ID ARHG3_HUMAN Reviewed; 526 AA. AC Q9NR81; A8K5U7; Q4FZB6; Q4QQI5; Q4QQQ0; Q59F00; Q6NUN3; Q7Z4U2; Q7Z5T2; AC Q9H7T4; DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 27-MAR-2024, entry version 182. DE RecName: Full=Rho guanine nucleotide exchange factor 3; DE AltName: Full=Exchange factor found in platelets and leukemic and neuronal tissues; DE Short=XPLN; GN Name=ARHGEF3; 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), AND TISSUE SPECIFICITY. RX PubMed=10873612; DOI=10.1006/bbrc.2000.2925; RA Thiesen S., Kuebart S., Ropers H.-H., Nothwang H.G.; RT "Isolation of two novel human RhoGEFs, ARHGEF3 and ARHGEF4, in 3p13-21 and RT 2q22."; RL Biochem. Biophys. Res. Commun. 273:364-369(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT VAL-335. RA Guo J.H., Yu L.; RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 71-526 (ISOFORMS 1/2/3), AND VARIANT VAL-335. RC TISSUE=Brain, and Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-335. 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4), AND VARIANT RP VAL-335. RC TISSUE=Hippocampus, 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 [8] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=12221096; DOI=10.1074/jbc.m207401200; RA Arthur W.T., Ellerbroek S.M., Der C.J., Burridge K., Wennerberg K.; RT "XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RT RhoC."; RL J. Biol. Chem. 277:42964-42972(2002). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; 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). CC -!- FUNCTION: Acts as a guanine nucleotide exchange factor (GEF) for RhoA CC and RhoB GTPases. {ECO:0000269|PubMed:12221096}. CC -!- SUBUNIT: Interacts with RHOA and RHOB. CC -!- INTERACTION: CC Q9NR81; Q8NHQ1: CEP70; NbExp=7; IntAct=EBI-10312733, EBI-739624; CC Q9NR81; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-10312733, EBI-742054; CC Q9NR81; O75031: HSF2BP; NbExp=3; IntAct=EBI-10312733, EBI-7116203; CC Q9NR81; Q9BYU1: PBX4; NbExp=3; IntAct=EBI-10312733, EBI-10302990; CC Q9NR81; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-10312733, EBI-79165; CC Q9NR81; P54274-2: TERF1; NbExp=3; IntAct=EBI-10312733, EBI-711018; CC Q9NR81; P36406: TRIM23; NbExp=5; IntAct=EBI-10312733, EBI-740098; CC Q9NR81; P14373: TRIM27; NbExp=8; IntAct=EBI-10312733, EBI-719493; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q9NR81-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9NR81-2; Sequence=VSP_011612; CC Name=3; CC IsoId=Q9NR81-3; Sequence=VSP_027205; CC Name=4; CC IsoId=Q9NR81-4; Sequence=VSP_027204, VSP_027206; CC -!- TISSUE SPECIFICITY: Widely expressed. Highest levels are found in adult CC brain and skeletal muscle. Lower levels are found in heart and kidney. CC {ECO:0000269|PubMed:10873612, ECO:0000269|PubMed:12221096}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH68513.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAB14891.