Full text data of GAPVD1
GAPVD1
(GAPEX5, KIAA1521, RAP6)
[Confidence: high (present in two of the MS resources)]
GTPase-activating protein and VPS9 domain-containing protein 1 (GAPex-5; Rab5-activating protein 6)
GTPase-activating protein and VPS9 domain-containing protein 1 (GAPex-5; Rab5-activating protein 6)
hRBCD
IPI00292753
IPI00292753 DKFZP434C212 protein GTPase activating protein and VPS9 domains 1 soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a not mentioned n/a found at its expected molecular weight found at molecular weight
IPI00292753 DKFZP434C212 protein GTPase activating protein and VPS9 domains 1 soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a not mentioned n/a found at its expected molecular weight found at molecular weight
UniProt
Q14C86
ID GAPD1_HUMAN Reviewed; 1478 AA.
AC Q14C86; A8MYK3; B0QZ62; B0QZ63; B0QZ64; Q14C76; Q2Q1W1; Q8ND92;
read moreAC Q8WU86; Q96CZ4; Q9NXQ1; Q9P207; Q9Y4N0;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 22-JAN-2014, entry version 74.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), IDENTIFICATION BY MASS
RP SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP 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.,
RA 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.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large 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.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA 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.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA 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.,
RA Rogers J., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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 MASS SPECTROMETRY.
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
RT phosphorylation 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,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., 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 MASS
RP SPECTROMETRY.
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.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient 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 MASS SPECTROMETRY.
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
RT the 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 MASS
RP SPECTROMETRY.
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.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a 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
RP AND SER-1096, AND MASS SPECTROMETRY.
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
RP AND SER-1019, AND MASS SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
RA Buerckstuemmer T., 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 MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Acts both as a GTPase-activating protein (GAP) and a
CC guanine nucleotide exchange factor (GEF), and participates in
CC various processes such as endocytosis, insulin receptor
CC internalization or LC2A4/GLUT4 trafficking. Acts as a GEF for the
CC Ras-related protein RAB31 by exchanging bound GDP for free GTP,
CC leading to regulate LC2A4/GLUT4 trafficking. In the absence of
CC insulin, it maintains RAB31 in an active state and promotes a
CC futile cycle between LC2A4/GLUT4 storage vesicles and early
CC endosomes, retaining LC2A4/GLUT4 inside the cells. Upon insulin
CC stimulation, it is translocated to the plasma membrane, releasing
CC LC2A4/GLUT4 from intracellular storage vesicles. Also involved in
CC EGFR trafficking and degradation, possibly by promoting EGFR
CC ubiquitination and subsequent degradation by the proteasome. Has
CC GEF activity for Rab5 and GAP activity for Ras.
CC -!- SUBUNIT: Interacts with TRIP10/CIP4 (By similarity). Interacts
CC with RAB5A.
CC -!- SUBCELLULAR LOCATION: Membrane; Peripheral membrane protein.
CC Endosome. Note=Recruited to the plasma membrane by TRIP10/CIP4 in
CC 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 -!- SIMILARITY: Belongs to the GAPVD1 family.
CC -!- SIMILARITY: Contains 1 Ras-GAP domain.
CC -!- SIMILARITY: Contains 1 VPS9 domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH21119.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH21119.1; Type=Frameshift; Positions=742;
CC Sequence=BAA90959.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAA90959.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence;
CC Sequence=BAA96045.3; Type=Erroneous initiation;
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DR EMBL; DQ233254; ABB71126.1; -; mRNA.
DR EMBL; AB040954; BAA96045.3; ALT_INIT; mRNA.
DR EMBL; AL627223; CAH71014.2; -; Genomic_DNA.
DR EMBL; AL354710; CAH71014.2; JOINED; Genomic_DNA.
DR EMBL; AL627223; CAO03611.1; -; Genomic_DNA.
DR EMBL; AL354710; CAO03611.1; JOINED; Genomic_DNA.
DR EMBL; AL354710; CAQ08737.1; -; Genomic_DNA.
