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{
"metadata": {
"accession": "PS50086",
"entry_id": null,
"type": "domain",
"go_terms": null,
"source_database": "profile",
"member_databases": null,
"integrated": "IPR000195",
"hierarchy": null,
"name": {
"name": "TBC/rab GAP domain profile",
"short": "TBC_RABGAP"
},
"description": [
{
"text": "<p>The ~200 amino acid TBC/rab GTPase-activating protein (GAP) domain is well\nconserved across species and has been found in a wide range of different\nproteins from plant adhesion molecules to mammalian oncogenes. The name TBC\nderives from the name of the murine protein Tbc1 in which this domain was\nfirst identified based on its similarity to sequences in the tre-2 oncogene,\nand the yeast regulators of mitosis, BUB2 and cdc16 [[cite:PUB00004496]]. The connection of\nthis domain with rab GTPase activation stems from subsequent in-depth sequence\nanalyses and alignments [[cite:PUB00005468]] and recent work demonstrating that it appears to\ncontain the catalytic activities of the yeast rab GAPs, GYP1, and GYP7 [[cite:PUB00018101]].\nThe TBC/rab GAP domain has also been named PTM after three proteins known to\ncontain it: the Drosophila pollux, the human oncoprotein TRE17 (oncoTRE17),\nand a myeloid cell line-expressed protein [[cite:PUB00018102]].\n\nThe TBC/rab GAP domain contains six conserved motifs named A to F [[cite:PUB00005468]]. A\nconserved arginine residue in the sequence motif B has been shown to be\ncritical for the full GAP activity [[cite:PUB00018101]]. Resolution of the 3D structure of the\nTBC/rab GAP domain of GYP1 has shown that it is a fully alpha-helical V-shaped\nmolecule. The conserved arginine residue is positioned at the\nside of the narrow cleft on the concave site of the V-shaped molecule. It has\nbeen proposed that this cleft is the binding site for the GTPase. The\nconserved arginine residue probably functions as a catalytic arginine finger\nanalogous to that seen in ras and Rho-GAPs. The two key features of the\narginine finger activation mechanism appear to be (i) the positioning of the\ncatalytically essential GTPase glutamine side chain via a hydrogen bonding\ninteraction between the glutamine carbamoyl-NH2 group and the main chain\ncarbonyl group of the GAP arginine, and (ii) the polarization of the gamma-\nphosphate group or the stabilization of charge on it via the interaction of\nthe positively charged side chain guanidinoyl group of the GAP arginine [[cite:PUB00014098]].\n\nSome proteins known to contain a TBC/rab GAP domain are listed below:\n\n - Yeast mitotic check point protein BUB2. BUB2 monitors spindle microtubule\n assembly during mitosis.\n - Yeast GTPase-activating proteins (GAPs) GYP 1 to 7. GAPs enhance the\n inherently slow GTPase activity of Ras-like proteins, which function as\n binary molecular switches controlling cellular pathways.\n - Yeast MIC1 protein.\n - Fission yeast cell division control protein 16 (CDC16). It is part of a\n checkpoint control system regulating septum formation.\n - Drosophila pollux, an adhesion molecule.\n - Mammalian rab GAPs.\n - Human TRE oncogene protein.\n - Human EBP50-PDZ interactor of 64 kDa (EPI64). It binds to the first PDZ\n domain of EBP50 and E3KARP [[cite:PUB00018103]].\n\nThe profile we developed covers the entire six conserved motifs of the\nTBC/rab GAP domain.</p>",
"llm": false,
"checked": false,
"updated": false
}
],
"wikipedia": null,
"literature": {
"PUB00018103": {
"PMID": 11285285,
"ISBN": null,
"volume": "153",
"issue": "1",
"year": 2001,
"title": "Identification of EPI64, a TBC/rabGAP domain-containing microvillar protein that binds to the first PDZ domain of EBP50 and E3KARP.",
"URL": null,
"raw_pages": "191-206",
"medline_journal": "J Cell Biol",
"ISO_journal": "J. Cell Biol.",
"authors": [
"Reczek D",
"Bretscher A."
