RHG31_HUMAN
ID RHG31_HUMAN Reviewed; 1444 AA.
AC Q2M1Z3; Q9ULL6;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Rho GTPase-activating protein 31;
DE AltName: Full=Cdc42 GTPase-activating protein;
GN Name=ARHGAP31; Synonyms=CDGAP, KIAA1204;
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 [LARGE SCALE MRNA], AND VARIANT SER-803.
RC TISSUE=Brain;
RX PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:337-345(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-803.
RC TISSUE=Brain;
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 [4]
RP FUNCTION.
RX PubMed=12192056; DOI=10.1128/mcb.22.18.6582-6591.2002;
RA Itoh R.E., Kurokawa K., Ohba Y., Yoshizaki H., Mochizuki N., Matsuda M.;
RT "Activation of rac and cdc42 video imaged by fluorescent resonance energy
RT transfer-based single-molecule probes in the membrane of living cells.";
RL Mol. Cell. Biol. 22:6582-6591(2002).
RN [5]
RP IDENTIFICATION, TISSUE SPECIFICITY, PHOSPHORYLATION, AND FUNCTION.
RX PubMed=16519628; DOI=10.1042/bc20050101;
RA Tcherkezian J., Triki I., Stenne R., Danek E.I., Lamarche-Vane N.;
RT "The human orthologue of CdGAP is a phosphoprotein and a GTPase-activating
RT protein for Cdc42 and Rac1 but not RhoA.";
RL Biol. Cell 98:445-456(2006).
RN [6]
RP INVOLVEMENT IN AOS1, AND VARIANT ILE-727.
RX PubMed=21565291; DOI=10.1016/j.ajhg.2011.04.013;
RA Southgate L., Machado R.D., Snape K.M., Primeau M., Dafou D., Ruddy D.M.,
RA Branney P.A., Fisher M., Lee G.J., Simpson M.A., He Y., Bradshaw T.Y.,
RA Blaumeiser B., Winship W.S., Reardon W., Maher E.R., FitzPatrick D.R.,
RA Wuyts W., Zenker M., Lamarche-Vane N., Trembath R.C.;
RT "Gain-of-function mutations of ARHGAP31, a Cdc42/Rac1 GTPase regulator,
RT cause syndromic cutis aplasia and limb anomalies.";
RL Am. J. Hum. Genet. 88:574-585(2011).
RN [7]
RP INTERACTION WITH RHOU.
RX PubMed=21565175; DOI=10.1016/j.bbrc.2011.04.116;
RA Naji L., Pacholsky D., Aspenstrom P.;
RT "ARHGAP30 is a Wrch-1-interacting protein involved in actin dynamics and
RT cell adhesion.";
RL Biochem. Biophys. Res. Commun. 409:96-102(2011).
RN [8]
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).
CC -!- FUNCTION: Functions as a GTPase-activating protein (GAP) for RAC1 and
CC CDC42. Required for cell spreading, polarized lamellipodia formation
CC and cell migration. {ECO:0000269|PubMed:12192056,
CC ECO:0000269|PubMed:16519628}.
CC -!- SUBUNIT: Interacts with ITSN1, which inhibits GAP activity. Interacts
CC with PARVA (By similarity). Interacts with GTP-loaded RHOU.
CC {ECO:0000250, ECO:0000269|PubMed:21565175}.
CC -!- INTERACTION:
CC Q2M1Z3; Q9Y490: TLN1; NbExp=2; IntAct=EBI-2803146, EBI-2462036;
CC -!- SUBCELLULAR LOCATION: Cell projection, lamellipodium. Cell junction,
CC focal adhesion {ECO:0000250}.
CC -!- DEVELOPMENTAL STAGE: Mainly expressed in fetal heart and muscle.
CC -!- PTM: Phosphorylation on Thr-789 reduces GAP activity. {ECO:0000250}.
CC -!- DISEASE: Adams-Oliver syndrome 1 (AOS1) [MIM:100300]: A disorder
CC characterized by the congenital absence of skin (aplasia cutis
CC congenita) in combination with transverse limb defects. Aplasia cutis
CC congenita can be located anywhere on the body, but in the vast majority
CC of the cases, it is present on the posterior parietal region where it
CC is often associated with an underlying defect of the parietal bones.
CC Limb abnormalities are typically limb truncation defects affecting the
CC distal phalanges or entire digits (true ectrodactyly). Only rarely,
CC metatarsals/metacarpals or more proximal limb structures are also
CC affected. Apart from transverse limb defects, syndactyly, most commonly
CC of second and third toes, can also be observed. The clinical features
CC are highly variable and can also include cardiovascular malformations,
CC brain abnormalities and vascular defects such as cutis marmorata and
CC dilated scalp veins. {ECO:0000269|PubMed:21565291}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA86518.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB033030; BAA86518.1; ALT_INIT; mRNA.
