by cell adhesion to the extracellular matrix.\n" ], "offsets": [ [ 0, 1411 ] ] } ]
[ { "id": "PMID-10026197_T6", "type": "Protein", "offsets": [ [ 86, 101 ] ], "text": [ "14-3-3 proteins" ], "normalized": [] }, { "id": "PMID-10026197_T7", "type": "Protein", "offsets": [ [ 103, 111 ] ], "text": [ "Integrin" ], "normalized": [] }, { "id": "PMID-10026197_T8", "type": "Ligand", "offsets": [ [ 112, 118 ] ], "text": [ "ligand" ], "normalized": [] }, { "id": "PMID-10026197_T14", "type": "Protein", "offsets": [ [ 226, 229 ] ], "text": [ "Cas" ], "normalized": [] }, { "id": "PMID-10026197_T15", "type": "Protein", "offsets": [ [ 279, 297 ] ], "text": [ "14-3-3zeta protein" ], "normalized": [] }, { "id": "PMID-10026197_T17", "type": "Protein", "offsets": [ [ 313, 316 ] ], "text": [ "Cas" ], "normalized": [] }, { "id": "PMID-10026197_T18", "type": "Protein", "offsets": [ [ 375, 383 ] ], "text": [ "proteins" ], "normalized": [] }, { "id": "PMID-10026197_T19", "type": "Eukaryote", "offsets": [ [ 397, 406 ] ], "text": [ "mammalian" ], "normalized": [] }, { "id": "PMID-10026197_T20", "type": "Cell", "offsets": [ [ 407, 412 ] ], "text": [ "cells" ], "normalized": [] }, { "id": "PMID-10026197_T22", "type": "AminoAcid", "offsets": [ [ 456, 469 ] ], "text": [ "phosphoserine" ], "normalized": [] }, { "id": "PMID-10026197_T23", "type": "ExperimentalMethod", "offsets": [ [ 496, 505 ] ], "text": [ "treatment" ], "normalized": [] }, { "id": "PMID-10026197_T24", "type": "Protein", "offsets": [ [ 509, 512 ] ], "text": [ "Cas" ], "normalized": [] }, { "id": "PMID-10026197_T25", "type": "Enzyme", "offsets": [ [ 520, 538 ] ], "text": [ "serine phosphatase" ], "normalized": [] }, { "id": "PMID-10026197_T28", "type": "Protein", "offsets": [ [ 575, 585 ] ], "text": [ "14-3-3zeta" ], "normalized": [] }, { "id": "PMID-10026197_T29", "type": "Protein", "offsets": [ [ 604, 618 ] ], "text": [ "Cas-14-3-3zeta" ], "normalized": [] }, { "id": "PMID-10026197_T32", "type": "Protein", "offsets": [ [ 660, 668 ] ], "text": [ "integrin" ], "normalized": [] }, { "id": "PMID-10026197_T35", "type": "Cell", "offsets": [ [ 704, 709 ] ], "text": [ "cells" ], "normalized": [] }, { "id": "PMID-10026197_T36", "type": "CellComponent", "offsets": [ [ 732, 752 ] ], "text": [ "extracellular matrix" ], "normalized": [] }, { "id": "PMID-10026197_T38", "type": "Protein", "offsets": [ [ 769, 772 ] ], "text": [ "Cas" ], "normalized": [] }, { "id": "PMID-10026197_T39", "type": "Protein", "offsets": [ [ 776, 786 ] ], "text": [ "14-3-3zeta" ], "normalized": [] }, { "id": "PMID-10026197_T43", "type": "Protein", "offsets": [ [ 965, 968 ] ], "text": [ "Cas" ], "normalized": [] }, { "id": "PMID-10026197_T44", "type": "Protein", "offsets": [ [ 973, 979 ] ], "text": [ "14-3-3" ], "normalized": [] }, { "id": "PMID-10026197_T46", "type": "Protein", "offsets": [ [ 1001, 1009 ] ], "text": [ "integrin" ], "normalized": [] }, { "id": "PMID-10026197_T47", "type": "Ligand", "offsets": [ [ 1010, 1016 ] ], "text": [ "ligand" ], "normalized": [] }, { "id": "PMID-10026197_T49", "type": "Protein", "offsets": [ [ 1042, 1050 ] ], "text": [ "proteins" ], "normalized": [] }, { "id": "PMID-10026197_T50", "type": "CellComponent", "offsets": [ [ 1119, 1139 ] ], "text": [ "extracellular matrix" ], "normalized": [] }, { "id": "PMID-10026197_T51", "type": "Protein", "offsets": [ [ 1185, 1200 ] ], "text": [ "14-3-3 proteins" ], "normalized": [] }, { "id": "PMID-10026197_T52", "type": "Protein", "offsets": [ [ 1216, 1224 ] ], "text": [ "integrin" ], "normalized": [] }, { "id": "PMID-10026197_T56", "type": "Protein", "offsets": [ [ 1285, 1288 ] ], "text": [ "Cas" ], "normalized": [] }, { "id": "PMID-10026197_T59", "type": "CellComponent", "offsets": [ [ 1389, 1409 ] ], "text": [ "extracellular matrix" ], "normalized": [] }, { "id": "PMID-10026197_T10", "type": "ProteinComplex", "offsets": [ [ 147, 164 ] ], "text": [ "complex formation" ], "normalized": [] }, { "id": "PMID-10026197_T4", "type": "Protein", "offsets": [ [ 52, 77 ] ], "text": [ "docking protein p130(Cas)" ], "normalized": [] } ]
[ { "id": "PMID-10026197_E1", "type": "CellAdhesion", "trigger": { "text": [ "Cell adhesion" ], "offsets": [ [ 0, 13 ] ] }, "arguments": [] }, { "id": "PMID-10026197_E2", "type": "RegulatoryProcess", "trigger": { "text": [ "regulates" ], "offsets": [ [ 14, 23 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026197_E1" }, { "role": "hasPatient", "ref_id": "PMID-10026197_E3" } ] }, { "id": "PMID-10026197_E3", "type": "BindingToProtein", "trigger": { "text": [ "interaction" ], "offsets": [ [ 28, 39 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T6" }, { "role": "hasPatient2", "ref_id": "PMID-10026197_T4" } ] }, { "id": "PMID-10026197_E4", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 119, 126 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T8" } ] }, { "id": "PMID-10026197_E6", "type": "BindingToProtein", "trigger": { "text": [ "interacts" ], "offsets": [ [ 298, 307 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T17" }, { "role": "hasPatient2", "ref_id": "PMID-10026197_T15" } ] }, { "id": "PMID-10026197_E7", "type": "BindingToProtein", "trigger": { "text": [ "interaction" ], "offsets": [ [ 427, 438 ] ] }, "arguments": [] }, { "id": "PMID-10026197_E8", "type": "Decrease", "trigger": { "text": [ "reduced" ], "offsets": [ [ 547, 554 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026197_T23" }, { "role": "hasPatient", "ref_id": "PMID-10026197_E9" } ] }, { "id": "PMID-10026197_E9", "type": "BindingToProtein", "trigger": { "text": [ "bind" ], "offsets": [ [ 570, 574 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T28" }, { "role": "hasPatient2", "ref_id": "PMID-10026197_T24" } ] }, { "id": "PMID-10026197_E10", "type": "BindingToProtein", "trigger": { "text": [ "interaction" ], "offsets": [ [ 619, 630 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T29" } ] }, { "id": "PMID-10026197_E11", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 647, 656 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026197_E13" }, { "role": "hasPatient", "ref_id": "PMID-10026197_E10" } ] }, { "id": "PMID-10026197_E12", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 669, 677 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026197_T32" }, { "role": "hasPatient", "ref_id": "PMID-10026197_E13" } ] }, { "id": "PMID-10026197_E13", "type": "CellAdhesion", "trigger": { "text": [ "cell adhesion" ], "offsets": [ [ 678, 691 ] ] }, "arguments": [] }, { "id": "PMID-10026197_E14", "type": "BindingToProtein", "trigger": { "text": [ "binding" ], "offsets": [ [ 758, 765 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T39" }, { "role": "hasPatient2", "ref_id": "PMID-10026197_T38" } ] }, { "id": "PMID-10026197_E15", "type": "NegativeRegulation", "trigger": { "text": [ "diminished" ], "offsets": [ [ 798, 808 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_E14" } ] }, { "id": "PMID-10026197_E16", "type": "Increase", "trigger": { "text": [ "induces" ], "offsets": [ [ 863, 870 ] ] }, "arguments": [] }, { "id": "PMID-10026197_E17", "type": "Localization", "trigger": { "text": [ "subcellular localization" ], "offsets": [ [ 937, 961 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T43" } ] }, { "id": "PMID-10026197_E18", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 988, 997 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026197_E19" }, { "role": "hasPatient", "ref_id": "PMID-10026197_E17" } ] }, { "id": "PMID-10026197_E19", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1017, 1024 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T47" } ] }, { "id": "PMID-10026197_E20", "type": "PositiveRegulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1225, 1234 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026197_T52" }, { "role": "hasPatient", "ref_id": "PMID-10026197_E21" } ] }, { "id": "PMID-10026197_E21", "type": "SignalingPathway", "trigger": { "text": [ "signaling pathways" ], "offsets": [ [ 1235, 1253 ] ] }, "arguments": [] }, { "id": "PMID-10026197_E22", "type": "BindingToProtein", "trigger": { "text": [ "interaction" ], "offsets": [ [ 1268, 1279 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T56" }, { "role": "hasPatient2", "ref_id": "PMID-10026197_T51" } ] }, { "id": "PMID-10026197_E23", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 1355, 1364 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026197_E24" } ] }, { "id": "PMID-10026197_E24", "type": "CellAdhesion", "trigger": { "text": [ "cell adhesion" ], "offsets": [ [ 1368, 1381 ] ] }, "arguments": [] }, { "id": "PMID-10026197_E5", "type": "SignalingPathway", "trigger": { "text": [ "signaling" ], "offsets": [ [ 137, 146 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026197_E4" } ] }, { "id": "PMID-10026197_E25", "type": "BindingToProtein", "trigger": { "text": [ "direct association" ], "offsets": [ [ 173, 191 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T14" } ] }, { "id": "PMID-10026197_E26", "type": "BindingToProtein", "trigger": { "text": [ "associate" ], "offsets": [ [ 384, 393 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T18" } ] }, { "id": "PMID-10026197_E27", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 1076, 1088 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T49" } ] }, { "id": "PMID-10026197_E28", "type": "CellAdhesion", "trigger": { "text": [ "cell attachment" ], "offsets": [ [ 1096, 1111 ] ] }, "arguments": [] }, { "id": "PMID-10026197_E29", "type": "Localization", "trigger": { "text": [ "subcellular localization" ], "offsets": [ [ 937, 961 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T44" } ] }, { "id": "PMID-10026197_E30", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 988, 997 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026197_E19" }, { "role": "hasPatient", "ref_id": "PMID-10026197_E29" } ] } ]
[]
[ { "arg1_id": "PMID-10026197_T20", "arg2_id": "PMID-10026197_T19", "id": "PMID-10026197_R3", "type": "fromSpecies", "normalized": [] } ]
7
PMID-10026210
[ { "id": "PMID-10026210__text", "type": "abstract", "text": [ "A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho. Small GTP-binding proteins of the Rho family play a critical role in signal transduction. However, there is still very limited information on how they are activated by cell surface receptors. Here, we used a consensus sequence for Dbl domains of Rho guanine nucleotide exchange factors (GEFs) to search DNA data bases, and identified a novel human GEF for Rho-related GTPases harboring structural features indicative of its possible regulatory mechanism(s). This protein contained a tandem DH/PH domain closely related to those of Rho-specific GEFs, a PDZ domain, a proline-rich domain, and an area of homology to Lsc, p115-RhoGEF, and a Drosophila RhoGEF that was termed Lsc-homology (LH) domain. This novel molecule, designated PDZ-RhoGEF, activated biological and biochemical pathways specific for Rho, and activation of these pathways required an intact DH and PH domain. However, the PDZ domain was dispensable for these functions, and mutants lacking the LH domain were more active, suggesting a negative regulatory role for the LH domain. A search for additional molecules exhibiting an LH domain revealed a limited homology with the catalytic region of a newly identified GTPase-activating protein for heterotrimeric G proteins, RGS14. This prompted us to investigate whether PDZ-RhoGEF could interact with representative members of each G protein family. We found that PDZ-RhoGEF was able to form, in vivo, stable complexes with two members of the Galpha12 family, Galpha12 and Galpha13, and that this interaction was mediated by the LH domain. Furthermore, we obtained evidence to suggest that PDZ-RhoGEF mediates the activation of Rho by Galpha12 and Galpha13. Together, these findings suggest the existence of a novel mechanism whereby the large family of cell surface receptors that transmit signals through heterotrimeric G proteins activate Rho-dependent pathways: by stimulating the activity of members of the Galpha12 family which, in turn, activate an exchange factor acting on Rho.\n" ], "offsets": [ [ 0, 2106 ] ] } ]
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factors" ], "normalized": [] }, { "id": "PMID-10026210_T16", "type": "Protein", "offsets": [ [ 392, 396 ] ], "text": [ "GEFs" ], "normalized": [] }, { "id": "PMID-10026210_T17", "type": "DNA", "offsets": [ [ 408, 411 ] ], "text": [ "DNA" ], "normalized": [] }, { "id": "PMID-10026210_T18", "type": "Eukaryote", "offsets": [ [ 447, 452 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10026210_T19", "type": "Protein", "offsets": [ [ 453, 456 ] ], "text": [ "GEF" ], "normalized": [] }, { "id": "PMID-10026210_T20", "type": "Protein", "offsets": [ [ 461, 464 ] ], "text": [ "Rho" ], "normalized": [] }, { "id": "PMID-10026210_T21", "type": "Enzyme", "offsets": [ [ 473, 480 ] ], "text": [ "GTPases" ], "normalized": [] }, { "id": "PMID-10026210_T22", "type": "Protein", "offsets": [ [ 568, 575 ] ], "text": [ "protein" ], "normalized": [] }, { "id": "PMID-10026210_T23", "type": "ProteinDomain", "offsets": [ [ 595, 607 ] ], "text": [ "DH/PH domain" ], "normalized": [] }, { "id": "PMID-10026210_T24", "type": "Protein", "offsets": [ [ 636, 639 ] ], "text": [ "Rho" ], "normalized": [] }, { "id": "PMID-10026210_T25", "type": "Protein", "offsets": [ [ 649, 653 ] ], "text": [ "GEFs" ], "normalized": [] }, { "id": "PMID-10026210_T26", "type": "ProteinDomain", "offsets": [ [ 657, 667 ] ], "text": [ "PDZ domain" ], "normalized": [] }, { "id": "PMID-10026210_T27", "type": "ProteinDomain", "offsets": [ [ 671, 690 ] ], "text": [ "proline-rich domain" ], "normalized": [] }, { "id": "PMID-10026210_T28", "type": "Protein", "offsets": [ [ 719, 722 ] ], "text": [ "Lsc" ], "normalized": [] }, { "id": "PMID-10026210_T29", "type": "Protein", "offsets": [ [ 724, 735 ] ], "text": [ "p115-RhoGEF" ], "normalized": [] }, { "id": "PMID-10026210_T30", "type": "Eukaryote", "offsets": [ [ 743, 753 ] ], "text": [ "Drosophila" ], "normalized": [] }, { "id": "PMID-10026210_T31", "type": "Protein", "offsets": [ [ 754, 760 ] ], "text": [ "RhoGEF" ], "normalized": [] }, { "id": "PMID-10026210_T32", "type": "ProteinDomain", "offsets": [ [ 791, 793 ] ], "text": [ "LH" ], "normalized": [] }, { "id": "PMID-10026210_T33", "type": "Protein", "offsets": [ [ 835, 845 ] ], "text": [ "PDZ-RhoGEF" ], "normalized": [] }, { "id": "PMID-10026210_T35", "type": "Protein", "offsets": [ [ 906, 909 ] ], "text": [ "Rho" ], "normalized": [] }, { "id": "PMID-10026210_T37", "type": "ProteinDomain", "offsets": [ [ 963, 965 ] ], "text": [ "DH" ], "normalized": [] }, { "id": "PMID-10026210_T38", "type": "ProteinDomain", "offsets": [ [ 970, 979 ] ], "text": [ "PH domain" ], "normalized": [] }, { "id": "PMID-10026210_T39", "type": "ProteinDomain", "offsets": [ [ 994, 1004 ] ], "text": [ "PDZ domain" ], "normalized": [] }, { "id": "PMID-10026210_T40", "type": "MutantProtein", "offsets": [ [ 1046, 1053 ] ], "text": [ "mutants" ], "normalized": [] }, { "id": "PMID-10026210_T41", "type": "ProteinDomain", "offsets": [ [ 1066, 1075 ] ], "text": [ "LH domain" ], "normalized": [] }, { "id": "PMID-10026210_T44", "type": "ProteinDomain", "offsets": [ [ 1140, 1149 ] ], "text": [ "LH domain" ], "normalized": [] }, { "id": "PMID-10026210_T45", "type": "ProteinDomain", "offsets": [ [ 1199, 1208 ] ], "text": [ "LH domain" ], "normalized": [] }, { "id": "PMID-10026210_T49", "type": "Protein", "offsets": [ [ 1315, 1340 ] ], "text": [ "heterotrimeric G proteins" ], "normalized": [] }, { "id": "PMID-10026210_T50", "type": "Protein", "offsets": [ [ 1342, 1347 ] ], "text": [ "RGS14" ], "normalized": [] }, { "id": "PMID-10026210_T51", "type": "Protein", "offsets": [ [ 1389, 1399 ] ], "text": [ "PDZ-RhoGEF" ], "normalized": [] }, { "id": "PMID-10026210_T53", "type": "Protein", "offsets": [ [ 1451, 1460 ] ], "text": [ "G protein" ], "normalized": [] }, { "id": "PMID-10026210_T54", "type": "Protein", "offsets": [ [ 1483, 1493 ] ], "text": [ "PDZ-RhoGEF" ], "normalized": [] }, { "id": "PMID-10026210_T55", "type": "Protein", "offsets": [ [ 1562, 1570 ] ], "text": [ "Galpha12" ], "normalized": [] }, { "id": "PMID-10026210_T56", "type": "Protein", "offsets": [ [ 1579, 1587 ] ], "text": [ "Galpha12" ], "normalized": [] }, { "id": "PMID-10026210_T57", "type": "Protein", "offsets": [ [ 1592, 1600 ] ], "text": [ "Galpha13" ], "normalized": [] }, { "id": "PMID-10026210_T60", "type": "ProteinDomain", "offsets": [ [ 1648, 1657 ] ], "text": [ "LH domain" ], "normalized": [] }, { "id": "PMID-10026210_T61", "type": "Protein", "offsets": [ [ 1709, 1719 ] ], "text": [ "PDZ-RhoGEF" ], "normalized": [] }, { "id": "PMID-10026210_T64", "type": "Protein", "offsets": [ [ 1747, 1750 ] ], "text": [ "Rho" ], "normalized": [] }, { "id": "PMID-10026210_T65", "type": "Protein", "offsets": [ [ 1754, 1762 ] ], "text": [ "Galpha12" ], "normalized": [] }, { "id": "PMID-10026210_T66", "type": "Protein", "offsets": [ [ 1767, 1775 ] ], "text": [ "Galpha13" ], "normalized": [] }, { "id": "PMID-10026210_T67", "type": "CellComponent", "offsets": [ [ 1873, 1885 ] ], "text": [ "cell surface" ], "normalized": [] }, { "id": "PMID-10026210_T68", "type": "Protein", "offsets": [ [ 1886, 1895 ] ], "text": [ "receptors" ], "normalized": [] }, { "id": "PMID-10026210_T69", "type": "Protein", "offsets": [ [ 1926, 1951 ] ], "text": [ "heterotrimeric G proteins" ], "normalized": [] }, { "id": "PMID-10026210_T73", "type": "Protein", "offsets": [ [ 2031, 2039 ] ], "text": [ "Galpha12" ], "normalized": [] }, { "id": "PMID-10026210_T76", "type": "Protein", "offsets": [ [ 2101, 2104 ] ], "text": [ "Rho" ], "normalized": [] }, { "id": "PMID-10026210_T2", "type": "Protein", "offsets": [ [ 30, 64 ] ], "text": [ "guanine nucleotide exchange factor" ], "normalized": [] }, { "id": "PMID-10026210_T3", "type": "Protein", "offsets": [ [ 105, 131 ] ], "text": [ "Small GTP-binding proteins" ], "normalized": [] }, { "id": "PMID-10026210_T6", "type": "ProteinDomain", "offsets": [ [ 699, 703 ] ], "text": [ "area" ], "normalized": [] }, { "id": "PMID-10026210_T43", "type": "Protein", "offsets": [ [ 1285, 1310 ] ], "text": [ "GTPase-activating protein" ], "normalized": [] }, { "id": "PMID-10026210_T46", "type": "ProteinComplex", "offsets": [ [ 1528, 1537 ] ], "text": [ "complexes" ], "normalized": [] }, { "id": "PMID-10026210_T71", "type": "Protein", "offsets": [ [ 2075, 2090 ] ], "text": [ "exchange factor" ], "normalized": [] } ]
