CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
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
24RLYVNSEKQLIQRLNubiquitination[1, 2]
49YRTAWIAKQQRINLDubiquitination[1]
233FSPSQQEKLFGEKGSubiquitination[1]
238QEKLFGEKGSDRFRQubiquitination[1]
1207FDNRTCRKLLASIAEubiquitination[1]
1270VRLLLESKEKKIREFubiquitination[1]
1336SVMNRIFKLAFYPNQubiquitination[1, 2]
1362EHIQRLSKVVTANHRubiquitination[1]
1397IRTISAYKTPRDKVQubiquitination[1]
1402AYKTPRDKVQCILRMubiquitination[1]
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. 
Interpro
 IPR001936; RasGAP.
 IPR008936; Rho_GTPase_activation_prot.
 IPR003123; VPS9.
 IPR013995; VPS9_subgr. 
Pfam
 PF00616; RasGAP
 PF02204; VPS9 
SMART
 SM00167; VPS9 
PROSITE
 PS00509; RAS_GTPASE_ACTIV_1
 PS50018; RAS_GTPASE_ACTIV_2
 PS51205; VPS9 
PRINTS