ID   RHG06_HUMAN             Reviewed;         974 AA.
AC   O43182; B2RWQ0; O43437; Q9P1B3; Q9UK81; Q9UK82;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2006, sequence version 3.
DT   13-SEP-2023, entry version 190.
DE   RecName: Full=Rho GTPase-activating protein 6;
DE   AltName: Full=Rho-type GTPase-activating protein 6;
DE   AltName: Full=Rho-type GTPase-activating protein RhoGAPX-1;
GN   Name=ARHGAP6; Synonyms=RHOGAP6;
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 [MRNA] (ISOFORMS 3; 4 AND 5), SEQUENCE REVISION,
RP   FUNCTION, SUBCELLULAR LOCATION, AND ALTERNATIVE SPLICING.
RC   TISSUE=Fetal kidney;
RX   PubMed=10699171; DOI=10.1093/hmg/9.4.477;
RA   Prakash S.K., Paylor R., Jenna S., Lamarche-Vane N., Armstrong D.L., Xu B.,
RA   Mancini M.A., Zoghbi H.Y.;
RT   "Functional analysis of ARHGAP6, a novel GTPase-activating protein for
RT   RhoA.";
RL   Hum. Mol. Genet. 9:477-488(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX   PubMed=9417914; DOI=10.1006/geno.1997.5040;
RA   Schaefer L., Prakash S.K., Zoghbi H.Y.;
RT   "Cloning and characterization of a novel rho-type GTPase-activating protein
RT   gene (ARHGAP6) from the critical region for microphthalmia with linear skin
RT   defects.";
RL   Genomics 46:268-277(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT GLU-791.
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   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-264; SER-673; SER-777 AND
RP   SER-939, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Platelet;
RX   PubMed=18088087; DOI=10.1021/pr0704130;
RA   Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA   Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT   "Phosphoproteome of resting human platelets.";
RL   J. Proteome Res. 7:526-534(2008).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363; SER-667; SER-673;
RP   SER-680; SER-711; SER-754; SER-772; SER-777; SER-786; SER-820; SER-928;
RP   SER-931 AND SER-939, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
CC   -!- FUNCTION: GTPase activator for the Rho-type GTPases by converting them
CC       to an inactive GDP-bound state. Could regulate the interactions of
CC       signaling molecules with the actin cytoskeleton. Promotes continuous
CC       elongation of cytoplasmic processes during cell motility and
CC       simultaneous retraction of the cell body changing the cell morphology.
CC       {ECO:0000269|PubMed:10699171}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10699171}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC       Name=3;
CC         IsoId=O43182-1; Sequence=Displayed;
CC       Name=1;
CC         IsoId=O43182-2; Sequence=VSP_001641, VSP_001642;
CC       Name=2;
CC         IsoId=O43182-3; Sequence=VSP_001638, VSP_001639, VSP_001640;
CC       Name=4;
CC         IsoId=O43182-4; Sequence=VSP_001637;
CC       Name=5;
CC         IsoId=O43182-5; Sequence=VSP_001637, VSP_001641, VSP_001642;
CC   -!- TISSUE SPECIFICITY: Highly expressed in kidney, heart and skeletal
CC       muscle followed by retina, lymphoblast, placenta, lung, brain, pancreas
CC       and liver.
CC   -!- MISCELLANEOUS: ARHGAP6 gene undergoes X inactivation.
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DR   EMBL; AF117067; AAF43261.1; -; mRNA.
DR   EMBL; AF177663; AAD53166.1; -; mRNA.
DR   EMBL; AF177665; AAD55087.1; -; mRNA.
DR   EMBL; AF012272; AAC98539.2; -; mRNA.
DR   EMBL; AF022212; AAC98540.2; -; mRNA.
DR   EMBL; BC150635; AAI50636.1; -; mRNA.
DR   CCDS; CCDS14140.1; -. [O43182-1]
DR   CCDS; CCDS14141.1; -. [O43182-4]
DR   CCDS; CCDS14142.1; -. [O43182-2]
DR   PIR; E59434; E59434.
DR   RefSeq; NP_001274171.1; NM_001287242.1.
DR   RefSeq; NP_006116.2; NM_006125.2. [O43182-2]
DR   RefSeq; NP_038267.1; NM_013423.2. [O43182-4]
DR   RefSeq; NP_038286.2; NM_013427.2. [O43182-1]
DR   AlphaFoldDB; O43182; -.
DR   SMR; O43182; -.
DR   BioGRID; 106888; 7.
DR   IntAct; O43182; 4.
DR   MINT; O43182; -.
DR   STRING; 9606.ENSP00000338967; -.
DR   iPTMnet; O43182; -.
DR   PhosphoSitePlus; O43182; -.
DR   BioMuta; ARHGAP6; -.
DR   jPOST; O43182; -.
DR   MassIVE; O43182; -.
DR   MaxQB; O43182; -.
DR   PaxDb; O43182; -.
DR   PeptideAtlas; O43182; -.
