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-MAY-2023, entry version 163.
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; 133.
DR   IntAct; Q8N392; 8.
DR   MINT; Q8N392; -.
DR   STRING; 9606.ENSP00000357131; -.
DR   GlyGen; Q8N392; 1 site, 1 O-linked glycan (1 site).
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   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   AGR; HGNC:21035; -.
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; 11483at2759; -.
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; 12 hits in 1153 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   CDD; cd04391; RhoGAP_ARHGAP18; 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; PTHR14963; RHO GTPASE ACTIVATING PROTEIN 18,19-RELATED; 1.
DR   PANTHER; PTHR14963:SF6; RHO GTPASE-ACTIVATING PROTEIN 18; 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.
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
//