],
"DOI_URL": "http://dx.doi.org/10.1083/jcb.153.1.191"
},
"PUB00018101": {
"PMID": 10508155,
"ISBN": null,
"volume": "18",
"issue": "19",
"year": 1999,
"title": "Identification of the catalytic domains and their functionally critical arginine residues of two yeast GTPase-activating proteins specific for Ypt/Rab transport GTPases.",
"URL": null,
"raw_pages": "5216-25",
"medline_journal": "EMBO J",
"ISO_journal": "EMBO J.",
"authors": [
"Albert S",
"Will E",
"Gallwitz D."
],
"DOI_URL": "http://dx.doi.org/10.1093/emboj/18.19.5216"
},
"PUB00005468": {
"PMID": 9255064,
"ISBN": null,
"volume": "22",
"issue": "7",
"year": 1997,
"title": "A shared domain between a spindle assembly checkpoint protein and Ypt/Rab-specific GTPase-activators.",
"URL": null,
"raw_pages": "243-4",
"medline_journal": "Trends Biochem Sci",
"ISO_journal": "Trends Biochem. Sci.",
"authors": [
"Neuwald AF."
],
"DOI_URL": "http://dx.doi.org/10.1016/S0968-0004(97)01073-6"
},
"PUB00018102": {
"PMID": 8654926,
"ISBN": null,
"volume": "10",
"issue": "9",
"year": 1996,
"title": "Pollux, a novel Drosophila adhesion molecule, belongs to a family of proteins expressed in plants, yeast, nematodes, and man.",
"URL": null,
"raw_pages": "1108-19",
"medline_journal": "Genes Dev",
"ISO_journal": "Genes Dev.",
"authors": [
"Zhang SD",
"Kassis J",
"Olde B",
"Mellerick DM",
"Odenwald WF."
],
"DOI_URL": "http://www.genesdev.org/cgi/content/abstract/10/9/1108"
},
"PUB00014098": {
"PMID": 11013213,
"ISBN": null,
"volume": "19",
"issue": "19",
"year": 2000,
"title": "Crystal structure of the GAP domain of Gyp1p: first insights into interaction with Ypt/Rab proteins.",
"URL": null,
"raw_pages": "5105-13",
"medline_journal": "EMBO J",
"ISO_journal": "EMBO J.",
"authors": [
"Rak A",
"Fedorov R",
"Alexandrov K",
"Albert S",
"Goody RS",
"Gallwitz D",
"Scheidig AJ."
],
"DOI_URL": "http://dx.doi.org/10.1093/emboj/19.19.5105"
},
"PUB00004496": {
"PMID": 7566974,
"ISBN": null,
"volume": "11",
"issue": "6",
"year": 1995,
"title": "Molecular cloning of a cDNA with a novel domain present in the tre-2 oncogene and the yeast cell cycle regulators BUB2 and cdc16.",
"URL": null,
"raw_pages": "1139-48",
"medline_journal": "Oncogene",
"ISO_journal": "Oncogene",
"authors": [
"Richardson PM",
"Zon LI."
],
"DOI_URL": null
}
},
"set_info": null,
"overlaps_with": null,
"counters": {
"subfamilies": 0,
"domain_architectures": 0,
"interactions": 0,
"matches": 115246,
"pathways": 0,
"proteins": 115137,
"proteomes": 3421,
"sets": 0,
"structural_models": {
"alphafold": 101151,
"bfvd": 0
},
"structures": 24,
"taxa": 11787
},
"entry_annotations": {},
"cross_references": {},
"is_llm": false,
"is_reviewed_llm": false,
"is_updated_llm": false,
"representative_structure": {
"accession": "2qq8",
"name": "Crystal structure of the putative RabGAP domain of human TBC1 domain family member 14"
}
}
}