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[]
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8
PMID-10026212
[ { "id": "PMID-10026212__text", "type": "abstract", "text": [ "Human geranylgeranyl diphosphate synthase. cDNA cloning and expression. Geranylgeranyl diphosphate (GGPP) synthase (GGPPSase) catalyzes the synthesis of GGPP, which is an important molecule responsible for the C20-prenylated protein biosynthesis and for the regulation of a nuclear hormone receptor (LXR.RXR). The human GGPPSase cDNA encodes a protein of 300 amino acids which shows 16% sequence identity with the known human farnesyl diphosphate (FPP) synthase (FPPSase). The GGPPSase expressed in Escherichia coli catalyzes the GGPP formation (240 nmol/min/mg) from FPP and isopentenyl diphosphate. The human GGPPSase behaves as an oligomeric molecule with 280 kDa on a gel filtration column and cross-reacts with an antibody directed against bovine brain GGPPSase, which differs immunochemically from bovine brain FPPSase. Northern blot analysis indicates the presence of two forms of the mRNA.\n" ], "offsets": [ [ 0, 898 ] ] } ]
[ { "id": "PMID-10026212_T1", "type": "Eukaryote", "offsets": [ [ 0, 5 ] ], "text": [ "Human" ], "normalized": [] }, { "id": "PMID-10026212_T2", "type": "Enzyme", "offsets": [ [ 6, 41 ] ], "text": [ "geranylgeranyl diphosphate synthase" ], "normalized": [] }, { "id": "PMID-10026212_T3", "type": "DNA", "offsets": [ [ 43, 47 ] ], "text": [ "cDNA" ], "normalized": [] }, { "id": "PMID-10026212_T8", "type": "Enzyme", "offsets": [ [ 116, 124 ] ], "text": [ "GGPPSase" ], "normalized": [] }, { "id": "PMID-10026212_T10", "type": "Chemical", "offsets": [ [ 153, 157 ] ], "text": [ "GGPP" ], "normalized": [] }, { "id": "PMID-10026212_T11", "type": "Protein", "offsets": [ [ 210, 232 ] ], "text": [ "C20-prenylated protein" ], "normalized": [] }, { "id": "PMID-10026212_T14", "type": "CellComponent", "offsets": [ [ 274, 281 ] ], "text": [ "nuclear" ], "normalized": [] }, { "id": "PMID-10026212_T15", "type": "Protein", "offsets": [ [ 282, 298 ] ], "text": [ "hormone receptor" ], "normalized": [] }, { "id": "PMID-10026212_T16", "type": "Eukaryote", "offsets": [ [ 314, 319 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10026212_T17", "type": "Enzyme", "offsets": [ [ 320, 328 ] ], "text": [ "GGPPSase" ], "normalized": [] }, { "id": "PMID-10026212_T18", "type": "DNA", "offsets": [ [ 329, 333 ] ], "text": [ "cDNA" ], "normalized": [] }, { "id": "PMID-10026212_T19", "type": "Protein", "offsets": [ [ 344, 351 ] ], "text": [ "protein" ], "normalized": [] }, { "id": "PMID-10026212_T20", "type": "AminoAcid", "offsets": [ [ 359, 370 ] ], "text": [ "amino acids" ], "normalized": [] }, { "id": "PMID-10026212_T21", "type": "Eukaryote", "offsets": [ [ 420, 425 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10026212_T25", "type": "Enzyme", "offsets": [ [ 463, 470 ] ], "text": [ "FPPSase" ], "normalized": [] }, { "id": "PMID-10026212_T26", "type": "Enzyme", "offsets": [ [ 477, 485 ] ], "text": [ "GGPPSase" ], "normalized": [] }, { "id": "PMID-10026212_T28", "type": "Eukaryote", "offsets": [ [ 499, 515 ] ], "text": [ "Escherichia coli" ], "normalized": [] }, { "id": "PMID-10026212_T29", "type": "Chemical", "offsets": [ [ 530, 534 ] ], "text": [ "GGPP" ], "normalized": [] }, { "id": "PMID-10026212_T30", "type": "Chemical", "offsets": [ [ 568, 571 ] ], "text": [ "FPP" ], "normalized": [] }, { "id": "PMID-10026212_T31", "type": "Chemical", "offsets": [ [ 576, 599 ] ], "text": [ "isopentenyl diphosphate" ], "normalized": [] }, { "id": "PMID-10026212_T32", "type": "Eukaryote", "offsets": [ [ 605, 610 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10026212_T33", "type": "Enzyme", "offsets": [ [ 611, 619 ] ], "text": [ "GGPPSase" ], "normalized": [] }, { "id": "PMID-10026212_T34", "type": "Eukaryote", "offsets": [ [ 745, 751 ] ], "text": [ "bovine" ], "normalized": [] }, { "id": "PMID-10026212_T35", "type": "Tissue", "offsets": [ [ 752, 757 ] ], "text": [ "brain" ], "normalized": [] }, { "id": "PMID-10026212_T36", "type": "Enzyme", "offsets": [ [ 758, 766 ] ], "text": [ "GGPPSase" ], "normalized": [] }, { "id": "PMID-10026212_T37", "type": "Eukaryote", "offsets": [ [ 804, 810 ] ], "text": [ "bovine" ], "normalized": [] }, { "id": "PMID-10026212_T38", "type": "Tissue", "offsets": [ [ 811, 816 ] ], "text": [ "brain" ], "normalized": [] }, { "id": "PMID-10026212_T39", "type": "Enzyme", "offsets": [ [ 817, 824 ] ], "text": [ "FPPSase" ], "normalized": [] }, { "id": "PMID-10026212_T40", "type": "MessengerRNA", "offsets": [ [ 892, 896 ] ], "text": [ "mRNA" ], "normalized": [] }, { "id": "PMID-10026212_T6", "type": "CatalyticActivity", "offsets": [ [ 126, 135 ] ], "text": [ "catalyzes" ], "normalized": [] }, { "id": "PMID-10026212_T23", "type": "CatalyticActivity", "offsets": [ [ 516, 525 ] ], "text": [ "catalyzes" ], "normalized": [] } ]
[ { "id": "PMID-10026212_E1", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 60, 70 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026212_T2" } ] }, { "id": "PMID-10026212_E2", "type": "MetabolicPathway", "trigger": { "text": [ "synthesis" ], "offsets": [ [ 140, 149 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026212_T10" }, { "role": "hasAgent", "ref_id": "PMID-10026212_T6" } ] }, { "id": "PMID-10026212_E3", "type": "ProteinBiosynthesis", "trigger": { "text": [ "biosynthesis" ], "offsets": [ [ 233, 245 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026212_T11" } ] }, { "id": "PMID-10026212_E4", "type": "RegulatoryProcess", "trigger": { "text": [ "regulation" ], "offsets": [ [ 258, 268 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026212_T15" } ] }, { "id": "PMID-10026212_E5", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 486, 495 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026212_T26" } ] }, { "id": "PMID-10026212_E6", "type": "MetabolicPathway", "trigger": { "text": [ "formation" ], "offsets": [ [ 535, 544 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026212_T23" }, { "role": "hasPatient", "ref_id": "PMID-10026212_T29" } ] }, { "id": "PMID-10026212_E7", "type": "MetabolicPathway", "trigger": { "text": [ "formation" ], "offsets": [ [ 535, 544 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026212_T23" }, { "role": "hasPatient", "ref_id": "PMID-10026212_T30" } ] }, { "id": "PMID-10026212_E8", "type": "MetabolicPathway", "trigger": { "text": [ "formation" ], "offsets": [ [ 535, 544 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026212_T23" }, { "role": "hasPatient", "ref_id": "PMID-10026212_T31" } ] } ]
[]
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9
PMID-10026226
[ { "id": "PMID-10026226__text", "type": "abstract", "text": [ "Skeletal muscle type ryanodine receptor is involved in calcium signaling in human B lymphocytes. The regulation of intracellular free Ca2+ concentration ([Ca2+]i) in B cells remains poorly understood and is presently explained almost solely by inositol 1,4,5-triphosphate (IP3)-mediated Ca2+ release, followed by activation of a store-operated channel mechanism. In fact, there are reports indicating that IP3 production does not always correlate with the magnitude of Ca2+ release. We demonstrate here that human B cells express a ryanodine receptor (RYR) that functions as a Ca2+ release channel during the B cell antigen receptor (BCR)-stimulated Ca2+ signaling process. Immunoblotting studies showed that both human primary CD19(+) B and DAKIKI cells express a 565-kDa immunoreactive protein that is indistinguishable in molecular size and immunoreactivity from the RYR. Selective reverse transcription-polymerase chain reaction, restriction fragment length polymorphism, and sequencing of cloned cDNA indicated that the major isoform of the RYR expressed in primary CD19(+) B and DAKIKI cells is identical to the skeletal muscle type (RYR1). Saturation analysis of [3H]ryanodine binding yielded Bmax = 150 fmol/mg of protein and Kd = 110 nM in DAKIKI cells. In fluo-3-loaded CD19(+) B and DAKIKI cells, 4-chloro-m-cresol, a potent activator of Ca2+ release mediated by the ryanodine-sensitive Ca2+ release channel, induced Ca2+ release in a dose-dependent and ryanodine-sensitive fashion. Furthermore, BCR-mediated Ca2+ release in CD19(+) B cells was significantly altered by 4-chloro-m-cresol and ryanodine. These results indicate that RYR1 functions as a Ca2+ release channel during BCR-stimulated Ca2+ signaling and suggest that complex Ca2+ signals that control the cellular activities of B cells may be generated by cooperation of the IP3 receptor and RYR1.\n" ], "offsets": [ [ 0, 1868 ] ] } ]
[ { "id": "PMID-10026226_T3", "type": "Ion", "offsets": [ [ 55, 62 ] ], "text": [ "calcium" ], "normalized": [] }, { "id": "PMID-10026226_T5", "type": "Eukaryote", "offsets": [ [ 76, 81 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10026226_T6", "type": "Cell", "offsets": [ [ 82, 95 ] ], "text": [ "B lymphocytes" ], "normalized": [] }, { "id": "PMID-10026226_T8", "type": "Ion", "offsets": [ [ 134, 138 ] ], "text": [ "Ca2+" ], "normalized": [] }, { "id": "PMID-10026226_T9", "type": "Cell", "offsets": [ [ 166, 173 ] ], "text": [ "B cells" ], "normalized": [] }, { "id": "PMID-10026226_T11", "type": "Chemical", "offsets": [ [ 273, 276 ] ], "text": [ "IP3" ], "normalized": [] }, { "id": "PMID-10026226_T13", "type": "Ion", "offsets": [ [ 287, 291 ] ], "text": [ "Ca2+" ], "normalized": [] }, { "id": "PMID-10026226_T17", "type": "Eukaryote", "offsets": [ [ 508, 513 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10026226_T18", "type": "Cell", "offsets": [ [ 514, 521 ] ], "text": [ "B cells" ], "normalized": [] }, { "id": "PMID-10026226_T21", "type": "Protein", "offsets": [ [ 552, 555 ] ], "text": [ "RYR" ], "normalized": [] }, { "id": "PMID-10026226_T22", "type": "Ion", "offsets": [ [ 577, 581 ] ], "text": [ "Ca2+" ], "normalized": [] }, { "id": "PMID-10026226_T24", "type": "Protein", "offsets": [ [ 590, 597 ] ], "text": [ "channel" ], "normalized": [] }, { "id": "PMID-10026226_T26", "type": "Protein", "offsets": [ [ 634, 637 ] ], "text": [ "BCR" ], "normalized": [] }, { "id": "PMID-10026226_T28", "type": "Ion", "offsets": [ [ 650, 654 ] ], "text": [ "Ca2+" ], "normalized": [] }, { "id": "PMID-10026226_T30", "type": "Eukaryote", "offsets": [ [ 714, 719 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10026226_T31", "type": "Cell", "offsets": [ [ 720, 737 ] ], "text": [ "primary CD19(+) B" ], "normalized": [] }, { "id": "PMID-10026226_T32", "type": "Cell", "offsets": [ [ 742, 754 ] ], "text": [ "DAKIKI cells" ], "normalized": [] }, { "id": "PMID-10026226_T34", "type": "Protein", "offsets": [ [ 788, 795 ] ], "text": [ "protein" ], "normalized": [] }, { "id": "PMID-10026226_T35", "type": "Protein", "offsets": [ [ 870, 873 ] ], "text": [ "RYR" ], "normalized": [] }, { "id": "PMID-10026226_T36", "type": "Protein", "offsets": [ [ 1046, 1049 ] ], "text": [ "RYR" ], "normalized": [] }, { "id": "PMID-10026226_T38", "type": "Cell", "offsets": [ [ 1063, 1080 ] ], "text": [ "primary CD19(+) B" ], "normalized": [] }, { "id": "PMID-10026226_T39", "type": "Cell", "offsets": [ [ 1085, 1097 ] ], "text": [ "DAKIKI cells" ], "normalized": [] }, { "id": "PMID-10026226_T40", "type": "Tissue", "offsets": [ [ 1118, 1138 ] ], "text": [ "skeletal muscle type" ], "normalized": [] }, { "id": "PMID-10026226_T41", "type": "Protein", "offsets": [ [ 1140, 1144 ] ], "text": [ "RYR1" ], "normalized": [] }, { "id": "PMID-10026226_T42", "type": "Chemical", "offsets": [ [ 1170, 1183 ] ], "text": [ "[3H]ryanodine" ], "normalized": [] }, { "id": "PMID-10026226_T43", "type": "Protein", "offsets": [ [ 1222, 1229 ] ], "text": [ "protein" ], "normalized": [] }, { "id": "PMID-10026226_T44", "type": "Cell", "offsets": [ [ 1249, 1261 ] ], "text": [ "DAKIKI cells" ], "normalized": [] }, { "id": "PMID-10026226_T45", "type": "Cell", "offsets": [ [ 1280, 1289 ] ], "text": [ "CD19(+) B" ], "normalized": [] }, { "id": "PMID-10026226_T46", "type": "Cell", "offsets": [ [ 1294, 1306 ] ], "text": [ "DAKIKI cells" ], "normalized": [] }, { "id": "PMID-10026226_T47", "type": "Chemical", "offsets": [ [ 1308, 1325 ] ], "text": [ "4-chloro-m-cresol" ], "normalized": [] }, { "id": "PMID-10026226_T49", "type": "Ion", "offsets": [ [ 1349, 1353 ] ], "text": [ "Ca2+" ], "normalized": [] }, { "id": "PMID-10026226_T52", "type": "Chemical", "offsets": [ [ 1378, 1387 ] ], "text": [ "ryanodine" ], "normalized": [] }, { "id": "PMID-10026226_T53", "type": "Ion", "offsets": [ [ 1398, 1402 ] ], "text": [ "Ca2+" ], "normalized": [] }, { "id": "PMID-10026226_T55", "type": "Protein", "offsets": [ [ 1411, 1418 ] ], "text": [ "channel" ], "normalized": [] }, { "id": "PMID-10026226_T57", "type": "Ion", "offsets": [ [ 1428, 1432 ] ], "text": [ "Ca2+" ], "normalized": [] }, { "id": "PMID-10026226_T59", "type": "Chemical", "offsets": [ [ 1465, 1474 ] ], "text": [ "ryanodine" ], "normalized": [] }, { "id": "PMID-10026226_T60", "type": "Protein", "offsets": [ [ 1507, 1510 ] ], "text": [ "BCR" ], "normalized": [] }, { "id": "PMID-10026226_T62", "type": "Ion", "offsets": [ [ 1520, 1524 ] ], "text": [ "Ca2+" ], "normalized": [] }, { "id": "PMID-10026226_T64", "type": "Cell", "offsets": [ [ 1536, 1551 ] ], "text": [ "CD19(+) B cells" ], "normalized": [] }, { "id": "PMID-10026226_T66", "type": "Chemical", "offsets": [ [ 1581, 1598 ] ], "text": [ "4-chloro-m-cresol" ], "normalized": [] }, { "id": "PMID-10026226_T67", "type": "Chemical", "offsets": [ [ 1603, 1612 ] ], "text": [ "ryanodine" ], "normalized": [] }, { "id": "PMID-10026226_T68", "type": "Protein", "offsets": [ [ 1642, 1646 ] ], "text": [ "RYR1" ], "normalized": [] }, { "id": "PMID-10026226_T69", "type": "Ion", "offsets": [ [ 1662, 1666 ] ], "text": [ "Ca2+" ], "normalized": [] }, { "id": "PMID-10026226_T71", "type": "Protein", "offsets": [ [ 1675, 1682 ] ], "text": [ "channel" ], "normalized": [] }, { "id": "PMID-10026226_T72", "type": "Protein", "offsets": [ [ 1690, 1693 ] ], "text": [ "BCR" ], "normalized": [] }, { "id": "PMID-10026226_T74", "type": "Ion", "offsets": [ [ 1705, 1709 ] ], "text": [ "Ca2+" ], "normalized": [] }, { "id": "PMID-10026226_T76", "type": "Ion", "offsets": [ [ 1745, 1749 ] ], "text": [ "Ca2+" ], "normalized": [] }, { "id": "PMID-10026226_T78", "type": "Cell", "offsets": [ [ 1798, 1805 ] ], "text": [ "B cells" ], "normalized": [] }, { "id": "PMID-10026226_T80", "type": "Protein", "offsets": [ [ 1845, 1857 ] ], "text": [ "IP3 receptor" ], "normalized": [] }, { "id": "PMID-10026226_T81", "type": "Protein", "offsets": [ [ 1862, 1866 ] ], "text": [ "RYR1" ], "normalized": [] }, { "id": "PMID-10026226_T1", "type": "Protein", "offsets": [ [ 0, 39 ] ], "text": [ "Skeletal muscle type ryanodine receptor" ], "normalized": [] }, { "id": "PMID-10026226_T10", "type": "Chemical", "offsets": [ [ 406, 409 ] ], "text": [ "IP3" ], "normalized": [] }, { "id": "PMID-10026226_T82", "type": "Ion", "offsets": [ [ 469, 473 ] ], "text": [ "Ca2+" ], "normalized": [] } ]