DR   ProteomicsDB; 48794; -. [O43182-1]
DR   ProteomicsDB; 48795; -. [O43182-2]
DR   ProteomicsDB; 48796; -. [O43182-3]
DR   ProteomicsDB; 48797; -. [O43182-4]
DR   ProteomicsDB; 48798; -. [O43182-5]
DR   TopDownProteomics; O43182-5; -. [O43182-5]
DR   Antibodypedia; 23727; 70 antibodies from 21 providers.
DR   DNASU; 395; -.
DR   Ensembl; ENST00000303025.10; ENSP00000302312.6; ENSG00000047648.23. [O43182-4]
DR   Ensembl; ENST00000337414.9; ENSP00000338967.4; ENSG00000047648.23. [O43182-1]
DR   Ensembl; ENST00000380718.1; ENSP00000370094.1; ENSG00000047648.23. [O43182-2]
DR   Ensembl; ENST00000380736.5; ENSP00000370112.1; ENSG00000047648.23. [O43182-4]
DR   Ensembl; ENST00000495242.5; ENSP00000435767.1; ENSG00000047648.23. [O43182-3]
DR   GeneID; 395; -.
DR   KEGG; hsa:395; -.
DR   MANE-Select; ENST00000337414.9; ENSP00000338967.4; NM_013427.3; NP_038286.2.
DR   UCSC; uc004cum.2; human. [O43182-1]
DR   AGR; HGNC:676; -.
DR   CTD; 395; -.
DR   DisGeNET; 395; -.
DR   GeneCards; ARHGAP6; -.
DR   HGNC; HGNC:676; ARHGAP6.
DR   HPA; ENSG00000047648; Low tissue specificity.
DR   MalaCards; ARHGAP6; -.
DR   MIM; 300118; gene.
DR   neXtProt; NX_O43182; -.
DR   OpenTargets; ENSG00000047648; -.
DR   PharmGKB; PA24960; -.
DR   VEuPathDB; HostDB:ENSG00000047648; -.
DR   eggNOG; KOG2710; Eukaryota.
DR   GeneTree; ENSGT00940000153904; -.
DR   HOGENOM; CLU_012874_0_0_1; -.
DR   InParanoid; O43182; -.
DR   OMA; WHSTLKC; -.
DR   OrthoDB; 5482290at2759; -.
DR   PhylomeDB; O43182; -.
DR   TreeFam; TF316710; -.
DR   PathwayCommons; O43182; -.
DR   Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR   Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR   SignaLink; O43182; -.
DR   SIGNOR; O43182; -.
DR   BioGRID-ORCS; 395; 14 hits in 779 CRISPR screens.
DR   ChiTaRS; ARHGAP6; human.
DR   GenomeRNAi; 395; -.
DR   Pharos; O43182; Tbio.
DR   PRO; PR:O43182; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   RNAct; O43182; Protein.
DR   Bgee; ENSG00000047648; Expressed in seminal vesicle and 187 other tissues.
DR   ExpressionAtlas; O43182; baseline and differential.
DR   Genevisible; O43182; HS.
DR   GO; GO:0015629; C:actin cytoskeleton; ISS:BHF-UCL.
DR   GO; GO:0005884; C:actin filament; NAS:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IMP:BHF-UCL.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005096; F:GTPase activator activity; TAS:Reactome.
DR   GO; GO:0016004; F:phospholipase activator activity; IDA:BHF-UCL.
DR   GO; GO:0043274; F:phospholipase binding; IPI:BHF-UCL.
DR   GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR   GO; GO:0030041; P:actin filament polymerization; NAS:UniProtKB.
DR   GO; GO:0007202; P:activation of phospholipase C activity; IDA:BHF-UCL.
DR   GO; GO:0048041; P:focal adhesion assembly; IEA:Ensembl.
DR   GO; GO:0051895; P:negative regulation of focal adhesion assembly; IMP:BHF-UCL.
DR   GO; GO:0051497; P:negative regulation of stress fiber assembly; IMP:BHF-UCL.
DR   GO; GO:0043547; P:positive regulation of GTPase activity; IEA:Ensembl.
DR   GO; GO:0010518; P:positive regulation of phospholipase activity; IDA:BHF-UCL.
DR   GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR   GO; GO:0007266; P:Rho protein signal transduction; TAS:ProtInc.
DR   CDD; cd04376; RhoGAP_ARHGAP6; 1.
DR   Gene3D; 1.10.555.10; Rho GTPase activation protein; 1.
DR   InterPro; IPR041852; ARHGAP6_RhoGAP.
DR   InterPro; IPR008936; Rho_GTPase_activation_prot.
DR   InterPro; IPR037863; RHOGAP6/36.
DR   InterPro; IPR000198; RhoGAP_dom.
DR   PANTHER; PTHR12635:SF6; RHO GTPASE-ACTIVATING PROTEIN 6; 1.
DR   PANTHER; PTHR12635; RHO-GTPASE-ACTIVATING PROTEIN 6 FAMILY MEMBER; 1.
DR   Pfam; PF00620; RhoGAP; 1.
DR   SMART; SM00324; RhoGAP; 1.
DR   SUPFAM; SSF48350; GTPase activation domain, GAP; 1.
