ARHG5_MOUSE
ID ARHG5_MOUSE Reviewed; 1581 AA.
AC E9Q7D5; Q8R172; Q922T1;
DT 20-JAN-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Rho guanine nucleotide exchange factor 5 {ECO:0000312|MGI:MGI:1858952};
GN Name=Arhgef5 {ECO:0000312|MGI:MGI:1858952};
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 {ECO:0000312|Ensembl:ENSMUSP00000031750};
RN [1] {ECO:0000312|Proteomes:UP000000589}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000312|Proteomes:UP000000589};
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 [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1167-1581.
RC STRAIN=FVB/N; TISSUE=Mammary tumor, and Salivary gland;
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 [3] {ECO:0000305}
RP FUNCTION, INTERACTION WITH GNB1; GNG2 AND RHOA, AND DISRUPTION PHENOTYPE.
RX PubMed=19713215; DOI=10.1074/jbc.m109.047282;
RA Wang Z., Kumamoto Y., Wang P., Gan X., Lehmann D., Smrcka A.V., Cohn L.,
RA Iwasaki A., Li L., Wu D.;
RT "Regulation of immature dendritic cell migration by RhoA guanine nucleotide
RT exchange factor Arhgef5.";
RL J. Biol. Chem. 284:28599-28606(2009).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-953 AND SER-1110, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Lung, and Spleen;
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).
RN [5] {ECO:0000305}
RP FUNCTION, INTERACTION WITH SRC, SUBCELLULAR LOCATION, DOMAIN, AND
RP PHOSPHORYLATION.
RX PubMed=21525037; DOI=10.1242/jcs.080291;
RA Kuroiwa M., Oneyama C., Nada S., Okada M.;
RT "The guanine nucleotide exchange factor Arhgef5 plays crucial roles in Src-
RT induced podosome formation.";
RL J. Cell Sci. 124:1726-1738(2011).
CC -!- FUNCTION: Guanine nucleotide exchange factor which activates Rho
CC GTPases (PubMed:19713215, PubMed:21525037). Strongly activates RHOA
CC (PubMed:19713215, PubMed:21525037). Also strongly activates RHOB,
CC weakly activates RHOC and RHOG and shows no effect on RHOD, RHOV, RHOQ
CC or RAC1 (PubMed:19713215). Involved in regulation of cell shape and
CC actin cytoskeletal organization (PubMed:21525037). Plays a role in
CC actin organization by generating a loss of actin stress fibers and the
CC formation of membrane ruffles and filopodia (By similarity). Required
CC for SRC-induced podosome formation (PubMed:21525037). Involved in
CC positive regulation of immature dendritic cell migration
CC (PubMed:19713215). {ECO:0000250|UniProtKB:Q12774,
CC ECO:0000269|PubMed:19713215, ECO:0000269|PubMed:21525037}.
CC -!- SUBUNIT: Interacts with SRC (PubMed:21525037). Forms a ternary complex
CC with SRC and the PI3K 85 kDa subunit (PubMed:21525037). Interacts with
CC and is activated by the heterodimer formed by GNB1 and GNG2
CC (PubMed:19713215). Interacts with ODAM (via C-terminus) (By
CC similarity). Interacts with RHOA (PubMed:19713215).
CC {ECO:0000250|UniProtKB:Q12774, ECO:0000269|PubMed:19713215,
CC ECO:0000269|PubMed:21525037}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q12774}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q12774}. Cell projection, podosome
CC {ECO:0000269|PubMed:21525037}.
CC -!- DOMAIN: The PH domain binds to phosphoinositides and is essential for
CC podosome formation. {ECO:0000269|PubMed:21525037}.
CC -!- PTM: Activation of SRC induces tyrosine phosphorylation of ARHGEF5.
CC {ECO:0000269|PubMed:21525037}.
CC -!- DISRUPTION PHENOTYPE: Chemotaxis of macrophages, T and B lymphocytes
CC and bone marrow-derived mature dendritic cells from mutant mice is not
CC affected but chemotaxis of immature dendritic cells is abolished.