DR EMBL; AL627223; CAQ08737.1; JOINED; Genomic_DNA.
DR EMBL; AL627223; CAO03610.1; -; Genomic_DNA.
DR EMBL; AL354710; CAO03610.1; JOINED; Genomic_DNA.
DR EMBL; AL354710; CAQ08735.1; -; Genomic_DNA.
DR EMBL; AL627223; CAQ08735.1; JOINED; Genomic_DNA.
DR EMBL; AL354710; CAQ08736.1; -; Genomic_DNA.
DR EMBL; AL627223; CAQ08736.1; JOINED; 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 PIR; T12506; T12506.
DR RefSeq; NP_001269608.1; NM_001282679.1.
DR RefSeq; NP_001269609.1; NM_001282680.1.
DR RefSeq; NP_001269610.1; NM_001282681.1.
DR RefSeq; XP_005251956.1; XM_005251899.1.
DR RefSeq; XP_005251958.1; XM_005251901.1.
DR RefSeq; XP_005251961.1; XM_005251904.1.
DR UniGene; Hs.495134; -.
DR ProteinModelPortal; Q14C86; -.
DR SMR; Q14C86; 1263-1477.
DR IntAct; Q14C86; 4.
DR MINT; MINT-1631145; -.
DR DMDM; 172046859; -.
DR PaxDb; Q14C86; -.
DR PRIDE; Q14C86; -.
DR Ensembl; ENST00000265956; ENSP00000265956; ENSG00000165219.
DR Ensembl; ENST00000297933; ENSP00000297933; ENSG00000165219.
DR Ensembl; ENST00000312123; ENSP00000309582; ENSG00000165219.
DR Ensembl; ENST00000394104; ENSP00000377664; ENSG00000165219.
DR Ensembl; ENST00000394105; ENSP00000377665; ENSG00000165219.
DR Ensembl; ENST00000470056; ENSP00000419767; ENSG00000165219.
DR Ensembl; ENST00000495955; ENSP00000419063; ENSG00000165219.
DR GeneID; 26130; -.
DR KEGG; hsa:26130; -.
DR UCSC; uc010mwx.3; human.
DR CTD; 26130; -.
DR GeneCards; GC09P128024; -.
DR H-InvDB; HIX0008383; -.
DR HGNC; HGNC:23375; GAPVD1.
DR HPA; HPA029386; -.
DR HPA; HPA029387; -.
DR MIM; 611714; gene.
DR neXtProt; NX_Q14C86; -.
DR PharmGKB; PA142671748; -.
DR eggNOG; NOG275317; -.
DR HOVERGEN; HBG107936; -.
DR OMA; EMVDSNE; -.
DR ChiTaRS; GAPVD1; human.
DR GeneWiki; GAPVD1; -.
DR GenomeRNAi; 26130; -.
DR NextBio; 48153; -.
DR PMAP-CutDB; Q14C86; -.
DR PRO; PR:Q14C86; -.
DR ArrayExpress; Q14C86; -.
DR Bgee; Q14C86; -.
DR Genevestigator; Q14C86; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
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:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IEA:GOC.
DR GO; GO:0051223; P:regulation of protein transport; IMP:UniProtKB.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 1.10.506.10; -; 1.
DR InterPro; IPR001936; RasGAP.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR003123; VPS9.
DR InterPro; IPR013995; VPS9_subgr.
DR Pfam; PF00616; RasGAP; 1.
DR Pfam; PF02204; VPS9; 1.
DR SMART; SM00167; VPS9; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR PROSITE; PS00509; RAS_GTPASE_ACTIV_1; FALSE_NEG.
DR PROSITE; PS50018; RAS_GTPASE_ACTIV_2; 1.
DR PROSITE; PS51205; VPS9; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Endocytosis; Endosome;
KW GTPase activation; Guanine-nucleotide releasing factor; Membrane;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1 1478 GTPase-activating protein and VPS9
FT domain-containing protein 1.
FT /FTId=PRO_0000324771.
