CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012430
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]
238QEKLFGEKGSDRFRQacetylation[3]
1327SVMNRIFKLAFYPNQubiquitination[1, 2]
Reference
 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861] 
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 SPDMDEITHG AHQLTSPPSQ SESLLAMFDP LSSHEGASAV 840
VRPKVHYARP SHPPPDPPIL EGAVGGNEAR LPNFGSHVLT PAEMEAFKQR HSYPERLVRS 900
RSSDIVSSVR RPMSDPSWNR RPGNEERELP PAAAIGATSL VAAPHSSSSS PSKDSSRGET 960
EERKDSDDEK SDRNRPWWRK RFVSAMPKAP IPFRKKEKQE KDKDDLGPDR FSTLTDDPSP 1020
RLSAQAQVAE DILDKYRNAI KRTSPSDGAM ANYESTGDNH DRDLSSKLLY HSDKEVMGDG 1080
ESAHDSPRDE ALQNISADDL PDSASQAAHP QDSAFSYRDA KKKLRLALCS ADSVAFPVLT 1140
HSTRNGLPDH TDPEDNEIVC FLKVQIAEAI NLQDKNLMAQ LQETMRCVCR FDNRTCRKLL 1200
ASIAEDYRKR APYIAYLTRC RQGLQTTQAH LERLLQRVLR DKEVANRYFT TVCVRLLLES 1260
KEKKIREFIQ DFQKLTAADD KTAQVEDFLQ FLYGAMAQDV IWQNASEEQL QDAQLAIERS 1320
VMNRIFKLAF YPNQDGDILR DQVLHEHIQR LSKVVTANHR ALQIPEVYLR EAPWPSAQSE 1380
IRTISAYKTP RDKVQCILRM CSTIMNLLSL ANEDSVPGAD DFVPVLVFVL IKANPPCLLS 1440
TVQYISSFYA SCLSGEESYW WMQFTAAVEF IKTIDDRK 1478 
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