ID RB3GP_HUMAN Reviewed; 981 AA. AC Q15042; A6H8Z3; C9J837; Q659F5; Q8TBB4; DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 171. DE RecName: Full=Rab3 GTPase-activating protein catalytic subunit; DE AltName: Full=RAB3 GTPase-activating protein 130 kDa subunit; DE AltName: Full=Rab3-GAP p130; DE Short=Rab3-GAP; GN Name=RAB3GAP1; Synonyms=KIAA0066, RAB3GAP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Bone marrow; RX PubMed=7584044; DOI=10.1093/dnares/1.5.223; RA Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N., RA Kawarabayasi Y., Ishikawa K., Tabata S.; RT "Prediction of the coding sequences of unidentified human genes. II. The RT coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of RT cDNA clones from human cell line KG-1."; RL DNA Res. 1:223-229(1994). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 439-981 (ISOFORM 1), AND VARIANT SER-598. RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 764-981. RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=9030515; DOI=10.1074/jbc.272.8.4655; RA Fukui K., Sasaki T., Imazumi K., Matsuura Y., Nakanishi H., Takai Y.; RT "Isolation and characterization of a GTPase activating protein specific for RT the Rab3 subfamily of small G proteins."; RL J. Biol. Chem. 272:4655-4658(1997). RN [6] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=9852129; DOI=10.1074/jbc.273.51.34580; RA Oishi H., Sasaki T., Nagano F., Ikeda W., Ohya T., Wada M., Ide N., RA Nakanishi H., Takai Y.; RT "Localization of the Rab3 small G protein regulators in nerve terminals and RT their involvement in Ca2+-dependent exocytosis."; RL J. Biol. Chem. 273:34580-34585(1998). RN [7] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF ARG-619; RP ARG-700; ARG-728 AND ARG-753. RX PubMed=10859313; DOI=10.1074/jbc.m003705200; RA Clabecq A., Henry J.-P., Darchen F.; RT "Biochemical characterization of Rab3-GTPase-activating protein reveals a RT mechanism similar to that of Ras-GAP."; RL J. Biol. Chem. 275:31786-31791(2000). RN [8] RP INVOLVEMENT IN WARBM1, AND FUNCTION. RX PubMed=15696165; DOI=10.1038/ng1517; RA Aligianis I.A., Johnson C.A., Gissen P., Chen D., Hampshire D., RA Hoffmann K., Maina E.N., Morgan N.V., Tee L., Morton J., Ainsworth J.R., RA Horn D., Rosser E., Cole T.R.P., Stolte-Dijkstra I., Fieggen K., RA Clayton-Smith J., Megarbane A., Shield J.P., Newbury-Ecob R., Dobyns W.B., RA Graham J.M., Kjaer K.W., Warburg M., Bond J., Trembath R.C., Harris L.W., RA Takai Y., Mundlos S., Tannahill D., Woods C.G., Maher E.R.; RT "Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro RT syndrome."; RL Nat. Genet. 37:221-223(2005). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [14] RP INTERACTION WITH LMAN1. RX PubMed=22337587; DOI=10.1074/mcp.m111.016444; RA Haines D.S., Lee J.E., Beauparlant S.L., Kyle D.B., den Besten W., RA Sweredoski M.J., Graham R.L., Hess S., Deshaies R.J.; RT "Protein interaction profiling of the p97 adaptor UBXD1 points to a role RT for the complex in modulating ERGIC-53 trafficking."; RL Mol. Cell. Proteomics 11:M111.016444-M111.016444(2012). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-379; SER-537; SER-664 AND RP THR-908, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-590, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [17] RP INVOLVEMENT IN MARTS2 AND WARBM1. RX PubMed=30730599; DOI=10.1002/ajmg.a.61065; RA Koparir A., Karatas O.F., Yilmaz S.S., Suer I., Ozer B., Yuceturk B., RA Ozen M.; RT "Revealing the functions of novel mutations in RAB3GAP1 in Martsolf and RT Warburg micro syndromes."; RL Am. J. Med. Genet. A 179:579-587(2019). RN [18] RP VARIANTS WARBM1 PRO-18 AND VAL-24, AND FUNCTION. RX PubMed=23420520; DOI=10.1002/humu.22296; RA Handley M.T., Morris-Rosendahl D.J., Brown S., Macdonald F., Hardy C., RA Bem D., Carpanini S.M., Borck G., Martorell L., Izzi C., Faravelli F., RA Accorsi P., Pinelli L., Basel-Vanagaite L., Peretz G., Abdel-Salam G.M., RA Zaki M.S., Jansen A., Mowat D., Glass I., Stewart H., Mancini G., RA Lederer D., Roscioli T., Giuliano F., Plomp A.S., Rolfs A., Graham J.M., RA Seemanova E., Poo P., Garcia-Cazorla A., Edery P., Jackson I.J., RA Maher E.R., Aligianis I.A.; RT "Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype RT correlations in Warburg micro syndrome and Martsolf syndrome."; RL Hum. Mutat. 34:686-696(2013). RN [19] RP CHARACTERIZATION OF VARIANTS WARBM1 PRO-18 AND VAL-24, FUNCTION, AND RP SUBCELLULAR LOCATION. RX PubMed=24891604; DOI=10.1083/jcb.201403026; RA Gerondopoulos A., Bastos R.N., Yoshimura S., Anderson R., Carpanini S., RA Aligianis I., Handley M.T., Barr F.A.; RT "Rab18 and a Rab18 GEF complex are required for normal ER structure."; RL J. Cell Biol. 205:707-720(2014). CC -!- FUNCTION: Catalytic subunit of the Rab3 GTPase-activating (Rab3GAP) CC complex composed of RAB3GAP1 and RAB3GAP2, which has GTPase-activating CC protein (GAP) activity towards various Rab3 subfamily members (RAB3A, CC RAB3B, RAB3C and RAB3D), RAB5A and RAB43, and guanine nucleotide CC exchange factor (GEF) activity towards RAB18 (PubMed:9030515, CC PubMed:10859313, PubMed:24891604). As part of the Rab3GAP complex, acts CC as a GAP for Rab3 proteins by converting active RAB3-GTP to the CC inactive form RAB3-GDP (PubMed:10859313). Rab3 proteins are involved in CC regulated exocytosis of neurotransmitters and hormones CC (PubMed:15696165). The Rab3GAP complex, acts as a GEF for RAB18 by CC promoting the conversion of inactive RAB18-GDP to the active form CC RAB18-GTP (PubMed:24891604). Required for recruiting and activating CC RAB18 at the endoplasmic reticulum (ER) membrane where it maintains CC proper ER structure (PubMed:24891604). Required for normal eye and CC brain development (PubMed:15696165, PubMed:23420520). May participate CC in neurodevelopmental processes such as proliferation, migration and CC differentiation before synapse formation, and non-synaptic vesicular CC release of neurotransmitters (PubMed:9030515, PubMed:9852129). CC {ECO:0000269|PubMed:10859313, ECO:0000269|PubMed:15696165, CC ECO:0000269|PubMed:23420520, ECO:0000269|PubMed:24891604, CC ECO:0000269|PubMed:9030515, ECO:0000269|PubMed:9852129}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=75 uM for GTP-loaded RAB3A {ECO:0000269|PubMed:10859313}; CC -!