ID GAPD1_HUMAN Reviewed; 1478 AA. AC Q14C86; A8MYK3; B0QZ62; B0QZ63; B0QZ64; Q14C76; Q2Q1W1; Q8ND92; Q8WU86; AC Q96CZ4; Q9NXQ1; Q9P207; Q9Y4N0; DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot. DT 18-MAR-2008, sequence version 2. DT 27-MAR-2024, entry version 152. DE RecName: Full=GTPase-activating protein and VPS9 domain-containing protein 1; DE AltName: Full=GAPex-5; DE AltName: Full=Rab5-activating protein 6; GN Name=GAPVD1; Synonyms=GAPEX5, KIAA1521, RAP6; 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 [MRNA] (ISOFORM 4), IDENTIFICATION BY MASS RP SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RAB5A. RX PubMed=16410077; DOI=10.1016/j.bbrc.2005.12.099; RA Hunker C.M., Galvis A., Kruk I., Giambini H., Veisaga M.L., Barbieri M.A.; RT "Rab5-activating protein 6, a novel endosomal protein with a role in RT endocytosis."; RL Biochem. Biophys. Res. Commun. 340:967-975(2006). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=10819331; DOI=10.1093/dnares/7.2.143; RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:143-150(2000). RN [3] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 139-996 (ISOFORM 5). RC TISSUE=Colon; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 675-1478 (ISOFORM 6). 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 [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-390 AND SER-1019, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1096, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-390 AND SER-1019, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-390; THR-458; SER-466; RP THR-470; SER-566; SER-902; SER-903; SER-1019 AND SER-1096, AND 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 [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466; SER-766; SER-902 AND RP SER-1096, AND 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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-390; SER-902; SER-966 AND RP SER-1019, AND 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 [17] 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 [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-902, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-227; THR-390; SER-466; RP SER-746; SER-876; SER-902; SER-903; SER-1019 AND SER-1096, AND RP 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 [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-757 AND THR-762, AND RP IDENTIFICATION BY 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 [21] RP INTERACTION WITH P.FALCIPARUM CK1 (MICROBIAL INFECTION), TISSUE RP SPECIFICITY, IDENTIFICATION BY MASS SPECTROMETRY, AND PHOSPHORYLATION AT RP THR-390; TYR-460; SER-902; SER-903; SER-914 AND SER-1103. RX PubMed=32356940; DOI=10.1002/iub.2294; RA Batty M.B., Schittenhelm R.B., Dorin-Semblat D., Doerig C., RA Garcia-Bustos J.F.; RT "Interaction of Plasmodium falciparum casein kinase 1 with components of RT host cell protein trafficking machinery."; RL IUBMB Life 72:1243-1249(2020). CC -!- FUNCTION: Acts both as a GTPase-activating protein (GAP) and a guanine CC nucleotide exchange factor (GEF), and participates in various processes CC such as endocytosis, insulin receptor internalization or LC2A4/GLUT4 CC trafficking. Acts as a GEF for the Ras-related protein RAB31 by CC exchanging bound GDP for free GTP, leading to regulate LC2A4/GLUT4 CC trafficking. In the absence of insulin, it maintains RAB31 in an active CC state and promotes a futile cycle between LC2A4/GLUT4 storage vesicles CC and early endosomes, retaining LC2A4/GLUT4 inside the cells. Upon CC insulin stimulation, it is translocated to the plasma membrane, CC releasing LC2A4/GLUT4 from intracellular storage vesicles. Also CC involved in EGFR trafficking and degradation, possibly by promoting CC EGFR ubiquitination and subsequent degradation by the proteasome. Has CC GEF activity for Rab5 and GAP activity for Ras. CC {ECO:0000269|PubMed:16410077}. CC -!