[ { "id": "PMID-10026226_E1", "type": "SignalingPathway", "trigger": { "text": [ "signaling" ], "offsets": [ [ 63, 72 ] ] }, "arguments": [] }, { "id": "PMID-10026226_E2", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 278, 286 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_E3" }, { "role": "hasAgent", "ref_id": "PMID-10026226_T11" } ] }, { "id": "PMID-10026226_E3", "type": "Transport", "trigger": { "text": [ "release" ], "offsets": [ [ 292, 299 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_T13" } ] }, { "id": "PMID-10026226_E4", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 313, 323 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_E5" } ] }, { "id": "PMID-10026226_E5", "type": "Transport", "trigger": { "text": [ "store-operated channel mechanism" ], "offsets": [ [ 329, 361 ] ] }, "arguments": [] }, { "id": "PMID-10026226_E6", "type": "GeneExpression", "trigger": { "text": [ "express" ], "offsets": [ [ 522, 529 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_T21" } ] }, { "id": "PMID-10026226_E7", "type": "Transport", "trigger": { "text": [ "release" ], "offsets": [ [ 582, 589 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026226_T24" }, { "role": "hasPatient", "ref_id": "PMID-10026226_T22" } ] }, { "id": "PMID-10026226_E8", "type": "Increase", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 639, 649 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_E9" }, { "role": "hasAgent", "ref_id": "PMID-10026226_T26" } ] }, { "id": "PMID-10026226_E9", "type": "SignalingPathway", "trigger": { "text": [ "signaling process" ], "offsets": [ [ 655, 672 ] ] }, "arguments": [] }, { "id": "PMID-10026226_E10", "type": "GeneExpression", "trigger": { "text": [ "express" ], "offsets": [ [ 755, 762 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_T34" } ] }, { "id": "PMID-10026226_E11", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1050, 1059 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_T36" } ] }, { "id": "PMID-10026226_E12", "type": "PositiveRegulation", "trigger": { "text": [ "activator" ], "offsets": [ [ 1336, 1345 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026226_T47" }, { "role": "hasPatient", "ref_id": "PMID-10026226_E13" } ] }, { "id": "PMID-10026226_E13", "type": "Transport", "trigger": { "text": [ "release" ], "offsets": [ [ 1354, 1361 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_T49" } ] }, { "id": "PMID-10026226_E14", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1362, 1370 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026226_T55" }, { "role": "hasPatient", "ref_id": "PMID-10026226_E13" } ] }, { "id": "PMID-10026226_E15", "type": "Transport", "trigger": { "text": [ "release" ], "offsets": [ [ 1403, 1410 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026226_T55" }, { "role": "hasPatient", "ref_id": "PMID-10026226_T53" } ] }, { "id": "PMID-10026226_E16", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1420, 1427 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_E17" } ] }, { "id": "PMID-10026226_E17", "type": "Transport", "trigger": { "text": [ "release" ], "offsets": [ [ 1433, 1440 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_T57" } ] }, { "id": "PMID-10026226_E18", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1511, 1519 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026226_T60" }, { "role": "hasPatient", "ref_id": "PMID-10026226_E19" } ] }, { "id": "PMID-10026226_E19", "type": "Transport", "trigger": { "text": [ "release" ], "offsets": [ [ 1525, 1532 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_T62" } ] }, { "id": "PMID-10026226_E20", "type": "Affecting", "trigger": { "text": [ "altered" ], "offsets": [ [ 1570, 1577 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_E19" }, { "role": "hasAgent", "ref_id": "PMID-10026226_T66" } ] }, { "id": "PMID-10026226_E21", "type": "Transport", "trigger": { "text": [ "release" ], "offsets": [ [ 1667, 1674 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026226_T71" }, { "role": "hasPatient", "ref_id": "PMID-10026226_T69" } ] }, { "id": "PMID-10026226_E22", "type": "Increase", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 1694, 1704 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026226_T72" }, { "role": "hasPatient", "ref_id": "PMID-10026226_E23" } ] }, { "id": "PMID-10026226_E23", "type": "SignalingPathway", "trigger": { "text": [ "signaling" ], "offsets": [ [ 1710, 1719 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_T74" } ] }, { "id": "PMID-10026226_E24", "type": "RegulatoryProcess", "trigger": { "text": [ "control" ], "offsets": [ [ 1763, 1770 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026226_T80" } ] }, { "id": "PMID-10026226_E26", "type": "RegulatoryProcess", "trigger": { "text": [ "regulation" ], "offsets": [ [ 101, 111 ] ] }, "arguments": [] }, { "id": "PMID-10026226_E27", "type": "Transport", "trigger": { "text": [ "release" ], "offsets": [ [ 474, 481 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_T82" } ] }, { "id": "PMID-10026226_E25", "type": "Affecting", "trigger": { "text": [ "altered" ], "offsets": [ [ 1570, 1577 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_E19" }, { "role": "hasAgent", "ref_id": "PMID-10026226_T67" } ] }, { "id": "PMID-10026226_E28", "type": "RegulatoryProcess", "trigger": { "text": [ "control" ], "offsets": [ [ 1763, 1770 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026226_T81" } ] } ]
[]
[ { "arg1_id": "PMID-10026226_T6", "arg2_id": "PMID-10026226_T5", "id": "PMID-10026226_R3", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10026226_T18", "arg2_id": "PMID-10026226_T17", "id": "PMID-10026226_R6", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10026226_T31", "arg2_id": "PMID-10026226_T30", "id": "PMID-10026226_R8", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10026226_T8", "arg2_id": "PMID-10026226_T9", "id": "PMID-10026226_R1", "type": "locatedIn", "normalized": [] }, { "arg1_id": "PMID-10026226_T41", "arg2_id": "PMID-10026226_T40", "id": "PMID-10026226_R4", "type": "locatedIn", "normalized": [] }, { "arg1_id": "PMID-10026226_T43", "arg2_id": "PMID-10026226_T44", "id": "PMID-10026226_R13", "type": "locatedIn", "normalized": [] } ]
10
PMID-10026247
[ { "id": "PMID-10026247__text", "type": "abstract", "text": [ "Zinc-binding site of an S100 protein revealed. Two crystal structures of Ca2+-bound human psoriasin (S100A7) in the Zn2+-loaded and Zn2+-free states. The crystal structure of human psoriasin (S100A7) in the native, calcium-bound form has been determined from two crystal forms of the protein crystallized with and without divalent zinc. The overall structures of the dimeric protein closely resemble the previously determined holmium-substituted structure. The structures also reveal a zinc-binding site of the protein, which is formed by three histidines and an aspartate residue. Together, these residues coordinate the zinc ion in a way similar to the pattern seen in certain metalloproteases and in particular the collagenase family of proteins. Sequence comparison suggests that this zinc site is present in a number of the remaining members of the S100 family. The structure of S100A7 crystallized in the absence of zinc further shows that loss of zinc results in a reorganization of the adjacent empty and distorted EF-hand loop, causing it to resemble a calcium-loaded EF-hand.\n" ], "offsets": [ [ 0, 1086 ] ] } ]
[ { "id": "PMID-10026247_T1", "type": "Ion", "offsets": [ [ 0, 4 ] ], "text": [ "Zinc" ], "normalized": [] }, { "id": "PMID-10026247_T3", "type": "Protein", "offsets": [ [ 24, 36 ] ], "text": [ "S100 protein" ], "normalized": [] }, { "id": "PMID-10026247_T4", "type": "Ion", "offsets": [ [ 73, 77 ] ], "text": [ "Ca2+" ], "normalized": [] }, { "id": "PMID-10026247_T6", "type": "Eukaryote", "offsets": [ [ 84, 89 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10026247_T7", "type": "Protein", "offsets": [ [ 90, 99 ] ], "text": [ "psoriasin" ], "normalized": [] }, { "id": "PMID-10026247_T8", "type": "Protein", "offsets": [ [ 101, 107 ] ], "text": [ "S100A7" ], "normalized": [] }, { "id": "PMID-10026247_T9", "type": "Ion", "offsets": [ [ 116, 120 ] ], "text": [ "Zn2+" ], "normalized": [] }, { "id": "PMID-10026247_T10", "type": "Ion", "offsets": [ [ 132, 136 ] ], "text": [ "Zn2+" ], "normalized": [] }, { "id": "PMID-10026247_T11", "type": "Eukaryote", "offsets": [ [ 175, 180 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10026247_T12", "type": "Protein", "offsets": [ [ 181, 190 ] ], "text": [ "psoriasin" ], "normalized": [] }, { "id": "PMID-10026247_T13", "type": "Protein", "offsets": [ [ 192, 198 ] ], "text": [ "S100A7" ], "normalized": [] }, { "id": "PMID-10026247_T14", "type": "Ion", "offsets": [ [ 215, 222 ] ], "text": [ "calcium" ], "normalized": [] }, { "id": "PMID-10026247_T16", "type": "Protein", "offsets": [ [ 284, 291 ] ], "text": [ "protein" ], "normalized": [] }, { "id": "PMID-10026247_T17", "type": "Ion", "offsets": [ [ 322, 335 ] ], "text": [ "divalent zinc" ], "normalized": [] }, { "id": "PMID-10026247_T18", "type": "Protein", "offsets": [ [ 367, 382 ] ], "text": [ "dimeric protein" ], "normalized": [] }, { "id": "PMID-10026247_T19", "type": "Chemical", "offsets": [ [ 426, 433 ] ], "text": [ "holmium" ], "normalized": [] }, { "id": "PMID-10026247_T20", "type": "Ion", "offsets": [ [ 486, 490 ] ], "text": [ "zinc" ], "normalized": [] }, { "id": "PMID-10026247_T22", "type": "BindingSiteOfProtein", "offsets": [ [ 499, 503 ] ], "text": [ "site" ], "normalized": [] }, { "id": "PMID-10026247_T23", "type": "Protein", "offsets": [ [ 511, 518 ] ], "text": [ "protein" ], "normalized": [] }, { "id": "PMID-10026247_T24", "type": "AminoAcid", "offsets": [ [ 545, 555 ] ], "text": [ "histidines" ], "normalized": [] }, { "id": "PMID-10026247_T25", "type": "AminoAcid", "offsets": [ [ 563, 580 ] ], "text": [ "aspartate residue" ], "normalized": [] }, { "id": "PMID-10026247_T26", "type": "Ion", "offsets": [ [ 622, 630 ] ], "text": [ "zinc ion" ], "normalized": [] }, { "id": "PMID-10026247_T27", "type": "Enzyme", "offsets": [ [ 679, 695 ] ], "text": [ "metalloproteases" ], "normalized": [] }, { "id": "PMID-10026247_T28", "type": "Enzyme", "offsets": [ [ 718, 729 ] ], "text": [ "collagenase" ], "normalized": [] }, { "id": "PMID-10026247_T29", "type": "Protein", "offsets": [ [ 740, 748 ] ], "text": [ "proteins" ], "normalized": [] }, { "id": "PMID-10026247_T30", "type": "Ion", "offsets": [ [ 789, 793 ] ], "text": [ "zinc" ], "normalized": [] }, { "id": "PMID-10026247_T31", "type": "Protein", "offsets": [ [ 854, 858 ] ], "text": [ "S100" ], "normalized": [] }, { "id": "PMID-10026247_T32", "type": "Protein", "offsets": [ [ 884, 890 ] ], "text": [ "S100A7" ], "normalized": [] }, { "id": "PMID-10026247_T33", "type": "Ion", "offsets": [ [ 922, 926 ] ], "text": [ "zinc" ], "normalized": [] }, { "id": "PMID-10026247_T34", "type": "Ion", "offsets": [ [ 954, 958 ] ], "text": [ "zinc" ], "normalized": [] }, { "id": "PMID-10026247_T35", "type": "Ion", "offsets": [ [ 1062, 1069 ] ], "text": [ "calcium" ], "normalized": [] }, { "id": "PMID-10026247_T36", "type": "BindingSiteOfProtein", "offsets": [ [ 13, 17 ] ], "text": [ "site" ], "normalized": [] }, { "id": "PMID-10026247_T37", "type": "BindingSiteOfProtein", "offsets": [ [ 794, 798 ] ], "text": [ "site" ], "normalized": [] } ]
[ { "id": "PMID-10026247_E1", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 5, 12 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026247_T1" }, { "role": "hasAgent", "ref_id": "PMID-10026247_T36" } ] }, { "id": "PMID-10026247_E2", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 78, 83 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026247_T4" }, { "role": "hasPatient", "ref_id": "PMID-10026247_T7" } ] }, { "id": "PMID-10026247_E3", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 223, 228 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026247_T14" } ] }, { "id": "PMID-10026247_E4", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 491, 498 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026247_T22" }, { "role": "hasPatient", "ref_id": "PMID-10026247_T20" } ] } ]
[]
[ { "arg1_id": "PMID-10026247_T7", "arg2_id": "PMID-10026247_T6", "id": "PMID-10026247_R1", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10026247_T12", "arg2_id": "PMID-10026247_T11", "id": "PMID-10026247_R2", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10026247_T23", "arg2_id": "PMID-10026247_T22", "id": "PMID-10026247_R5", "type": "hasPart", "normalized": [] }, { "arg1_id": "PMID-10026247_T3", "arg2_id": "PMID-10026247_T36", "id": "PMID-10026247_R6", "type": "hasPart", "normalized": [] }, { "arg1_id": "PMID-10026247_T31", "arg2_id": "PMID-10026247_T37", "id": "PMID-10026247_R3", "type": "hasPart", "normalized": [] } ]
11
PMID-10029623
[ { "id": "PMID-10029623__text", "type": "abstract", "text": [ "Formiminotransferase cyclodeaminase is an organ-specific autoantigen recognized by sera of patients with autoimmune hepatitis. Anti-liver cytosol type 1 autoantibodies have been reported in association with anti-liver-kidney microsome type 1 autoantibodies in 30% of patients with autoimmune hepatitis type II. In 10% of cases, anti-liver cytosol type 1 antibodies are the only liver-related circulating autoantibodies. The liver cytosol antigen is a liver-specific 62-kilodalton protein present in the cell as an oligomer of approximately 240 kilodaltons. The aim of this study was to identify the antigen recognized by anti-liver cytosol antibody. To identify the liver cytosol antigen, an anti-liver cytosol type 1-positive serum was used for the screening of a complementary DNA library from HepG2 cells. Double immunodiffusion method was used to show the identity between the cytosolic and the cloned protein. The sequence of two isolated clones showed 85.2% homology with the formiminotransferase cyclodeaminase (FTCD) enzyme from pig liver. Antibodies purified by affinity with the recombinant protein and sera from mice immunized with FTCD recognized a 62-kilodalton human cytosolic protein when tested by immunoblot. The identity of precipitation lines was found between the cytosolic antigen and FTCD. This enzyme is a liver-specific antigen recognized by the sera of patients with autoimmune hepatitis.\n" ], "offsets": [ [ 0, 1414 ] ] } ]
[ { "id": "PMID-10029623_T1", "type": "Enzyme", "offsets": [ [ 0, 35 ] ], "text": [ "Formiminotransferase cyclodeaminase" ], "normalized": [] }, { "id": "PMID-10029623_T2", "type": "Protein", "offsets": [ [ 42, 68 ] ], "text": [ "organ-specific autoantigen" ], "normalized": [] }, { "id": "PMID-10029623_T4", "type": "Protein", "offsets": [ [ 328, 364 ] ], "text": [ "anti-liver cytosol type 1 antibodies" ], "normalized": [] }, { "id": "PMID-10029623_T5", "type": "Tissue", "offsets": [ [ 378, 383 ] ], "text": [ "liver" ], "normalized": [] }, { "id": "PMID-10029623_T6", "type": "Protein", "offsets": [ [ 404, 418 ] ], "text": [ "autoantibodies" ], "normalized": [] }, { "id": "PMID-10029623_T7", "type": "Protein", "offsets": [ [ 127, 167 ] ], "text": [ "Anti-liver cytosol type 1 autoantibodies" ], "normalized": [] }, { "id": "PMID-10029623_T8", "type": "Protein", "offsets": [ [ 424, 445 ] ], "text": [ "liver cytosol antigen" ], "normalized": [] }, { "id": "PMID-10029623_T9", "type": "Protein", "offsets": [ [ 621, 648 ] ], "text": [ "anti-liver cytosol antibody" ], "normalized": [] }, { "id": "PMID-10029623_T10", "type": "Protein", "offsets": [ [ 666, 687 ] ], "text": [ "liver cytosol antigen" ], "normalized": [] }, { "id": "PMID-10029623_T11", "type": "Eukaryote", "offsets": [ [ 1037, 1040 ] ], "text": [ "pig" ], "normalized": [] }, { "id": "PMID-10029623_T12", "type": "Tissue", "offsets": [ [ 1041, 1046 ] ], "text": [ "liver" ], "normalized": [] }, { "id": "PMID-10029623_T13", "type": "Protein", "offsets": [ [ 1048, 1058 ] ], "text": [ "Antibodies" ], "normalized": [] }, { "id": "PMID-10029623_T14", "type": "Enzyme", "offsets": [ [ 1317, 1323 ] ], "text": [ "enzyme" ], "normalized": [] }, { "id": "PMID-10029623_T15", "type": "Protein", "offsets": [ [ 1329, 1351 ] ], "text": [ "liver-specific antigen" ], "normalized": [] }, { "id": "PMID-10029623_T17", "type": "Protein", "offsets": [ [ 207, 256 ] ], "text": [ "anti-liver-kidney microsome type 1 autoantibodies" ], "normalized": [] } ]
[ { "id": "PMID-10029623_E1", "type": "Disease", "trigger": { "text": [ "autoimmune hepatitis" ], "offsets": [ [ 105, 125 ] ] }, "arguments": [] }, { "id": "PMID-10029623_E2", "type": "Disease", "trigger": { "text": [ "autoimmune hepatitis" ], "offsets": [ [ 1392, 1412 ] ] }, "arguments": [] }, { "id": "PMID-10029623_E3", "type": "Disease", "trigger": { "text": [ "autoimmune hepatitis type II" ], "offsets": [ [ 281, 309 ] ] }, "arguments": [] } ]
[]
[ { "arg1_id": "PMID-10029623_T6", "arg2_id": "PMID-10029623_T5", "id": "PMID-10029623_R1", "type": "locatedIn", "normalized": [] }, { "arg1_id": "PMID-10029623_T12", "arg2_id": "PMID-10029623_T11", "id": "PMID-10029623_R2", "type": "fromSpecies", "normalized": [] } ]
12
PMID-10030672
[ { "id": "PMID-10030672__text", "type": "abstract", "text": [ "Identification of a human HECT family protein with homology to the Drosophila tumor suppressor gene hyperplastic discs. Use of the differential display technique to isolate progestin-regulated genes in T-47D human breast cancer cells led to identification of a novel gene, EDD. The cDNA sequence contains a 2799 amino acid open reading frame sharing 40% identity with the predicted 2894 amino acid product of the Drosophila melanogaster tumor suppressor gene hyperplastic discs, while the carboxy-terminal 889 amino acids show 96% identity to a rat 100 kDa HECT domain protein. EDD mRNA was progestin-induced in T-47D cells and was highly abundant in testes and expressed at moderately high levels in other tissues, suggesting a broad role for EDD. Anti-EDD antibodies immunoprecipitated an approximately 300 kDa protein from T-47D cell lysates. HECT family proteins function as E3 ubiquitin-protein ligases, targeting specific proteins for ubiquitin-mediated proteolysis. EDD is likely to function as an E3 as in vitro translated protein bound ubiquitin reversibly through a conserved HECT domain cysteine residue. EDD was localized by FISH to chromosome 8q22, a locus disrupted in a variety of cancers. Given the homology between EDD and the hyperplastic discs protein, which is required for control of imaginal disc growth in Drosophila, EDD potentially has a role in regulation of cell proliferation or differentiation.\n" ], "offsets": [ [ 0, 1424 ] ] } ]