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAD92898.1; Type=Erroneous initiation; 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; AF249744; AAF79954.1; -; mRNA. DR EMBL; AL136832; CAB66766.1; -; mRNA. DR EMBL; AF433662; AAP97313.1; -; mRNA. DR EMBL; AK024340; BAB14891.1; ALT_INIT; mRNA. DR EMBL; AK291412; BAF84101.1; -; mRNA. DR EMBL; AB209661; BAD92898.1; ALT_INIT; mRNA. DR EMBL; CH471055; EAW65326.1; -; Genomic_DNA. DR EMBL; BC054345; AAH54345.2; -; mRNA. DR EMBL; BC068513; AAH68513.1; ALT_INIT; mRNA. DR EMBL; BC098122; AAH98122.2; -; mRNA. DR EMBL; BC098272; AAH98272.2; -; mRNA. DR EMBL; BC099715; AAH99715.1; -; mRNA. DR EMBL; BC104723; AAI04724.2; -; mRNA. DR CCDS; CCDS2878.1; -. [Q9NR81-1] DR CCDS; CCDS46854.1; -. [Q9NR81-2] DR CCDS; CCDS46855.1; -. [Q9NR81-3] DR RefSeq; NP_001122087.1; NM_001128615.1. [Q9NR81-2] DR RefSeq; NP_001122088.1; NM_001128616.1. [Q9NR81-3] DR RefSeq; NP_001276627.1; NM_001289698.1. DR RefSeq; NP_062455.1; NM_019555.2. [Q9NR81-1] DR RefSeq; XP_005265243.1; XM_005265186.4. DR RefSeq; XP_005265244.1; XM_005265187.3. DR AlphaFoldDB; Q9NR81; -. DR SMR; Q9NR81; -. DR BioGRID; 119115; 16. DR IntAct; Q9NR81; 11. DR MINT; Q9NR81; -. DR STRING; 9606.ENSP00000341071; -. DR iPTMnet; Q9NR81; -. DR PhosphoSitePlus; Q9NR81; -. DR BioMuta; ARHGEF3; -. DR DMDM; 52782760; -. DR EPD; Q9NR81; -. DR jPOST; Q9NR81; -. DR MassIVE; Q9NR81; -. DR MaxQB; Q9NR81; -. DR PaxDb; 9606-ENSP00000341071; -. DR PeptideAtlas; Q9NR81; -. DR ProteomicsDB; 82296; -. [Q9NR81-1] DR ProteomicsDB; 82297; -. [Q9NR81-2] DR ProteomicsDB; 82298; -. [Q9NR81-3] DR ProteomicsDB; 82299; -. [Q9NR81-4] DR Antibodypedia; 31503; 207 antibodies from 24 providers. DR DNASU; 50650; -. DR Ensembl; ENST00000296315.8; ENSP00000296315.3; ENSG00000163947.12. [Q9NR81-1] DR Ensembl; ENST00000338458.8; ENSP00000341071.4; ENSG00000163947.12. [Q9NR81-2] DR Ensembl; ENST00000413728.6; ENSP00000410922.2; ENSG00000163947.12. [Q9NR81-3] DR GeneID; 50650; -. DR KEGG; hsa:50650; -. DR MANE-Select; ENST00000296315.8; ENSP00000296315.3; NM_019555.3; NP_062455.1. DR UCSC; uc003dif.3; human. [Q9NR81-1] DR AGR; HGNC:683; -. DR CTD; 50650; -. DR DisGeNET; 50650; -. DR GeneCards; ARHGEF3; -. DR HGNC; HGNC:683; ARHGEF3. DR HPA; ENSG00000163947; Low tissue specificity. DR MIM; 612115; gene. DR neXtProt; NX_Q9NR81; -. DR OpenTargets; ENSG00000163947; -. DR PharmGKB; PA24973; -. DR VEuPathDB; HostDB:ENSG00000163947; -. DR eggNOG; KOG4305; Eukaryota. DR GeneTree; ENSGT00940000158385; -. DR InParanoid; Q9NR81; -. DR OMA; QCVFREM; -. DR OrthoDB; 24012at2759; -. DR PhylomeDB; Q9NR81; -. DR TreeFam; TF328974; -. DR PathwayCommons; Q9NR81; -. 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 SignaLink; Q9NR81; -. DR SIGNOR; Q9NR81; -. DR BioGRID-ORCS; 50650; 18 hits in 1153 CRISPR screens. DR ChiTaRS; ARHGEF3; human. DR GeneWiki; ARHGEF3; -. DR GenomeRNAi; 50650; -. DR Pharos; Q9NR81; Tbio. DR PRO; PR:Q9NR81; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q9NR81; Protein. DR Bgee; ENSG00000163947; Expressed in renal glomerulus and 194 other cell types or tissues. DR ExpressionAtlas; Q9NR81; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; TAS:Reactome. DR GO; GO:0035025; P:positive regulation of Rho protein signal transduction; 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; cd10572; PH_RhoGEF3_XPLN; 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 InterPro; IPR035899; DBL_dom_sf. DR InterPro; IPR000219; DH-domain. DR InterPro; IPR001331; GDS_CDC24_CS. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR001849; PH_domain. DR InterPro; IPR044129; PH_RhoGEF3_XPLN. DR PANTHER; PTHR46006:SF2; RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 3; 1. DR PANTHER; PTHR46006; RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR AT 64C, ISOFORM A; 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 PROSITE; PS00741; DH_1; 1. DR PROSITE; PS50010; DH_2; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR Genevisible; Q9NR81; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cytoplasm; Guanine-nucleotide releasing factor; KW Phosphoprotein; Reference proteome. FT CHAIN 1..526 FT /note="Rho guanine nucleotide exchange factor 3" FT /id="PRO_0000080911" FT DOMAIN 122..304 FT /note="DH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062" FT DOMAIN 291..449 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT REGION 20..40 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 464..526 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 464..479 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 509..526 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 47 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 70 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q7Z628" FT VAR_SEQ 1..202 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_027204" FT VAR_SEQ 1..32 FT /note="MVAKDYPFYLTVKRANCSLELPPASGPAKDAE -> MDSSTAMNQCSCRGME FT ENKERPKRQRQNNFPMFPSPKAWNFRGRKRKQSTQDEDAVSLCSLDIS (in FT isoform 2)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_011612" FT VAR_SEQ 1..32 FT /note="MVAKDYPFYLTVKRANCSLELPPASGPAKDAE -> MIEVCHHNWLLWLCPS FT KFGIFMCCLASTTGQMELRRTR (in isoform 3)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_027205" FT VAR_SEQ 203..204 FT /note="GW -> MK (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_027206" FT VARIANT 13 FT /note="K -> R (in dbSNP:rs3732507)" FT /id="VAR_021935" FT VARIANT 335 FT /note="L -> V (in dbSNP:rs3772219)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3, FT ECO:0000269|Ref.6" FT /id="VAR_021936" FT CONFLICT 410 FT /note="I -> T (in Ref. 3; AAP97313)" FT /evidence="ECO:0000305" SQ SEQUENCE 526 AA; 59783 MW; 0FE8248AB52D1CBC CRC64; MVAKDYPFYL TVKRANCSLE LPPASGPAKD AEEPSNKRVK PLSRVTSLAN LIPPVKATPL KRFSQTLQRS ISFRSESRPD ILAPRPWSRN AAPSSTKRRD SKLWSETFDV CVNQMLTSKE IKRQEAIFEL SQGEEDLIED LKLAKKAYHD PMLKLSIMTE QELNQIFGTL DSLIPLHEEL LSQLRDVRKP DGSTEHVGPI LVGWLPCLSS YDSYCSNQVA AKALLDHKKQ DHRVQDFLQR CLESPFSRKL DLWNFLDIPR SRLVKYPLLL REILRHTPND NPDQQHLEEA INIIQGIVAE INTKTGESEC RYYKERLLYL EEGQKDSLID SSRVLCCHGE LKNNRGVKLH VFLFQEVLVI TRAVTHNEQL CYQLYRQPIP VKDLLLEDLQ DGEVRLGGSL RGAFSNNERI KNFFRVSFKN GSQSQTHSLQ ANDTFNKQQW LNCIRQAKET VLCAAGQAGV LDSEGSFLNP TTGSRELQGE TKLEQMDQSD SESDCSMDTS EVSLDCERME QTDSSCGNSR HGESNV //