RHG10_HUMAN
ID RHG10_HUMAN Reviewed; 786 AA.
AC A1A4S6; A1L0S5; Q2VPC4; Q2VPC5; Q96EV3; Q96S75;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Rho GTPase-activating protein 10;
DE AltName: Full=GTPase regulator associated with focal adhesion kinase 2;
DE AltName: Full=Graf-related protein 2;
DE AltName: Full=Rho-type GTPase-activating protein 10;
GN Name=ARHGAP10; Synonyms=GRAF2;
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], FUNCTION, INTERACTION WITH PKN3, TISSUE
RP SPECIFICITY, PHOSPHORYLATION, AND VARIANT VAL-684.
RX PubMed=11432776; DOI=10.1093/oxfordjournals.jbchem.a002958;
RA Shibata H., Oishi K., Yamagiwa A., Matsumoto M., Mukai H., Ono Y.;
RT "PKNbeta interacts with the SH3 domains of Graf and a novel Graf related
RT protein, Graf2, which are GTPase activating proteins for Rho family.";
RL J. Biochem. 130:23-31(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [3]
RP STRUCTURE BY NMR OF 728-786.
RG Northeast structural genomics consortium (NESG);
RT "Solution NMR structure of SH3 domain 1 of Rho GTPase-activating protein 10
RT from Homo sapiens, Northeast structural genomics consortium (NESG) target
RT HR9129A.";
RL Submitted (JAN-2014) to the PDB data bank.
CC -!- FUNCTION: GTPase activator for the small GTPases RhoA and Cdc42 by
CC converting them to an inactive GDP-bound state. Essential for PTKB2
CC regulation of cytoskeletal organization via Rho family GTPases.
CC Inhibits PAK2 proteolytic fragment PAK-2p34 kinase activity and changes
CC its localization from the nucleus to the perinuclear region. Stabilizes
CC PAK-2p34 thereby increasing stimulation of cell death (By similarity).
CC {ECO:0000250, ECO:0000269|PubMed:11432776}.
CC -!- SUBUNIT: Interacts with PKN3. Interacts with caspase-activated PAK2
CC proteolytic fragment PAK-2p34; the interaction does not affect ARHGAP10
CC GTPase activation activity towards RHOA and CDC42. Interacts via its
CC SH3 domain with PTK2/FAK1. Interacts with PTK2B/PYK2; the interaction
CC negatively regulates ARHGAP10 GTPase-activating activity (By
CC similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC A1A4S6; Q6P5Z2: PKN3; NbExp=5; IntAct=EBI-1390944, EBI-1384335;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cytoplasm, perinuclear
CC region {ECO:0000250}. Cell membrane {ECO:0000250}. Note=Association to
CC cell membrane is dependent on PH domain. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: High levels of expression in heart and skeletal
CC muscle. {ECO:0000269|PubMed:11432776}.
CC -!- PTM: Phosphorylated. Phosphorylated in vitro by constitutive active
CC PKN3. {ECO:0000269|PubMed:11432776}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI26900.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AB050785; BAB61771.1; -; mRNA.
DR EMBL; BC011920; AAH11920.2; -; mRNA.
DR EMBL; BC109029; AAI09030.1; -; mRNA.
DR EMBL; BC109030; AAI09031.1; -; mRNA.
DR EMBL; BC126899; AAI26900.1; ALT_FRAME; mRNA.
DR EMBL; BC128055; AAI28056.1; -; mRNA.
DR CCDS; CCDS34075.1; -.
DR RefSeq; NP_078881.3; NM_024605.3.
DR PDB; 2MIO; NMR; -; A=728-786.
DR PDBsum; 2MIO; -.
DR AlphaFoldDB; A1A4S6; -.
DR BMRB; A1A4S6; -.
DR SMR; A1A4S6; -.
DR BioGRID; 122784; 26.
DR CORUM; A1A4S6; -.
DR IntAct; A1A4S6; 11.
DR MINT; A1A4S6; -.
DR STRING; 9606.ENSP00000336923; -.
DR iPTMnet; A1A4S6; -.
DR PhosphoSitePlus; A1A4S6; -.
DR BioMuta; ARHGAP10; -.
DR EPD; A1A4S6; -.
DR jPOST; A1A4S6; -.
DR MassIVE; A1A4S6; -.
DR MaxQB; A1A4S6; -.
DR PaxDb; A1A4S6; -.
DR PeptideAtlas; A1A4S6; -.
DR PRIDE; A1A4S6; -.
DR ProteomicsDB; 92; -.
DR Antibodypedia; 45497; 111 antibodies from 16 providers.
DR DNASU; 79658; -.
DR Ensembl; ENST00000336498.8; ENSP00000336923.3; ENSG00000071205.12.
DR GeneID; 79658; -.
DR KEGG; hsa:79658; -.
DR MANE-Select; ENST00000336498.8; ENSP00000336923.3; NM_024605.4; NP_078881.3.
DR UCSC; uc003ilf.4; human.
DR CTD; 79658; -.
DR DisGeNET; 79658; -.
DR GeneCards; ARHGAP10; -.
DR HGNC; HGNC:26099; ARHGAP10.
DR HPA; ENSG00000071205; Low tissue specificity.
DR MIM; 609746; gene.
DR neXtProt; NX_A1A4S6; -.
DR OpenTargets; ENSG00000071205; -.
DR PharmGKB; PA134904544; -.
DR VEuPathDB; HostDB:ENSG00000071205; -.
