RHG18_HUMAN
ID RHG18_HUMAN Reviewed; 663 AA.
AC Q8N392; E1P575; Q58EZ3; Q6P679; Q6PJD7; Q96S64;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Rho GTPase-activating protein 18;
DE AltName: Full=MacGAP {ECO:0000303|PubMed:21865595};
DE AltName: Full=Rho-type GTPase-activating protein 18;
GN Name=ARHGAP18 {ECO:0000312|HGNC:HGNC:21035};
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] (ISOFORM 1), AND VARIANT ALA-23.
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING
RP (ISOFORM 2).
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ALA-23.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-23.
RC TISSUE=Brain {ECO:0000312|EMBL:AAI07417.1}, and
RC Uterus {ECO:0000312|EMBL:AAH39611.1};
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 39-663 (ISOFORM 1).
RC TISSUE=Mast cell;
RA Uchida T., Kuramasu A., Okumura K., Nakao A., Ogawa H., Ra C.;
RT "Molecular cloning and characterization of a novel GTPase activating
RT Protein that regulated mast cell degranulation.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP INTERACTION WITH MPHOSPH6.
RX PubMed=15231747; DOI=10.1101/gr.2122004;
RA Lehner B., Sanderson C.M.;
RT "A protein interaction framework for human mRNA degradation.";
RL Genome Res. 14:1315-1323(2004).
RN [7]
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 [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-365.
RX PubMed=21865595; DOI=10.1091/mbc.e11-04-0364;
RA Maeda M., Hasegawa H., Hyodo T., Ito S., Asano E., Yuang H., Funasaka K.,
RA Shimokata K., Hasegawa Y., Hamaguchi M., Senga T.;
RT "ARHGAP18, a GTPase-activating protein for RhoA, controls cell shape,
RT spreading, and motility.";
RL Mol. Biol. Cell 22:3840-3852(2011).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-158; SER-263 AND SER-610, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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).
RN [10]
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).
RN [11]
RP FUNCTION.
RX PubMed=25778702; DOI=10.1038/nature14215;
RA Porazinski S., Wang H., Asaoka Y., Behrndt M., Miyamoto T., Morita H.,
RA Hata S., Sasaki T., Krens S.F., Osada Y., Asaka S., Momoi A., Linton S.,
RA Miesfeld J.B., Link B.A., Senga T., Castillo-Morales A., Urrutia A.O.,
RA Shimizu N., Nagase H., Matsuura S., Bagby S., Kondoh H., Nishina H.,
RA Heisenberg C.P., Furutani-Seiki M.;
RT "YAP is essential for tissue tension to ensure vertebrate 3D body shape.";
RL Nature 521:217-221(2015).
CC -!- FUNCTION: Rho GTPase activating protein that suppresses F-actin
CC polymerization by inhibiting Rho. Rho GTPase activating proteins act by
CC converting Rho-type GTPases to an inactive GDP-bound state
CC (PubMed:21865595). Plays a key role in tissue tension and 3D tissue
CC shape by regulating cortical actomyosin network formation. Acts
CC downstream of YAP1 and inhibits actin polymerization, which in turn
CC reduces nuclear localization of YAP1 (PubMed:25778702). Regulates cell
CC shape, spreading, and migration (PubMed:21865595).
CC {ECO:0000269|PubMed:21865595, ECO:0000269|PubMed:25778702}.
CC -!- SUBUNIT: Interacts with MPHOSPH6. {ECO:0000269|PubMed:15231747}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21865595}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8N392-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N392-2; Sequence=VSP_052092;
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH17223.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=AAH39611.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=AAH62417.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=BAB61887.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL834511; CAD39167.2; -; mRNA.
DR EMBL; AL450310; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW48076.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW48077.1; -; Genomic_DNA.
DR EMBL; BC017223; AAH17223.1; ALT_SEQ; mRNA.
DR EMBL; BC039611; AAH39611.1; ALT_SEQ; mRNA.
DR EMBL; BC062417; AAH62417.1; ALT_SEQ; mRNA.
DR EMBL; BC101708; AAI01709.1; -; mRNA.
DR EMBL; BC107416; AAI07417.1; -; mRNA.
DR EMBL; BC111940; AAI11941.1; -; mRNA.
DR EMBL; AB053293; BAB61887.1; ALT_INIT; mRNA.
DR CCDS; CCDS34535.1; -. [Q8N392-1]
DR PIR; G59432; G59432.
DR RefSeq; NP_277050.2; NM_033515.2. [Q8N392-1]
DR AlphaFoldDB; Q8N392; -.
DR SMR; Q8N392; -.
DR BioGRID; 125050; 57.
DR IntAct; Q8N392; 8.
DR MINT; Q8N392; -.
DR STRING; 9606.ENSP00000357131; -.
DR iPTMnet; Q8N392; -.
DR PhosphoSitePlus; Q8N392; -.
DR SwissPalm; Q8N392; -.
DR BioMuta; ARHGAP18; -.
DR DMDM; 296452981; -.
DR EPD; Q8N392; -.
DR jPOST; Q8N392; -.
DR MassIVE; Q8N392; -.
DR MaxQB; Q8N392; -.
DR PaxDb; Q8N392; -.
DR PeptideAtlas; Q8N392; -.
DR PRIDE; Q8N392; -.
DR ProteomicsDB; 71779; -. [Q8N392-1]
DR ProteomicsDB; 71780; -. [Q8N392-2]
DR Antibodypedia; 46605; 188 antibodies from 30 providers.
