Tag | Content |
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CPLM ID | CPLM-012431 |
UniProt Accession | |
Genbank Protein ID | |
Genbank Nucleotide ID | |
Protein Name | GTPase-activating protein and VPS9 domain-containing protein 1 |
Protein Synonyms/Alias | GAPex-5; Rab5-activating protein 6 |
Gene Name | GAPVD1 |
Gene Synonyms/Alias | GAPEX5; KIAA1521; RAP6 |
Created Date | July 27, 2013 |
Organism | Homo sapiens (Human) |
NCBI Taxa ID | 9606 |
Lysine Modification | Position | Peptide | Type | References |
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24 | RLYVNSEKQLIQRLN | ubiquitination | [1, 2] | 49 | YRTAWIAKQQRINLD | ubiquitination | [1] | 233 | FSPSQQEKLFGEKGS | ubiquitination | [1] | 238 | QEKLFGEKGSDRFRQ | ubiquitination | [1] | 1207 | FDNRTCRKLLASIAE | ubiquitination | [1] | 1270 | VRLLLESKEKKIREF | ubiquitination | [1] | 1336 | SVMNRIFKLAFYPNQ | ubiquitination | [1, 2] | 1362 | EHIQRLSKVVTANHR | ubiquitination | [1] | 1397 | IRTISAYKTPRDKVQ | ubiquitination | [1] | 1402 | AYKTPRDKVQCILRM | ubiquitination | [1] |
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Reference | [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments. Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA. Mol Cell Proteomics. 2013 Mar;12(3):825-31. [ PMID: 23266961] [2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties. Chen Z, Zhou Y, Song J, Zhang Z. Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [ PMID: 23603789] |
Functional Description | Acts both as a GTPase-activating protein (GAP) and a guanine nucleotide exchange factor (GEF), and participates in various processes such as endocytosis, insulin receptor internalization or LC2A4/GLUT4 trafficking. Acts as a GEF for the Ras-related protein RAB31 by exchanging bound GDP for free GTP, leading to regulate LC2A4/GLUT4 trafficking. In the absence of insulin, it maintains RAB31 in an active state and promotes a futile cycle between LC2A4/GLUT4 storage vesicles and early endosomes, retaining LC2A4/GLUT4 inside the cells. Upon insulin stimulation, it is translocated to the plasma membrane, releasing LC2A4/GLUT4 from intracellular storage vesicles. Also involved in EGFR trafficking and degradation, possibly by promoting EGFR ubiquitination and subsequent degradation by the proteasome. Has GEF activity for Rab5 and GAP activity for Ras. |
Sequence Annotation | DOMAIN 131 353 Ras-GAP. DOMAIN 1338 1478 VPS9. MOD_RES 390 390 Phosphothreonine. MOD_RES 458 458 Phosphothreonine. MOD_RES 466 466 Phosphoserine. MOD_RES 470 470 Phosphothreonine. MOD_RES 566 566 Phosphoserine. MOD_RES 766 766 Phosphoserine. MOD_RES 902 902 Phosphoserine. MOD_RES 903 903 Phosphoserine. MOD_RES 966 966 Phosphoserine. MOD_RES 1019 1019 Phosphoserine. MOD_RES 1096 1096 Phosphoserine. MOD_RES 1105 1105 Phosphoserine (By similarity). |