- SUBUNIT: Interacts with TRIP10/CIP4 (By similarity). Interacts with CC RAB5A. {ECO:0000250, ECO:0000269|PubMed:16410077}. CC -!- SUBUNIT: (Microbial infection) Interacts with P.falciparum (strain 3D7) CC CK1. {ECO:0000269|PubMed:32356940}. CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:16410077}; CC Peripheral membrane protein {ECO:0000269|PubMed:16410077}. Endosome CC {ECO:0000269|PubMed:16410077}. Note=Recruited to the plasma membrane by CC TRIP10/CIP4 in response to insulin. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; CC IsoId=Q14C86-1; Sequence=Displayed; CC Name=2; CC IsoId=Q14C86-2; Sequence=VSP_032362; CC Name=3; CC IsoId=Q14C86-3; Sequence=VSP_032361, VSP_032362; CC Name=4; CC IsoId=Q14C86-4; Sequence=VSP_032358, VSP_032362; CC Name=5; CC IsoId=Q14C86-5; Sequence=VSP_032359; CC Name=6; CC IsoId=Q14C86-6; Sequence=VSP_032360, VSP_032362; CC -!- TISSUE SPECIFICITY: Expressed in erythrocytes (at protein level). CC {ECO:0000269|PubMed:32356940}. CC -!- SIMILARITY: Belongs to the GAPVD1 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH21119.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH21119.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAA90959.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAA90959.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC Sequence=BAA96045.3; Type=Erroneous initiation; 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; DQ233254; ABB71126.1; -; mRNA. DR EMBL; AB040954; BAA96045.3; ALT_INIT; mRNA. DR EMBL; AL354710; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL627223; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471090; EAW87622.1; -; Genomic_DNA. DR EMBL; CH471090; EAW87623.1; -; Genomic_DNA. DR EMBL; BC013635; AAH13635.1; -; mRNA. DR EMBL; BC021119; AAH21119.1; ALT_SEQ; mRNA. DR EMBL; BC114937; AAI14938.1; -; mRNA. DR EMBL; BC114962; AAI14963.1; -; mRNA. DR EMBL; AK000126; BAA90959.1; ALT_SEQ; mRNA. DR EMBL; AL080196; CAB45770.1; -; mRNA. DR EMBL; AL834325; CAD38993.1; -; mRNA. DR CCDS; CCDS35138.1; -. [Q14C86-6] DR CCDS; CCDS65130.1; -. [Q14C86-4] DR CCDS; CCDS65131.1; -. [Q14C86-2] DR CCDS; CCDS65132.1; -. [Q14C86-1] DR CCDS; CCDS83414.1; -. [Q14C86-3] DR PIR; T12506; T12506. DR RefSeq; NP_001269608.1; NM_001282679.1. [Q14C86-1] DR RefSeq; NP_001269609.1; NM_001282680.1. [Q14C86-2] DR RefSeq; NP_001269610.1; NM_001282681.1. [Q14C86-4] DR RefSeq; NP_001317707.1; NM_001330778.1. [Q14C86-3] DR RefSeq; NP_056450.2; NM_015635.3. [Q14C86-6] DR RefSeq; XP_005251958.1; XM_005251901.3. DR RefSeq; XP_005251961.1; XM_005251904.3. [Q14C86-3] DR RefSeq; XP_006717107.1; XM_006717044.3. DR RefSeq; XP_011516801.1; XM_011518499.2. [Q14C86-6] DR RefSeq; XP_011516802.1; XM_011518500.2. [Q14C86-6] DR RefSeq; XP_011516804.1; XM_011518502.2. DR RefSeq; XP_016870089.1; XM_017014600.1. DR RefSeq; XP_016870090.1; XM_017014601.1. DR RefSeq; XP_016870091.1; XM_017014602.1. DR RefSeq; XP_016870092.1; XM_017014603.1. DR RefSeq; XP_016870093.1; XM_017014604.1. DR RefSeq; XP_016870095.1; XM_017014606.1. [Q14C86-4] DR