DR EMBL; AC092981; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC112163; AAI12164.1; -; mRNA.
DR EMBL; BC112165; AAI12166.1; -; mRNA.
DR CCDS; CCDS43135.1; -.
DR PIR; A59437; A59437.
DR RefSeq; NP_065805.2; NM_020754.3.
DR AlphaFoldDB; Q2M1Z3; -.
DR SMR; Q2M1Z3; -.
DR BioGRID; 121578; 44.
DR IntAct; Q2M1Z3; 22.
DR MINT; Q2M1Z3; -.
DR STRING; 9606.ENSP00000264245; -.
DR iPTMnet; Q2M1Z3; -.
DR PhosphoSitePlus; Q2M1Z3; -.
DR BioMuta; ARHGAP31; -.
DR DMDM; 296452881; -.
DR EPD; Q2M1Z3; -.
DR jPOST; Q2M1Z3; -.
DR MassIVE; Q2M1Z3; -.
DR MaxQB; Q2M1Z3; -.
DR PaxDb; Q2M1Z3; -.
DR PeptideAtlas; Q2M1Z3; -.
DR PRIDE; Q2M1Z3; -.
DR ProteomicsDB; 61343; -.
DR Antibodypedia; 49897; 37 antibodies from 15 providers.
DR DNASU; 57514; -.
DR Ensembl; ENST00000264245.9; ENSP00000264245.4; ENSG00000031081.11.
DR GeneID; 57514; -.
DR KEGG; hsa:57514; -.
DR MANE-Select; ENST00000264245.9; ENSP00000264245.4; NM_020754.4; NP_065805.2.
DR UCSC; uc003ecj.5; human.
DR CTD; 57514; -.
DR DisGeNET; 57514; -.
DR GeneCards; ARHGAP31; -.
DR GeneReviews; ARHGAP31; -.
DR HGNC; HGNC:29216; ARHGAP31.
DR HPA; ENSG00000031081; Low tissue specificity.
DR MalaCards; ARHGAP31; -.
DR MIM; 100300; phenotype.
DR MIM; 610911; gene.
DR neXtProt; NX_Q2M1Z3; -.
DR OpenTargets; ENSG00000031081; -.
DR Orphanet; 974; Adams-Oliver syndrome.
DR PharmGKB; PA165696843; -.
DR VEuPathDB; HostDB:ENSG00000031081; -.
DR eggNOG; KOG1449; Eukaryota.
DR GeneTree; ENSGT00940000159458; -.
DR HOGENOM; CLU_006917_0_0_1; -.
DR InParanoid; Q2M1Z3; -.
DR OMA; RTNPYID; -.
DR OrthoDB; 1300981at2759; -.
DR PhylomeDB; Q2M1Z3; -.
DR TreeFam; TF351451; -.
DR PathwayCommons; Q2M1Z3; -.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013420; RHOU GTPase cycle.
DR SignaLink; Q2M1Z3; -.
DR SIGNOR; Q2M1Z3; -.
DR BioGRID-ORCS; 57514; 15 hits in 1072 CRISPR screens.
DR ChiTaRS; ARHGAP31; human.
DR GeneWiki; ARHGAP31; -.
DR GenomeRNAi; 57514; -.
DR Pharos; Q2M1Z3; Tbio.
DR PRO; PR:Q2M1Z3; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q2M1Z3; protein.
DR Bgee; ENSG00000031081; Expressed in cardiac muscle of right atrium and 177 other tissues.
DR ExpressionAtlas; Q2M1Z3; baseline and differential.
DR Genevisible; Q2M1Z3; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; IBA:GO_Central.
DR GO; GO:0005096; F:GTPase activator activity; IBA:GO_Central.
DR GO; GO:0017124; F:SH3 domain binding; IEA:Ensembl.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IBA:GO_Central.
DR Gene3D; 1.10.555.10; -; 1.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR000198; RhoGAP_dom.
DR Pfam; PF00620; RhoGAP; 1.