DR eggNOG; KOG1451; Eukaryota.
DR GeneTree; ENSGT00940000159559; -.
DR HOGENOM; CLU_011532_2_0_1; -.
DR InParanoid; A1A4S6; -.
DR OMA; WLNTQSP; -.
DR OrthoDB; 693048at2759; -.
DR PhylomeDB; A1A4S6; -.
DR TreeFam; TF316851; -.
DR PathwayCommons; A1A4S6; -.
DR Reactome; R-HSA-211728; Regulation of PAK-2p34 activity by PS-GAP/RHG10.
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 SignaLink; A1A4S6; -.
DR SIGNOR; A1A4S6; -.
DR BioGRID-ORCS; 79658; 10 hits in 1070 CRISPR screens.
DR ChiTaRS; ARHGAP10; human.
DR GenomeRNAi; 79658; -.
DR Pharos; A1A4S6; Tbio.
DR PRO; PR:A1A4S6; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; A1A4S6; protein.
DR Bgee; ENSG00000071205; Expressed in mucosa of stomach and 132 other tissues.
DR ExpressionAtlas; A1A4S6; baseline and differential.
DR Genevisible; A1A4S6; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005096; F:GTPase activator activity; IBA:GO_Central.
DR GO; GO:0007010; P:cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR CDD; cd12065; SH3_GRAF2; 1.
DR Gene3D; 1.10.555.10; -; 1.
DR Gene3D; 1.20.1270.60; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR035486; GRAF2.
DR InterPro; IPR035485; GRAF2_SH3.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR000198; RhoGAP_dom.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR12552:SF5; PTHR12552:SF5; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00620; RhoGAP; 1.
DR Pfam; PF14604; SH3_9; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00324; RhoGAP; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50238; RHOGAP; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasm; GTPase activation; Membrane;
KW Phosphoprotein; Reference proteome; SH3 domain.
FT CHAIN 1..786
FT /note="Rho GTPase-activating protein 10"
FT /id="PRO_0000304914"
FT DOMAIN 7..262
FT /note="BAR"
FT DOMAIN 265..372
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 389..574
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT DOMAIN 728..786
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 576..608
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 621..727
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 582..601
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 629..647
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 673..708
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 488
FT /note="P -> S (in dbSNP:rs17024215)"
FT /id="VAR_049141"
FT VARIANT 684
FT /note="M -> V (in dbSNP:rs2276932)"
FT /evidence="ECO:0000269|PubMed:11432776"
FT /id="VAR_035114"
FT CONFLICT 712
FT /note="F -> S (in Ref. 2; AAI09030)"
FT /evidence="ECO:0000305"
FT CONFLICT 750
FT /note="E -> D (in Ref. 1; BAB61771)"
FT /evidence="ECO:0000305"
FT STRAND 728..730
FT /evidence="ECO:0007829|PDB:2MIO"
FT STRAND 732..737
FT /evidence="ECO:0007829|PDB:2MIO"
FT STRAND 743..746
FT /evidence="ECO:0007829|PDB:2MIO"
FT STRAND 754..760
FT /evidence="ECO:0007829|PDB:2MIO"
FT STRAND 766..771
FT /evidence="ECO:0007829|PDB:2MIO"
FT STRAND 774..779
FT /evidence="ECO:0007829|PDB:2MIO"
FT HELIX 780..782
FT /evidence="ECO:0007829|PDB:2MIO"
FT STRAND 783..785
FT /evidence="ECO:0007829|PDB:2MIO"
SQ SEQUENCE 786 AA; 89375 MW; 7D7006CEAC0094BD CRC64;
MGLQPLEFSD CYLDSPWFRE RIRAHEAELE RTNKFIKELI KDGKNLIAAT KSLSVAQRKF
AHSLRDFKFE FIGDAVTDDE RCIDASLREF SNFLKNLEEQ REIMALSVTE TLIKPLEKFR
KEQLGAVKEE KKKFDKETEK NYSLIDKHLN LSAKKKDSHL QEADIQVEQN RQHFYELSLE
YVCKLQEIQE RKKFEFVEPM LSFFQGMFTF YHQGHELAKD FNHYKMELQI NIQNTRNRFE
GTRSEVEELM NKIRQNPKDH KRASQFTAEG YLYVQEKRPA PFGSSWVKHY CMYRKAAKKF
NMIPFEHRSG GKLGDGEVFF LKECTKRHTD SIDRRFCFDI EAADRPGVSL TMQAFSEEER
KQWLEALGGK EALSHSFNTA IIPRPEGNAQ LDKMGFTIIR KCISAVETRG INDQGLYRVV
GVSSKVQRLL SMLMDVKTCN EVDLENSADW EVKTITSALK QYLRSLPEPL MTYELHGDFI
VPAKSGSPES RVNAIHFLVH KLPEKNKEML DILVKHLTNV SNHSKQNLMT VANLGVVFGP
TLMRPQEETV AALMDLKFQN IVVEILIENH EKIFRTPPDT TFPEPTCLSA SPPNAPPRQS
KRQGQRTKRP VAVYNLCLEL EDGDNPYPSK EDTPTSSLDS LSSPSPVTTA VPGPPGPDKN
HLLADGGSFG DWASTIPGQT RSSMVQWLNP QSPTTTSSNS AVTPLSPGSS PFPFSPPATV
ADKPPESIRS RKARAVYPCE AEHSSELSFE IGAIFEDVQT SREPGWLEGT LNGKRGLIPQ
NYVKLL