FT DOMAIN 131 353 Ras-GAP.
FT DOMAIN 1338 1478 VPS9.
FT MOD_RES 390 390 Phosphothreonine.
FT MOD_RES 458 458 Phosphothreonine.
FT MOD_RES 466 466 Phosphoserine.
FT MOD_RES 470 470 Phosphothreonine.
FT MOD_RES 566 566 Phosphoserine.
FT MOD_RES 766 766 Phosphoserine.
FT MOD_RES 902 902 Phosphoserine.
FT MOD_RES 903 903 Phosphoserine.
FT MOD_RES 966 966 Phosphoserine.
FT MOD_RES 1019 1019 Phosphoserine.
FT MOD_RES 1096 1096 Phosphoserine.
FT MOD_RES 1105 1105 Phosphoserine (By similarity).
FT VAR_SEQ 557 577 Missing (in isoform 4).
FT /FTId=VSP_032358.
FT VAR_SEQ 810 835 Missing (in isoform 5).
FT /FTId=VSP_032359.
FT VAR_SEQ 810 810 G -> DFLYILQPKQHFQHIEAEADMRIQLSSS (in
FT isoform 6).
FT /FTId=VSP_032360.
FT VAR_SEQ 989 1015 Missing (in isoform 3).
FT /FTId=VSP_032361.
FT VAR_SEQ 1057 1074 Missing (in isoform 2, isoform 3, isoform
FT 4 and isoform 6).
FT /FTId=VSP_032362.
FT CONFLICT 294 294 V -> E (in Ref. 1; ABB71126).
FT CONFLICT 306 306 C -> R (in Ref. 1; ABB71126).
FT CONFLICT 352 352 A -> T (in Ref. 7; BAA90959).
FT CONFLICT 366 366 S -> C (in Ref. 1; ABB71126).
FT CONFLICT 419 419 N -> D (in Ref. 7; BAA90959).
FT CONFLICT 455 455 L -> F (in Ref. 1; ABB71126).
FT CONFLICT 471 471 P -> L (in Ref. 1; ABB71126).
FT CONFLICT 530 530 M -> I (in Ref. 6; AAH21119).
FT CONFLICT 532 532 E -> G (in Ref. 7; BAA90959).
FT CONFLICT 741 741 C -> F (in Ref. 6; AAH21119).
FT CONFLICT 902 902 S -> G (in Ref. 7; BAA90959).
FT CONFLICT 931 931 P -> S (in Ref. 6; AAH13635).
FT CONFLICT 1037 1037 R -> W (in Ref. 1; ABB71126).
FT CONFLICT 1162 1162 L -> S (in Ref. 1; ABB71126).
FT CONFLICT 1425 1425 V -> L (in Ref. 1; ABB71126).
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
//
ID GAPD1_HUMAN Reviewed; 1478 AA.
AC Q14C86; A8MYK3; B0QZ62; B0QZ63; B0QZ64; Q14C76; Q2Q1W1; Q8ND92;
read moreAC Q8WU86; Q96CZ4; Q9NXQ1; Q9P207; Q9Y4N0;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 22-JAN-2014, entry version 74.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), IDENTIFICATION BY MASS
RP SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP 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.,
RA 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.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large 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.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA 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.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA 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.,
RA Rogers J., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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 MASS SPECTROMETRY.
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
RT phosphorylation 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,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., 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 MASS
RP SPECTROMETRY.
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.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient 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 MASS SPECTROMETRY.
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
RT the 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 MASS
RP SPECTROMETRY.
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.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a 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
RP AND SER-1096, AND MASS SPECTROMETRY.
