ARHG4_MOUSE
ID ARHG4_MOUSE Reviewed; 484 AA.
AC Q7TNR9; Q80TJ6;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2004, sequence version 2.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Rho guanine nucleotide exchange factor 4;
DE AltName: Full=APC-stimulated guanine nucleotide exchange factor;
DE Short=Asef;
GN Name=Arhgef4; Synonyms=Kiaa1112;
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 205-484.
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 [4]
RP SEQUENCE REVISION.
RA Okazaki N., Kikuno R., Nagase T., Ohara O., Koga H.;
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10947987; DOI=10.1126/science.289.5482.1194;
RA Kawasaki Y., Senda T., Ishidate T., Koyama R., Morishita T., Iwayama Y.,
RA Higuchi O., Akiyama T.;
RT "Asef, a link between the tumor suppressor APC and G-protein signaling.";
RL Science 289:1194-1197(2000).
RN [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19893577; DOI=10.1038/embor.2009.233;
RA Kawasaki Y., Tsuji S., Muroya K., Furukawa S., Shibata Y., Okuno M.,
RA Ohwada S., Akiyama T.;
RT "The adenomatous polyposis coli-associated exchange factors Asef and Asef2
RT are required for adenoma formation in Apc(Min/+)mice.";
RL EMBO Rep. 10:1355-1362(2009).
CC -!- FUNCTION: Acts as guanine nucleotide exchange factor (GEF) for RHOA,
CC RAC1 and CDC42 GTPases. Binding of APC may activate RAC1 GEF activity.
CC The APC-ARHGEF4 complex seems to be involved in cell migration as well
CC as in E-cadherin-mediated cell-cell adhesion (By similarity). Required
CC for MMP9 up-regulation via the JNK signaling pathway in colorectal
CC tumor cells. Involved in tumor angiogenesis and may play a role in
CC intestinal adenoma formation and tumor progression. {ECO:0000250,
CC ECO:0000269|PubMed:19893577}.
CC -!- SUBUNIT: Interacts with RHOA and RAC1, and APC. Found in a complex
CC consisting of ARHGEF4, APC and CTNNB1 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10947987}.
CC Note=Colocalized with APC in the synapse of olfactory glomerulus.
CC -!- TISSUE SPECIFICITY: Expressed in colon epithelial cells. Highly
CC expressed in CNS, including hippocampus, olfactory bulb and cerebellum.
CC Expression is aberrantly enhanced in most colorectal tumors.
CC {ECO:0000269|PubMed:10947987, ECO:0000269|PubMed:19893577}.
CC -!- DOMAIN: In an autoinhibited form the SH3 domain binds intramolecularly
CC to the DH domain, thus blocking the Rac-binding site. {ECO:0000250}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BC055804; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AC107738; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC055804; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK122448; BAC65730.2; -; mRNA.
DR CCDS; CCDS14872.1; -.
DR RefSeq; NP_898840.2; NM_183019.2.
DR AlphaFoldDB; Q7TNR9; -.
DR SMR; Q7TNR9; -.
DR STRING; 10090.ENSMUSP00000035980; -.
DR PhosphoSitePlus; Q7TNR9; -.
DR MaxQB; Q7TNR9; -.
DR PaxDb; Q7TNR9; -.
DR PRIDE; Q7TNR9; -.
DR ProteomicsDB; 283263; -.
DR DNASU; 226970; -.
DR Ensembl; ENSMUST00000047664; ENSMUSP00000035980; ENSMUSG00000037509.
DR GeneID; 226970; -.
DR KEGG; mmu:226970; -.
DR UCSC; uc007api.1; mouse.
DR CTD; 50649; -.
DR MGI; MGI:2442507; Arhgef4.
DR VEuPathDB; HostDB:ENSMUSG00000037509; -.
DR eggNOG; KOG3519; Eukaryota.
DR GeneTree; ENSGT00940000160622; -.
DR HOGENOM; CLU_008436_2_1_1; -.
DR InParanoid; Q7TNR9; -.
DR OrthoDB; 55078at2759; -.
DR PhylomeDB; Q7TNR9; -.
DR TreeFam; TF316832; -.
DR BioGRID-ORCS; 226970; 4 hits in 59 CRISPR screens.
DR ChiTaRS; Arhgef4; mouse.
DR PRO; PR:Q7TNR9; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q7TNR9; protein.
DR Bgee; ENSMUSG00000037509; Expressed in central gray substance of midbrain and 174 other tissues.
DR ExpressionAtlas; Q7TNR9; baseline and differential.
DR Genevisible; Q7TNR9; MM.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0046847; P:filopodium assembly; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0030032; P:lamellipodium assembly; ISS:UniProtKB.
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; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR Pfam; PF00018; SH3_1; 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; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50002; SH3; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Guanine-nucleotide releasing factor; Reference proteome;
KW SH3 domain.
FT CHAIN 1..484
FT /note="Rho guanine nucleotide exchange factor 4"
FT /id="PRO_0000080915"
FT DOMAIN 1..46
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 78..262
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 293..400
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 51..75
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 51..72
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 484 AA; 56679 MW; D4DCDE8623F110FE CRC64;
MDDQELGFKA GDVIEVMDAT NREWWWGRVA DGEGWFPASF VRLRVNQDEP ADDYEAPRAG
AREADDSGPE AQSCKDQMRT NVINEILSTE RDYIKHLRDI CEGYVRQCRK REDMFSEEQL
RTIFGNIEDI YRCQKAFVKA LEQKFNTERP HLSELGACFL EHQADFQIYS EYCNNHPNAC
VELSRLTKLS KYVYFFEACR LLQRMIDISL DGFLLTPVQK ICKYPLQLAE LLKYTHPQHR
DFKNVEAALH AMKNVAQLIN ERKRRLENID KIAQWQSSIE DWEGEDLLVR SSELIHSGEL
TRVTQPQARS QQRMFFLFDR QLIYCKKDLL RRDVLYYKGR LDMDDLEVVD VEDGKDRDLH
VSVKNAFRLY CGTTGDSHLL CARKPEQKQR WLKAFARERE QVRLDQETGF SITELQRKQA
MLNASKQQAT GKPKAVGRPG YLTRHKHPSL PASRPQQQVL VLAEPRRKPS NFWHSISRLA
PFRK