DR SMART; SM00324; RhoGAP; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR PROSITE; PS50238; RHOGAP; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell projection; GTPase activation; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..1444
FT /note="Rho GTPase-activating protein 31"
FT /id="PRO_0000320114"
FT DOMAIN 21..216
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT REGION 398..427
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 504..631
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 688..893
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 906..1108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1211..1346
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 504..527
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 602..621
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 718..734
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 776..793
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 804..819
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 820..838
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 869..893
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 953..987
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1065..1086
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1212..1251
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1252..1267
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1289..1307
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 272
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A6X8Z5"
FT MOD_RES 286
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:A6X8Z5"
FT MOD_RES 346
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A6X8Z5"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A6X8Z5"
FT MOD_RES 387
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A6X8Z5"
FT MOD_RES 476
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A6X8Z5"
FT MOD_RES 679
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:A6X8Z5"
FT MOD_RES 701
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A6X8Z5"
FT MOD_RES 712
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A6X8Z5"
FT MOD_RES 778
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A6X8Z5"
FT MOD_RES 789
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:A6X8Z5"
FT MOD_RES 974
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A6X8Z5"
FT MOD_RES 1105
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A6X8Z5"
FT MOD_RES 1106
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A6X8Z5"
FT MOD_RES 1178
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A6X8Z5"
FT VARIANT 221
FT /note="P -> L (in dbSNP:rs751793)"
FT /id="VAR_039122"
FT VARIANT 727
FT /note="T -> I (in dbSNP:rs539048828)"
FT /evidence="ECO:0000269|PubMed:21565291"
FT /id="VAR_065919"
FT VARIANT 803
FT /note="G -> S (in dbSNP:rs3732413)"
FT /evidence="ECO:0000269|PubMed:10574462,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_039123"
FT VARIANT 1115
FT /note="I -> L (in dbSNP:rs12107254)"
FT /id="VAR_039124"
FT VARIANT 1366
FT /note="V -> M (in dbSNP:rs3796360)"
FT /id="VAR_039125"
FT VARIANT 1380
FT /note="T -> I (in dbSNP:rs9852894)"
FT /id="VAR_039126"
SQ SEQUENCE 1444 AA; 156985 MW; B1AF26D24506BF11 CRC64;
MKNKGAKQKL KRKGAASAFG CDLTEYLESS GQDVPYVLKS CAEFIETHGI VDGIYRLSGV
TSNIQRLRQE FGSDQCPDLT REVYLQDIHC VGSLCKLYFR ELPNPLLTYE LYEKFTEAVS
HCPEEGQLAR IQNVIQELPP SHYRTLEYLI RHLAHIASFS SKTNMHARNL ALVWAPNLLR
SKEIEATGCN GDAAFLAVRV QQVVIEFILN HVDQIFNNGA PGSLENDENR PIMKSLTLPA
LSLPMKLVSL EEAQARSLAT NHPARKERRE NSLPEIVPPM GTLFHTVLEL PDNKRKLSSK
SKKWKSIFNL GRSGSDSKSK LSRNGSVFVR GQRLSVEKAT IRPAKSMDSL CSVPVEGKET
KGNFNRTVTT GGFFIPATKM HSTGTGSSCD LTKQEGEWGQ EGMPPGAEGG FDVSSDRSHL
QGAQARPPPE QLKVFRPVED PESEQTAPKM LGMFYTSNDS PSKSVFTSSL FQMEPSPRNQ
RKALNISEPF AVSVPLRVSA VISTNSTPCR TPPKELQSLS SLEEFSFHGS ESGGWPEEEK
PLGAETSAAS VPKKAGLEDA KAVPEAPGTV ECSKGLSQEP GAHLEEKKTP ESSLSSQHLN
ELEKRPNPEK VVEEGREAGE MESSTLQESP RARAEAVLLH EMDEDDLANA LIWPEIQQEL
KIIESEEELS SLPPPALKTS PIQPILESSL GPFIPSEPPG SLPCGSFPAP VSTPLEVWTR
DPANQSTQGA STAASREKPE PEQGLHPDLA SLAPLEIVPF EKASPQATVE VGGPGNLSPP
LPPAPPPPTP LEESTPVLLS KGGPEREDSS RKLRTDLYID QLKSQDSPEI SSLCQGEEAT
PRHSDKQNSK NAASEGKGCG FPSPTREVEI VSQEEEDVTH SVQEPSDCDE DDTVTDIAQH
GLEMVEPWEE PQWVTSPLHS PTLKDAHKAQ VQGLQGHQLE KRLSHRPSLR QSHSLDSKPT
VKSQWTLEVP SSSSCANLET ERNSDPLQPQ APRREITGWD EKALRSFREF SGLKGAEAPP
NQKGPSGVQP NPAETSPISL AEGKELGTHL GHSSPQIRQG GVPGPESSKE SSPSVQDSTS
PGEHPAKLQL KSTECGPPKG KNRPSSLNLD PAIPIADLFW FENVASFSSP GMQVSEPGDP
KVTWMTSSYC KADPWRVYSQ DPQDLDIVAH ALTGRRNSAP VSVSAVRTSF MVKMCQARAV
PVIPPKIQYT QIPQPLPSQS SGENGVQPLE RSQEGPSSTS GTTQKPAKDD SPSSLESSKE
EKPKQDPGAI KSSPVDATAP CMCEGPTLSP EPGSSNLLST QDAVVQCRKR MSETEPSGDN
LLSSKLERPS GGSKPFHRSR PGRPQSLILF SPPFPIMDHL PPSSTVTDSK VLLSPIRSPT
QTVSPGLLCG ELAENTWVTP EGVTLRNKMT IPKNGQRLET STSCFYQPQR RSVILDGRSG
RQIE
