ARHG1_HUMAN
ID ARHG1_HUMAN Reviewed; 912 AA.
AC Q92888; O00513; Q6NX52; Q8N4J4; Q96BF4; Q96F17; Q9BSB1;
DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 29-AUG-2003, sequence version 2.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Rho guanine nucleotide exchange factor 1;
DE AltName: Full=115 kDa guanine nucleotide exchange factor;
DE Short=p115-RhoGEF;
DE Short=p115RhoGEF;
DE AltName: Full=Sub1.5;
GN Name=ARHGEF1;
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] (ISOFORM 1), FUNCTION, INTERACTION WITH RHOA,
RP AND TISSUE SPECIFICITY.
RX PubMed=8810315; DOI=10.1074/jbc.271.41.25452;
RA Hart M.J., Sharma S., el Masry N., Qiu R.-G., McCabe P., Polakis P.,
RA Bollag G.;
RT "Identification of a novel guanine nucleotide exchange factor for the rho
RT GTPase.";
RL J. Biol. Chem. 271:25452-25458(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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] (ISOFORMS 1; 2; 3 AND 4).
RC TISSUE=B-cell, Muscle, Placenta, and Uterus;
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 21-912 (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=9135076; DOI=10.1038/sj.onc.1200994;
RA Aasheim H.-C., Pedeutour F., Smeland E.B.;
RT "Characterization, expression and chromosomal localization of a human gene
RT homologous to the mouse Lsc oncogene, with strongest expression in
RT hematopoetic tissues.";
RL Oncogene 14:1747-1752(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 60-912 (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP FUNCTION.
RX PubMed=9641915; DOI=10.1126/science.280.5372.2109;
RA Kozasa T., Jiang X., Hart M.J., Sternweis P.M., Singer W.D., Gilman A.G.,
RA Bollag G., Sternweis P.C.;
RT "p115 RhoGEF, a GTPase activating protein for Galpha12 and Galpha13.";
RL Science 280:2109-2111(1998).
RN [8]
RP FUNCTION, AND INTERACTION WITH GNA13.
RX PubMed=9641916; DOI=10.1126/science.280.5372.2112;
RA Hart M.J., Jiang X., Kozasa T., Roscoe W., Singer W.D., Gilman A.G.,
RA Sternweis P.C., Bollag G.;
RT "Direct stimulation of the guanine nucleotide exchange activity of p115
RT RhoGEF by Galpha13.";
RL Science 280:2112-2114(1998).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=10747909; DOI=10.1074/jbc.m000415200;
RA Bhattacharyya R., Wedegaertner P.B.;
RT "Galpha 13 requires palmitoylation for plasma membrane localization, Rho-
RT dependent signaling, and promotion of p115-RhoGEF membrane binding.";
RL J. Biol. Chem. 275:14992-14999(2000).
RN [10]
RP INTERACTION WITH CTNNAL1.
RX PubMed=12270917; DOI=10.1074/jbc.m202447200;
RA Park B., Nguyen N.T., Dutt P., Merdek K.D., Bashar M., Sterpetti P.,
RA Tosolini A., Testa J.R., Toksoz D.;
RT "Association of Lbc Rho guanine nucleotide exchange factor with alpha-
RT catenin-related protein, alpha-catulin/CTNNAL1, supports serum response
RT factor activation.";
RL J. Biol. Chem. 277:45361-45370(2002).
RN [11]
RP PHOSPHORYLATION BY PKCA.
RX PubMed=12754211; DOI=10.1074/jbc.m303900200;
RA Holinstat M., Mehta D., Kozasa T., Minshall R.D., Malik A.B.;
RT "PKCa-induced p115RhoGEF phosphorylation signals endothelial cytoskeletal
RT rearrangement.";
RL J. Biol. Chem. 278:28793-28798(2003).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-863, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP FUNCTION, PHOSPHORYLATION AT TYR-738, AND MUTAGENESIS OF TYR-487 AND
RP TYR-738.