- SUBUNIT: The Rab3 GTPase-activating complex is a heterodimer composed CC of RAB3GAP1 and RAB3GAP2 (By similarity). The Rab3 GTPase-activating CC complex interacts with DMXL2 (By similarity). Interacts with LMAN1 CC (PubMed:22337587). {ECO:0000250|UniProtKB:P69735, CC ECO:0000269|PubMed:22337587}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:24891604, CC ECO:0000269|PubMed:9852129}. Endoplasmic reticulum CC {ECO:0000269|PubMed:24891604}. Note=In neurons, it is enriched in the CC synaptic soluble fraction. {ECO:0000269|PubMed:9852129}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q15042-1; Sequence=Displayed; CC Name=2; CC IsoId=Q15042-3; Sequence=VSP_054068; CC Name=3; CC IsoId=Q15042-4; Sequence=VSP_054475, VSP_054476; CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:9030515}. CC -!- DISEASE: Warburg micro syndrome 1 (WARBM1) [MIM:600118]: A rare, CC autosomal recessive syndrome characterized by microcephaly, CC microphthalmia, microcornia, congenital cataracts, optic atrophy, CC cortical dysplasia, in particular corpus callosum hypoplasia, severe CC intellectual disability, spastic diplegia, and hypogonadism. CC {ECO:0000269|PubMed:15696165, ECO:0000269|PubMed:23420520, CC ECO:0000269|PubMed:24891604, ECO:0000269|PubMed:30730599}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Martsolf syndrome 2 (MARTS2) [MIM:619420]: An autosomal CC recessive disorder characterized by congenital cataracts, mildly to CC severely impaired intellectual development, and facial dysmorphism. CC Other features include brain malformations, microcephaly, and CC hypogonadism-hypogenitalism. {ECO:0000269|PubMed:30730599}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the Rab3-GAP catalytic subunit family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BC071602; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=CAH56411.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D31886; BAA06684.1; -; mRNA. DR EMBL; AC017031; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC020602; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC022977; AAH22977.1; -; mRNA. DR EMBL; BC071602; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; BC146809; AAI46810.1; -; mRNA. DR EMBL; AL096752; CAH56411.1; ALT_SEQ; mRNA. DR CCDS; CCDS33294.1; -. [Q15042-1] DR CCDS; CCDS54402.1; -. [Q15042-3] DR RefSeq; NP_001165906.1; NM_001172435.1. [Q15042-3] DR RefSeq; NP_036365.1; NM_012233.2. [Q15042-1] DR AlphaFoldDB; Q15042; -. DR SMR; Q15042; -. DR BioGRID; 116590; 154. DR IntAct; Q15042; 29. DR STRING; 9606.ENSP00000411418; -. DR GlyGen; Q15042; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q15042; -. DR PhosphoSitePlus; Q15042; -. DR SwissPalm; Q15042; -. DR BioMuta; RAB3GAP1; -. DR DMDM; 62511099; -. DR EPD; Q15042; -. DR jPOST; Q15042; -. DR MassIVE; Q15042; -. DR MaxQB; Q15042; -. DR PaxDb; 9606-ENSP00000411418; -. DR PeptideAtlas; Q15042; -. DR ProteomicsDB; 60390; -. [Q15042-1] DR ProteomicsDB; 789; -. DR ProteomicsDB; 8989; -. DR Pumba; Q15042; -. DR Antibodypedia; 33565; 215 antibodies from 29 providers. DR DNASU; 22930; -. DR Ensembl; ENST00000264158.13; ENSP00000264158.8; ENSG00000115839.19. [Q15042-1] DR Ensembl; ENST00000442034.5; ENSP00000411418.1; ENSG00000115839.19. [Q15042-3] DR GeneID; 22930; -. DR KEGG; hsa:22930; -. DR MANE-Select; ENST00000264158.13; ENSP00000264158.8; NM_012233.3; NP_036365.1. DR UCSC; uc002tuj.4; human. [Q15042-1] DR AGR; HGNC:17063; -. DR CTD; 22930; -. DR DisGeNET; 22930; -. DR GeneCards; RAB3GAP1; -. DR GeneReviews; RAB3GAP1; -. DR HGNC; HGNC:17063; RAB3GAP1. DR HPA; ENSG00000115839; Low tissue specificity. DR MalaCards; RAB3GAP1; -. DR MIM; 600118; phenotype. DR MIM; 602536; gene. DR MIM; 619420; phenotype. DR