CC {ECO:0000269|PubMed:19713215}.
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DR EMBL; AC153885; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC158671; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006829; AAH06829.1; -; mRNA.
DR EMBL; BC025127; AAH25127.1; -; mRNA.
DR CCDS; CCDS51759.1; -.
DR RefSeq; NP_598435.1; NM_133674.1.
DR RefSeq; XP_006506450.1; XM_006506387.2.
DR AlphaFoldDB; E9Q7D5; -.
DR SMR; E9Q7D5; -.
DR STRING; 10090.ENSMUSP00000031750; -.
DR iPTMnet; E9Q7D5; -.
DR PhosphoSitePlus; E9Q7D5; -.
DR MaxQB; E9Q7D5; -.
DR PaxDb; E9Q7D5; -.
DR PeptideAtlas; E9Q7D5; -.
DR PRIDE; E9Q7D5; -.
DR ProteomicsDB; 265081; -.
DR Antibodypedia; 18513; 344 antibodies from 36 providers.
DR Ensembl; ENSMUST00000031750; ENSMUSP00000031750; ENSMUSG00000033542.
DR GeneID; 54324; -.
DR KEGG; mmu:54324; -.
DR UCSC; uc009bsn.1; mouse.
DR UCSC; uc009bso.2; mouse.
DR CTD; 7984; -.
DR MGI; MGI:1858952; Arhgef5.
DR VEuPathDB; HostDB:ENSMUSG00000033542; -.
DR eggNOG; KOG3523; Eukaryota.
DR GeneTree; ENSGT01030000234571; -.
DR HOGENOM; CLU_003633_0_0_1; -.
DR InParanoid; E9Q7D5; -.
DR OMA; QDDVMLG; -.
DR OrthoDB; 1176939at2759; -.
DR PhylomeDB; E9Q7D5; -.
DR TreeFam; TF342609; -.
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-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 Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013408; RHOG GTPase cycle.
DR BioGRID-ORCS; 54324; 6 hits in 71 CRISPR screens.
DR ChiTaRS; Arhgef5; mouse.
DR PRO; PR:E9Q7D5; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; E9Q7D5; protein.
DR Bgee; ENSMUSG00000033542; Expressed in placenta labyrinth and 191 other tissues.
DR ExpressionAtlas; E9Q7D5; baseline and differential.
DR Genevisible; E9Q7D5; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0071944; C:cell periphery; ISO:MGI.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0002102; C:podosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISO:MGI.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0030036; P:actin cytoskeleton organization; IDA:MGI.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR GO; GO:0061484; P:hematopoietic stem cell homeostasis; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0002408; P:myeloid dendritic cell chemotaxis; IMP:MGI.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:MGI.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISO:MGI.
DR GO; GO:0071803; P:positive regulation of podosome assembly; IGI:MGI.
DR GO; GO:1904591; P:positive regulation of protein import; ISO:MGI.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; ISO:MGI.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISO:MGI.
DR GO; GO:0051493; P:regulation of cytoskeleton organization; ISO:MGI.
DR GO; GO:0043087; P:regulation of GTPase activity; ISO:MGI.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR029212; ARHGEF5/35_N.
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; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF15441; ARHGEF5_35; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR Pfam; PF14604; SH3_9; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS00741; DH_1; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell projection; Cytoplasm;
KW Guanine-nucleotide releasing factor; Lipid-binding; Nucleus;
KW Phosphoprotein; Reference proteome; SH3 domain.
