ARHGC_MOUSE
ID ARHGC_MOUSE Reviewed; 1543 AA.
AC Q8R4H2; E9QPW9; Q80U18;
DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Rho guanine nucleotide exchange factor 12;
DE AltName: Full=Leukemia-associated RhoGEF;
GN Name=Arhgef12; Synonyms=Kiaa0382, Larg;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zinovyeva M.V., Sveshnikova E.V., Visser J.M., Belyavsky A.V.;
RT "A novel murine gene encoding guanine nucleotide exchange factor and
RT expressed in non-differentiated hematopoietic cells.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=12492428; DOI=10.1046/j.1460-9568.2002.02402.x;
RA Kuner R., Swiercz J.M., Zywietz A., Tappe A., Offermanns S.;
RT "Characterization of the expression of PDZ-RhoGEF, LARG and
RT G(alpha)12/G(alpha)13 proteins in the murine nervous system.";
RL Eur. J. Neurosci. 16:2333-2341(2002).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1327, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-309 AND SER-1327, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: May play a role in the regulation of RhoA GTPase by guanine
CC nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as
CC guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as
CC GTPase-activating protein (GAP) for GNA12 and GNA13 (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with GNA12 and GNA13, probably through the RGS-like
CC domain, with RHOA, PLXNB1 and PLXNB2, and through its PDZ domain with
CC IGF1R beta subunit. Interacts with GCSAM. {ECO:0000250}.
CC -!- INTERACTION:
CC Q8R4H2; Q8CJH3: Plxnb1; NbExp=2; IntAct=EBI-8046267, EBI-2637650;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Membrane {ECO:0000305}.
CC Note=Translocated to the membrane upon stimulation. {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, predominantly in neuronal cell
CC bodies. {ECO:0000269|PubMed:12492428}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC65549.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF467766; AAL87100.1; -; mRNA.
DR EMBL; AK122267; BAC65549.1; ALT_INIT; mRNA.
DR EMBL; AC110169; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC160123; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS90543.1; -.
DR RefSeq; XP_006510649.1; XM_006510586.3.
DR AlphaFoldDB; Q8R4H2; -.
DR BMRB; Q8R4H2; -.
DR SMR; Q8R4H2; -.
DR BioGRID; 213578; 23.
DR IntAct; Q8R4H2; 6.
DR MINT; Q8R4H2; -.
DR STRING; 10090.ENSMUSP00000126598; -.
DR iPTMnet; Q8R4H2; -.
DR PhosphoSitePlus; Q8R4H2; -.
DR EPD; Q8R4H2; -.
DR jPOST; Q8R4H2; -.
DR MaxQB; Q8R4H2; -.
DR PaxDb; Q8R4H2; -.
DR PeptideAtlas; Q8R4H2; -.
DR PRIDE; Q8R4H2; -.
DR ProteomicsDB; 277285; -.
DR Antibodypedia; 9144; 171 antibodies from 27 providers.
DR Ensembl; ENSMUST00000072767; ENSMUSP00000072547; ENSMUSG00000059495.
DR UCSC; uc009pbb.1; mouse.
DR MGI; MGI:1916882; Arhgef12.
DR VEuPathDB; HostDB:ENSMUSG00000059495; -.
DR eggNOG; KOG3520; Eukaryota.
DR GeneTree; ENSGT00940000157662; -.
DR HOGENOM; CLU_003962_1_0_1; -.
DR InParanoid; Q8R4H2; -.
DR Reactome; R-MMU-193648; NRAGE signals death through JNK.
DR Reactome; R-MMU-416482; G alpha (12/13) signalling events.
DR Reactome; R-MMU-416572; Sema4D induced cell migration and growth-cone collapse.
DR Reactome; R-MMU-8980692; RHOA GTPase cycle.
DR Reactome; R-MMU-9013026; RHOB GTPase cycle.
DR Reactome; R-MMU-9013106; RHOC GTPase cycle.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR BioGRID-ORCS; 69632; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Arhgef12; mouse.
DR PRO; PR:Q8R4H2; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8R4H2; protein.
DR Bgee; ENSMUSG00000059495; Expressed in vestibular membrane of cochlear duct and 246 other tissues.
DR ExpressionAtlas; Q8R4H2; baseline and differential.
DR Genevisible; Q8R4H2; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001664; F:G protein-coupled receptor binding; ISO:MGI.
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:0007186; P:G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0010259; P:multicellular organism aging; IMP:MGI.
DR GO; GO:0008217; P:regulation of blood pressure; IMP:MGI.
DR GO; GO:0007266; P:Rho protein signal transduction; IEA:InterPro.
DR CDD; cd13390; PH_LARG; 1.
DR CDD; cd08754; RGS_LARG; 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 Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR037801; ARHGEF12_PH.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR001331; GDS_CDC24_CS.
DR InterPro; IPR037884; LARG_RGS.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
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; PF00595; PDZ; 1.
DR Pfam; PF17838; PH_16; 1.