RX PubMed=20098430; DOI=10.1038/nm.2079;
RA Guilluy C., Bregeon J., Toumaniantz G., Rolli-Derkinderen M.,
RA Retailleau K., Loufrani L., Henrion D., Scalbert E., Bril A., Torres R.M.,
RA Offermanns S., Pacaud P., Loirand G.;
RT "The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on
RT vascular tone and blood pressure.";
RL Nat. Med. 16:183-190(2010).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-863, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-409; THR-695 AND SER-863, 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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-374, AND IDENTIFICATION BY
RP 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 [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 42-252.
RX PubMed=11524686; DOI=10.1038/nsb0901-805;
RA Chen Z., Wells C.D., Sternweis P.C., Sprang S.R.;
RT "Structure of the rgRGS domain of p115RhoGEF.";
RL Nat. Struct. Biol. 8:805-809(2001).
RN [22]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-165.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [23]
RP INVOLVEMENT IN IMD62, VARIANT IMD62 285-ARG--THR-912, CHARACTERIZATION OF
RP VARIANT IMD62 285-ARG--THR-912, AND FUNCTION.
RX PubMed=30521495; DOI=10.1172/jci120572;
RA Bouafia A., Lofek S., Bruneau J., Chentout L., Lamrini H., Trinquand A.,
RA Deau M.C., Heurtier L., Meignin V., Picard C., Macintyre E., Alibeu O.,
RA Bras M., Molina T.J., Cavazzana M., Andre-Schmutz I., Durandy A.,
RA Fischer A., Oksenhendler E., Kracker S.;
RT "Loss of ARHGEF1 causes a human primary antibody deficiency.";
RL J. Clin. Invest. 129:1047-1060(2019).
CC -!- FUNCTION: Seems to play a role in the regulation of RhoA GTPase by
CC guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13)
CC subunits (PubMed:9641915, PubMed:9641916). Acts as GTPase-activating
CC protein (GAP) for GNA12 and GNA13, and as guanine nucleotide exchange
CC factor (GEF) for RhoA GTPase (PubMed:9641915, PubMed:9641916,
CC PubMed:8810315, PubMed:30521495). Activated G alpha 13/GNA13 stimulates
CC the RhoGEF activity through interaction with the RGS-like domain
CC (PubMed:9641916). This GEF activity is inhibited by binding to
CC activated GNA12 (PubMed:9641916). Mediates angiotensin-2-induced RhoA
CC activation (PubMed:20098430). {ECO:0000269|PubMed:20098430,
CC ECO:0000269|PubMed:30521495, ECO:0000269|PubMed:8810315,
CC ECO:0000269|PubMed:9641915, ECO:0000269|PubMed:9641916}.
CC -!- SUBUNIT: Interacts with RHOA, GNA12 and GNA13. Homooligomerizes through
CC the coiled coil region. May interact with CCPG1 (By similarity).
CC Interacts with CTNNAL1. {ECO:0000250, ECO:0000269|PubMed:12270917,
CC ECO:0000269|PubMed:8810315, ECO:0000269|PubMed:9641916}.
CC -!- INTERACTION:
CC Q92888; Q14344: GNA13; NbExp=3; IntAct=EBI-465400, EBI-465387;
CC Q92888; P15884: TCF4; NbExp=3; IntAct=EBI-465400, EBI-533224;
CC Q92888; Q7DB74: espH; Xeno; NbExp=7; IntAct=EBI-465400, EBI-7864788;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10747909}. Membrane
CC {ECO:0000269|PubMed:10747909}. Note=Translocated to the membrane by
CC activated GNA13 or LPA stimulation.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q92888-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92888-2; Sequence=VSP_008125;
CC Name=3;
CC IsoId=Q92888-3; Sequence=VSP_037766;
CC Name=4;
CC IsoId=Q92888-4; Sequence=VSP_037766, VSP_008125, VSP_057289;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:8810315, ECO:0000269|PubMed:9135076}.
CC -!- DOMAIN: The RGSL domain, also known as rgRGS domain, is necessary but
CC not sufficient for GAP activity.
CC -!- DOMAIN: The DH domain is involved in interaction with CCPG1.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated by PKCA. Angiotensin-2 induced Tyr-738
CC phosphorylation is mediated by JAK2. {ECO:0000269|PubMed:12754211,
CC ECO:0000269|PubMed:20098430}.