[ { "id": "PMID-10030672_T3", "type": "Eukaryote", "offsets": [ [ 67, 77 ] ], "text": [ "Drosophila" ], "normalized": [] }, { "id": "PMID-10030672_T4", "type": "Gene", "offsets": [ [ 100, 118 ] ], "text": [ "hyperplastic discs" ], "normalized": [] }, { "id": "PMID-10030672_T5", "type": "Chemical", "offsets": [ [ 173, 182 ] ], "text": [ "progestin" ], "normalized": [] }, { "id": "PMID-10030672_T7", "type": "Gene", "offsets": [ [ 193, 198 ] ], "text": [ "genes" ], "normalized": [] }, { "id": "PMID-10030672_T8", "type": "Cell", "offsets": [ [ 202, 207 ] ], "text": [ "T-47D" ], "normalized": [] }, { "id": "PMID-10030672_T17", "type": "Eukaryote", "offsets": [ [ 413, 436 ] ], "text": [ "Drosophila melanogaster" ], "normalized": [] }, { "id": "PMID-10030672_T18", "type": "Gene", "offsets": [ [ 459, 477 ] ], "text": [ "hyperplastic discs" ], "normalized": [] }, { "id": "PMID-10030672_T24", "type": "MessengerRNA", "offsets": [ [ 578, 586 ] ], "text": [ "EDD mRNA" ], "normalized": [] }, { "id": "PMID-10030672_T25", "type": "Chemical", "offsets": [ [ 591, 600 ] ], "text": [ "progestin" ], "normalized": [] }, { "id": "PMID-10030672_T27", "type": "Cell", "offsets": [ [ 612, 623 ] ], "text": [ "T-47D cells" ], "normalized": [] }, { "id": "PMID-10030672_T28", "type": "Tissue", "offsets": [ [ 651, 657 ] ], "text": [ "testes" ], "normalized": [] }, { "id": "PMID-10030672_T41", "type": "Protein", "offsets": [ [ 941, 950 ] ], "text": [ "ubiquitin" ], "normalized": [] }, { "id": "PMID-10030672_T49", "type": "Protein", "offsets": [ [ 1045, 1054 ] ], "text": [ "ubiquitin" ], "normalized": [] }, { "id": "PMID-10030672_T50", "type": "ProteinDomain", "offsets": [ [ 1086, 1097 ] ], "text": [ "HECT domain" ], "normalized": [] }, { "id": "PMID-10030672_T51", "type": "AminoAcid", "offsets": [ [ 1098, 1114 ] ], "text": [ "cysteine residue" ], "normalized": [] }, { "id": "PMID-10030672_T52", "type": "Gene", "offsets": [ [ 1116, 1119 ] ], "text": [ "EDD" ], "normalized": [] }, { "id": "PMID-10030672_T59", "type": "Eukaryote", "offsets": [ [ 1329, 1339 ] ], "text": [ "Drosophila" ], "normalized": [] }, { "id": "PMID-10030672_T60", "type": "Gene", "offsets": [ [ 1341, 1344 ] ], "text": [ "EDD" ], "normalized": [] }, { "id": "PMID-10030672_T11", "type": "Eukaryote", "offsets": [ [ 208, 213 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10030672_T2", "type": "Tissue", "offsets": [ [ 1305, 1318 ] ], "text": [ "imaginal disc" ], "normalized": [] }, { "id": "PMID-10030672_T1", "type": "Protein", "offsets": [ [ 26, 45 ] ], "text": [ "HECT family protein" ], "normalized": [] }, { "id": "PMID-10030672_T12", "type": "Eukaryote", "offsets": [ [ 20, 25 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10030672_T13", "type": "ProteinIdentification", "offsets": [ [ 0, 14 ] ], "text": [ "Identification" ], "normalized": [] }, { "id": "PMID-10030672_T14", "type": "Gene", "offsets": [ [ 78, 99 ] ], "text": [ "tumor suppressor gene" ], "normalized": [] }, { "id": "PMID-10030672_T15", "type": "Cell", "offsets": [ [ 214, 233 ] ], "text": [ "breast cancer cells" ], "normalized": [] }, { "id": "PMID-10030672_T16", "type": "Gene", "offsets": [ [ 273, 276 ] ], "text": [ "EDD" ], "normalized": [] }, { "id": "PMID-10030672_T19", "type": "Gene", "offsets": [ [ 437, 458 ] ], "text": [ "tumor suppressor gene" ], "normalized": [] }, { "id": "PMID-10030672_T20", "type": "Eukaryote", "offsets": [ [ 545, 548 ] ], "text": [ "rat" ], "normalized": [] }, { "id": "PMID-10030672_T21", "type": "Protein", "offsets": [ [ 557, 576 ] ], "text": [ "HECT domain protein" ], "normalized": [] }, { "id": "PMID-10030672_T22", "type": "Protein", "offsets": [ [ 813, 820 ] ], "text": [ "protein" ], "normalized": [] }, { "id": "PMID-10030672_T23", "type": "Gene", "offsets": [ [ 744, 747 ] ], "text": [ "EDD" ], "normalized": [] }, { "id": "PMID-10030672_T30", "type": "Cell", "offsets": [ [ 826, 836 ] ], "text": [ "T-47D cell" ], "normalized": [] }, { "id": "PMID-10030672_T31", "type": "Protein", "offsets": [ [ 846, 866 ] ], "text": [ "HECT family proteins" ], "normalized": [] }, { "id": "PMID-10030672_T32", "type": "Enzyme", "offsets": [ [ 879, 907 ] ], "text": [ "E3 ubiquitin-protein ligases" ], "normalized": [] }, { "id": "PMID-10030672_T34", "type": "Enzyme", "offsets": [ [ 1005, 1007 ] ], "text": [ "E3" ], "normalized": [] }, { "id": "PMID-10030672_T35", "type": "Protein", "offsets": [ [ 973, 976 ] ], "text": [ "EDD" ], "normalized": [] }, { "id": "PMID-10030672_T36", "type": "Protein", "offsets": [ [ 1232, 1235 ] ], "text": [ "EDD" ], "normalized": [] }, { "id": "PMID-10030672_T37", "type": "Chromosome", "offsets": [ [ 1145, 1160 ] ], "text": [ "chromosome 8q22" ], "normalized": [] }, { "id": "PMID-10030672_T10", "type": "Protein", "offsets": [ [ 1244, 1270 ] ], "text": [ "hyperplastic discs protein" ], "normalized": [] } ]
[ { "id": "PMID-10030672_E1", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 183, 192 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10030672_T5" }, { "role": "hasPatient", "ref_id": "PMID-10030672_T7" } ] }, { "id": "PMID-10030672_E2", "type": "Increase", "trigger": { "text": [ "induced" ], "offsets": [ [ 601, 608 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10030672_T25" }, { "role": "hasPatient", "ref_id": "PMID-10030672_T24" } ] }, { "id": "PMID-10030672_E3", "type": "TranscriptionOfGene", "trigger": { "text": [ "expressed" ], "offsets": [ [ 662, 671 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10030672_T24" } ] }, { "id": "PMID-10030672_E4", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 951, 959 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10030672_T41" }, { "role": "hasPatient", "ref_id": "PMID-10030672_E8" } ] }, { "id": "PMID-10030672_E7", "type": "BindingToProtein", "trigger": { "text": [ "bound" ], "offsets": [ [ 1039, 1044 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10030672_T49" } ] }, { "id": "PMID-10030672_E9", "type": "Growth", "trigger": { "text": [ "growth" ], "offsets": [ [ 1319, 1325 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10030672_T2" } ] }, { "id": "PMID-10030672_E6", "type": "RegulatoryProcess", "trigger": { "text": [ "control" ], "offsets": [ [ 1294, 1301 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10030672_E9" } ] }, { "id": "PMID-10030672_E5", "type": "RegulatoryProcess", "trigger": { "text": [ "regulation" ], "offsets": [ [ 1371, 1381 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10030672_T60" } ] }, { "id": "PMID-10030672_E8", "type": "ProteinCatabolism", "trigger": { "text": [ "proteolysis" ], "offsets": [ [ 960, 971 ] ] }, "arguments": [] }, { "id": "PMID-10030672_E10", "type": "CellGrowth", "trigger": { "text": [ "cell proliferation" ], "offsets": [ [ 1385, 1403 ] ] }, "arguments": [] }, { "id": "PMID-10030672_E11", "type": "CellDifferentiation", "trigger": { "text": [ "differentiation" ], "offsets": [ [ 1407, 1422 ] ] }, "arguments": [] } ]
[]
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13
PMID-10030676
[ { "id": "PMID-10030676__text", "type": "abstract", "text": [ "Isolation and characterization of a human homologue of the latrophilin gene from a region of 1p31.1 implicated in breast cancer. We have identified a region of chromosome 1p31.1 that shows high frequency loss of heterozygosity (LOH) in human breast cancer. This region forms part of a 7 Mb YAC/BAC contig. In order to identify candidate sequences, mutation of which might contribute to the development of disease, we have carried out mapping studies of ESTs localized to 1p31.1. This analysis, coupled with library screening and a modified 5' RACE-PCR strategy, resulted in the identification and characterization of a novel gene (LPHH1) which is located adjacent to the smallest region of overlapping loss (SRO) seen in tumours. The 4209 bp open reading frame of the 7 kb LPHH1 transcript encodes a peptide which shows approximately 65% identity to rat latrophilin, a G-coupled, seven span transmembrane protein, which binds alpha-latrotoxin. In the human sequence, whilst conservation of the transmembrane domain is high, the intra- and extracellular domains show two regions of variable structure, which are presumably generated by alternative splicing. Surprisingly, while expression of the rat gene is tightly restricted to neurological and perhaps some endocrine cells, the human sequence appears to be expressed very widely in all normal tissues tested. Northern and RT-PCR analysis of a panel of tumour cell lines showed that LPHH1 expression was variable, apparently elevated in some lines and absent or markedly reduced in others. Furthermore, characterization of the range of transcripts encoded in a breast tumour cell line, compared to normal breast, suggested that gene product variability was higher in the tumour.\n" ], "offsets": [ [ 0, 1730 ] ] } ]
[ { "id": "PMID-10030676_T1", "type": "Eukaryote", "offsets": [ [ 36, 41 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10030676_T2", "type": "Protein", "offsets": [ [ 59, 70 ] ], "text": [ "latrophilin" ], "normalized": [] }, { "id": "PMID-10030676_T3", "type": "Gene", "offsets": [ [ 71, 75 ] ], "text": [ "gene" ], "normalized": [] }, { "id": "PMID-10030676_T5", "type": "Chromosome", "offsets": [ [ 160, 170 ] ], "text": [ "chromosome" ], "normalized": [] }, { "id": "PMID-10030676_T6", "type": "Eukaryote", "offsets": [ [ 236, 241 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10030676_T10", "type": "Gene", "offsets": [ [ 625, 629 ] ], "text": [ "gene" ], "normalized": [] }, { "id": "PMID-10030676_T11", "type": "Gene", "offsets": [ [ 631, 636 ] ], "text": [ "LPHH1" ], "normalized": [] }, { "id": "PMID-10030676_T13", "type": "OpenReadingFrame", "offsets": [ [ 742, 760 ] ], "text": [ "open reading frame" ], "normalized": [] }, { "id": "PMID-10030676_T14", "type": "Protein", "offsets": [ [ 773, 778 ] ], "text": [ "LPHH1" ], "normalized": [] }, { "id": "PMID-10030676_T15", "type": "Transcript", "offsets": [ [ 779, 789 ] ], "text": [ "transcript" ], "normalized": [] }, { "id": "PMID-10030676_T16", "type": "Peptide", "offsets": [ [ 800, 807 ] ], "text": [ "peptide" ], "normalized": [] }, { "id": "PMID-10030676_T17", "type": "Eukaryote", "offsets": [ [ 850, 853 ] ], "text": [ "rat" ], "normalized": [] }, { "id": "PMID-10030676_T18", "type": "Protein", "offsets": [ [ 854, 865 ] ], "text": [ "latrophilin" ], "normalized": [] }, { "id": "PMID-10030676_T19", "type": "Protein", "offsets": [ [ 891, 912 ] ], "text": [ "transmembrane protein" ], "normalized": [] }, { "id": "PMID-10030676_T21", "type": "Protein", "offsets": [ [ 926, 942 ] ], "text": [ "alpha-latrotoxin" ], "normalized": [] }, { "id": "PMID-10030676_T22", "type": "Eukaryote", "offsets": [ [ 951, 956 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10030676_T23", "type": "ProteinDomain", "offsets": [ [ 994, 1014 ] ], "text": [ "transmembrane domain" ], "normalized": [] }, { "id": "PMID-10030676_T27", "type": "Eukaryote", "offsets": [ [ 1195, 1198 ] ], "text": [ "rat" ], "normalized": [] }, { "id": "PMID-10030676_T28", "type": "Gene", "offsets": [ [ 1199, 1203 ] ], "text": [ "gene" ], "normalized": [] }, { "id": "PMID-10030676_T29", "type": "Cell", "offsets": [ [ 1229, 1241 ] ], "text": [ "neurological" ], "normalized": [] }, { "id": "PMID-10030676_T30", "type": "Cell", "offsets": [ [ 1259, 1274 ] ], "text": [ "endocrine cells" ], "normalized": [] }, { "id": "PMID-10030676_T31", "type": "Eukaryote", "offsets": [ [ 1280, 1285 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10030676_T32", "type": "Sequence", "offsets": [ [ 1286, 1294 ] ], "text": [ "sequence" ], "normalized": [] }, { "id": "PMID-10030676_T34", "type": "Tissue", "offsets": [ [ 1345, 1352 ] ], "text": [ "tissues" ], "normalized": [] }, { "id": "PMID-10030676_T35", "type": "Cell", "offsets": [ [ 1404, 1421 ] ], "text": [ "tumour cell lines" ], "normalized": [] }, { "id": "PMID-10030676_T36", "type": "Gene", "offsets": [ [ 1434, 1439 ] ], "text": [ "LPHH1" ], "normalized": [] }, { "id": "PMID-10030676_T38", "type": "Transcript", "offsets": [ [ 1587, 1598 ] ], "text": [ "transcripts" ], "normalized": [] }, { "id": "PMID-10030676_T39", "type": "Cell", "offsets": [ [ 1612, 1635 ] ], "text": [ "breast tumour cell line" ], "normalized": [] }, { "id": "PMID-10030676_T40", "type": "GeneProduct", "offsets": [ [ 1679, 1691 ] ], "text": [ "gene product" ], "normalized": [] }, { "id": "PMID-10030676_T4", "type": "Chromosome", "offsets": [ [ 83, 99 ] ], "text": [ "region of 1p31.1" ], "normalized": [] }, { "id": "PMID-10030676_T24", "type": "ProteinDomain", "offsets": [ [ 1028, 1060 ] ], "text": [ "intra- and extracellular domains" ], "normalized": [] }, { "id": "PMID-10030676_T43", "type": "Tissue", "offsets": [ [ 1656, 1662 ] ], "text": [ "breast" ], "normalized": [] } ]
[ { "id": "PMID-10030676_E1", "type": "Mutation", "trigger": { "text": [ "mutation" ], "offsets": [ [ 348, 356 ] ] }, "arguments": [] }, { "id": "PMID-10030676_E2", "type": "Disease", "trigger": { "text": [ "disease" ], "offsets": [ [ 405, 412 ] ] }, "arguments": [] }, { "id": "PMID-10030676_E3", "type": "BindingToProtein", "trigger": { "text": [ "binds" ], "offsets": [ [ 920, 925 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10030676_T21" }, { "role": "hasPatient2", "ref_id": "PMID-10030676_T19" } ] }, { "id": "PMID-10030676_E4", "type": "Splicing", "trigger": { "text": [ "alternative splicing" ], "offsets": [ [ 1135, 1155 ] ] }, "arguments": [] }, { "id": "PMID-10030676_E5", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1177, 1187 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10030676_T28" } ] }, { "id": "PMID-10030676_E6", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1309, 1318 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10030676_T32" } ] }, { "id": "PMID-10030676_E7", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1440, 1450 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10030676_T36" } ] }, { "id": "PMID-10030676_E8", "type": "Disease", "trigger": { "text": [ "breast cancer" ], "offsets": [ [ 114, 127 ] ] }, "arguments": [] }, { "id": "PMID-10030676_E9", "type": "Disease", "trigger": { "text": [ "breast cancer" ], "offsets": [ [ 242, 255 ] ] }, "arguments": [] }, { "id": "PMID-10030676_E10", "type": "Disease", "trigger": { "text": [ "tumours" ], "offsets": [ [ 721, 728 ] ] }, "arguments": [] }, { "id": "PMID-10030676_E11", "type": "Disease", "trigger": { "text": [ "tumour" ], "offsets": [ [ 1722, 1728 ] ] }, "arguments": [] } ]
[]
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14
PMID-10036181
[ { "id": "PMID-10036181__text", "type": "abstract", "text": [ "Discovery of three novel orphan G-protein-coupled receptors. We have discovered three novel human genes, GPR34, GPR44, and GPR45, encoding family A G-protein-coupled receptors (GPCRs). The receptor encoded by GPR34 is most similar to the P2Y receptor subfamily, while the receptor encoded by GPR44 is most similar to chemoattractant receptors. The receptor encoded by GPR45 is the mammalian orthologue of a putative lysophosphatidic acid receptor from Xenopus laevis. Partial sequence of GPR34 was discovered during a search of the GenBank database of expressed sequence tags (ESTs). This sequence information was used both to isolate the full-length translational open reading frame from a human genomic library and to assemble a contig from additional GPR34 EST cDNAs. Northern blot and in situ hybridization analyses revealed GPR34 mRNA transcripts in several human and rat brain regions. Also, we used polymerase chain reaction (PCR) to amplify human genomic DNA using degenerate oligonucleotides designed from sequences encoding transmembrane domains 3 and 7 of opioid and somatostatin receptors. Two PCR products partially encoding novel GPCRs, named GPR44 and GPR45, were discovered and used to isolate the full-length translational open reading frames from a human genomic library. Both GPR44 and GPR45 are expressed in the central nervous system and periphery. For chromosomal localization, fluorescence in situ hybridization analysis was performed to assign GPR34 to chromosomes 4p12 and Xp11. 3, GPR44 to chromosome 11q12-q13.3, and GPR45 to chromosome 2q11. 1-q12.\n" ], "offsets": [ [ 0, 1577 ] ] } ]