Keyword | Alternative splicing; Complete proteome; Endocytosis; Endosome; GTPase activation; Guanine-nucleotide releasing factor; Membrane; Phosphoprotein; Reference proteome. |
Sequence Source | UniProt (SWISSPROT/TrEMBL); GenBank; EMBL |
Protein Length | 1478 AA |
Protein Sequence | MVKLDIHTLA HHLKQERLYV NSEKQLIQRL NADVLKTAEK LYRTAWIAKQ QRINLDRLII 60 TSAEASPAEC CQHAKILEDT QFVDGYKQLG FQETAYGEFL SRLRENPRLI ASSLVAGEKL 120 NQENTQSVIY TVFTSLYGNC IMQEDESYLL QVLRYLIEFE LKESDNPRRL LRRGTCAFSI 180 LFKLFSEGLF SAKLFLTATL HEPIMQLLVE DEDHLETDPN KLIERFSPSQ QEKLFGEKGS 240 DRFRQKVQEM VESNEAKLVA LVNKFIGYLK QNTYCFPHSL RWIVSQMYKT LSCVDRLEVG 300 EVRAMCTDLL LACFICPAVV NPEQYGIISD APINEVARFN LMQVGRLLQQ LAMTGSEEGD 360 PRTKSSLGKF DKSCVAAFLD VVIGGRAVET PPLSSVNLLE GLSRTVVYIT YSQLITLVNF 420 MKSVMSGDQL REDRMALDNL LANLPPAKPG KSSSLEMTPY NTPQLSPATT PANKKNRLPI 480 ATRSRSRTNM LMDLHMDHEG SSQETIQEVQ PEEVLVISLG TGPQLTPGMM SENEVLNMQL 540 SDGGQGDVPV DENKLHGKPD KTLRFSLCSD NLEGISEGPS NRSNSVSSLD LEGESVSELG 600 AGPSGSNGVE ALQLLEHEQA TTQDNLDDKL RKFEIRDMMG LTDDRDISET VSETWSTDVL 660 GSDFDPNIDE DRLQEIAGAA AENMLGSLLC LPGSGSVLLD PCTGSTISET TSEAWSVEVL 720 PSDSEAPDLK QEERLQELES CSGLGSTSDD TDVREVSSRP STPGLSVVSG ISATSEDIPN 780 KIEDLRSECS SDFGGKDSVT SPDMDEITHD FLYILQPKQH FQHIEAEADM RIQLSSSAHQ 840 LTSPPSQSES LLAMFDPLSS HEGASAVVRP KVHYARPSHP PPDPPILEGA VGGNEARLPN 900 FGSHVLTPAE MEAFKQRHSY PERLVRSRSS DIVSSVRRPM SDPSWNRRPG NEERELPPAA 960 AIGATSLVAA PHSSSSSPSK DSSRGETEER KDSDDEKSDR NRPWWRKRFV SAMPKAPIPF 1020 RKKEKQEKDK DDLGPDRFST LTDDPSPRLS AQAQVAEDIL DKYRNAIKRT SPSDGAMANY 1080 ESTEVMGDGE SAHDSPRDEA LQNISADDLP DSASQAAHPQ DSAFSYRDAK KKLRLALCSA 1140 DSVAFPVLTH STRNGLPDHT DPEDNEIVCF LKVQIAEAIN LQDKNLMAQL QETMRCVCRF 1200 DNRTCRKLLA SIAEDYRKRA PYIAYLTRCR QGLQTTQAHL ERLLQRVLRD KEVANRYFTT 1260 VCVRLLLESK EKKIREFIQD FQKLTAADDK TAQVEDFLQF LYGAMAQDVI WQNASEEQLQ 1320 DAQLAIERSV MNRIFKLAFY PNQDGDILRD QVLHEHIQRL SKVVTANHRA LQIPEVYLRE 1380 APWPSAQSEI RTISAYKTPR DKVQCILRMC STIMNLLSLA NEDSVPGADD FVPVLVFVLI 1440 KANPPCLLST VQYISSFYAS CLSGEESYWW MQFTAAVEFI KTIDDRK 1487 |
Gene Ontology | GO:0005829; C:cytosol; IDA:UniProtKB. GO:0005768; C:endosome; IEA:UniProtKB-SubCell. GO:0016020; C:membrane; IEA:UniProtKB-SubCell. GO:0032794; F:GTPase activating protein binding; IMP:UniProtKB. GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW. GO:0005085; F:guanyl-nucleotide exchange factor activity; IMP:UniProtKB. GO:0006897; P:endocytosis; IEA:UniProtKB-KW. GO:0043547; P:positive regulation of GTPase activity; IEA:GOC. GO:0051223; P:regulation of protein transport; IMP:UniProtKB. GO:0051056; P:regulation of small GTPase mediated signal transduction; IEA:InterPro. GO:0007165; P:signal transduction; IEA:InterPro. |
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