CC -!- DISEASE: Immunodeficiency 62 (IMD62) [MIM:618459]: An autosomal
CC recessive, primary immunologic disorder characterized by recurrent
CC severe respiratory tract infections and bronchiectasis, due to antibody
CC deficiency. Affected individuals have an abnormal B cell
CC immunophenotype, with low levels of circulating memory B cells.
CC {ECO:0000269|PubMed:30521495}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA70356.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA70356.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
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DR EMBL; U64105; AAB17896.1; -; mRNA.
DR EMBL; AC010616; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC243967; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471126; EAW57084.1; -; Genomic_DNA.
DR EMBL; BC005155; AAH05155.2; -; mRNA.
DR EMBL; BC011726; AAH11726.1; -; mRNA.
DR EMBL; BC015652; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC034013; AAH34013.2; -; mRNA.
DR EMBL; BC067262; AAH67262.1; -; mRNA.
DR EMBL; Y09160; CAA70356.1; ALT_SEQ; mRNA.
DR EMBL; BT007421; AAP36089.1; -; mRNA.
DR CCDS; CCDS12590.1; -. [Q92888-3]
DR CCDS; CCDS12591.1; -. [Q92888-1]
DR CCDS; CCDS12592.1; -. [Q92888-2]
DR RefSeq; NP_004697.2; NM_004706.3. [Q92888-1]
DR RefSeq; NP_945328.1; NM_198977.1. [Q92888-2]
DR RefSeq; NP_945353.1; NM_199002.1. [Q92888-3]
DR PDB; 1IAP; X-ray; 1.90 A; A=42-252.
DR PDB; 1SHZ; X-ray; 2.85 A; C/F=7-239.
DR PDB; 3AB3; X-ray; 2.40 A; B/D=1-233.
DR PDB; 3ODO; X-ray; 2.90 A; A/B=395-766.
DR PDB; 3ODW; X-ray; 3.20 A; A/B=240-766.
DR PDB; 3ODX; X-ray; 3.20 A; A/B=353-766.
DR PDB; 3P6A; X-ray; 2.50 A; A/B=395-766.
DR PDBsum; 1IAP; -.
DR PDBsum; 1SHZ; -.
DR PDBsum; 3AB3; -.
DR PDBsum; 3ODO; -.
DR PDBsum; 3ODW; -.
DR PDBsum; 3ODX; -.
DR PDBsum; 3P6A; -.
DR AlphaFoldDB; Q92888; -.
DR SMR; Q92888; -.
DR BioGRID; 114585; 119.
DR CORUM; Q92888; -.
DR IntAct; Q92888; 35.
DR MINT; Q92888; -.
DR STRING; 9606.ENSP00000337261; -.
DR BindingDB; Q92888; -.
DR ChEMBL; CHEMBL4295918; -.
DR GlyGen; Q92888; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q92888; -.
DR MetOSite; Q92888; -.
DR PhosphoSitePlus; Q92888; -.
DR BioMuta; ARHGEF1; -.
DR DMDM; 34395524; -.
DR CPTAC; CPTAC-1231; -.
DR EPD; Q92888; -.
DR jPOST; Q92888; -.
DR MassIVE; Q92888; -.
DR MaxQB; Q92888; -.
DR PaxDb; Q92888; -.
DR PeptideAtlas; Q92888; -.
DR PRIDE; Q92888; -.
DR ProteomicsDB; 66748; -.
DR ProteomicsDB; 75572; -. [Q92888-1]
DR ProteomicsDB; 75573; -. [Q92888-2]
DR ProteomicsDB; 75574; -. [Q92888-3]
DR Antibodypedia; 2765; 282 antibodies from 34 providers.
DR DNASU; 9138; -.
DR Ensembl; ENST00000337665.8; ENSP00000337261.3; ENSG00000076928.18. [Q92888-3]
DR Ensembl; ENST00000347545.8; ENSP00000344429.3; ENSG00000076928.18. [Q92888-2]
DR Ensembl; ENST00000354532.8; ENSP00000346532.3; ENSG00000076928.18. [Q92888-1]
DR Ensembl; ENST00000378152.8; ENSP00000367394.3; ENSG00000076928.18. [Q92888-4]
DR GeneID; 9138; -.