[ { "id": "PMID-10036181_T1", "type": "Protein", "offsets": [ [ 32, 59 ] ], "text": [ "G-protein-coupled receptors" ], "normalized": [] }, { "id": "PMID-10036181_T3", "type": "Eukaryote", "offsets": [ [ 92, 97 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10036181_T4", "type": "Gene", "offsets": [ [ 98, 103 ] ], "text": [ "genes" ], "normalized": [] }, { "id": "PMID-10036181_T5", "type": "Gene", "offsets": [ [ 105, 110 ] ], "text": [ "GPR34" ], "normalized": [] }, { "id": "PMID-10036181_T6", "type": "Gene", "offsets": [ [ 112, 117 ] ], "text": [ "GPR44" ], "normalized": [] }, { "id": "PMID-10036181_T7", "type": "Gene", "offsets": [ [ 123, 128 ] ], "text": [ "GPR45" ], "normalized": [] }, { "id": "PMID-10036181_T9", "type": "Protein", "offsets": [ [ 148, 175 ] ], "text": [ "G-protein-coupled receptors" ], "normalized": [] }, { "id": "PMID-10036181_T10", "type": "Protein", "offsets": [ [ 177, 182 ] ], "text": [ "GPCRs" ], "normalized": [] }, { "id": "PMID-10036181_T11", "type": "Protein", "offsets": [ [ 189, 197 ] ], "text": [ "receptor" ], "normalized": [] }, { "id": "PMID-10036181_T12", "type": "Gene", "offsets": [ [ 209, 214 ] ], "text": [ "GPR34" ], "normalized": [] }, { "id": "PMID-10036181_T13", "type": "Protein", "offsets": [ [ 238, 260 ] ], "text": [ "P2Y receptor subfamily" ], "normalized": [] }, { "id": "PMID-10036181_T14", "type": "Protein", "offsets": [ [ 272, 280 ] ], "text": [ "receptor" ], "normalized": [] }, { "id": "PMID-10036181_T15", "type": "Gene", "offsets": [ [ 292, 297 ] ], "text": [ "GPR44" ], "normalized": [] }, { "id": "PMID-10036181_T16", "type": "Protein", "offsets": [ [ 317, 342 ] ], "text": [ "chemoattractant receptors" ], "normalized": [] }, { "id": "PMID-10036181_T17", "type": "Protein", "offsets": [ [ 348, 356 ] ], "text": [ "receptor" ], "normalized": [] }, { "id": "PMID-10036181_T18", "type": "Gene", "offsets": [ [ 368, 373 ] ], "text": [ "GPR45" ], "normalized": [] }, { "id": "PMID-10036181_T19", "type": "Eukaryote", "offsets": [ [ 381, 390 ] ], "text": [ "mammalian" ], "normalized": [] }, { "id": "PMID-10036181_T20", "type": "Protein", "offsets": [ [ 416, 446 ] ], "text": [ "lysophosphatidic acid receptor" ], "normalized": [] }, { "id": "PMID-10036181_T21", "type": "Eukaryote", "offsets": [ [ 452, 466 ] ], "text": [ "Xenopus laevis" ], "normalized": [] }, { "id": "PMID-10036181_T22", "type": "Gene", "offsets": [ [ 488, 493 ] ], "text": [ "GPR34" ], "normalized": [] }, { "id": "PMID-10036181_T23", "type": "OpenReadingFrame", "offsets": [ [ 665, 683 ] ], "text": [ "open reading frame" ], "normalized": [] }, { "id": "PMID-10036181_T24", "type": "Eukaryote", "offsets": [ [ 691, 696 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10036181_T25", "type": "Gene", "offsets": [ [ 754, 759 ] ], "text": [ "GPR34" ], "normalized": [] }, { "id": "PMID-10036181_T26", "type": "DNA", "offsets": [ [ 764, 769 ] ], "text": [ "cDNAs" ], "normalized": [] }, { "id": "PMID-10036181_T27", "type": "Gene", "offsets": [ [ 829, 834 ] ], "text": [ "GPR34" ], "normalized": [] }, { "id": "PMID-10036181_T28", "type": "MessengerRNA", "offsets": [ [ 835, 851 ] ], "text": [ "mRNA transcripts" ], "normalized": [] }, { "id": "PMID-10036181_T29", "type": "Eukaryote", "offsets": [ [ 863, 868 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10036181_T30", "type": "Eukaryote", "offsets": [ [ 873, 876 ] ], "text": [ "rat" ], "normalized": [] }, { "id": "PMID-10036181_T31", "type": "Tissue", "offsets": [ [ 877, 890 ] ], "text": [ "brain regions" ], "normalized": [] }, { "id": "PMID-10036181_T32", "type": "Eukaryote", "offsets": [ [ 949, 954 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10036181_T33", "type": "DNA", "offsets": [ [ 955, 966 ] ], "text": [ "genomic DNA" ], "normalized": [] }, { "id": "PMID-10036181_T34", "type": "Sequence", "offsets": [ [ 1015, 1024 ] ], "text": [ "sequences" ], "normalized": [] }, { "id": "PMID-10036181_T38", "type": "Protein", "offsets": [ [ 1144, 1149 ] ], "text": [ "GPCRs" ], "normalized": [] }, { "id": "PMID-10036181_T39", "type": "Protein", "offsets": [ [ 1157, 1162 ] ], "text": [ "GPR44" ], "normalized": [] }, { "id": "PMID-10036181_T40", "type": "Protein", "offsets": [ [ 1167, 1172 ] ], "text": [ "GPR45" ], "normalized": [] }, { "id": "PMID-10036181_T41", "type": "OpenReadingFrame", "offsets": [ [ 1240, 1259 ] ], "text": [ "open reading frames" ], "normalized": [] }, { "id": "PMID-10036181_T42", "type": "Eukaryote", "offsets": [ [ 1267, 1272 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10036181_T43", "type": "Protein", "offsets": [ [ 1295, 1300 ] ], "text": [ "GPR44" ], "normalized": [] }, { "id": "PMID-10036181_T44", "type": "Protein", "offsets": [ [ 1305, 1310 ] ], "text": [ "GPR45" ], "normalized": [] }, { "id": "PMID-10036181_T46", "type": "Chromosome", "offsets": [ [ 1374, 1385 ] ], "text": [ "chromosomal" ], "normalized": [] }, { "id": "PMID-10036181_T48", "type": "Gene", "offsets": [ [ 1468, 1473 ] ], "text": [ "GPR34" ], "normalized": [] }, { "id": "PMID-10036181_T49", "type": "Chromosome", "offsets": [ [ 1477, 1488 ] ], "text": [ "chromosomes" ], "normalized": [] }, { "id": "PMID-10036181_T50", "type": "Gene", "offsets": [ [ 1507, 1512 ] ], "text": [ "GPR44" ], "normalized": [] }, { "id": "PMID-10036181_T51", "type": "Chromosome", "offsets": [ [ 1516, 1526 ] ], "text": [ "chromosome" ], "normalized": [] }, { "id": "PMID-10036181_T52", "type": "Gene", "offsets": [ [ 1544, 1549 ] ], "text": [ "GPR45" ], "normalized": [] }, { "id": "PMID-10036181_T53", "type": "Chromosome", "offsets": [ [ 1553, 1563 ] ], "text": [ "chromosome" ], "normalized": [] }, { "id": "PMID-10036181_T2", "type": "ProteinDomain", "offsets": [ [ 1034, 1063 ] ], "text": [ "transmembrane domains 3 and 7" ], "normalized": [] }, { "id": "PMID-10036181_T8", "type": "Protein", "offsets": [ [ 1067, 1100 ] ], "text": [ "opioid and somatostatin receptors" ], "normalized": [] }, { "id": "PMID-10036181_T35", "type": "Tissue", "offsets": [ [ 1332, 1368 ] ], "text": [ "central nervous system and periphery" ], "normalized": [] }, { "id": "PMID-10036181_T36", "type": "ExperimentalMethod", "offsets": [ [ 1386, 1398 ] ], "text": [ "localization" ], "normalized": [] } ]
[ { "id": "PMID-10036181_E1", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1315, 1324 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036181_T43" } ] }, { "id": "PMID-10036181_E2", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1315, 1324 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036181_T44" } ] } ]
[]
[ { "arg1_id": "PMID-10036181_T4", "arg2_id": "PMID-10036181_T3", "id": "PMID-10036181_R1", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036181_T5", "arg2_id": "PMID-10036181_T9", "id": "PMID-10036181_R2", "type": "encodes", "normalized": [] }, { "arg1_id": "PMID-10036181_T6", "arg2_id": "PMID-10036181_T9", "id": "PMID-10036181_R3", "type": "encodes", "normalized": [] }, { "arg1_id": "PMID-10036181_T7", "arg2_id": "PMID-10036181_T9", "id": "PMID-10036181_R4", "type": "encodes", "normalized": [] }, { "arg1_id": "PMID-10036181_T12", "arg2_id": "PMID-10036181_T11", "id": "PMID-10036181_R5", "type": "encodes", "normalized": [] }, { "arg1_id": "PMID-10036181_T15", "arg2_id": "PMID-10036181_T14", "id": "PMID-10036181_R6", "type": "encodes", "normalized": [] }, { "arg1_id": "PMID-10036181_T17", "arg2_id": "PMID-10036181_T19", "id": "PMID-10036181_R7", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036181_T18", "arg2_id": "PMID-10036181_T17", "id": "PMID-10036181_R8", "type": "encodes", "normalized": [] }, { "arg1_id": "PMID-10036181_T20", "arg2_id": "PMID-10036181_T21", "id": "PMID-10036181_R9", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036181_T27", "arg2_id": "PMID-10036181_T28", "id": "PMID-10036181_R10", "type": "encodes", "normalized": [] }, { "arg1_id": "PMID-10036181_T28", "arg2_id": "PMID-10036181_T31", "id": "PMID-10036181_R11", "type": "locatedIn", "normalized": [] }, { "arg1_id": "PMID-10036181_T31", "arg2_id": "PMID-10036181_T29", "id": "PMID-10036181_R12", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036181_T31", "arg2_id": "PMID-10036181_T30", "id": "PMID-10036181_R13", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036181_T33", "arg2_id": "PMID-10036181_T32", "id": "PMID-10036181_R14", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036181_T48", "arg2_id": "PMID-10036181_T49", "id": "PMID-10036181_R19", "type": "locatedIn", "normalized": [] }, { "arg1_id": "PMID-10036181_T50", "arg2_id": "PMID-10036181_T51", "id": "PMID-10036181_R20", "type": "locatedIn", "normalized": [] }, { "arg1_id": "PMID-10036181_T52", "arg2_id": "PMID-10036181_T53", "id": "PMID-10036181_R21", "type": "locatedIn", "normalized": [] }, { "arg1_id": "PMID-10036181_T23", "arg2_id": "PMID-10036181_T24", "id": "PMID-10036181_R22", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036181_T34", "arg2_id": "PMID-10036181_T2", "id": "PMID-10036181_R15", "type": "encodes", "normalized": [] }, { "arg1_id": "PMID-10036181_T8", "arg2_id": "PMID-10036181_T2", "id": "PMID-10036181_R16", "type": "hasPart", "normalized": [] }, { "arg1_id": "PMID-10036181_T41", "arg2_id": "PMID-10036181_T42", "id": "PMID-10036181_R17", "type": "fromSpecies", "normalized": [] } ]
15
PMID-10036186
[ { "id": "PMID-10036186__text", "type": "abstract", "text": [ "A gene upregulated in the acoustically damaged chick basilar papilla encodes a novel WD40 repeat protein. The chick WDR1 gene is expressed at higher levels in the chick basilar papilla after acoustic overstimulation. The 3.3-kb WDR1 cDNA encodes a novel 67-kDa protein containing nine WD40 repeats, motifs that mediate protein-protein interactions. The predicted WDR1 protein has high sequence identity to WD40-repeat proteins in budding yeast (Saccharomyces cerevisiae), two slime molds (Dictyostelium discoideum and Physarum polycephalum), and the roundworm (Caenorhabditis elegans). The yeast and P. polycephalum proteins bind actin, suggesting that the novel chick protein may be an actin-binding protein. Sequence database comparisons identified mouse and human cDNAs with high sequence identity to the chick WDR1 cDNA. The mouse Wdr1 and human WDR1 proteins showed 95% sequence identity to each other and 86% identity to the chick WDR1 protein. Northern blot analysis of total RNA from the chick basilar papilla after noise trauma revealed increased levels of a 3.1-kb transcript in the lesioned area. The WDR1 gene was mapped to human chromosome 4, between 22 and 24 cM from the telomere of 4p.\n" ], "offsets": [ [ 0, 1202 ] ] } ]
[ { "id": "PMID-10036186_T3", "type": "Eukaryote", "offsets": [ [ 47, 52 ] ], "text": [ "chick" ], "normalized": [] }, { "id": "PMID-10036186_T4", "type": "Tissue", "offsets": [ [ 53, 68 ] ], "text": [ "basilar papilla" ], "normalized": [] }, { "id": "PMID-10036186_T7", "type": "Eukaryote", "offsets": [ [ 110, 115 ] ], "text": [ "chick" ], "normalized": [] }, { "id": "PMID-10036186_T8", "type": "Gene", "offsets": [ [ 116, 120 ] ], "text": [ "WDR1" ], "normalized": [] }, { "id": "PMID-10036186_T10", "type": "Eukaryote", "offsets": [ [ 163, 168 ] ], "text": [ "chick" ], "normalized": [] }, { "id": "PMID-10036186_T11", "type": "Tissue", "offsets": [ [ 169, 184 ] ], "text": [ "basilar papilla" ], "normalized": [] }, { "id": "PMID-10036186_T33", "type": "Protein", "offsets": [ [ 630, 635 ] ], "text": [ "actin" ], "normalized": [] }, { "id": "PMID-10036186_T36", "type": "Protein", "offsets": [ [ 687, 692 ] ], "text": [ "actin" ], "normalized": [] }, { "id": "PMID-10036186_T42", "type": "Eukaryote", "offsets": [ [ 808, 813 ] ], "text": [ "chick" ], "normalized": [] }, { "id": "PMID-10036186_T44", "type": "Eukaryote", "offsets": [ [ 829, 834 ] ], "text": [ "mouse" ], "normalized": [] }, { "id": "PMID-10036186_T45", "type": "Protein", "offsets": [ [ 835, 839 ] ], "text": [ "Wdr1" ], "normalized": [] }, { "id": "PMID-10036186_T46", "type": "Eukaryote", "offsets": [ [ 844, 849 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10036186_T48", "type": "Eukaryote", "offsets": [ [ 931, 936 ] ], "text": [ "chick" ], "normalized": [] }, { "id": "PMID-10036186_T51", "type": "Eukaryote", "offsets": [ [ 996, 1001 ] ], "text": [ "chick" ], "normalized": [] }, { "id": "PMID-10036186_T52", "type": "Tissue", "offsets": [ [ 1002, 1017 ] ], "text": [ "basilar papilla" ], "normalized": [] }, { "id": "PMID-10036186_T55", "type": "Eukaryote", "offsets": [ [ 1136, 1141 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10036186_T56", "type": "Chromosome", "offsets": [ [ 1142, 1154 ] ], "text": [ "chromosome 4" ], "normalized": [] }, { "id": "PMID-10036186_T5", "type": "Protein", "offsets": [ [ 85, 104 ] ], "text": [ "WD40 repeat protein" ], "normalized": [] }, { "id": "PMID-10036186_T6", "type": "Gene", "offsets": [ [ 2, 6 ] ], "text": [ "gene" ], "normalized": [] }, { "id": "PMID-10036186_T12", "type": "DNA", "offsets": [ [ 228, 237 ] ], "text": [ "WDR1 cDNA" ], "normalized": [] }, { "id": "PMID-10036186_T13", "type": "Protein", "offsets": [ [ 261, 268 ] ], "text": [ "protein" ], "normalized": [] }, { "id": "PMID-10036186_T14", "type": "ProteinDomain", "offsets": [ [ 285, 297 ] ], "text": [ "WD40 repeats" ], "normalized": [] }, { "id": "PMID-10036186_T17", "type": "ProteinDomain", "offsets": [ [ 299, 305 ] ], "text": [ "motifs" ], "normalized": [] }, { "id": "PMID-10036186_T18", "type": "Protein", "offsets": [ [ 363, 375 ] ], "text": [ "WDR1 protein" ], "normalized": [] }, { "id": "PMID-10036186_T19", "type": "Protein", "offsets": [ [ 406, 426 ] ], "text": [ "WD40-repeat proteins" ], "normalized": [] }, { "id": "PMID-10036186_T20", "type": "Eukaryote", "offsets": [ [ 430, 443 ] ], "text": [ "budding yeast" ], "normalized": [] }, { "id": "PMID-10036186_T21", "type": "Eukaryote", "offsets": [ [ 445, 469 ] ], "text": [ "Saccharomyces cerevisiae" ], "normalized": [] }, { "id": "PMID-10036186_T22", "type": "Eukaryote", "offsets": [ [ 476, 487 ] ], "text": [ "slime molds" ], "normalized": [] }, { "id": "PMID-10036186_T23", "type": "Eukaryote", "offsets": [ [ 489, 513 ] ], "text": [ "Dictyostelium discoideum" ], "normalized": [] }, { "id": "PMID-10036186_T24", "type": "Eukaryote", "offsets": [ [ 518, 539 ] ], "text": [ "Physarum polycephalum" ], "normalized": [] }, { "id": "PMID-10036186_T25", "type": "Eukaryote", "offsets": [ [ 550, 559 ] ], "text": [ "roundworm" ], "normalized": [] }, { "id": "PMID-10036186_T26", "type": "Eukaryote", "offsets": [ [ 561, 583 ] ], "text": [ "Caenorhabditis elegans" ], "normalized": [] }, { "id": "PMID-10036186_T1", "type": "Eukaryote", "offsets": [ [ 590, 595 ] ], "text": [ "yeast" ], "normalized": [] }, { "id": "PMID-10036186_T27", "type": "Eukaryote", "offsets": [ [ 600, 615 ] ], "text": [ "P. polycephalum" ], "normalized": [] }, { "id": "PMID-10036186_T28", "type": "Protein", "offsets": [ [ 616, 624 ] ], "text": [ "proteins" ], "normalized": [] }, { "id": "PMID-10036186_T29", "type": "Protein", "offsets": [ [ 669, 676 ] ], "text": [ "protein" ], "normalized": [] }, { "id": "PMID-10036186_T30", "type": "Eukaryote", "offsets": [ [ 663, 668 ] ], "text": [ "chick" ], "normalized": [] }, { "id": "PMID-10036186_T31", "type": "DNA", "offsets": [ [ 814, 823 ] ], "text": [ "WDR1 cDNA" ], "normalized": [] }, { "id": "PMID-10036186_T34", "type": "Eukaryote", "offsets": [ [ 751, 756 ] ], "text": [ "mouse" ], "normalized": [] }, { "id": "PMID-10036186_T35", "type": "Eukaryote", "offsets": [ [ 761, 766 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10036186_T38", "type": "DNA", "offsets": [ [ 767, 772 ] ], "text": [ "cDNAs" ], "normalized": [] }, { "id": "PMID-10036186_T39", "type": "SequenceHomologyAnalysis", "offsets": [ [ 710, 739 ] ], "text": [ "Sequence database comparisons" ], "normalized": [] }, { "id": "PMID-10036186_T40", "type": "Protein", "offsets": [ [ 850, 863 ] ], "text": [ "WDR1 proteins" ], "normalized": [] }, { "id": "PMID-10036186_T41", "type": "Protein", "offsets": [ [ 937, 949 ] ], "text": [ "WDR1 protein" ], "normalized": [] }, { "id": "PMID-10036186_T43", "type": "RNA", "offsets": [ [ 983, 986 ] ], "text": [ "RNA" ], "normalized": [] }, { "id": "PMID-10036186_T49", "type": "Transcript", "offsets": [ [ 1075, 1085 ] ], "text": [ "transcript" ], "normalized": [] }, { "id": "PMID-10036186_T50", "type": "Tissue", "offsets": [ [ 1093, 1106 ] ], "text": [ "lesioned area" ], "normalized": [] }, { "id": "PMID-10036186_T53", "type": "Gene", "offsets": [ [ 1112, 1121 ] ], "text": [ "WDR1 gene" ], "normalized": [] } ]
[ { "id": "PMID-10036186_E1", "type": "PositiveRegulationOfGeneExpression", "trigger": { "text": [ "upregulated" ], "offsets": [ [ 7, 18 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036186_T6" } ] }, { "id": "PMID-10036186_E5", "type": "BindingToProtein", "trigger": { "text": [ "bind" ], "offsets": [ [ 625, 629 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036186_T33" }, { "role": "hasPatient2", "ref_id": "PMID-10036186_T28" } ] }, { "id": "PMID-10036186_E6", "type": "BindingToProtein", "trigger": { "text": [ "binding" ], "offsets": [ [ 693, 700 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036186_T36" }, { "role": "hasPatient2", "ref_id": "PMID-10036186_T29" } ] }, { "id": "PMID-10036186_E2", "type": "PositiveRegulationOfGeneExpression", "trigger": { "text": [ "expressed at higher levels" ], "offsets": [ [ 129, 155 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036186_T8" } ] }, { "id": "PMID-10036186_E3", "type": "RegulatoryProcess", "trigger": { "text": [ "mediate" ], "offsets": [ [ 311, 318 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036186_E4" }, { "role": "hasAgent", "ref_id": "PMID-10036186_T17" } ] }, { "id": "PMID-10036186_E4", "type": "BindingToProtein", "trigger": { "text": [ "protein-protein interaction" ], "offsets": [ [ 319, 346 ] ] }, "arguments": [] }, { "id": "PMID-10036186_E7", "type": "Increase", "trigger": { "text": [ "increased levels" ], "offsets": [ [ 1046, 1062 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036186_T49" } ] } ]
[]