RefSeq; XP_016870096.1; XM_017014607.1. DR RefSeq; XP_016870097.1; XM_017014608.1. DR RefSeq; XP_016870098.1; XM_017014609.1. [Q14C86-3] DR AlphaFoldDB; Q14C86; -. DR SMR; Q14C86; -. DR BioGRID; 117568; 187. DR IntAct; Q14C86; 32. DR MINT; Q14C86; -. DR STRING; 9606.ENSP00000377665; -. DR GlyCosmos; Q14C86; 1 site, 1 glycan. DR GlyGen; Q14C86; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q14C86; -. DR MetOSite; Q14C86; -. DR PhosphoSitePlus; Q14C86; -. DR BioMuta; GAPVD1; -. DR DMDM; 172046859; -. DR EPD; Q14C86; -. DR jPOST; Q14C86; -. DR MassIVE; Q14C86; -. DR MaxQB; Q14C86; -. DR PaxDb; 9606-ENSP00000377664; -. DR PeptideAtlas; Q14C86; -. DR ProteomicsDB; 60308; -. [Q14C86-1] DR ProteomicsDB; 60309; -. [Q14C86-2] DR ProteomicsDB; 60310; -. [Q14C86-3] DR ProteomicsDB; 60311; -. [Q14C86-4] DR ProteomicsDB; 60312; -. [Q14C86-5] DR ProteomicsDB; 60313; -. [Q14C86-6] DR Pumba; Q14C86; -. DR Antibodypedia; 30544; 121 antibodies from 19 providers. DR DNASU; 26130; -. DR Ensembl; ENST00000297933.11; ENSP00000297933.6; ENSG00000165219.23. [Q14C86-2] DR Ensembl; ENST00000312123.13; ENSP00000309582.9; ENSG00000165219.23. [Q14C86-4] DR Ensembl; ENST00000394104.6; ENSP00000377664.2; ENSG00000165219.23. [Q14C86-1] DR Ensembl; ENST00000394105.6; ENSP00000377665.2; ENSG00000165219.23. [Q14C86-6] DR Ensembl; ENST00000470056.5; ENSP00000419767.1; ENSG00000165219.23. [Q14C86-3] DR Ensembl; ENST00000495955.5; ENSP00000419063.1; ENSG00000165219.23. [Q14C86-1] DR GeneID; 26130; -. DR KEGG; hsa:26130; -. DR MANE-Select; ENST00000297933.11; ENSP00000297933.6; NM_001282680.3; NP_001269609.1. [Q14C86-2] DR UCSC; uc004bpq.5; human. [Q14C86-1] DR AGR; HGNC:23375; -. DR CTD; 26130; -. DR DisGeNET; 26130; -. DR GeneCards; GAPVD1; -. DR HGNC; HGNC:23375; GAPVD1. DR HPA; ENSG00000165219; Low tissue specificity. DR MalaCards; GAPVD1; -. DR MIM; 611714; gene. DR neXtProt; NX_Q14C86; -. DR OpenTargets; ENSG00000165219; -. DR Orphanet; 656; Genetic steroid-resistant nephrotic syndrome. DR PharmGKB; PA142671748; -. DR VEuPathDB; HostDB:ENSG00000165219; -. DR eggNOG; KOG2319; Eukaryota. DR GeneTree; ENSGT00940000156611; -. DR HOGENOM; CLU_002165_1_0_1; -. DR InParanoid; Q14C86; -. DR OMA; ENHEIML; -. DR OrthoDB; 20678at2759; -. DR PhylomeDB; Q14C86; -. DR TreeFam; TF105908; -. DR PathwayCommons; Q14C86; -. DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis. DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs. DR SignaLink; Q14C86; -. DR BioGRID-ORCS; 26130; 10 hits in 1054 CRISPR screens. DR ChiTaRS; GAPVD1; human. DR GeneWiki; GAPVD1; -. DR GenomeRNAi; 26130; -. DR Pharos; Q14C86; Tbio. DR PRO; PR:Q14C86; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q14C86; Protein. DR Bgee; ENSG00000165219; Expressed in bronchial epithelial cell and 213 other cell types or tissues. DR ExpressionAtlas; Q14C86; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0030139; C:endocytic vesicle; IBA:GO_Central. DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL. DR GO; GO:0032794; F:GTPase activating protein binding; IMP:UniProtKB. DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IMP:UniProtKB. DR GO; GO:0031267; F:small GTPase binding; IBA:GO_Central. DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW. DR GO; GO:0051223; P:regulation of protein transport; IMP:UniProtKB. DR CDD; cd05129; RasGAP_RAP6; 1. DR Gene3D; 1.10.246.120; -; 1. DR Gene3D; 1.20.1050.80; VPS9 domain; 1. DR InterPro; IPR041545; DUF5601. DR