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   27-MAR-2024, entry version 136.
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   GlyGen; Q2M1Z3; 1 site, 1 O-linked glycan (1 site).
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; 9606-ENSP00000264245; -.
DR   PeptideAtlas; Q2M1Z3; -.
DR   ProteomicsDB; 61343; -.
DR   Antibodypedia; 49897; 38 antibodies from 16 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   AGR; HGNC:29216; -.
DR   CTD; 57514; -.
DR   DisGeNET; 57514; -.
DR   GeneCards; 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; TVMSLWT; -.
DR   OrthoDB; 5308605at2759; -.
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; 17 hits in 1150 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 178 other cell types or tissues.
DR   ExpressionAtlas; Q2M1Z3; baseline and differential.
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   CDD; cd04384; RhoGAP_CdGAP; 1.
DR   Gene3D; 1.10.555.10; Rho GTPase activation protein; 1.
DR   InterPro; IPR008936; Rho_GTPase_activation_prot.
DR   InterPro; IPR000198; RhoGAP_dom.
DR   PANTHER; PTHR15729; CDC42 GTPASE-ACTIVATING PROTEIN; 1.
DR   PANTHER; PTHR15729:SF3; RHO GTPASE-ACTIVATING PROTEIN 31; 1.
DR   Pfam; PF00620; RhoGAP; 1.
DR   SMART; SM00324; RhoGAP; 1.
DR   SUPFAM; SSF48350; GTPase activation domain, GAP; 1.
DR   PROSITE; PS50238; RHOGAP; 1.
DR   Genevisible; Q2M1Z3; HS.
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
//