[ { "arg1_id": "PMID-10036186_T4", "arg2_id": "PMID-10036186_T3", "id": "PMID-10036186_R3", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036186_T8", "arg2_id": "PMID-10036186_T7", "id": "PMID-10036186_R5", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036186_T11", "arg2_id": "PMID-10036186_T10", "id": "PMID-10036186_R7", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036186_T45", "arg2_id": "PMID-10036186_T44", "id": "PMID-10036186_R24", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036186_T52", "arg2_id": "PMID-10036186_T51", "id": "PMID-10036186_R27", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036186_T56", "arg2_id": "PMID-10036186_T55", "id": "PMID-10036186_R28", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036186_T6", "arg2_id": "PMID-10036186_T5", "id": "PMID-10036186_R1", "type": "encodes", "normalized": [] }, { "arg1_id": "PMID-10036186_T12", "arg2_id": "PMID-10036186_T13", "id": "PMID-10036186_R6", "type": "encodes", "normalized": [] }, { "arg1_id": "PMID-10036186_T13", "arg2_id": "PMID-10036186_T14", "id": "PMID-10036186_R8", "type": "hasPart", "normalized": [] }, { "arg1_id": "PMID-10036186_T19", "arg2_id": "PMID-10036186_T20", "id": "PMID-10036186_R9", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036186_T19", "arg2_id": "PMID-10036186_T22", "id": "PMID-10036186_R10", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036186_T19", "arg2_id": "PMID-10036186_T25", "id": "PMID-10036186_R11", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036186_T28", "arg2_id": "PMID-10036186_T27", "id": "PMID-10036186_R12", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036186_T28", "arg2_id": "PMID-10036186_T1", "id": "PMID-10036186_R13", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036186_T29", "arg2_id": "PMID-10036186_T30", "id": "PMID-10036186_R14", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036186_T31", "arg2_id": "PMID-10036186_T42", "id": "PMID-10036186_R15", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036186_T38", "arg2_id": "PMID-10036186_T34", "id": "PMID-10036186_R16", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036186_T38", "arg2_id": "PMID-10036186_T35", "id": "PMID-10036186_R17", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036186_T40", "arg2_id": "PMID-10036186_T46", "id": "PMID-10036186_R18", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036186_T41", "arg2_id": "PMID-10036186_T48", "id": "PMID-10036186_R19", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10036186_T49", "arg2_id": "PMID-10036186_T50", "id": "PMID-10036186_R20", "type": "locatedIn", "normalized": [] }, { "arg1_id": "PMID-10036186_T53", "arg2_id": "PMID-10036186_T56", "id": "PMID-10036186_R21", "type": "locatedIn", "normalized": [] } ]
16
PMID-10036192
[ { "id": "PMID-10036192__text", "type": "abstract", "text": [ "DCAMKL1, a brain-specific transmembrane protein on 13q12.3 that is similar to doublecortin (DCX). Mutations in the human doublecortin (DCX), a brain-specific putative signaling protein, cause X-linked lissencephaly and subcortical band heterotopia. A predicted 740-amino-acid protein from human brain has two distinct regions, an N-terminal 345-amino-acid region 78% similar to the DCX protein and a C-terminal 427-amino-acid region that contains two transmembrane domains and is 98% homologous to a rat Ca2+/calmodulin-dependent protein kinase. We have designated this protein DCAMKL1. It maps to chromosome 13q12.3-q13, within a 540-kb YAC clone containing markers D13S805 and D13S1164. Northern analysis detected three major transcript isoforms of the DCAMKL1 gene expressed differentially and predominantly in human fetal and adult brain and during mouse embryogenesis (11-17 dpc). These results and its homology with the DCX and Ca2+/calmodulin dependent kinase proteins suggest a likely role for DCAMKL1 transmembrane protein in developing and adult brain, possibly in a pathway of cortical development.\n" ], "offsets": [ [ 0, 1110 ] ] } ]
[ { "id": "PMID-10036192_T1", "type": "Protein", "offsets": [ [ 0, 7 ] ], "text": [ "DCAMKL1" ], "normalized": [] }, { "id": "PMID-10036192_T2", "type": "Tissue", "offsets": [ [ 11, 16 ] ], "text": [ "brain" ], "normalized": [] }, { "id": "PMID-10036192_T3", "type": "Protein", "offsets": [ [ 26, 47 ] ], "text": [ "transmembrane protein" ], "normalized": [] }, { "id": "PMID-10036192_T4", "type": "Protein", "offsets": [ [ 78, 90 ] ], "text": [ "doublecortin" ], "normalized": [] }, { "id": "PMID-10036192_T5", "type": "Protein", "offsets": [ [ 92, 95 ] ], "text": [ "DCX" ], "normalized": [] }, { "id": "PMID-10036192_T7", "type": "Eukaryote", "offsets": [ [ 115, 120 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10036192_T8", "type": "Protein", "offsets": [ [ 121, 133 ] ], "text": [ "doublecortin" ], "normalized": [] }, { "id": "PMID-10036192_T9", "type": "Protein", "offsets": [ [ 135, 138 ] ], "text": [ "DCX" ], "normalized": [] }, { "id": "PMID-10036192_T10", "type": "Tissue", "offsets": [ [ 143, 148 ] ], "text": [ "brain" ], "normalized": [] }, { "id": "PMID-10036192_T11", "type": "Protein", "offsets": [ [ 167, 184 ] ], "text": [ "signaling protein" ], "normalized": [] }, { "id": "PMID-10036192_T14", "type": "AminoAcid", "offsets": [ [ 265, 275 ] ], "text": [ "amino-acid" ], "normalized": [] }, { "id": "PMID-10036192_T15", "type": "Protein", "offsets": [ [ 276, 283 ] ], "text": [ "protein" ], "normalized": [] }, { "id": "PMID-10036192_T16", "type": "Eukaryote", "offsets": [ [ 289, 294 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10036192_T17", "type": "Tissue", "offsets": [ [ 295, 300 ] ], "text": [ "brain" ], "normalized": [] }, { "id": "PMID-10036192_T18", "type": "AminoAcid", "offsets": [ [ 345, 355 ] ], "text": [ "amino-acid" ], "normalized": [] }, { "id": "PMID-10036192_T19", "type": "Protein", "offsets": [ [ 382, 393 ] ], "text": [ "DCX protein" ], "normalized": [] }, { "id": "PMID-10036192_T20", "type": "AminoAcid", "offsets": [ [ 415, 425 ] ], "text": [ "amino-acid" ], "normalized": [] }, { "id": "PMID-10036192_T21", "type": "ProteinDomain", "offsets": [ [ 451, 472 ] ], "text": [ "transmembrane domains" ], "normalized": [] }, { "id": "PMID-10036192_T22", "type": "Eukaryote", "offsets": [ [ 500, 503 ] ], "text": [ "rat" ], "normalized": [] }, { "id": "PMID-10036192_T25", "type": "Protein", "offsets": [ [ 570, 577 ] ], "text": [ "protein" ], "normalized": [] }, { "id": "PMID-10036192_T26", "type": "Protein", "offsets": [ [ 578, 585 ] ], "text": [ "DCAMKL1" ], "normalized": [] }, { "id": "PMID-10036192_T27", "type": "Chromosome", "offsets": [ [ 598, 608 ] ], "text": [ "chromosome" ], "normalized": [] }, { "id": "PMID-10036192_T28", "type": "Transcript", "offsets": [ [ 728, 738 ] ], "text": [ "transcript" ], "normalized": [] }, { "id": "PMID-10036192_T29", "type": "Gene", "offsets": [ [ 755, 767 ] ], "text": [ "DCAMKL1 gene" ], "normalized": [] }, { "id": "PMID-10036192_T31", "type": "Eukaryote", "offsets": [ [ 814, 819 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10036192_T32", "type": "Tissue", "offsets": [ [ 820, 825 ] ], "text": [ "fetal" ], "normalized": [] }, { "id": "PMID-10036192_T33", "type": "Tissue", "offsets": [ [ 830, 841 ] ], "text": [ "adult brain" ], "normalized": [] }, { "id": "PMID-10036192_T34", "type": "Eukaryote", "offsets": [ [ 853, 858 ] ], "text": [ "mouse" ], "normalized": [] }, { "id": "PMID-10036192_T36", "type": "Protein", "offsets": [ [ 926, 929 ] ], "text": [ "DCX" ], "normalized": [] }, { "id": "PMID-10036192_T39", "type": "Protein", "offsets": [ [ 1002, 1009 ] ], "text": [ "DCAMKL1" ], "normalized": [] }, { "id": "PMID-10036192_T40", "type": "Protein", "offsets": [ [ 1010, 1031 ] ], "text": [ "transmembrane protein" ], "normalized": [] }, { "id": "PMID-10036192_T41", "type": "Tissue", "offsets": [ [ 1050, 1061 ] ], "text": [ "adult brain" ], "normalized": [] }, { "id": "PMID-10036192_T23", "type": "Enzyme", "offsets": [ [ 504, 544 ] ], "text": [ "Ca2+/calmodulin-dependent protein kinase" ], "normalized": [] }, { "id": "PMID-10036192_T24", "type": "Protein", "offsets": [ [ 934, 975 ] ], "text": [ "Ca2+/calmodulin dependent kinase proteins" ], "normalized": [] } ]
[ { "id": "PMID-10036192_E1", "type": "Mutation", "trigger": { "text": [ "Mutations" ], "offsets": [ [ 98, 107 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036192_T8" } ] }, { "id": "PMID-10036192_E2", "type": "Disease", "trigger": { "text": [ "X-linked lissencephaly" ], "offsets": [ [ 192, 214 ] ] }, "arguments": [] }, { "id": "PMID-10036192_E3", "type": "Disease", "trigger": { "text": [ "subcortical band heterotopia" ], "offsets": [ [ 219, 247 ] ] }, "arguments": [] }, { "id": "PMID-10036192_E4", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 768, 777 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036192_T29" } ] }, { "id": "PMID-10036192_E5", "type": "DevelopmentalProcess", "trigger": { "text": [ "embryogenesis" ], "offsets": [ [ 859, 872 ] ] }, "arguments": [] }, { "id": "PMID-10036192_E6", "type": "DevelopmentalProcess", "trigger": { "text": [ "cortical development" ], "offsets": [ [ 1088, 1108 ] ] }, "arguments": [] } ]
[]
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17
PMID-10036195
[ { "id": "PMID-10036195__text", "type": "abstract", "text": [ "The human POP2 gene: identification, sequencing, and mapping to the critical region of the 5q- syndrome.\n" ], "offsets": [ [ 0, 105 ] ] } ]
[ { "id": "PMID-10036195_T1", "type": "Eukaryote", "offsets": [ [ 4, 9 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10036195_T2", "type": "Gene", "offsets": [ [ 10, 19 ] ], "text": [ "POP2 gene" ], "normalized": [] } ]
[ { "id": "PMID-10036195_E1", "type": "Disease", "trigger": { "text": [ "5q- syndrome" ], "offsets": [ [ 91, 103 ] ] }, "arguments": [] } ]
[]
[]
18
PMID-10036235
[ { "id": "PMID-10036235__text", "type": "abstract", "text": [ "ARF6 requirement for Rac ruffling suggests a role for membrane trafficking in cortical actin rearrangements. The ARF6 GTPase regulates a novel endosomal-plasma membrane recycling pathway and influences cortical actin remodeling. Here we examined the relationship between ARF6 and Rac1, a Rho family GTPase, implicated in cortical actin rearrangements. Endogenous Rac1 colocalized with ARF6 at the plasma membrane and on the ARF6 recycling endosome in untransfected HeLa and primary human fibroblast cells. In transfected HeLa cells Rac1 and ARF6 also colocalized. Cells expressing wild-type ARF6 or Rac1 formed actin-containing surface protrusions and membrane ruffles, respectively, upon treatment with the G protein activator aluminum fluoride. Aluminum fluoride-treatment of cells transfected with equivalent amounts of plasmid resulted in enhanced membrane ruffling, with protrusions appearing as Rac expression was lowered. Co-expression of the dominant negative, GTP binding-defective ARF6 T27N mutant inhibited the aluminum fluoride-induced ruffling observed in cells expressing Rac1, and the constitutive ruffling observed in cells expressing the activated Rac1 Q61L mutant. In contrast, co-expression of the GTP-binding-defective, T17N mutant of either Rac1 or Cdc42 with ARF6 did not inhibit the aluminum fluoride-induced surface protrusions, nor did inactivation of Rho with C3-transferase. These observations suggest that ARF6, a non-Rho family GTPase, can, by itself, alter cortical actin and can influence the ability of Rac1 to form lamellipodia, in part, by regulating its trafficking to the plasma membrane.\n" ], "offsets": [ [ 0, 1625 ] ] } ]
[ { "id": "PMID-10036235_T1", "type": "Enzyme", "offsets": [ [ 0, 4 ] ], "text": [ "ARF6" ], "normalized": [] }, { "id": "PMID-10036235_T3", "type": "CellComponent", "offsets": [ [ 54, 62 ] ], "text": [ "membrane" ], "normalized": [] }, { "id": "PMID-10036235_T5", "type": "Protein", "offsets": [ [ 78, 92 ] ], "text": [ "cortical actin" ], "normalized": [] }, { "id": "PMID-10036235_T7", "type": "Enzyme", "offsets": [ [ 113, 124 ] ], "text": [ "ARF6 GTPase" ], "normalized": [] }, { "id": "PMID-10036235_T9", "type": "CellComponent", "offsets": [ [ 143, 168 ] ], "text": [ "endosomal-plasma membrane" ], "normalized": [] }, { "id": "PMID-10036235_T10", "type": "Protein", "offsets": [ [ 202, 216 ] ], "text": [ "cortical actin" ], "normalized": [] }, { "id": "PMID-10036235_T12", "type": "Enzyme", "offsets": [ [ 271, 275 ] ], "text": [ "ARF6" ], "normalized": [] }, { "id": "PMID-10036235_T13", "type": "Enzyme", "offsets": [ [ 280, 284 ] ], "text": [ "Rac1" ], "normalized": [] }, { "id": "PMID-10036235_T14", "type": "Enzyme", "offsets": [ [ 299, 305 ] ], "text": [ "GTPase" ], "normalized": [] }, { "id": "PMID-10036235_T15", "type": "Protein", "offsets": [ [ 321, 335 ] ], "text": [ "cortical actin" ], "normalized": [] }, { "id": "PMID-10036235_T17", "type": "Enzyme", "offsets": [ [ 363, 367 ] ], "text": [ "Rac1" ], "normalized": [] }, { "id": "PMID-10036235_T18", "type": "Enzyme", "offsets": [ [ 385, 389 ] ], "text": [ "ARF6" ], "normalized": [] }, { "id": "PMID-10036235_T19", "type": "CellComponent", "offsets": [ [ 397, 412 ] ], "text": [ "plasma membrane" ], "normalized": [] }, { "id": "PMID-10036235_T20", "type": "Enzyme", "offsets": [ [ 424, 428 ] ], "text": [ "ARF6" ], "normalized": [] }, { "id": "PMID-10036235_T21", "type": "Cell", "offsets": [ [ 465, 469 ] ], "text": [ "HeLa" ], "normalized": [] }, { "id": "PMID-10036235_T22", "type": "Eukaryote", "offsets": [ [ 482, 487 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10036235_T23", "type": "Cell", "offsets": [ [ 488, 504 ] ], "text": [ "fibroblast cells" ], "normalized": [] }, { "id": "PMID-10036235_T24", "type": "Cell", "offsets": [ [ 521, 531 ] ], "text": [ "HeLa cells" ], "normalized": [] }, { "id": "PMID-10036235_T25", "type": "Enzyme", "offsets": [ [ 532, 536 ] ], "text": [ "Rac1" ], "normalized": [] }, { "id": "PMID-10036235_T26", "type": "Enzyme", "offsets": [ [ 541, 545 ] ], "text": [ "ARF6" ], "normalized": [] }, { "id": "PMID-10036235_T27", "type": "Cell", "offsets": [ [ 564, 569 ] ], "text": [ "Cells" ], "normalized": [] }, { "id": "PMID-10036235_T29", "type": "Enzyme", "offsets": [ [ 591, 595 ] ], "text": [ "ARF6" ], "normalized": [] }, { "id": "PMID-10036235_T30", "type": "Enzyme", "offsets": [ [ 599, 603 ] ], "text": [ "Rac1" ], "normalized": [] }, { "id": "PMID-10036235_T32", "type": "Protein", "offsets": [ [ 708, 717 ] ], "text": [ "G protein" ], "normalized": [] }, { "id": "PMID-10036235_T34", "type": "InorganicChemical", "offsets": [ [ 728, 745 ] ], "text": [ "aluminum fluoride" ], "normalized": [] }, { "id": "PMID-10036235_T35", "type": "InorganicChemical", "offsets": [ [ 747, 764 ] ], "text": [ "Aluminum fluoride" ], "normalized": [] }, { "id": "PMID-10036235_T36", "type": "Cell", "offsets": [ [ 778, 783 ] ], "text": [ "cells" ], "normalized": [] }, { "id": "PMID-10036235_T38", "type": "Enzyme", "offsets": [ [ 901, 904 ] ], "text": [ "Rac" ], "normalized": [] }, { "id": "PMID-10036235_T44", "type": "InorganicChemical", "offsets": [ [ 1022, 1039 ] ], "text": [ "aluminum fluoride" ], "normalized": [] }, { "id": "PMID-10036235_T47", "type": "Cell", "offsets": [ [ 1069, 1074 ] ], "text": [ "cells" ], "normalized": [] }, { "id": "PMID-10036235_T49", "type": "Enzyme", "offsets": [ [ 1086, 1090 ] ], "text": [ "Rac1" ], "normalized": [] }, { "id": "PMID-10036235_T51", "type": "Cell", "offsets": [ [ 1134, 1139 ] ], "text": [ "cells" ], "normalized": [] }, { "id": "PMID-10036235_T58", "type": "Enzyme", "offsets": [ [ 1262, 1266 ] ], "text": [ "Rac1" ], "normalized": [] }, { "id": "PMID-10036235_T59", "type": "Enzyme", "offsets": [ [ 1281, 1285 ] ], "text": [ "ARF6" ], "normalized": [] }, { "id": "PMID-10036235_T61", "type": "InorganicChemical", "offsets": [ [ 1306, 1323 ] ], "text": [ "aluminum fluoride" ], "normalized": [] }, { "id": "PMID-10036235_T62", "type": "Enzyme", "offsets": [ [ 1386, 1400 ] ], "text": [ "C3-transferase" ], "normalized": [] }, { "id": "PMID-10036235_T63", "type": "Enzyme", "offsets": [ [ 1434, 1438 ] ], "text": [ "ARF6" ], "normalized": [] }, { "id": "PMID-10036235_T64", "type": "Enzyme", "offsets": [ [ 1457, 1463 ] ], "text": [ "GTPase" ], "normalized": [] }, { "id": "PMID-10036235_T65", "type": "Protein", "offsets": [ [ 1487, 1501 ] ], "text": [ "cortical actin" ], "normalized": [] }, { "id": "PMID-10036235_T66", "type": "Enzyme", "offsets": [ [ 1535, 1539 ] ], "text": [ "Rac1" ], "normalized": [] }, { "id": "PMID-10036235_T67", "type": "CellComponent", "offsets": [ [ 1548, 1560 ] ], "text": [ "lamellipodia" ], "normalized": [] }, { "id": "PMID-10036235_T70", "type": "CellComponent", "offsets": [ [ 1608, 1623 ] ], "text": [ "plasma membrane" ], "normalized": [] }, { "id": "PMID-10036235_T72", "type": "CellComponent", "offsets": [ [ 439, 447 ] ], "text": [ "endosome" ], "normalized": [] }, { "id": "PMID-10036235_T73", "type": "CellComponent", "offsets": [ [ 652, 668 ] ], "text": [ "membrane ruffles" ], "normalized": [] }, { "id": "PMID-10036235_T31", "type": "CellComponent", "offsets": [ [ 611, 647 ] ], "text": [ "actin-containing surface protrusions" ], "normalized": [] }, { "id": "PMID-10036235_T41", "type": "MutantProtein", "offsets": [ [ 969, 1007 ] ], "text": [ "GTP binding-defective ARF6 T27N mutant" ], "normalized": [] }, { "id": "PMID-10036235_T42", "type": "MutantProtein", "offsets": [ [ 1165, 1181 ] ], "text": [ "Rac1 Q61L mutant" ], "normalized": [] }, { "id": "PMID-10036235_T54", "type": "Enzyme", "offsets": [ [ 1270, 1275 ] ], "text": [ "Cdc42" ], "normalized": [] }, { "id": "PMID-10036235_T56", "type": "MutantProtein", "offsets": [ [ 1217, 1251 ] ], "text": [ "GTP-binding-defective, T17N mutant" ], "normalized": [] }, { "id": "PMID-10036235_T57", "type": "CellComponent", "offsets": [ [ 1332, 1351 ] ], "text": [ "surface protrusions" ], "normalized": [] }, { "id": "PMID-10036235_T78", "type": "Enzyme", "offsets": [ [ 1377, 1380 ] ], "text": [ "Rho" ], "normalized": [] } ]
