ARHG3_HUMAN
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 03-AUG-2022, entry version 174.
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 guanine nucleotide exchange factor (GEF) for RhoA and
CC 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};
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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. [Q9NR81-2]
DR RefSeq; XP_005265244.1; XM_005265187.3.
DR AlphaFoldDB; Q9NR81; -.
DR SMR; Q9NR81; -.
DR BioGRID; 119115; 14.
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; Q9NR81; -.
DR PeptideAtlas; Q9NR81; -.
DR PRIDE; Q9NR81; -.
DR ProteomicsDB; 82296; -. [Q9NR81-1]
DR ProteomicsDB; 82297; -. [Q9NR81-2]
DR ProteomicsDB; 82298; -. [Q9NR81-3]
DR ProteomicsDB; 82299; -. [Q9NR81-4]
DR Antibodypedia; 31503; 189 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 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; 849206at2759; -.
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; 17 hits in 1075 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 192 other tissues.
DR ExpressionAtlas; Q9NR81; baseline and differential.
DR Genevisible; Q9NR81; HS.
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; -; 1.
DR Gene3D; 2.30.29.30; -; 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 Pfam; PF00621; RhoGEF; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR PROSITE; PS00741; DH_1; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
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