DR KEGG; hsa:9138; -.
DR MANE-Select; ENST00000354532.8; ENSP00000346532.3; NM_004706.4; NP_004697.2.
DR UCSC; uc002orx.4; human. [Q92888-1]
DR CTD; 9138; -.
DR DisGeNET; 9138; -.
DR GeneCards; ARHGEF1; -.
DR HGNC; HGNC:681; ARHGEF1.
DR HPA; ENSG00000076928; Tissue enhanced (lymphoid).
DR MalaCards; ARHGEF1; -.
DR MIM; 601855; gene.
DR MIM; 618459; phenotype.
DR neXtProt; NX_Q92888; -.
DR OpenTargets; ENSG00000076928; -.
DR PharmGKB; PA24966; -.
DR VEuPathDB; HostDB:ENSG00000076928; -.
DR eggNOG; KOG3520; Eukaryota.
DR GeneTree; ENSGT00940000161180; -.
DR HOGENOM; CLU_003962_2_0_1; -.
DR InParanoid; Q92888; -.
DR OrthoDB; 319635at2759; -.
DR PhylomeDB; Q92888; -.
DR TreeFam; TF106495; -.
DR PathwayCommons; Q92888; -.
DR Reactome; R-HSA-193648; NRAGE signals death through JNK.
DR Reactome; R-HSA-416482; G alpha (12/13) signalling events.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013026; RHOB GTPase cycle.
DR Reactome; R-HSA-9013106; RHOC GTPase cycle.
DR SignaLink; Q92888; -.
DR SIGNOR; Q92888; -.
DR BioGRID-ORCS; 9138; 18 hits in 1084 CRISPR screens.
DR ChiTaRS; ARHGEF1; human.
DR EvolutionaryTrace; Q92888; -.
DR GeneWiki; ARHGEF1; -.
DR GenomeRNAi; 9138; -.
DR Pharos; Q92888; Tbio.
DR PRO; PR:Q92888; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q92888; protein.
DR Bgee; ENSG00000076928; Expressed in granulocyte and 184 other tissues.
DR ExpressionAtlas; Q92888; baseline and differential.
DR Genevisible; Q92888; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IBA:GO_Central.
DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
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; cd08755; RGS_p115RhoGEF; 1.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.10.167.10; -; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR037887; p115RhoGEF_RGS.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR041020; PH_16.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR015212; RGS-like_dom.
DR InterPro; IPR036305; RGS_sf.
DR InterPro; IPR044926; RGS_subdomain_2.
DR Pfam; PF17838; PH_16; 1.
DR Pfam; PF09128; RGS-like; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF48097; SSF48097; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasm;
KW GTPase activation; Guanine-nucleotide releasing factor; Membrane;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..912
FT /note="Rho guanine nucleotide exchange factor 1"
FT /id="PRO_0000080906"
FT DOMAIN 41..232
FT /note="RGSL"
FT DOMAIN 416..605
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 647..760
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 248..413
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 763..802
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 841..865
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 865..896
FT /evidence="ECO:0000255"
FT COMPBIAS 248..263
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 279..299
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 378..398
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 779..797
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 374
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 409
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 695
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 738
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000269|PubMed:20098430"
FT MOD_RES 863
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1
FT /note="M -> MASLSTWSSPAEPREM (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_037766"
FT VAR_SEQ 76..108
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008125"
FT VAR_SEQ 831..912
FT /note="VLSLKQLLFPAEEDNGAGPPRDGDGVPGGGPLSPARTQEIQENLLSLEETMK
FT QLEELEEEFCRLRPLLSQLGGNSVPQPGCT -> GVGGGILPPETPPVSAWGELCPPAW
FT LHLRFPPRKAFCKKERNGGEDVRDHPHPHSCRSISHPEGLRRGSCGPRLGGAQLGLLAP
FT HEPRPSLPPALCLGDSGLHSGGHHGDPGHLSIACGGHPSTPTPKCLRSVFIP (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_057289"
FT VARIANT 165
FT /note="M -> V (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035969"
FT VARIANT 285..912
FT /note="Missing (in IMD62; impairs RhoA GTPase activation
FT and GNA12- and GNA13-mediated signaling; reduces actin
FT polymerization; dbSNP:rs1568815169)"
FT /evidence="ECO:0000269|PubMed:30521495"
FT /id="VAR_082652"
FT VARIANT 375
FT /note="P -> L (in dbSNP:rs2303797)"
FT /id="VAR_033521"
FT MUTAGEN 487
FT /note="Y->F: No effect."