[ { "id": "PMID-10036235_E1", "type": "CellularProcess", "trigger": { "text": [ "Rac ruffling" ], "offsets": [ [ 21, 33 ] ] }, "arguments": [] }, { "id": "PMID-10036235_E2", "type": "Transport", "trigger": { "text": [ "trafficking" ], "offsets": [ [ 63, 74 ] ] }, "arguments": [] }, { "id": "PMID-10036235_E3", "type": "CellularComponentOrganizationAndBiogenesis", "trigger": { "text": [ "rearrangements" ], "offsets": [ [ 93, 107 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_T5" } ] }, { "id": "PMID-10036235_E4", "type": "RegulatoryProcess", "trigger": { "text": [ "regulates" ], "offsets": [ [ 125, 134 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10036235_T7" }, { "role": "hasPatient", "ref_id": "PMID-10036235_E25" } ] }, { "id": "PMID-10036235_E5", "type": "CellularComponentOrganizationAndBiogenesis", "trigger": { "text": [ "remodeling" ], "offsets": [ [ 217, 227 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_T10" } ] }, { "id": "PMID-10036235_E6", "type": "CellularComponentOrganizationAndBiogenesis", "trigger": { "text": [ "rearrangements" ], "offsets": [ [ 336, 350 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_T15" } ] }, { "id": "PMID-10036235_E7", "type": "GeneExpression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 570, 580 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10036235_T27" }, { "role": "hasPatient", "ref_id": "PMID-10036235_T29" } ] }, { "id": "PMID-10036235_E8", "type": "PositiveRegulation", "trigger": { "text": [ "activator" ], "offsets": [ [ 718, 727 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_T32" }, { "role": "hasAgent", "ref_id": "PMID-10036235_T34" } ] }, { "id": "PMID-10036235_E9", "type": "CellularComponentOrganizationAndBiogenesis", "trigger": { "text": [ "membrane ruffling" ], "offsets": [ [ 852, 869 ] ] }, "arguments": [] }, { "id": "PMID-10036235_E10", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 905, 915 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_T38" } ] }, { "id": "PMID-10036235_E11", "type": "GeneExpression", "trigger": { "text": [ "Co-expression" ], "offsets": [ [ 929, 942 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_T41" } ] }, { "id": "PMID-10036235_E13", "type": "NegativeRegulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1008, 1017 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10036235_E11" }, { "role": "hasPatient", "ref_id": "PMID-10036235_E17" } ] }, { "id": "PMID-10036235_E14", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1040, 1047 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_E15" }, { "role": "hasAgent", "ref_id": "PMID-10036235_T44" } ] }, { "id": "PMID-10036235_E15", "type": "CellularComponentOrganizationAndBiogenesis", "trigger": { "text": [ "ruffling" ], "offsets": [ [ 1048, 1056 ] ] }, "arguments": [] }, { "id": "PMID-10036235_E16", "type": "GeneExpression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1075, 1085 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10036235_T47" }, { "role": "hasPatient", "ref_id": "PMID-10036235_T49" } ] }, { "id": "PMID-10036235_E17", "type": "CellularComponentOrganizationAndBiogenesis", "trigger": { "text": [ "constitutive ruffling" ], "offsets": [ [ 1100, 1121 ] ] }, "arguments": [] }, { "id": "PMID-10036235_E18", "type": "GeneExpression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1140, 1150 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10036235_T51" }, { "role": "hasPatient", "ref_id": "PMID-10036235_T42" } ] }, { "id": "PMID-10036235_E19", "type": "PositiveRegulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1155, 1164 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_T42" } ] }, { "id": "PMID-10036235_E20", "type": "GeneExpression", "trigger": { "text": [ "co-expression" ], "offsets": [ [ 1196, 1209 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_T56" } ] }, { "id": "PMID-10036235_E22", "type": "NegativeRegulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 1294, 1301 ] ] }, "arguments": [] }, { "id": "PMID-10036235_E23", "type": "RegulatoryProcess", "trigger": { "text": [ "regulating" ], "offsets": [ [ 1574, 1584 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_E24" } ] }, { "id": "PMID-10036235_E24", "type": "Transport", "trigger": { "text": [ "trafficking" ], "offsets": [ [ 1589, 1600 ] ] }, "arguments": [] }, { "id": "PMID-10036235_E25", "type": "Pathway", "trigger": { "text": [ "recycling pathway" ], "offsets": [ [ 169, 186 ] ] }, "arguments": [] }, { "id": "PMID-10036235_E26", "type": "Increase", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 843, 851 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_E9" } ] }, { "id": "PMID-10036235_E27", "type": "Decrease", "trigger": { "text": [ "lowered" ], "offsets": [ [ 920, 927 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_E10" } ] }, { "id": "PMID-10036235_E12", "type": "Increase", "trigger": { "text": [ "induced" ], "offsets": [ [ 1324, 1331 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10036235_T61" }, { "role": "hasPatient", "ref_id": "PMID-10036235_T57" } ] }, { "id": "PMID-10036235_E21", "type": "NegativeRegulation", "trigger": { "text": [ "inactivation" ], "offsets": [ [ 1361, 1373 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_T78" }, { "role": "hasAgent", "ref_id": "PMID-10036235_T62" } ] }, { "id": "PMID-10036235_E28", "type": "GeneExpression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 570, 580 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10036235_T27" }, { "role": "hasPatient", "ref_id": "PMID-10036235_T30" } ] }, { "id": "PMID-10036235_E29", "type": "NegativeRegulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1008, 1017 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10036235_E11" }, { "role": "hasPatient", "ref_id": "PMID-10036235_E15" } ] } ]
[]
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19
PMID-10037602
[ { "id": "PMID-10037602__text", "type": "abstract", "text": [ "Function of WW domains as phosphoserine- or phosphothreonine-binding modules. Protein-interacting modules help determine the specificity of signal transduction events, and protein phosphorylation can modulate the assembly of such modules into specific signaling complexes. Although phosphotyrosine-binding modules have been well-characterized, phosphoserine- or phosphothreonine-binding modules have not been described. WW domains are small protein modules found in various proteins that participate in cell signaling or regulation. WW domains of the essential mitotic prolyl isomerase Pin1 and the ubiquitin ligase Nedd4 bound to phosphoproteins, including physiological substrates of enzymes, in a phosphorylation-dependent manner. The Pin1 WW domain functioned as a phosphoserine- or phosphothreonine-binding module, with properties similar to those of SRC homology 2 domains. Phosphoserine- or phosphothreonine-binding activity was required for Pin1 to interact with its substrates in vitro and to perform its essential function in vivo.\n" ], "offsets": [ [ 0, 1042 ] ] } ]
[ { "id": "PMID-10037602_T1", "type": "ProteinDomain", "offsets": [ [ 12, 22 ] ], "text": [ "WW domains" ], "normalized": [] }, { "id": "PMID-10037602_T2", "type": "AminoAcid", "offsets": [ [ 26, 39 ] ], "text": [ "phosphoserine" ], "normalized": [] }, { "id": "PMID-10037602_T3", "type": "AminoAcid", "offsets": [ [ 44, 60 ] ], "text": [ "phosphothreonine" ], "normalized": [] }, { "id": "PMID-10037602_T7", "type": "Protein", "offsets": [ [ 172, 179 ] ], "text": [ "protein" ], "normalized": [] }, { "id": "PMID-10037602_T9", "type": "AminoAcid", "offsets": [ [ 282, 297 ] ], "text": [ "phosphotyrosine" ], "normalized": [] }, { "id": "PMID-10037602_T11", "type": "AminoAcid", "offsets": [ [ 344, 357 ] ], "text": [ "phosphoserine" ], "normalized": [] }, { "id": "PMID-10037602_T12", "type": "AminoAcid", "offsets": [ [ 362, 378 ] ], "text": [ "phosphothreonine" ], "normalized": [] }, { "id": "PMID-10037602_T14", "type": "ProteinDomain", "offsets": [ [ 420, 430 ] ], "text": [ "WW domains" ], "normalized": [] }, { "id": "PMID-10037602_T15", "type": "Protein", "offsets": [ [ 441, 448 ] ], "text": [ "protein" ], "normalized": [] }, { "id": "PMID-10037602_T16", "type": "Protein", "offsets": [ [ 474, 482 ] ], "text": [ "proteins" ], "normalized": [] }, { "id": "PMID-10037602_T17", "type": "Cell", "offsets": [ [ 503, 507 ] ], "text": [ "cell" ], "normalized": [] }, { "id": "PMID-10037602_T20", "type": "ProteinDomain", "offsets": [ [ 533, 543 ] ], "text": [ "WW domains" ], "normalized": [] }, { "id": "PMID-10037602_T21", "type": "Enzyme", "offsets": [ [ 561, 585 ] ], "text": [ "mitotic prolyl isomerase" ], "normalized": [] }, { "id": "PMID-10037602_T22", "type": "Enzyme", "offsets": [ [ 586, 590 ] ], "text": [ "Pin1" ], "normalized": [] }, { "id": "PMID-10037602_T25", "type": "Enzyme", "offsets": [ [ 616, 621 ] ], "text": [ "Nedd4" ], "normalized": [] }, { "id": "PMID-10037602_T27", "type": "AminoAcid", "offsets": [ [ 631, 646 ] ], "text": [ "phosphoproteins" ], "normalized": [] }, { "id": "PMID-10037602_T28", "type": "Enzyme", "offsets": [ [ 686, 693 ] ], "text": [ "enzymes" ], "normalized": [] }, { "id": "PMID-10037602_T30", "type": "Enzyme", "offsets": [ [ 738, 742 ] ], "text": [ "Pin1" ], "normalized": [] }, { "id": "PMID-10037602_T31", "type": "ProteinDomain", "offsets": [ [ 743, 752 ] ], "text": [ "WW domain" ], "normalized": [] }, { "id": "PMID-10037602_T32", "type": "AminoAcid", "offsets": [ [ 769, 782 ] ], "text": [ "phosphoserine" ], "normalized": [] }, { "id": "PMID-10037602_T33", "type": "AminoAcid", "offsets": [ [ 787, 803 ] ], "text": [ "phosphothreonine" ], "normalized": [] }, { "id": "PMID-10037602_T35", "type": "ProteinDomain", "offsets": [ [ 856, 878 ] ], "text": [ "SRC homology 2 domains" ], "normalized": [] }, { "id": "PMID-10037602_T36", "type": "AminoAcid", "offsets": [ [ 880, 893 ] ], "text": [ "Phosphoserine" ], "normalized": [] }, { "id": "PMID-10037602_T37", "type": "AminoAcid", "offsets": [ [ 898, 914 ] ], "text": [ "phosphothreonine" ], "normalized": [] }, { "id": "PMID-10037602_T39", "type": "Enzyme", "offsets": [ [ 949, 953 ] ], "text": [ "Pin1" ], "normalized": [] }, { "id": "PMID-10037602_T8", "type": "ProteinComplex", "offsets": [ [ 262, 271 ] ], "text": [ "complexes" ], "normalized": [] }, { "id": "PMID-10037602_T23", "type": "Enzyme", "offsets": [ [ 599, 615 ] ], "text": [ "ubiquitin ligase" ], "normalized": [] }, { "id": "PMID-10037602_T24", "type": "Substrate", "offsets": [ [ 672, 682 ] ], "text": [ "substrates" ], "normalized": [] }, { "id": "PMID-10037602_T42", "type": "Substrate", "offsets": [ [ 975, 985 ] ], "text": [ "substrates" ], "normalized": [] } ]
[ { "id": "PMID-10037602_E1", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 61, 68 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T2" } ] }, { "id": "PMID-10037602_E3", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 298, 305 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T9" } ] }, { "id": "PMID-10037602_E4", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 379, 386 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T11" } ] }, { "id": "PMID-10037602_E5", "type": "SignalingPathway", "trigger": { "text": [ "signaling" ], "offsets": [ [ 508, 517 ] ] }, "arguments": [] }, { "id": "PMID-10037602_E6", "type": "RegulatoryProcess", "trigger": { "text": [ "regulation" ], "offsets": [ [ 521, 531 ] ] }, "arguments": [] }, { "id": "PMID-10037602_E7", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 622, 627 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T27" } ] }, { "id": "PMID-10037602_E8", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 700, 715 ] ] }, "arguments": [] }, { "id": "PMID-10037602_E9", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 804, 811 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T32" } ] }, { "id": "PMID-10037602_E10", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 915, 922 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T36" } ] }, { "id": "PMID-10037602_E11", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 957, 965 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T42" } ] }, { "id": "PMID-10037602_E12", "type": "SignalingPathway", "trigger": { "text": [ "signal transduction" ], "offsets": [ [ 140, 159 ] ] }, "arguments": [] }, { "id": "PMID-10037602_E2", "type": "BindingToProtein", "trigger": { "text": [ "Protein-interacting" ], "offsets": [ [ 78, 97 ] ] }, "arguments": [] }, { "id": "PMID-10037602_E13", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 180, 195 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T7" } ] }, { "id": "PMID-10037602_E14", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 379, 386 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T12" } ] }, { "id": "PMID-10037602_E15", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 915, 922 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T37" } ] }, { "id": "PMID-10037602_E16", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 957, 965 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T39" } ] }, { "id": "PMID-10037602_E17", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 804, 811 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T33" } ] }, { "id": "PMID-10037602_E18", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 61, 68 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T3" } ] }, { "id": "PMID-10037602_E19", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 622, 627 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T20" } ] } ]
[]
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20
PMID-10037736
[ { "id": "PMID-10037736__text", "type": "abstract", "text": [ "Molecular cloning and functional characterization of a new Cap'n' collar family transcription factor Nrf3. The NF-E2-binding sites or Maf recognition elements (MARE) are essential cis-acting elements in the regulatory regions of erythroid-specific genes recognized by the erythroid transcription factor NF-E2, composed of p45 and MafK. Recently, two p45-related factors Nrf1 and Nrf2 were isolated, and they are now collectively grouped as the Cap'n' collar (CNC) family. CNC factors bind to MARE through heterodimer formation with small Maf proteins. We report here the identification and characterization of a novel CNC factor, Nrf3, encoding a predicted 73-kDa protein with a basic region-leucine zipper domain highly homologous to those of other CNC proteins. In vitro and in vivo analyses showed that Nrf3 can heterodimerize with MafK and that this complex binds to the MARE in the chicken beta-globin enhancer and can activate transcription. Nrf3 mRNA is highly expressed in human placenta and B cell and monocyte lineage. Chromosomal localization of human Nrf3 is 7p14-15, which lies near the hoxA gene locus. As the genetic loci of p45, nrf1, and nrf2 have been mapped close to those of hoxC, hoxB, and hoxD, respectively, the present study strongly argues for the idea that a single ancestral gene for the CNC family members may have been localized near the ancestral Hox cluster and have diverged to give rise to four closely related CNC factors through chromosome duplication.\n" ], "offsets": [ [ 0, 1488 ] ] } ]
