RHG06_HUMAN
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 03-AUG-2022, entry version 184.
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; 6.
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 PRIDE; 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; 67 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 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; GPEQYML; -.
DR OrthoDB; 419555at2759; -.
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 705 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; -; 1.
DR InterPro; IPR041852; ARHGAP6_RhoGAP.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR030772; RhoGAP6.
DR InterPro; IPR037863; RHOGAP6/36.
DR InterPro; IPR000198; RhoGAP_dom.
DR PANTHER; PTHR12635; PTHR12635; 1.
DR PANTHER; PTHR12635:SF6; PTHR12635:SF6; 1.
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 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