DR   PROSITE; PS50238; RHOGAP; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cytoplasm; GTPase activation; Phosphoprotein;
KW   Reference proteome; SH3-binding.
FT   CHAIN           1..974
FT                   /note="Rho GTPase-activating protein 6"
FT                   /id="PRO_0000056704"
FT   DOMAIN          401..602
FT                   /note="Rho-GAP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT   REGION          1..120
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          322..361
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          639..672
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          709..729
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          742..838
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          860..945
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           342..352
FT                   /note="SH3-binding"
FT   COMPBIAS        1..25
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        88..102
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        322..351
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        742..801
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        912..935
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         37
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O54834"
FT   MOD_RES         264
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18088087"
FT   MOD_RES         363
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         667
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         673
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18088087,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         680
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         711
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         754
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         772
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         777
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18088087,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         786
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         820
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         928
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         931
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         939
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18088087,
FT                   ECO:0007744|PubMed:23186163"
FT   VAR_SEQ         1..203
FT                   /note="Missing (in isoform 4 and isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:10699171"
FT                   /id="VSP_001637"
FT   VAR_SEQ         196
FT                   /note="E -> ELELYDLQILGTKPPMNSDTHRNFDPTATLRNQ (in isoform
FT                   2)"
FT                   /evidence="ECO:0000303|PubMed:9417914"
FT                   /id="VSP_001638"
FT   VAR_SEQ         637..658
FT                   /note="SPDMLQSEVSFSVGGRHSSTDS -> TSSVLPAAVQACPQYPASMFTP (in
FT                   isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:9417914"
FT                   /id="VSP_001639"
FT   VAR_SEQ         659..974
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:9417914"
FT                   /id="VSP_001640"
FT   VAR_SEQ         726..765
FT                   /note="DLSEEPFDIWGTWHSTLKSGSKDPGMTGSSGDIFESSSLR -> GNWSLASR
FT                   RWPKQATLLLLHVAWCGALRTFSSSLPYLMFL (in isoform 1 and isoform
FT                   5)"
FT                   /evidence="ECO:0000303|PubMed:10699171,
FT                   ECO:0000303|PubMed:9417914"
FT                   /id="VSP_001641"
FT   VAR_SEQ         766..974
FT                   /note="Missing (in isoform 1 and isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:10699171,
FT                   ECO:0000303|PubMed:9417914"
FT                   /id="VSP_001642"
FT   VARIANT         791
FT                   /note="D -> E (in dbSNP:rs1009758)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_024453"
FT   CONFLICT        231
FT                   /note="A -> P (in Ref. 1; AAF43261/AAD55087 and 2;
FT                   AAC98539/AAC98540)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   974 AA;  105947 MW;  BEE22EB54F019E30 CRC64;
     MSAQSLLHSV FSCSSPASSS AASAKGFSKR KLRQTRSLDP ALIGGCGSDE AGAEGSARGA
     TAGRLYSPSL PAESLGPRLA SSSRGPPPRA TRLPPPGPLC SSFSTPSTPQ EKSPSGSFHF
     DYEVPLGRGG LKKSMAWDLP SVLAGPASSR SASSILCSSG GGPNGIFASP RRWLQQRKFQ
     SPPDSRGHPY VVWKSEGDFT WNSMSGRSVR LRSVPIQSLS ELERARLQEV AFYQLQQDCD
     LSCQITIPKD GQKRKKSLRK KLDSLGKEKN KDKEFIPQAF GMPLSQVIAN DRAYKLKQDL
     QRDEQKDASD FVASLLPFGN KRQNKELSSS NSSLSSTSET PNESTSPNTP EPAPRARRRG
     AMSVDSITDL DDNQSRLLEA LQLSLPAEAQ SKKEKARDKK LSLNPIYRQV PRLVDSCCQH
     LEKHGLQTVG IFRVGSSKKR VRQLREEFDR GIDVSLEEEH SVHDVAALLK EFLRDMPDPL
     LTRELYTAFI NTLLLEPEEQ LGTLQLLIYL LPPCNCDTLH RLLQFLSIVA RHADDNISKD
     GQEVTGNKMT SLNLATIFGP NLLHKQKSSD KEFSVQSSAR AEESTAIIAV VQKMIENYEA
     LFMVPPDLQN EVLISLLETD PDVVDYLLRR KASQSSSPDM LQSEVSFSVG GRHSSTDSNK
     ASSGDISPYD NNSPVLSERS LLAMQEDAAP GGSEKLYRVP GQFMLVGHLS SSKSRESSPG
     PRLGKDLSEE PFDIWGTWHS TLKSGSKDPG MTGSSGDIFE SSSLRAGPCS LSQGNLSPNW
     PRWQGSPAEL DSDTQGARRT QAAAPATEGR AHPAVSRACS TPHVQVAGKA ERPTARSEQY
     LTLSGAHDLS ESELDVAGLQ SRATPQCQRP HGSGRDDKRP PPPYPGPGKP AAAAAWIQGP
     PEGVETPTDQ GGQAAEREQQ VTQKKLSSAN SLPAGEQDSP RLGDAGWLDW QRERWQIWEL
     LSTDNPDALP ETLV
//