[ { "id": "PMID-10037736_T1", "type": "TranscriptionFactor", "offsets": [ [ 80, 100 ] ], "text": [ "transcription factor" ], "normalized": [] }, { "id": "PMID-10037736_T2", "type": "TranscriptionFactor", "offsets": [ [ 101, 105 ] ], "text": [ "Nrf3" ], "normalized": [] }, { "id": "PMID-10037736_T5", "type": "TranscriptionFactorBindingSiteOfDNA", "offsets": [ [ 134, 158 ] ], "text": [ "Maf recognition elements" ], "normalized": [] }, { "id": "PMID-10037736_T6", "type": "TranscriptionFactorBindingSiteOfDNA", "offsets": [ [ 160, 164 ] ], "text": [ "MARE" ], "normalized": [] }, { "id": "PMID-10037736_T7", "type": "Cell", "offsets": [ [ 229, 238 ] ], "text": [ "erythroid" ], "normalized": [] }, { "id": "PMID-10037736_T8", "type": "Gene", "offsets": [ [ 248, 253 ] ], "text": [ "genes" ], "normalized": [] }, { "id": "PMID-10037736_T9", "type": "Cell", "offsets": [ [ 272, 281 ] ], "text": [ "erythroid" ], "normalized": [] }, { "id": "PMID-10037736_T10", "type": "TranscriptionFactor", "offsets": [ [ 282, 302 ] ], "text": [ "transcription factor" ], "normalized": [] }, { "id": "PMID-10037736_T11", "type": "TranscriptionFactor", "offsets": [ [ 303, 308 ] ], "text": [ "NF-E2" ], "normalized": [] }, { "id": "PMID-10037736_T12", "type": "ProteinSubunit", "offsets": [ [ 322, 325 ] ], "text": [ "p45" ], "normalized": [] }, { "id": "PMID-10037736_T13", "type": "ProteinSubunit", "offsets": [ [ 330, 334 ] ], "text": [ "MafK" ], "normalized": [] }, { "id": "PMID-10037736_T14", "type": "ProteinSubunit", "offsets": [ [ 350, 353 ] ], "text": [ "p45" ], "normalized": [] }, { "id": "PMID-10037736_T15", "type": "TranscriptionFactor", "offsets": [ [ 362, 369 ] ], "text": [ "factors" ], "normalized": [] }, { "id": "PMID-10037736_T16", "type": "TranscriptionFactor", "offsets": [ [ 370, 374 ] ], "text": [ "Nrf1" ], "normalized": [] }, { "id": "PMID-10037736_T17", "type": "TranscriptionFactor", "offsets": [ [ 379, 383 ] ], "text": [ "Nrf2" ], "normalized": [] }, { "id": "PMID-10037736_T18", "type": "TranscriptionFactor", "offsets": [ [ 472, 483 ] ], "text": [ "CNC factors" ], "normalized": [] }, { "id": "PMID-10037736_T20", "type": "TranscriptionFactorBindingSiteOfDNA", "offsets": [ [ 492, 496 ] ], "text": [ "MARE" ], "normalized": [] }, { "id": "PMID-10037736_T22", "type": "Protein", "offsets": [ [ 538, 550 ] ], "text": [ "Maf proteins" ], "normalized": [] }, { "id": "PMID-10037736_T23", "type": "TranscriptionFactor", "offsets": [ [ 618, 628 ] ], "text": [ "CNC factor" ], "normalized": [] }, { "id": "PMID-10037736_T24", "type": "Gene", "offsets": [ [ 630, 634 ] ], "text": [ "Nrf3" ], "normalized": [] }, { "id": "PMID-10037736_T25", "type": "Protein", "offsets": [ [ 664, 671 ] ], "text": [ "protein" ], "normalized": [] }, { "id": "PMID-10037736_T26", "type": "bZIP", "offsets": [ [ 692, 713 ] ], "text": [ "leucine zipper domain" ], "normalized": [] }, { "id": "PMID-10037736_T27", "type": "TranscriptionFactor", "offsets": [ [ 750, 762 ] ], "text": [ "CNC proteins" ], "normalized": [] }, { "id": "PMID-10037736_T28", "type": "TranscriptionFactor", "offsets": [ [ 806, 810 ] ], "text": [ "Nrf3" ], "normalized": [] }, { "id": "PMID-10037736_T30", "type": "ProteinSubunit", "offsets": [ [ 835, 839 ] ], "text": [ "MafK" ], "normalized": [] }, { "id": "PMID-10037736_T31", "type": "TranscriptionFactorComplex", "offsets": [ [ 854, 861 ] ], "text": [ "complex" ], "normalized": [] }, { "id": "PMID-10037736_T33", "type": "TranscriptionFactorBindingSiteOfDNA", "offsets": [ [ 875, 879 ] ], "text": [ "MARE" ], "normalized": [] }, { "id": "PMID-10037736_T34", "type": "Eukaryote", "offsets": [ [ 887, 894 ] ], "text": [ "chicken" ], "normalized": [] }, { "id": "PMID-10037736_T35", "type": "Gene", "offsets": [ [ 895, 906 ] ], "text": [ "beta-globin" ], "normalized": [] }, { "id": "PMID-10037736_T36", "type": "Enhancer", "offsets": [ [ 907, 915 ] ], "text": [ "enhancer" ], "normalized": [] }, { "id": "PMID-10037736_T39", "type": "TranscriptionFactor", "offsets": [ [ 948, 952 ] ], "text": [ "Nrf3" ], "normalized": [] }, { "id": "PMID-10037736_T40", "type": "MessengerRNA", "offsets": [ [ 953, 957 ] ], "text": [ "mRNA" ], "normalized": [] }, { "id": "PMID-10037736_T42", "type": "Eukaryote", "offsets": [ [ 981, 986 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10037736_T43", "type": "Cell", "offsets": [ [ 987, 995 ] ], "text": [ "placenta" ], "normalized": [] }, { "id": "PMID-10037736_T44", "type": "Cell", "offsets": [ [ 1000, 1006 ] ], "text": [ "B cell" ], "normalized": [] }, { "id": "PMID-10037736_T45", "type": "Cell", "offsets": [ [ 1011, 1027 ] ], "text": [ "monocyte lineage" ], "normalized": [] }, { "id": "PMID-10037736_T46", "type": "Chromosome", "offsets": [ [ 1029, 1040 ] ], "text": [ "Chromosomal" ], "normalized": [] }, { "id": "PMID-10037736_T48", "type": "Eukaryote", "offsets": [ [ 1057, 1062 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10037736_T49", "type": "TranscriptionFactor", "offsets": [ [ 1063, 1067 ] ], "text": [ "Nrf3" ], "normalized": [] }, { "id": "PMID-10037736_T50", "type": "HomeoboxTF", "offsets": [ [ 1100, 1109 ] ], "text": [ "hoxA gene" ], "normalized": [] }, { "id": "PMID-10037736_T51", "type": "HomeoboxTF", "offsets": [ [ 1195, 1199 ] ], "text": [ "hoxC" ], "normalized": [] }, { "id": "PMID-10037736_T52", "type": "HomeoboxTF", "offsets": [ [ 1201, 1205 ] ], "text": [ "hoxB" ], "normalized": [] }, { "id": "PMID-10037736_T53", "type": "HomeoboxTF", "offsets": [ [ 1211, 1215 ] ], "text": [ "hoxD" ], "normalized": [] }, { "id": "PMID-10037736_T54", "type": "Gene", "offsets": [ [ 1302, 1306 ] ], "text": [ "gene" ], "normalized": [] }, { "id": "PMID-10037736_T55", "type": "HomeoboxTF", "offsets": [ [ 1377, 1388 ] ], "text": [ "Hox cluster" ], "normalized": [] }, { "id": "PMID-10037736_T56", "type": "TranscriptionFactor", "offsets": [ [ 1444, 1455 ] ], "text": [ "CNC factors" ], "normalized": [] }, { "id": "PMID-10037736_T57", "type": "Chromosome", "offsets": [ [ 1464, 1474 ] ], "text": [ "chromosome" ], "normalized": [] }, { "id": "PMID-10037736_T3", "type": "TranscriptionFactorBindingSiteOfDNA", "offsets": [ [ 111, 130 ] ], "text": [ "NF-E2-binding sites" ], "normalized": [] }, { "id": "PMID-10037736_T4", "type": "RegulatoryDNARegion", "offsets": [ [ 207, 225 ] ], "text": [ "regulatory regions" ], "normalized": [] }, { "id": "PMID-10037736_T59", "type": "TranscriptionFactorBindingSiteOfDNA", "offsets": [ [ 180, 199 ] ], "text": [ "cis-acting elements" ], "normalized": [] }, { "id": "PMID-10037736_T60", "type": "BasicDomain", "offsets": [ [ 679, 691 ] ], "text": [ "basic region" ], "normalized": [] }, { "id": "PMID-10037736_T47", "type": "Chromosome", "offsets": [ [ 1071, 1078 ] ], "text": [ "7p14-15" ], "normalized": [] }, { "id": "PMID-10037736_T61", "type": "Locus", "offsets": [ [ 1110, 1115 ] ], "text": [ "locus" ], "normalized": [] }, { "id": "PMID-10037736_T62", "type": "ProteinSubunit", "offsets": [ [ 1140, 1143 ] ], "text": [ "p45" ], "normalized": [] }, { "id": "PMID-10037736_T63", "type": "TranscriptionFactor", "offsets": [ [ 1145, 1149 ] ], "text": [ "nrf1" ], "normalized": [] }, { "id": "PMID-10037736_T64", "type": "TranscriptionFactor", "offsets": [ [ 1155, 1159 ] ], "text": [ "nrf2" ], "normalized": [] } ]
[ { "id": "PMID-10037736_E1", "type": "BindingOfTranscriptionFactorToDNA", "trigger": { "text": [ "bind" ], "offsets": [ [ 484, 488 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037736_T18" }, { "role": "hasPatient", "ref_id": "PMID-10037736_T20" } ] }, { "id": "PMID-10037736_E2", "type": "Heterodimerization", "trigger": { "text": [ "heterodimer formation" ], "offsets": [ [ 505, 526 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037736_T22" } ] }, { "id": "PMID-10037736_E3", "type": "Heterodimerization", "trigger": { "text": [ "heterodimerize" ], "offsets": [ [ 815, 829 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037736_T30" } ] }, { "id": "PMID-10037736_E4", "type": "BindingOfTranscriptionFactorToDNA", "trigger": { "text": [ "binds" ], "offsets": [ [ 862, 867 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037736_T31" }, { "role": "hasPatient", "ref_id": "PMID-10037736_T33" } ] }, { "id": "PMID-10037736_E5", "type": "PositiveRegulationOfTranscription", "trigger": { "text": [ "activate" ], "offsets": [ [ 924, 932 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037736_T31" }, { "role": "hasPatient", "ref_id": "PMID-10037736_E6" } ] }, { "id": "PMID-10037736_E6", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 933, 946 ] ] }, "arguments": [] }, { "id": "PMID-10037736_E7", "type": "PositiveRegulationOfTranscriptionOfGene", "trigger": { "text": [ "expressed" ], "offsets": [ [ 968, 977 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037736_T40" } ] }, { "id": "PMID-10037736_E9", "type": "Mutation", "trigger": { "text": [ "duplication" ], "offsets": [ [ 1475, 1486 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037736_T57" } ] }, { "id": "PMID-10037736_E8", "type": "Heterodimerization", "trigger": { "text": [ "heterodimerize" ], "offsets": [ [ 815, 829 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037736_T28" } ] } ]
[]
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21
PMID-10037746
[ { "id": "PMID-10037746__text", "type": "abstract", "text": [ "Molecular characterization of a third member of the guanylyl cyclase-activating protein subfamily. The mammalian retina contains at least two guanylyl cyclases (GC1 and GC2) and two guanylyl cyclase-activating proteins (GCAP1 and GCAP2). Here we present evidence of the presence of a new photoreceptor-specific GCAP, termed GCAP3, which is closely related to GCAP1. The sequence similarity of GCAP3 with GCAP1 and GCAP2 is 57 and 49%, respectively. Recombinant GCAP3 and GCAP2 stimulate GC1 and GC2 in low [Ca2+]free and inhibit GCs when [Ca2+]free is elevated, unlike GCAP1, which only stimulates GC1. GCAP3 is encoded by a distinct gene present in other mammalian species but could not be detected by genomic Southern blotting in rodents, amphibians, and lower vertebrates. The intron/exon arrangement of the GCAP3 gene is identical to that of the other GCAP genes. While the GCAP1 and GCAP2 genes are arranged in a tail-to-tail array on chromosome 6p in human, the GCAP3 gene is located on 3q13.1, suggesting an ancestral gene duplication/translocation event. The identification of multiple Ca2+-binding proteins that interact with GC is suggestive of complex regulatory mechanisms for photoreceptor GC.\n" ], "offsets": [ [ 0, 1207 ] ] } ]
[ { "id": "PMID-10037746_T4", "type": "Eukaryote", "offsets": [ [ 103, 112 ] ], "text": [ "mammalian" ], "normalized": [] }, { "id": "PMID-10037746_T5", "type": "Tissue", "offsets": [ [ 113, 119 ] ], "text": [ "retina" ], "normalized": [] }, { "id": "PMID-10037746_T6", "type": "Enzyme", "offsets": [ [ 142, 159 ] ], "text": [ "guanylyl cyclases" ], "normalized": [] }, { "id": "PMID-10037746_T7", "type": "Enzyme", "offsets": [ [ 161, 164 ] ], "text": [ "GC1" ], "normalized": [] }, { "id": "PMID-10037746_T8", "type": "Enzyme", "offsets": [ [ 169, 172 ] ], "text": [ "GC2" ], "normalized": [] }, { "id": "PMID-10037746_T12", "type": "Protein", "offsets": [ [ 220, 225 ] ], "text": [ "GCAP1" ], "normalized": [] }, { "id": "PMID-10037746_T13", "type": "Protein", "offsets": [ [ 230, 235 ] ], "text": [ "GCAP2" ], "normalized": [] }, { "id": "PMID-10037746_T14", "type": "Protein", "offsets": [ [ 288, 301 ] ], "text": [ "photoreceptor" ], "normalized": [] }, { "id": "PMID-10037746_T15", "type": "Protein", "offsets": [ [ 311, 315 ] ], "text": [ "GCAP" ], "normalized": [] }, { "id": "PMID-10037746_T16", "type": "Protein", "offsets": [ [ 324, 329 ] ], "text": [ "GCAP3" ], "normalized": [] }, { "id": "PMID-10037746_T17", "type": "Protein", "offsets": [ [ 359, 364 ] ], "text": [ "GCAP1" ], "normalized": [] }, { "id": "PMID-10037746_T18", "type": "Protein", "offsets": [ [ 393, 398 ] ], "text": [ "GCAP3" ], "normalized": [] }, { "id": "PMID-10037746_T19", "type": "Protein", "offsets": [ [ 404, 409 ] ], "text": [ "GCAP1" ], "normalized": [] }, { "id": "PMID-10037746_T20", "type": "Protein", "offsets": [ [ 414, 419 ] ], "text": [ "GCAP2" ], "normalized": [] }, { "id": "PMID-10037746_T21", "type": "Protein", "offsets": [ [ 461, 466 ] ], "text": [ "GCAP3" ], "normalized": [] }, { "id": "PMID-10037746_T22", "type": "Protein", "offsets": [ [ 471, 476 ] ], "text": [ "GCAP2" ], "normalized": [] }, { "id": "PMID-10037746_T24", "type": "Enzyme", "offsets": [ [ 487, 490 ] ], "text": [ "GC1" ], "normalized": [] }, { "id": "PMID-10037746_T25", "type": "Enzyme", "offsets": [ [ 495, 498 ] ], "text": [ "GC2" ], "normalized": [] }, { "id": "PMID-10037746_T26", "type": "Ion", "offsets": [ [ 506, 516 ] ], "text": [ "[Ca2+]free" ], "normalized": [] }, { "id": "PMID-10037746_T28", "type": "Enzyme", "offsets": [ [ 529, 532 ] ], "text": [ "GCs" ], "normalized": [] }, { "id": "PMID-10037746_T29", "type": "Ion", "offsets": [ [ 538, 548 ] ], "text": [ "[Ca2+]free" ], "normalized": [] }, { "id": "PMID-10037746_T30", "type": "Protein", "offsets": [ [ 569, 574 ] ], "text": [ "GCAP1" ], "normalized": [] }, { "id": "PMID-10037746_T32", "type": "Enzyme", "offsets": [ [ 598, 601 ] ], "text": [ "GC1" ], "normalized": [] }, { "id": "PMID-10037746_T33", "type": "Protein", "offsets": [ [ 603, 608 ] ], "text": [ "GCAP3" ], "normalized": [] }, { "id": "PMID-10037746_T34", "type": "Gene", "offsets": [ [ 634, 638 ] ], "text": [ "gene" ], "normalized": [] }, { "id": "PMID-10037746_T35", "type": "Eukaryote", "offsets": [ [ 656, 665 ] ], "text": [ "mammalian" ], "normalized": [] }, { "id": "PMID-10037746_T36", "type": "Eukaryote", "offsets": [ [ 732, 739 ] ], "text": [ "rodents" ], "normalized": [] }, { "id": "PMID-10037746_T37", "type": "Eukaryote", "offsets": [ [ 741, 751 ] ], "text": [ "amphibians" ], "normalized": [] }, { "id": "PMID-10037746_T38", "type": "Eukaryote", "offsets": [ [ 757, 774 ] ], "text": [ "lower vertebrates" ], "normalized": [] }, { "id": "PMID-10037746_T39", "type": "Gene", "offsets": [ [ 811, 821 ] ], "text": [ "GCAP3 gene" ], "normalized": [] }, { "id": "PMID-10037746_T40", "type": "Gene", "offsets": [ [ 856, 866 ] ], "text": [ "GCAP genes" ], "normalized": [] }, { "id": "PMID-10037746_T41", "type": "Gene", "offsets": [ [ 878, 883 ] ], "text": [ "GCAP1" ], "normalized": [] }, { "id": "PMID-10037746_T42", "type": "Gene", "offsets": [ [ 888, 899 ] ], "text": [ "GCAP2 genes" ], "normalized": [] }, { "id": "PMID-10037746_T43", "type": "Chromosome", "offsets": [ [ 940, 950 ] ], "text": [ "chromosome" ], "normalized": [] }, { "id": "PMID-10037746_T44", "type": "Eukaryote", "offsets": [ [ 957, 962 ] ], "text": [ "human" ], "normalized": [] }, { "id": "PMID-10037746_T45", "type": "Gene", "offsets": [ [ 968, 978 ] ], "text": [ "GCAP3 gene" ], "normalized": [] }, { "id": "PMID-10037746_T46", "type": "Gene", "offsets": [ [ 1025, 1029 ] ], "text": [ "gene" ], "normalized": [] }, { "id": "PMID-10037746_T50", "type": "Protein", "offsets": [ [ 1094, 1115 ] ], "text": [ "Ca2+-binding proteins" ], "normalized": [] }, { "id": "PMID-10037746_T52", "type": "Enzyme", "offsets": [ [ 1135, 1137 ] ], "text": [ "GC" ], "normalized": [] }, { "id": "PMID-10037746_T53", "type": "Protein", "offsets": [ [ 1189, 1202 ] ], "text": [ "photoreceptor" ], "normalized": [] }, { "id": "PMID-10037746_T54", "type": "Enzyme", "offsets": [ [ 1203, 1205 ] ], "text": [ "GC" ], "normalized": [] }, { "id": "PMID-10037746_T1", "type": "Protein", "offsets": [ [ 52, 87 ] ], "text": [ "guanylyl cyclase-activating protein" ], "normalized": [] }, { "id": "PMID-10037746_T2", "type": "Protein", "offsets": [ [ 182, 218 ] ], "text": [ "guanylyl cyclase-activating proteins" ], "normalized": [] }, { "id": "PMID-10037746_T3", "type": "Chromosome", "offsets": [ [ 993, 999 ] ], "text": [ "3q13.1" ], "normalized": [] } ]
[ { "id": "PMID-10037746_E3", "type": "PositiveRegulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 477, 486 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037746_T21" }, { "role": "hasPatient", "ref_id": "PMID-10037746_T24" } ] }, { "id": "PMID-10037746_E4", "type": "NegativeRegulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 521, 528 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037746_T28" }, { "role": "hasAgent", "ref_id": "PMID-10037746_T21" } ] }, { "id": "PMID-10037746_E5", "type": "PositiveRegulation", "trigger": { "text": [ "stimulates" ], "offsets": [ [ 587, 597 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037746_T30" }, { "role": "hasPatient", "ref_id": "PMID-10037746_T32" } ] }, { "id": "PMID-10037746_E6", "type": "Mutation", "trigger": { "text": [ "duplication/translocation event" ], "offsets": [ [ 1030, 1061 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037746_T46" } ] }, { "id": "PMID-10037746_E8", "type": "BindingToProtein", "trigger": { "text": [ "interact" ], "offsets": [ [ 1121, 1129 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037746_T52" }, { "role": "hasPatient2", "ref_id": "PMID-10037746_T50" } ] }, { "id": "PMID-10037746_E1", "type": "RegulatoryProcess", "trigger": { "text": [ "regulatory mechanisms" ], "offsets": [ [ 1163, 1184 ] ] }, "arguments": [] }, { "id": "PMID-10037746_E2", "type": "PositiveRegulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 477, 486 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037746_T22" }, { "role": "hasPatient", "ref_id": "PMID-10037746_T24" } ] }, { "id": "PMID-10037746_E7", "type": "PositiveRegulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 477, 486 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037746_T21" }, { "role": "hasPatient", "ref_id": "PMID-10037746_T25" } ] }, { "id": "PMID-10037746_E9", "type": "PositiveRegulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 477, 486 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037746_T22" }, { "role": "hasPatient", "ref_id": "PMID-10037746_T25" } ] }, { "id": "PMID-10037746_E10", "type": "NegativeRegulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 521, 528 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037746_T28" }, { "role": "hasAgent", "ref_id": "PMID-10037746_T22" } ] } ]
[]
[ { "arg1_id": "PMID-10037746_T5", "arg2_id": "PMID-10037746_T4", "id": "PMID-10037746_R1", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10037746_T6", "arg2_id": "PMID-10037746_T5", "id": "PMID-10037746_R2", "type": "locatedIn", "normalized": [] }, { "arg1_id": "PMID-10037746_T34", "arg2_id": "PMID-10037746_T33", "id": "PMID-10037746_R3", "type": "encodes", "normalized": [] }, { "arg1_id": "PMID-10037746_T34", "arg2_id": "PMID-10037746_T35", "id": "PMID-10037746_R4", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10037746_T43", "arg2_id": "PMID-10037746_T44", "id": "PMID-10037746_R5", "type": "fromSpecies", "normalized": [] }, { "arg1_id": "PMID-10037746_T41", "arg2_id": "PMID-10037746_T43", "id": "PMID-10037746_R6", "type": "locatedIn", "normalized": [] }, { "arg1_id": "PMID-10037746_T42", "arg2_id": "PMID-10037746_T43", "id": "PMID-10037746_R7", "type": "locatedIn", "normalized": [] } ]

Dataset Card for BioNLP 2013 GRO

GRO Task: Populating the Gene Regulation Ontology with events and relations. A data set from the bio NLP shared tasks competition from 2013

Citation Information

@inproceedings{kim-etal-2013-gro,
    title = "{GRO} Task: Populating the Gene Regulation Ontology with events and relations",
    author = "Kim, Jung-jae  and
      Han, Xu  and
      Lee, Vivian  and
      Rebholz-Schuhmann, Dietrich",
    booktitle = "Proceedings of the {B}io{NLP} Shared Task 2013 Workshop",
    month = aug,
    year = "2013",
    address = "Sofia, Bulgaria",
    publisher = "Association for Computational Linguistics",
    url = "https://aclanthology.org/W13-2007",
    pages = "50--57",
}
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