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
RP AND SER-1019, AND MASS SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
RA Buerckstuemmer T., 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 MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Acts both as a GTPase-activating protein (GAP) and a
CC guanine nucleotide exchange factor (GEF), and participates in
CC various processes such as endocytosis, insulin receptor
CC internalization or LC2A4/GLUT4 trafficking. Acts as a GEF for the
CC Ras-related protein RAB31 by exchanging bound GDP for free GTP,
CC leading to regulate LC2A4/GLUT4 trafficking. In the absence of
CC insulin, it maintains RAB31 in an active state and promotes a
CC futile cycle between LC2A4/GLUT4 storage vesicles and early
CC endosomes, retaining LC2A4/GLUT4 inside the cells. Upon insulin
CC stimulation, it is translocated to the plasma membrane, releasing
CC LC2A4/GLUT4 from intracellular storage vesicles. Also involved in
CC EGFR trafficking and degradation, possibly by promoting EGFR
CC ubiquitination and subsequent degradation by the proteasome. Has
CC GEF activity for Rab5 and GAP activity for Ras.
CC -!- SUBUNIT: Interacts with TRIP10/CIP4 (By similarity). Interacts
CC with RAB5A.
CC -!- SUBCELLULAR LOCATION: Membrane; Peripheral membrane protein.
CC Endosome. Note=Recruited to the plasma membrane by TRIP10/CIP4 in
CC 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 -!- SIMILARITY: Belongs to the GAPVD1 family.
CC -!- SIMILARITY: Contains 1 Ras-GAP domain.
CC -!- SIMILARITY: Contains 1 VPS9 domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH21119.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH21119.1; Type=Frameshift; Positions=742;
CC Sequence=BAA90959.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAA90959.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence;
CC Sequence=BAA96045.3; Type=Erroneous initiation;
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DR EMBL; DQ233254; ABB71126.1; -; mRNA.
DR EMBL; AB040954; BAA96045.3; ALT_INIT; mRNA.
DR EMBL; AL627223; CAH71014.2; -; Genomic_DNA.
DR EMBL; AL354710; CAH71014.2; JOINED; Genomic_DNA.
DR EMBL; AL627223; CAO03611.1; -; Genomic_DNA.
DR EMBL; AL354710; CAO03611.1; JOINED; Genomic_DNA.
DR EMBL; AL354710; CAQ08737.1; -; Genomic_DNA.
DR EMBL; AL627223; CAQ08737.1; JOINED; Genomic_DNA.
DR EMBL; AL627223; CAO03610.1; -; Genomic_DNA.
DR EMBL; AL354710; CAO03610.1; JOINED; Genomic_DNA.
DR EMBL; AL354710; CAQ08735.1; -; Genomic_DNA.
DR EMBL; AL627223; CAQ08735.1; JOINED; Genomic_DNA.
DR EMBL; AL354710; CAQ08736.1; -; Genomic_DNA.
DR EMBL; AL627223; CAQ08736.1; JOINED; 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 PIR; T12506; T12506.
DR RefSeq; NP_001269608.1; NM_001282679.1.
DR RefSeq; NP_001269609.1; NM_001282680.1.
DR RefSeq; NP_001269610.1; NM_001282681.1.
DR RefSeq; XP_005251956.1; XM_005251899.1.
DR RefSeq; XP_005251958.1; XM_005251901.1.
DR RefSeq; XP_005251961.1; XM_005251904.1.
DR UniGene; Hs.495134; -.
DR ProteinModelPortal; Q14C86; -.
DR SMR; Q14C86; 1263-1477.
DR IntAct; Q14C86; 4.
DR MINT; MINT-1631145; -.
DR DMDM; 172046859; -.
DR PaxDb; Q14C86; -.
DR PRIDE; Q14C86; -.
DR Ensembl; ENST00000265956; ENSP00000265956; ENSG00000165219.
DR Ensembl; ENST00000297933; ENSP00000297933; ENSG00000165219.
DR Ensembl; ENST00000312123; ENSP00000309582; ENSG00000165219.
DR Ensembl; ENST00000394104; ENSP00000377664; ENSG00000165219.
DR Ensembl; ENST00000394105; ENSP00000377665; ENSG00000165219.
DR Ensembl; ENST00000470056; ENSP00000419767; ENSG00000165219.
DR Ensembl; ENST00000495955; ENSP00000419063; ENSG00000165219.