InterPro; IPR001936; RasGAP_dom. DR InterPro; IPR008936; Rho_GTPase_activation_prot. DR InterPro; IPR003123; VPS9. DR InterPro; IPR045046; Vps9-like. DR InterPro; IPR037191; VPS9_dom_sf. DR PANTHER; PTHR23101:SF25; GTPASE-ACTIVATING PROTEIN AND VPS9 DOMAIN-CONTAINING PROTEIN 1; 1. DR PANTHER; PTHR23101; RAB GDP/GTP EXCHANGE FACTOR; 1. DR Pfam; PF18151; DUF5601; 1. DR Pfam; PF00616; RasGAP; 1. DR Pfam; PF02204; VPS9; 1. DR SMART; SM00167; VPS9; 1. DR SUPFAM; SSF48350; GTPase activation domain, GAP; 1. DR SUPFAM; SSF109993; VPS9 domain; 1. DR PROSITE; PS50018; RAS_GTPASE_ACTIV_2; 1. DR PROSITE; PS51205; VPS9; 1. DR Genevisible; Q14C86; HS. PE 1: Evidence at protein level; KW Alternative splicing; Endocytosis; Endosome; GTPase activation; KW Guanine-nucleotide releasing factor; Membrane; Phosphoprotein; KW Reference proteome. FT CHAIN 1..1478 FT /note="GTPase-activating protein and VPS9 domain-containing FT protein 1" FT /id="PRO_0000324771" FT DOMAIN 131..353 FT /note="Ras-GAP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00167" FT DOMAIN 1338..1478 FT /note="VPS9" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00550" FT REGION 574..608 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 739..820 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 846..874 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 889..1023 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1043..1064 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 574..592 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 740..776 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 955..979 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 991..1011 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 227 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 390 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:32356940, FT ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 458 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 460 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:32356940" FT MOD_RES 466 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 470 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 566 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 569 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PAR5" FT MOD_RES 742 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PAR5" FT MOD_RES 746 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 757 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 762 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 766 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 876 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 902 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:32356940, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 903 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:32356940, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163" FT MOD_RES 908 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PAR5" FT MOD_RES 914 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:32356940" FT MOD_RES 966 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 1019 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 1046 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PAR5" FT MOD_RES 1096 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1103 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:32356940" FT VAR_SEQ 557..577 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:16410077" FT /id="VSP_032358" FT VAR_SEQ 810..835 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_032359" FT VAR_SEQ 810 FT /note="G -> DFLYILQPKQHFQHIEAEADMRIQLSSS (in isoform 6)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_032360" FT VAR_SEQ 989..1015 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_032361" FT VAR_SEQ 1057..1074 FT /note="Missing (in isoform 2, isoform 3, isoform 4 and FT isoform 6)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:16410077, ECO:0000303|PubMed:17974005" FT /id="VSP_032362" FT CONFLICT 294 FT /note="V -> E (in Ref. 1; ABB71126)" FT /evidence="ECO:0000305" FT CONFLICT 306 FT /note="C -> R (in Ref. 1; ABB71126)" FT /evidence="ECO:0000305" FT CONFLICT 352 FT /note="A -> T (in Ref. 7; BAA90959)" FT /evidence="ECO:0000305" FT CONFLICT 366 FT /note="S -> C (in Ref. 1; ABB71126)" FT /evidence="ECO:0000305" FT CONFLICT 419 FT /note="N -> D (in Ref. 7; BAA90959)" FT /evidence="ECO:0000305" FT CONFLICT 455 FT /note="L -> F (in Ref. 1; ABB71126)" FT /evidence="ECO:0000305" FT CONFLICT 471 FT /note="P -> L (in Ref. 1; ABB71126)" FT /evidence="ECO:0000305" FT CONFLICT 530 FT /note="M -> I (in Ref. 6; AAH21119)" FT /evidence="ECO:0000305" FT CONFLICT 532 FT /note="E -> G (in Ref. 7; BAA90959)" FT /evidence="ECO:0000305" FT CONFLICT 741 FT /note="C -> F (in Ref. 6; AAH21119)" FT /evidence="ECO:0000305" FT CONFLICT 902 FT /note="S -> G (in Ref. 7; BAA90959)" FT /evidence="ECO:0000305" FT CONFLICT 931 FT /note="P -> S (in Ref. 6; AAH13635)" FT /evidence="ECO:0000305" FT CONFLICT 1037 FT /note="R -> W (in Ref. 1; ABB71126)" FT /evidence="ECO:0000305" FT CONFLICT 1162 FT /note="L -> S (in Ref. 1; ABB71126)" FT /evidence="ECO:0000305" FT CONFLICT 1425 FT /note="V -> L (in Ref. 1; ABB71126)" FT /evidence="ECO:0000305" SQ SEQUENCE 1478 AA; 164980 MW; DD429B0EB207276C CRC64; MVKLDIHTLA HHLKQERLYV NSEKQLIQRL NADVLKTAEK LYRTAWIAKQ QRINLDRLII TSAEASPAEC CQHAKILEDT QFVDGYKQLG FQETAYGEFL SRLRENPRLI ASSLVAGEKL NQENTQSVIY TVFTSLYGNC IMQEDESYLL QVLRYLIEFE LKESDNPRRL LRRGTCAFSI LFKLFSEGLF SAKLFLTATL HEPIMQLLVE DEDHLETDPN KLIERFSPSQ QEKLFGEKGS DRFRQKVQEM VESNEAKLVA LVNKFIGYLK QNTYCFPHSL RWIVSQMYKT LSCVDRLEVG EVRAMCTDLL LACFICPAVV NPEQYGIISD APINEVARFN LMQVGRLLQQ LAMTGSEEGD PRTKSSLGKF DKSCVAAFLD VVIGGRAVET PPLSSVNLLE GLSRTVVYIT YSQLITLVNF MKSVMSGDQL REDRMALDNL LANLPPAKPG KSSSLEMTPY NTPQLSPATT PANKKNRLPI ATRSRSRTNM LMDLHMDHEG SSQETIQEVQ PEEVLVISLG TGPQLTPGMM SENEVLNMQL SDGGQGDVPV DENKLHGKPD KTLRFSLCSD NLEGISEGPS NRSNSVSSLD LEGESVSELG AGPSGSNGVE ALQLLEHEQA TTQDNLDDKL RKFEIRDMMG LTDDRDISET VSETWSTDVL GSDFDPNIDE DRLQEIAGAA AENMLGSLLC LPGSGSVLLD PCTGSTISET TSEAWSVEVL PSDSEAPDLK QEERLQELES CSGLGSTSDD TDVREVSSRP STPGLSVVSG ISATSEDIPN KIEDLRSECS SDFGGKDSVT SPDMDEITHG AHQLTSPPSQ SESLLAMFDP LSSHEGASAV VRPKVHYARP SHPPPDPPIL EGAVGGNEAR LPNFGSHVLT PAEMEAFKQR HSYPERLVRS RSSDIVSSVR RPMSDPSWNR RPGNEERELP PAAAIGATSL VAAPHSSSSS PSKDSSRGET EERKDSDDEK SDRNRPWWRK RFVSAMPKAP IPFRKKEKQE KDKDDLGPDR FSTLTDDPSP RLSAQAQVAE DILDKYRNAI KRTSPSDGAM ANYESTGDNH DRDLSSKLLY HSDKEVMGDG ESAHDSPRDE ALQNISADDL PDSASQAAHP QDSAFSYRDA KKKLRLALCS ADSVAFPVLT HSTRNGLPDH TDPEDNEIVC FLKVQIAEAI NLQDKNLMAQ LQETMRCVCR FDNRTCRKLL ASIAEDYRKR APYIAYLTRC RQGLQTTQAH LERLLQRVLR DKEVANRYFT TVCVRLLLES KEKKIREFIQ DFQKLTAADD KTAQVEDFLQ FLYGAMAQDV IWQNASEEQL QDAQLAIERS VMNRIFKLAF YPNQDGDILR DQVLHEHIQR LSKVVTANHR ALQIPEVYLR EAPWPSAQSE IRTISAYKTP RDKVQCILRM CSTIMNLLSL ANEDSVPGAD DFVPVLVFVL IKANPPCLLS TVQYISSFYA SCLSGEESYW WMQFTAAVEF IKTIDDRK //