FT CHAIN 1..1581
FT /note="Rho guanine nucleotide exchange factor 5"
FT /id="PRO_0000435143"
FT DOMAIN 1158..1342
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 1375..1488
FT /note="PH"
FT /evidence="ECO:0000255"
FT DOMAIN 1494..1555
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 25..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 159..274
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 316..643
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 659..700
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 741..810
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 829..1051
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 185..230
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 316..339
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 347..380
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 477..491
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 497..544
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 565..610
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 749..794
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 829..845
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 863..931
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 937..951
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 972..1001
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1002..1019
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 446
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12774"
FT MOD_RES 953
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 969
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12774"
FT MOD_RES 1029
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12774"
FT MOD_RES 1110
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 1581 AA; 176664 MW; CE61F8807C1C4102 CRC64;
MEAEEPEYGV STEVPDIEEL KTIPEGIMRS SQIPALDPEA QEDRDPSYKW TDGHRPVMNQ
SKVLRDMGDH TPNSMAIFFK KESSDMETSQ EILLAEACNT PDQQEAVIQS LKDRLSRTIA
APELLACAVQ EEWLDIPSKL DNRVGAELQS ELMSLTLAVS KEKEEEETSP DTSIPRGSWP
PCKTHPGETE QTQGSGSELL RQGKQLQLEA TQENQGQEGF LQSQEAQGLE EQEGQEVEIQ
EEGTLNEGIC FGGLLGEQEE VEEGFNGNEE EQKQGQIQSY MLLGGQWENE GLSGELEGLN
YSERGQENRE RRVWVLRDSE EEGQDQESRE VEERRVATQY TENQRLVEKS EIVKRKQRDH
DQTGKVMPVR DQKEVVDSGD RVQGNGDSGG QTAVEGSRPG EDSKPSLPVA SVDPEVLSPG
TLFPGISSSV ADIPQIQKEP VCEELSPQAP ALEPTEWSHQ PISPPASFAP EESLDNRTHN
SQQEEFRLRK GIEVVSASTS VAPSGTRDSP PFSPPNVFSS TATLSPVSSS VILPEETPTA
SASADTPHHC GPCETPPLPA KSSRYPCATS DTANPHSPLS SYTGVTQHLR SNSFPGSHRT
EQTPDSLGMS LSFSHLELPQ RPPKPAIYGS LTPRRNRRSR DGIVFSDSST ALFALKQDSE
EFTSNPERPS SPHGSPTWGS PQNSAFAIGS PANVSSPPTV SMDMTIREAL LPIPPEKRHS
YSHIVERDGL LHEVASTLKR HSHPPPLTLS SGLHRSSKGS FSLVPDSTVA RQHRPLPSTP
ESPNHTQTSI PSRLRYNKPL PPTPDMPEFY HPSISSSYIS RMYRPLPPVP IIDPSSEPPP
LPPKSRGRSK SIQGGVIHSG GQAKPRPNNQ DWTASTLSVG RTSWPPATGR STESLPLTSR
CNNEVSPGLA FSNMTNLLSP SSPTTPWIPD LQRPTTKDES GLTEESEPPV RGSFRRSAPQ
EEFNNTRRSA LGSRKNSEKP LHHQLEKASS WPHRRDPART SESSSEQVVL GQVPNKQKGW
NRQGLRRPSI LPESSSDLRN PAAGRLPGSS DSVVFREKKP KEGMGGFSRR CSKLISSQLL
YQEYSDVVLN KEIQSQQRLD SLAEPHGLSS PRHRRKALVS SDSYLQRLSM ASSGSLWQEI
PVVRNSTVLL SMTHEDQKLQ EAKFELIVSE ASYLRSLNIA VDHFQHSAQL RGTLSNQDHQ
WLFSRLQDVR DVSTTFLSDL EENFENNIFS FQVCDVVLNH AADFHRVYLP YVTNQTYQER
TFQSLMNSNS SFREVLEKLE SDPICQRLSL KSFLILPFQR ITRLKLLLQN ILKRTQPGSS
EEAEATKAHH ALEKLIRDCN SNVQRMRRTE ELIYLSQKIE FECKIFPLIS QSRWLVKSGE
LTALEFSVSP GLRRKLTTRP VHLHLFNDCL LLSRPREGSR FLVFDHAPFS SIRGEKCEMK
LHGPHKNLFR LFLLHNAQGT QVEFLFRTET QSEKLRWISA LAMPREELDL LECYDSPQVQ
CLRAYKPREN DELALEKADV VMVTQQSSDG WLEGVRLSDG EQGWFPVQQV EFISNPEVRA
QNLKEAHRVK TAKLQLVEQQ V