FT /evidence="ECO:0000269|PubMed:20098430"
FT MUTAGEN 738
FT /note="Y->F: Lowers the exchange activity."
FT /evidence="ECO:0000269|PubMed:20098430"
FT CONFLICT 257..259
FT /note="EPA -> DPP (in Ref. 1; AAB17896)"
FT /evidence="ECO:0000305"
FT CONFLICT 305..308
FT /note="VGMP -> GGDA (in Ref. 5; CAA70356)"
FT /evidence="ECO:0000305"
FT CONFLICT 339
FT /note="Missing (in Ref. 5; CAA70356)"
FT /evidence="ECO:0000305"
FT CONFLICT 346..352
FT /note="LGDSSPQ -> PGGLIPA (in Ref. 5; CAA70356)"
FT /evidence="ECO:0000305"
FT CONFLICT 549
FT /note="C -> S (in Ref. 5; CAA70356)"
FT /evidence="ECO:0000305"
FT CONFLICT 752
FT /note="C -> S (in Ref. 5; CAA70356)"
FT /evidence="ECO:0000305"
FT CONFLICT 776
FT /note="S -> R (in Ref. 1; AAB17896)"
FT /evidence="ECO:0000305"
FT CONFLICT 862
FT /note="L -> R (in Ref. 5; CAA70356)"
FT /evidence="ECO:0000305"
FT CONFLICT 876
FT /note="S -> R (in Ref. 5; CAA70356)"
FT /evidence="ECO:0000305"
FT CONFLICT 883
FT /note="Q -> T (in Ref. 5; CAA70356)"
FT /evidence="ECO:0000305"
FT STRAND 18..20
FT /evidence="ECO:0007829|PDB:1SHZ"
FT TURN 26..33
FT /evidence="ECO:0007829|PDB:3AB3"
FT HELIX 49..52
FT /evidence="ECO:0007829|PDB:1IAP"
FT HELIX 56..69
FT /evidence="ECO:0007829|PDB:1IAP"
FT HELIX 73..84
FT /evidence="ECO:0007829|PDB:1IAP"
FT HELIX 89..103
FT /evidence="ECO:0007829|PDB:1IAP"
FT HELIX 116..122
FT /evidence="ECO:0007829|PDB:1IAP"
FT TURN 127..129
FT /evidence="ECO:0007829|PDB:1IAP"
FT HELIX 132..144
FT /evidence="ECO:0007829|PDB:1IAP"
FT HELIX 147..162
FT /evidence="ECO:0007829|PDB:1IAP"
FT HELIX 169..176
FT /evidence="ECO:0007829|PDB:1IAP"
FT HELIX 183..203
FT /evidence="ECO:0007829|PDB:1IAP"
FT HELIX 205..207
FT /evidence="ECO:0007829|PDB:1IAP"
FT HELIX 212..228
FT /evidence="ECO:0007829|PDB:1IAP"
FT TURN 399..401
FT /evidence="ECO:0007829|PDB:3ODO"
FT HELIX 404..407
FT /evidence="ECO:0007829|PDB:3ODO"
FT HELIX 413..441
FT /evidence="ECO:0007829|PDB:3P6A"
FT HELIX 443..449
FT /evidence="ECO:0007829|PDB:3P6A"
FT HELIX 454..460
FT /evidence="ECO:0007829|PDB:3P6A"
FT HELIX 464..484
FT /evidence="ECO:0007829|PDB:3P6A"
FT HELIX 493..500
FT /evidence="ECO:0007829|PDB:3P6A"
FT HELIX 502..517
FT /evidence="ECO:0007829|PDB:3P6A"