neXtProt; NX_Q15042; -. DR OpenTargets; ENSG00000115839; -. DR Orphanet; 1387; Cataract-intellectual disability-hypogonadism syndrome. DR Orphanet; 2510; Micro syndrome. DR PharmGKB; PA134969639; -. DR VEuPathDB; HostDB:ENSG00000115839; -. DR eggNOG; KOG2390; Eukaryota. DR GeneTree; ENSGT00390000006705; -. DR HOGENOM; CLU_012561_1_0_1; -. DR InParanoid; Q15042; -. DR OMA; PNMGCCL; -. DR OrthoDB; 5491837at2759; -. DR PhylomeDB; Q15042; -. DR TreeFam; TF314500; -. DR PathwayCommons; Q15042; -. DR Reactome; R-HSA-6811436; COPI-independent Golgi-to-ER retrograde traffic. DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs. DR SABIO-RK; Q15042; -. DR SignaLink; Q15042; -. DR SIGNOR; Q15042; -. DR BioGRID-ORCS; 22930; 22 hits in 1159 CRISPR screens. DR ChiTaRS; RAB3GAP1; human. DR GeneWiki; RAB3GAP1; -. DR GenomeRNAi; 22930; -. DR Pharos; Q15042; Tbio. DR PRO; PR:Q15042; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q15042; Protein. DR Bgee; ENSG00000115839; Expressed in hair follicle and 216 other cell types or tissues. DR ExpressionAtlas; Q15042; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0071782; C:endoplasmic reticulum tubular network; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:GO_Central. DR GO; GO:0005811; C:lipid droplet; IDA:GO_Central. DR GO; GO:0098794; C:postsynapse; IEA:GOC. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; TAS:Reactome. DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB. DR GO; GO:0007420; P:brain development; IMP:BHF-UCL. DR GO; GO:0043010; P:camera-type eye development; IMP:BHF-UCL. DR GO; GO:0097051; P:establishment of protein localization to endoplasmic reticulum membrane; IMP:UniProtKB. DR GO; GO:0060079; P:excitatory postsynaptic potential; ISS:ParkinsonsUK-UCL. DR GO; GO:0060325; P:face morphogenesis; IMP:BHF-UCL. DR GO; GO:0021854; P:hypothalamus development; IMP:BHF-UCL. DR GO; GO:0034389; P:lipid droplet organization; IMP:MGI. DR GO; GO:2000786; P:positive regulation of autophagosome assembly; IMP:GO_Central. DR GO; GO:1903373; P:positive regulation of endoplasmic reticulum tubular network organization; IMP:UniProtKB. DR GO; GO:0061646; P:positive regulation of glutamate neurotransmitter secretion in response to membrane depolarization; ISS:ParkinsonsUK-UCL. DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:UniProtKB. DR GO; GO:1903061; P:positive regulation of protein lipidation; IMP:GO_Central. DR GO; GO:1903233; P:regulation of calcium ion-dependent exocytosis of neurotransmitter; ISS:ParkinsonsUK-UCL. DR GO; GO:0043087; P:regulation of GTPase activity; IDA:UniProtKB. DR GO; GO:0048172; P:regulation of short-term neuronal synaptic plasticity; ISS:ParkinsonsUK-UCL. DR InterPro; IPR045700; Rab3GAP1. DR InterPro; IPR045698; Rab3GAP1_C. DR InterPro; IPR026147; Rab3GAP1_conserved. DR PANTHER; PTHR21422; RAB3 GTPASE-ACTIVATING PROTEIN CATALYTIC SUBUNIT; 1. DR PANTHER; PTHR21422:SF9; RAB3 GTPASE-ACTIVATING PROTEIN CATALYTIC SUBUNIT; 1. DR Pfam; PF19533; Rab3-GAP_cat_C; 1. DR Pfam; PF13890; Rab3-GTPase_cat; 1. DR Genevisible; Q15042; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cataract; Cytoplasm; Disease variant; KW Endoplasmic reticulum; GTPase activation; Intellectual disability; KW Phosphoprotein; Reference proteome. FT CHAIN 1..981 FT /note="Rab3 GTPase-activating protein