DR Pfam; PF09128; RGS-like; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR SMART; SM00228; PDZ; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF48097; SSF48097; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS00741; DH_1; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Acetylation; Coiled coil; Cytoplasm; GTPase activation;
KW Guanine-nucleotide releasing factor; Membrane; Phosphoprotein;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9NZN5"
FT CHAIN 2..1543
FT /note="Rho guanine nucleotide exchange factor 12"
FT /id="PRO_0000080931"
FT DOMAIN 72..151
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 367..558
FT /note="RGSL"
FT DOMAIN 787..977
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 1019..1132
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 1..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 281..355
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 574..710
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1137..1158
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1386..1405
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1441..1468
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 194..262
FT /evidence="ECO:0000255"
FT COILED 981..1004
FT /evidence="ECO:0000255"
FT COMPBIAS 13..60
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 310..329
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 574..596
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 628..642
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 651..690
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1446..1464
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZN5"
FT MOD_RES 41
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZN5"
FT MOD_RES 309
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 341
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZN5"
FT MOD_RES 637
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZN5"
FT MOD_RES 736
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZN5"
FT MOD_RES 1288
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZN5"
FT MOD_RES 1327
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 1377
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZN5"
FT MOD_RES 1457
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZN5"
FT MOD_RES 1540
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZN5"
FT CONFLICT 307
FT /note="A -> V (in Ref. 2; BAC65549)"
FT /evidence="ECO:0000305"
FT CONFLICT 320
FT /note="L -> S (in Ref. 1; AAL87100)"
FT /evidence="ECO:0000305"
FT CONFLICT 334
FT /note="E -> QE (in Ref. 2; BAC65549)"
FT /evidence="ECO:0000305"
FT CONFLICT 1447
FT /note="A -> T (in Ref. 2; BAC65549)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1543 AA; 172349 MW; 9A3D0B3BB8E40A86 CRC64;
MSGTQSTITD RFPLKKPIRH GSILNRESPT DKKQKVERSS SHDFDPTDSS SKKTKSSSEE
SRSEIYGLVQ RCVIIQKDDN GFGLTVSGDN PVFVQSVKED GAAMRAGVQT GDRIIKVNGT
LVTHSNHLEV VKLIRSGSYV ALTVQGRPPG SPQIPLADSE VEPSVTGHMS PIMTSPHSPG
AAGNMERITS PVLVGEENNV VHNQKVEILR KMLQKEQERL QLLQEDYNRT ATQRLLKEIQ
EAKKHIPQLQ EQLSKATGSA QDGAVIAPSR PLGDALTLSE AEADPGDGLC RTDWSSGDAS
RPSSDSADSP KSSLRERSYL EEAPERSEGV QDAEPQSLVG SPSTRGAPHI IGAEDDDFGT
EHEQINGQCS CFQSIELLKS RPAHLAVFLH HVVSQFDPAT LLCYLYSDLY KQTNSKETRR
VFLEFHQFFL DRSAHLKVPV PEEISVDLEK RRPELIPEDL HRLYIQTMQE RVHPEVQRHL
EDFRQKRSMG LTLAESELTK LDAERDKDRG TLEKERACAE QIVTKIEEVL MTAQAVEEER
SSTMQYVILM YMKYLGVKVK EPRNLEHKRG RIGFLPKIKQ SMKKDREGEE KGKRRGFPSI
LGPPRRPSRH DNSAIGRAME IQKSRHPKHL STPSSVSPEP QDPAKLRQSG VANEGTDTGY
LPASSMSSAT SGTALSQEGG RENDTGTKQV GEASAPGDCL DSTPRVPTTV FDFPPPLLDQ
VQEEECEVER VAEHGTPKPF RKFDSIAFGE SQSEDEQFEN DLETDPPNWQ QLVSREVLLG
LKPSEIKRQE VINELFYTER AHVRTLKVLD QVFYQRVSRE GILSPSELRK IFSNLEDILQ
LHVGLNEQMK AVRKRNETSV IDHIGEDLLI WFSGPGEEKL KHAAATFCSN QPFALEMIKS
RQKKDSRFHT FVQDAESNPL CRRLQLKDII PTQMQRLTKY PLLLDNIAKY TEWPPEREKV
KKAADHCRQI LNYVNQAVRE AENKQRLEDY QRRLDTSNLK LSEYPNVDEL RNLDLTKRKM
IHEGPLVWKV NRDKSIDLYT LLLEDILVLL QKQDDRLVLR CHSKILASTA DSKHTFSPVI
KLSTVLVRQV ATDNKALFVI SMSDNGAQIY ELVAQTVSEK TVWQDLICRM AASVKEQSTK
PIPLPQPPPC EGDNDEEEPA KLKVEHHDLS VAGLQSPDRV LGLESPLISS KPQSHSLNTP
GKSAAEHLFV TATQFAKEQH ANGALKEGDG GYPVTIPGPH LPVSEERWAL DALRNLGLLK
QLLVQQLGLT EKSTQEDWQS FSRYGPASEE VQADSGIRDL ENVKACHARE GQMSFKTGTG
DIATCDSPRT STESCAAQDS VILASQDSQA SNVLVMDHMI LTPEMPPAEP EGGLDESGEH
FFDAREAHSD DNPSEGDGAV KKEEKDVNLR ISGNCLILDG YDAVQESSTD EEVASSFPLQ
PVTGIPAVDS SHQQQHSPQN VHPEGPVSPF TPEFLVQRHW RAMEDTCFEI QSPSCTDSQS
QILEYIHKIE ADLEHLKKVE ESYALLCQRL AGSALPDKLS DKS
