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 24-JAN-2024, entry version 208. 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 DEL, CHARACTERIZATION RP OF VARIANT IMD62 285-ARG--THR-912 DEL, 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 a 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 154. DR CORUM; Q92888; -. DR IntAct; Q92888; 36. 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; 9606-ENSP00000337261; -. DR PeptideAtlas; Q92888; -. DR ProteomicsDB; 66748; -. DR ProteomicsDB; 75572; -. [Q92888-1] DR ProteomicsDB; 75573; -. [Q92888-2] DR ProteomicsDB; 75574; -. [Q92888-3] DR Pumba; Q92888; -. DR Antibodypedia; 2765; 307 antibodies from 34 providers. DR DNASU; 9138; -. DR Ensembl; ENST00000337665.8; ENSP00000337261.3; ENSG00000076928.20. [Q92888-3] DR Ensembl; ENST00000347545.8; ENSP00000344429.3; ENSG00000076928.20. [Q92888-2] DR Ensembl; ENST00000354532.8; ENSP00000346532.3; ENSG00000076928.20. [Q92888-1] DR Ensembl; ENST00000378152.8; ENSP00000367394.3; ENSG00000076928.20. [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 AGR; HGNC:681; -. 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; 2875542at2759; -. 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; 20 hits in 1163 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 186 other cell types or tissues. DR ExpressionAtlas; Q92888; baseline and differential. 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; cd14679; PH_p115RhoGEF; 1. DR CDD; cd08755; RGS_p115RhoGEF; 1. DR CDD; cd00160; RhoGEF; 1. DR Gene3D; 1.20.900.10; Dbl homology (DH) domain; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 1.10.167.10; Regulator of G-protein Signalling 4, domain 2; 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 PANTHER; PTHR45872:SF4; RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 1; 1. DR PANTHER; PTHR45872; RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 2, ISOFORM D; 1. 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; DBL homology domain (DH-domain); 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF48097; Regulator of G-protein signaling, RGS; 1. DR PROSITE; PS50010; DH_2; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR Genevisible; Q92888; HS. 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 RhoAGTPase activation and FT 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 //