DR GeneID; 26130; -.
DR KEGG; hsa:26130; -.
DR UCSC; uc010mwx.3; human.
DR CTD; 26130; -.
DR GeneCards; GC09P128024; -.
DR H-InvDB; HIX0008383; -.
DR HGNC; HGNC:23375; GAPVD1.
DR HPA; HPA029386; -.
DR HPA; HPA029387; -.
DR MIM; 611714; gene.
DR neXtProt; NX_Q14C86; -.
DR PharmGKB; PA142671748; -.
DR eggNOG; NOG275317; -.
DR HOVERGEN; HBG107936; -.
DR OMA; EMVDSNE; -.
DR ChiTaRS; GAPVD1; human.
DR GeneWiki; GAPVD1; -.
DR GenomeRNAi; 26130; -.
DR NextBio; 48153; -.
DR PMAP-CutDB; Q14C86; -.
DR PRO; PR:Q14C86; -.
DR ArrayExpress; Q14C86; -.
DR Bgee; Q14C86; -.
DR Genevestigator; Q14C86; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
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:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IEA:GOC.
DR GO; GO:0051223; P:regulation of protein transport; IMP:UniProtKB.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 1.10.506.10; -; 1.
DR InterPro; IPR001936; RasGAP.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR003123; VPS9.
DR InterPro; IPR013995; VPS9_subgr.
DR Pfam; PF00616; RasGAP; 1.
DR Pfam; PF02204; VPS9; 1.
DR SMART; SM00167; VPS9; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR PROSITE; PS00509; RAS_GTPASE_ACTIV_1; FALSE_NEG.
DR PROSITE; PS50018; RAS_GTPASE_ACTIV_2; 1.
DR PROSITE; PS51205; VPS9; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Endocytosis; Endosome;
KW GTPase activation; Guanine-nucleotide releasing factor; Membrane;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1 1478 GTPase-activating protein and VPS9
FT domain-containing protein 1.
FT /FTId=PRO_0000324771.
FT DOMAIN 131 353 Ras-GAP.
FT DOMAIN 1338 1478 VPS9.
FT MOD_RES 390 390 Phosphothreonine.
FT MOD_RES 458 458 Phosphothreonine.
FT MOD_RES 466 466 Phosphoserine.
FT MOD_RES 470 470 Phosphothreonine.
FT MOD_RES 566 566 Phosphoserine.
FT MOD_RES 766 766 Phosphoserine.
FT MOD_RES 902 902 Phosphoserine.
FT MOD_RES 903 903 Phosphoserine.
FT MOD_RES 966 966 Phosphoserine.
FT MOD_RES 1019 1019 Phosphoserine.
FT MOD_RES 1096 1096 Phosphoserine.
FT MOD_RES 1105 1105 Phosphoserine (By similarity).
FT VAR_SEQ 557 577 Missing (in isoform 4).
FT /FTId=VSP_032358.
FT VAR_SEQ 810 835 Missing (in isoform 5).
FT /FTId=VSP_032359.
FT VAR_SEQ 810 810 G -> DFLYILQPKQHFQHIEAEADMRIQLSSS (in
FT isoform 6).
FT /FTId=VSP_032360.
FT VAR_SEQ 989 1015 Missing (in isoform 3).
FT /FTId=VSP_032361.
FT VAR_SEQ 1057 1074 Missing (in isoform 2, isoform 3, isoform
FT 4 and isoform 6).
FT /FTId=VSP_032362.
FT CONFLICT 294 294 V -> E (in Ref. 1; ABB71126).
FT CONFLICT 306 306 C -> R (in Ref. 1; ABB71126).
FT CONFLICT 352 352 A -> T (in Ref. 7; BAA90959).
FT CONFLICT 366 366 S -> C (in Ref. 1; ABB71126).
FT CONFLICT 419 419 N -> D (in Ref. 7; BAA90959).
FT CONFLICT 455 455 L -> F (in Ref. 1; ABB71126).