catalytic subunit" FT /id="PRO_0000191655" FT REGION 592..613 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 908..937 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 83 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q80UJ7" FT MOD_RES 379 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 537 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 579 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q80UJ7" FT MOD_RES 581 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q80UJ7" FT MOD_RES 590 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 664 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 908 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..50 FT /note="MAADSEPESEVFEITDFTTASEWERFISKVEEVLNDWKLIGNSLGKPLEK FT -> MFSLIS (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_054475" FT VAR_SEQ 903 FT /note="R -> RLTESSDE (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_054068" FT VAR_SEQ 972..981 FT /note="GAFSSDTSFF -> VKIIDGDV (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_054476" FT VARIANT 18 FT /note="T -> P (in WARBM1; abolishes GEF activity towards FT RAB18; loss of RAB18 membrane association; no effect on GAP FT activity; no effect on GAP activity towards the RAB3 FT proteins RAB5A or RAB43; dbSNP:rs587777154)" FT /evidence="ECO:0000269|PubMed:23420520, FT ECO:0000269|PubMed:24891604" FT /id="VAR_086019" FT VARIANT 24 FT /note="E -> V (in WARBM1; abolishes GEF activity towards FT RAB18; loss of RAB18 membrane association; no effect on GAP FT activity; no effect on GAP activity towards the RAB3 FT proteins RAB5A or RAB43; dbSNP:rs587777155)" FT /evidence="ECO:0000269|PubMed:23420520, FT ECO:0000269|PubMed:24891604" FT /id="VAR_086020" FT VARIANT 598 FT /note="N -> S (in dbSNP:rs10445686)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_051716" FT MUTAGEN 619 FT /note="R->A: No effect." FT /evidence="ECO:0000269|PubMed:10859313" FT MUTAGEN 700 FT /note="R->A: No effect." FT /evidence="ECO:0000269|PubMed:10859313" FT MUTAGEN 728 FT /note="R->A: Loss of function." FT /evidence="ECO:0000269|PubMed:10859313" FT MUTAGEN 753 FT /note="R->A: No effect." FT /evidence="ECO:0000269|PubMed:10859313" SQ SEQUENCE 981 AA; 110524 MW; 0673611C5C49641C CRC64; MAADSEPESE VFEITDFTTA SEWERFISKV EEVLNDWKLI GNSLGKPLEK GIFTSGTWEE KSDEISFADF KFSVTHHYLV QESTDKEGKD ELLEDVVPQS MQDLLGMNND FPPRAHCLVR WYGLREFVVI APAAHSDAVL SESKCNLLLS SVSIALGNTG CQVPLFVQIH HKWRRMYVGE CQGPGVRTDF EMVHLRKVPN QYTHLSGLLD IFKSKIGCPL TPLPPVSIAI RFTYVLQDWQ QYFWPQQPPD IDALVGGEVG GLEFGKLPFG ACEDPISELH LATTWPHLTE GIIVDNDVYS DLDPIQAPHW SVRVRKAENP QCLLGDFVTE FFKICRRKES TDEILGRSAF EEEGKETADI THALSKLTEP ASVPIHKLSV SNMVHTAKKK IRKHRGVEES PLNNDVLNTI LLFLFPDAVS EKPLDGTTST DNNNPPSESE DYNLYNQFKS APSDSLTYKL ALCLCMINFY HGGLKGVAHL WQEFVLEMRF RWENNFLIPG LASGPPDLRC CLLHQKLQML NCCIERKKAR DEGKKTSASD VTNIYPGDAG KAGDQLVPDN LKETDKEKGE VGKSWDSWSD SEEEFFECLS DTEELKGNGQ ESGKKGGPKE MANLRPEGRL YQHGKLTLLH NGEPLYIPVT QEPAPMTEDL LEEQSEVLAK LGTSAEGAHL RARMQSACLL SDMESFKAAN PGCSLEDFVR WYSPRDYIEE EVIDEKGNVV LKGELSARMK IPSNMWVEAW ETAKPIPARR QRRLFDDTRE AEKVLHYLAI QKPADLARHL LPCVIHAAVL KVKEEESLEN ISSVKKIIKQ IISHSSKVLH FPNPEDKKLE EIIHQITNVE ALIARARSLK AKFGTEKCEQ EEEKEDLERF VSCLLEQPEV LVTGAGRGHA GRIIHKLFVN AQRAAAMTPP EEELKRMGSP EERRQNSVSD FPPPAGREFI LRTTVPRPAP YSKALPQRMY SVLTKEDFRL AGAFSSDTSF F //