DR DNASU; 93663; -.
DR Ensembl; ENST00000368149.3; ENSP00000357131.2; ENSG00000146376.11. [Q8N392-1]
DR GeneID; 93663; -.
DR KEGG; hsa:93663; -.
DR MANE-Select; ENST00000368149.3; ENSP00000357131.2; NM_033515.3; NP_277050.2.
DR UCSC; uc003qbr.4; human. [Q8N392-1]
DR CTD; 93663; -.
DR DisGeNET; 93663; -.
DR GeneCards; ARHGAP18; -.
DR HGNC; HGNC:21035; ARHGAP18.
DR HPA; ENSG00000146376; Low tissue specificity.
DR MIM; 613351; gene.
DR neXtProt; NX_Q8N392; -.
DR OpenTargets; ENSG00000146376; -.
DR PharmGKB; PA134884487; -.
DR VEuPathDB; HostDB:ENSG00000146376; -.
DR eggNOG; KOG2200; Eukaryota.
DR GeneTree; ENSGT00940000157142; -.
DR HOGENOM; CLU_023268_2_1_1; -.
DR InParanoid; Q8N392; -.
DR OMA; QHNMESQ; -.
DR OrthoDB; 700544at2759; -.
DR PhylomeDB; Q8N392; -.
DR TreeFam; TF314044; -.
DR PathwayCommons; Q8N392; -.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013106; RHOC GTPase cycle.
DR SignaLink; Q8N392; -.
DR SIGNOR; Q8N392; -.
DR BioGRID-ORCS; 93663; 11 hits in 1076 CRISPR screens.
DR ChiTaRS; ARHGAP18; human.
DR GenomeRNAi; 93663; -.
DR Pharos; Q8N392; Tbio.
DR PRO; PR:Q8N392; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q8N392; protein.
DR Bgee; ENSG00000146376; Expressed in germinal epithelium of ovary and 186 other tissues.
DR Genevisible; Q8N392; HS.
DR GO; GO:0005737; C:cytoplasm; IMP:UniProtKB.
DR GO; GO:0005881; C:cytoplasmic microtubule; IDA:CACAO.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0001726; C:ruffle; IDA:CACAO.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0005096; F:GTPase activator activity; IMP:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0030833; P:regulation of actin filament polymerization; IMP:UniProtKB.
DR GO; GO:2000145; P:regulation of cell motility; IMP:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; IMP:UniProtKB.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IMP:UniProtKB.
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 Alternative splicing; Cytoplasm; GTPase activation; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..663
FT /note="Rho GTPase-activating protein 18"
FT /id="PRO_0000245789"
FT DOMAIN 324..523
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT REGION 15..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 179..227
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 243..277
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 182..198
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 66
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K0Q5"
FT MOD_RES 69
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K0Q5"
FT MOD_RES 158
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 263
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 610
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..45
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14574404"
FT /id="VSP_052092"
FT VARIANT 23
FT /note="T -> A (in dbSNP:rs3752536)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17974005, ECO:0000269|Ref.3"
FT /id="VAR_060460"
FT VARIANT 91
FT /note="N -> S (in dbSNP:rs11544371)"
FT /id="VAR_060461"
FT VARIANT 165
FT /note="Q -> H (in dbSNP:rs11544372)"
FT /id="VAR_060462"
FT MUTAGEN 365
FT /note="R->A: Abolishes GTPase activation activity."
FT /evidence="ECO:0000269|PubMed:21865595"
FT CONFLICT 307
FT /note="K -> E (in Ref. 4; AAH17223)"
FT /evidence="ECO:0000305"
FT CONFLICT 467
FT /note="N -> K (in Ref. 4; AAH62417)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 663 AA; 74977 MW; 2DD127301026928D CRC64;
MSWLSSSQGV VLTAYHPSGK DQTVGNSHAK AGEEATSSRR YGQYTMNQES TTIKVMEKPP
FDRSISQDSL DELSMEDYWI ELENIKKSSE NSQEDQEVVV VKEPDEGELE EEWLKEAGLS
NLFGESAGDP QESIVFLSTL TRTQAAAVQK RVETVSQTLR KKNKQYQIPD VRDIFAQQRE
SKETAPGGTE SQSLRTNENK YQGRDDEASN LVGEEKLIPP EETPAPETDI NLEVSFAEQA
LNQKESSKEK IQKSKGDDAT LPSFRLPKDK TGTTRIGDLA PQDMKKVCHL ALIELTALYD
VLGIELKQQK AVKIKTKDSG LFCVPLTALL EQDQRKVPGM RIPLIFQKLI SRIEERGLET
EGLLRIPGAA IRIKNLCQEL EAKFYEGTFN WESVKQHDAA SLLKLFIREL PQPLLSVEYL
KAFQAVQNLP TKKQQLQALN LLVILLPDAN RDTLKALLEF LQRVIDNKEK NKMTVMNVAM
VMAPNLFMCH ALGLKSSEQR EFVMAAGTAN TMHLLIKYQK LLWTIPKFIV NQVRKQNTEN
HKKDKRAMKK LLKKMAYDRE KYEKQDKSTN DADVPQGVIR VQAPHLSKVS MAIQLTEELK
ASDVLARFLS QESGVAQTLK KGEVFLYEIG GNIGERCLDD DTYMKDLYQL NPNAEWVIKS
KPL