FT CONFLICT 471 471 P -> L (in Ref. 1; ABB71126).
FT CONFLICT 530 530 M -> I (in Ref. 6; AAH21119).
FT CONFLICT 532 532 E -> G (in Ref. 7; BAA90959).
FT CONFLICT 741 741 C -> F (in Ref. 6; AAH21119).
FT CONFLICT 902 902 S -> G (in Ref. 7; BAA90959).
FT CONFLICT 931 931 P -> S (in Ref. 6; AAH13635).
FT CONFLICT 1037 1037 R -> W (in Ref. 1; ABB71126).
FT CONFLICT 1162 1162 L -> S (in Ref. 1; ABB71126).
FT CONFLICT 1425 1425 V -> L (in Ref. 1; ABB71126).
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
//
MIM
611714
*RECORD*
*FIELD* NO
611714
*FIELD* TI
*611714 GTPase-ACTIVATING PROTEIN AND VPS9 DOMAINS 1; GAPVD1
;;RAB5-ACTIVATING PROTEIN 6; RAP6;;
read moreRAB5 EXCHANGE FACTOR; GAPEX5;;
KIAA1521
*FIELD* TX
CLONING
Hunker et al. (2006) identified a Rab GTPase guanine nucleotide exchange
factor (GEF), which they named RAP6 (Rab5-activating protein-6), as a
protein of approximately 150 kD that interacted with Rab5a (179512) in
HeLa cells. After isolating and characterizing the protein by mass
spectrometry, they identified it by database analysis as GAPVD1. The
deduced 1,439-amino acid protein has a predicted molecular mass of 158
kD. It contains a C-terminal Vps9-like motif, which is found in other
Rab5 GEFs, and an N-terminal RasGAP-like domain (RGD) similar to those
found in GAP proteins that specifically interact with Ras proteins. An
antibody raised to RAP6 localized the protein to the plasma membrane and
intracellular vesicles.
GENE FUNCTION
Hunker et al. (2006) confirmed that RAP6 binds to Rab5 and Ras through
the Vps9 and RGD domains, respectively. Overexpression of RAP6 affected
both fluid phase and receptor-mediated endocytosis. Hunker et al. (2006)
suggested that RAP6 may play a role in endocytosis by regulating
endosome morphology.
Su et al. (2007) studied the same protein, which they called Rab5
exchange factor (GAPEX5), in epidermal growth factor receptor (EGFR;
131550) trafficking and degradation. Depletion of the protein delayed
EGFR degradation, whereas overexpression had the reverse effect. Su et
al. (2007) proposed that GAPEX5 affects EGFR degradation by mediating
receptor ubiquitination through its RGD domain and may be an important
mediator of carcinogenesis resulting from mutations in the Ras proteins.
Kitano et al. (2008) found that GAPEX5 is the guanine nucleotide
exchange factor essential for activation of RAB5 (179512) during
engulfment of apoptotic cells. GAPEX5 was bound to a microtubule
tip-associating protein, EB1 (603108), whose depletion inhibited Rab5
activation during phagocytosis. Kitano et al. (2008) therefore proposed
a mechanistic model in which the recruitment of GAPEX5 to phagosomes
through the microtubule network induces transient RAB5 activation.
MAPPING
By database analysis, Hunker et al. (2006) identified the GAPVD1 gene on
chromosome 9q33.3.
*FIELD* RF
1. Hunker, C. M.; Galvis, A.; Kruk, I.; Giambini, H.; Veisaga, M.
L.; Barbieri, M. A.: Rab5-activating protein 6, a novel endosomal
protein with a role in endocytosis. Biochem. Biophys. Res. Commun. 340:
967-975, 2006.
2. Kitano, M.; Nakaya, M.; Nakamura, T.; Nagata, S.; Matsuda, M.:
Imaging of Rab5 activity identifies essential regulators for phagosome
maturation. Nature 453: 241-245, 2008.
3. Su, X.; Kong, C.; Stahl, P. D.: GAPex-5 mediates ubiquitination,
trafficking, and degradation of epidermal growth factor receptor. J.