FT HELIX 519..532
FT /evidence="ECO:0007829|PDB:3P6A"
FT HELIX 534..544
FT /evidence="ECO:0007829|PDB:3P6A"
FT HELIX 547..549
FT /evidence="ECO:0007829|PDB:3P6A"
FT HELIX 554..557
FT /evidence="ECO:0007829|PDB:3P6A"
FT HELIX 560..577
FT /evidence="ECO:0007829|PDB:3P6A"
FT HELIX 582..621
FT /evidence="ECO:0007829|PDB:3P6A"
FT HELIX 625..629
FT /evidence="ECO:0007829|PDB:3P6A"
FT HELIX 633..635
FT /evidence="ECO:0007829|PDB:3P6A"
FT STRAND 636..638
FT /evidence="ECO:0007829|PDB:3P6A"
FT STRAND 644..646
FT /evidence="ECO:0007829|PDB:3ODX"
FT STRAND 648..661
FT /evidence="ECO:0007829|PDB:3P6A"
FT STRAND 663..681
FT /evidence="ECO:0007829|PDB:3P6A"
FT STRAND 684..686
FT /evidence="ECO:0007829|PDB:3P6A"
FT STRAND 694..697
FT /evidence="ECO:0007829|PDB:3ODO"
FT STRAND 706..709
FT /evidence="ECO:0007829|PDB:3P6A"
FT HELIX 710..712
FT /evidence="ECO:0007829|PDB:3P6A"
FT STRAND 713..717
FT /evidence="ECO:0007829|PDB:3P6A"
FT STRAND 719..721
FT /evidence="ECO:0007829|PDB:3ODO"
FT STRAND 724..729
FT /evidence="ECO:0007829|PDB:3P6A"
FT STRAND 737..741
FT /evidence="ECO:0007829|PDB:3P6A"
FT HELIX 745..760
FT /evidence="ECO:0007829|PDB:3P6A"
SQ SEQUENCE 912 AA; 102435 MW; 1E773D041652190D CRC64;
MEDFARGAAS PGPSRPGLVP VSIIGAEDED FENELETNSE EQNSQFQSLE QVKRRPAHLM
ALLQHVALQF EPGPLLCCLH ADMLGSLGPK EAKKAFLDFY HSFLEKTAVL RVPVPPNVAF
ELDRTRADLI SEDVQRRFVQ EVVQSQQVAV GRQLEDFRSK RLMGMTPWEQ ELAQLEAWVG
RDRASYEARE RHVAERLLMH LEEMQHTIST DEEKSAAVVN AIGLYMRHLG VRTKSGDKKS
GRNFFRKKVM GNRRSDEPAK TKKGLSSILD AARWNRGEPQ VPDFRHLKAE VDAEKPGATD
RKGGVGMPSR DRNIGAPGQD TPGVSLHPLS LDSPDREPGA DAPLELGDSS PQGPMSLESL
APPESTDEGA ETESPEPGDE GEPGRSGLEL EPEEPPGWRE LVPPDTLHSL PKSQVKRQEV
ISELLVTEAA HVRMLRVLHD LFFQPMAECL FFPLEELQNI FPSLDELIEV HSLFLDRLMK
RRQESGYLIE EIGDVLLARF DGAEGSWFQK ISSRFCSRQS FALEQLKAKQ RKDPRFCAFV
QEAESRPRCR RLQLKDMIPT EMQRLTKYPL LLQSIGQNTE EPTEREKVEL AAECCREILH
HVNQAVRDME DLLRLKDYQR RLDLSHLRQS SDPMLSEFKN LDITKKKLVH EGPLTWRVTK
DKAVEVHVLL LDDLLLLLQR QDERLLLKSH SRTLTPTPDG KTMLRPVLRL TSAMTREVAT
DHKAFYVLFT WDQEAQIYEL VAQTVSERKN WCALITETAG SLKVPAPASR PKPRPSPSST
REPLLSSSEN GNGGRETSPA DARTERILSD LLPFCRPGPE GQLAATALRK VLSLKQLLFP
AEEDNGAGPP RDGDGVPGGG PLSPARTQEI QENLLSLEET MKQLEELEEE FCRLRPLLSQ
LGGNSVPQPG CT