Biol. Chem. 282: 21278-21278, 2007.
*FIELD* CN
Ada Hamosh - updated: 6/12/2008
*FIELD* CD
Alan F. Scott: 1/3/2008
*FIELD* ED
alopez: 06/17/2008
terry: 6/12/2008
carol: 1/4/2008
carol: 1/3/2008
*RECORD*
*FIELD* NO
611714
*FIELD* TI
*611714 GTPase-ACTIVATING PROTEIN AND VPS9 DOMAINS 1; GAPVD1
;;RAB5-ACTIVATING PROTEIN 6; RAP6;;
read moreRAB5 EXCHANGE FACTOR; GAPEX5;;
KIAA1521
*FIELD* TX
CLONING
Hunker et al. (2006) identified a Rab GTPase guanine nucleotide exchange
factor (GEF), which they named RAP6 (Rab5-activating protein-6), as a
protein of approximately 150 kD that interacted with Rab5a (179512) in
HeLa cells. After isolating and characterizing the protein by mass
spectrometry, they identified it by database analysis as GAPVD1. The
deduced 1,439-amino acid protein has a predicted molecular mass of 158
kD. It contains a C-terminal Vps9-like motif, which is found in other
Rab5 GEFs, and an N-terminal RasGAP-like domain (RGD) similar to those
found in GAP proteins that specifically interact with Ras proteins. An
antibody raised to RAP6 localized the protein to the plasma membrane and
intracellular vesicles.
GENE FUNCTION
Hunker et al. (2006) confirmed that RAP6 binds to Rab5 and Ras through
the Vps9 and RGD domains, respectively. Overexpression of RAP6 affected
both fluid phase and receptor-mediated endocytosis. Hunker et al. (2006)
suggested that RAP6 may play a role in endocytosis by regulating
endosome morphology.
Su et al. (2007) studied the same protein, which they called Rab5
exchange factor (GAPEX5), in epidermal growth factor receptor (EGFR;
131550) trafficking and degradation. Depletion of the protein delayed
EGFR degradation, whereas overexpression had the reverse effect. Su et
al. (2007) proposed that GAPEX5 affects EGFR degradation by mediating
receptor ubiquitination through its RGD domain and may be an important
mediator of carcinogenesis resulting from mutations in the Ras proteins.
Kitano et al. (2008) found that GAPEX5 is the guanine nucleotide
exchange factor essential for activation of RAB5 (179512) during
engulfment of apoptotic cells. GAPEX5 was bound to a microtubule
tip-associating protein, EB1 (603108), whose depletion inhibited Rab5
activation during phagocytosis. Kitano et al. (2008) therefore proposed
a mechanistic model in which the recruitment of GAPEX5 to phagosomes
through the microtubule network induces transient RAB5 activation.
MAPPING
By database analysis, Hunker et al. (2006) identified the GAPVD1 gene on
chromosome 9q33.3.
*FIELD* RF
1. Hunker, C. M.; Galvis, A.; Kruk, I.; Giambini, H.; Veisaga, M.
L.; Barbieri, M. A.: Rab5-activating protein 6, a novel endosomal
protein with a role in endocytosis. Biochem. Biophys. Res. Commun. 340:
967-975, 2006.
2. Kitano, M.; Nakaya, M.; Nakamura, T.; Nagata, S.; Matsuda, M.:
Imaging of Rab5 activity identifies essential regulators for phagosome
maturation. Nature 453: 241-245, 2008.
3. Su, X.; Kong, C.; Stahl, P. D.: GAPex-5 mediates ubiquitination,
trafficking, and degradation of epidermal growth factor receptor. J.
Biol. Chem. 282: 21278-21278, 2007.
*FIELD* CN
Ada Hamosh - updated: 6/12/2008
*FIELD* CD
Alan F. Scott: 1/3/2008
*FIELD* ED
alopez: 06/17/2008
terry: 6/12/2008
carol: 1/4/2008
carol: 1/3/2008