ARHGP_MOUSE
ID ARHGP_MOUSE Reviewed; 618 AA.
AC Q9CWR0; Q3TYF3; Q8R1Q4;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 25-MAY-2022, entry version 132.
DE RecName: Full=Rho guanine nucleotide exchange factor 25;
DE AltName: Full=Guanine nucleotide exchange factor GEFT;
DE AltName: Full=Rac/Cdc42/Rho exchange factor GEFT;
DE AltName: Full=RhoA/Rac/Cdc42 guanine nucleotide exchange factor GEFT;
DE AltName: Full=p63RhoGEF;
GN Name=Arhgef25; Synonyms=D10Ertd610e, Geft;
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] (ISOFORM 1).
RC STRAIN=C57BL/6J;
RX PubMed=12547822; DOI=10.1074/jbc.m208896200;
RA Guo X., Stafford L.J., Bryan B., Xia C., Ma W., Wu X., Liu D., Songyang Z.,
RA Liu M.;
RT "A Rac/Cdc42-specific exchange factor, GEFT, induces cell proliferation,
RT transformation, and migration.";
RL J. Biol. Chem. 278:13207-13215(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Visual cortex;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 313-618.
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [4]
RP FUNCTION, INTERACTION WITH RHO GTPASES, AND TISSUE SPECIFICITY.
RX PubMed=15322108; DOI=10.1074/jbc.m406216200;
RA Bryan B., Kumar V., Stafford L.J., Cai Y., Wu G., Liu M.;
RT "GEFT, a Rho family guanine nucleotide exchange factor, regulates neurite
RT outgrowth and dendritic spine formation.";
RL J. Biol. Chem. 279:45824-45832(2004).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=16314529; DOI=10.1128/mcb.25.24.11089-11101.2005;
RA Bryan B.A., Mitchell D.C., Zhao L., Ma W., Stafford L.J., Teng B.B.,
RA Liu M.;
RT "Modulation of muscle regeneration, myogenesis, and adipogenesis by the Rho
RT family guanine nucleotide exchange factor GEFT.";
RL Mol. Cell. Biol. 25:11089-11101(2005).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=16496360; DOI=10.1002/jnr.20814;
RA Bryan B.A., Cai Y., Liu M.;
RT "The Rho-family guanine nucleotide exchange factor GEFT enhances retinoic
RT acid- and cAMP-induced neurite outgrowth.";
RL J. Neurosci. Res. 83:1151-1159(2006).
RN [7]
RP INTERACTION WITH BVES, AND SUBCELLULAR LOCATION.
RX PubMed=18541910; DOI=10.1073/pnas.0802345105;
RA Smith T.K., Hager H.A., Francis R., Kilkenny D.M., Lo C.W., Bader D.M.;
RT "Bves directly interacts with GEFT, and controls cell shape and movement
RT through regulation of Rac1/Cdc42 activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:8298-8303(2008).
CC -!- FUNCTION: May play a role in actin cytoskeleton reorganization in
CC different tissues since its activation induces formation of actin
CC stress fibers. It works as a guanine nucleotide exchange factor for Rho
CC family of small GTPases. Links specifically G alpha q/11-coupled
CC receptors to RHOA activation (By similarity). May be an important
CC regulator of processes involved in axon and dendrite formation. In
CC neurons seems to be an exchange factor primarily for RAC1. Involved in
CC skeletal myogenesis. {ECO:0000250, ECO:0000269|PubMed:15322108,
CC ECO:0000269|PubMed:16314529, ECO:0000269|PubMed:16496360}.
CC -!- SUBUNIT: Interacts with activated GNAQ and GNA11 (By similarity).
CC Interacts (via the DH domain) with BVES (via the C-terminus cytoplasmic
CC tail). Interacts with RHOA, CDC42 and RAC1. {ECO:0000250,
CC ECO:0000269|PubMed:15322108, ECO:0000269|PubMed:18541910}.
CC -!- INTERACTION:
CC Q9CWR0; Q9ES83: Bves; NbExp=2; IntAct=EBI-15708245, EBI-7705661;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere {ECO:0000250}.
CC Cell membrane {ECO:0000269|PubMed:18541910}. Cytoplasm, myofibril
CC {ECO:0000269|PubMed:18541910}. Note=Highly colocalizes with actin
CC regions. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9CWR0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9CWR0-2; Sequence=VSP_031876;
CC -!- TISSUE SPECIFICITY: Highly expressed in excitable tissues, such as
CC brain, heart and muscle. Elevated expression in hippocampus and
CC cerebellum. {ECO:0000269|PubMed:15322108, ECO:0000269|PubMed:16314529,
CC ECO:0000269|PubMed:16496360}.
CC -!- INDUCTION: Transcriptionally up-regulated during myogenic
CC differentiation and down-regulated during adipogenic differentiation.
CC Protein levels up-regulated during retinoic acid and dibutyric cAMP-
CC induced outgrowth of neurites. {ECO:0000269|PubMed:16314529,
CC ECO:0000269|PubMed:16496360}.
CC -!- DOMAIN: The guanine nucleotide exchange activity is autoinhibited by
CC the PH domain. {ECO:0000250}.
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DR EMBL; AF487515; AAO49464.1; -; mRNA.
DR EMBL; AK010452; BAB26951.1; -; mRNA.
DR EMBL; AK158684; BAE34610.1; -; mRNA.
DR EMBL; BC023367; AAH23367.1; -; mRNA.
DR CCDS; CCDS24231.1; -. [Q9CWR0-1]
DR CCDS; CCDS48715.1; -. [Q9CWR0-2]
DR RefSeq; NP_001159885.1; NM_001166413.1.
DR RefSeq; NP_082303.2; NM_028027.3.
DR AlphaFoldDB; Q9CWR0; -.
DR SMR; Q9CWR0; -.
DR DIP; DIP-46119N; -.
DR IntAct; Q9CWR0; 1.
DR STRING; 10090.ENSMUSP00000019611; -.
DR iPTMnet; Q9CWR0; -.
DR PhosphoSitePlus; Q9CWR0; -.
DR MaxQB; Q9CWR0; -.
DR PaxDb; Q9CWR0; -.
DR PRIDE; Q9CWR0; -.
DR ProteomicsDB; 282014; -. [Q9CWR0-1]
DR ProteomicsDB; 282015; -. [Q9CWR0-2]
DR DNASU; 52666; -.
DR GeneID; 52666; -.
DR KEGG; mmu:52666; -.
DR CTD; 115557; -.
DR MGI; MGI:1277173; Arhgef25.
DR eggNOG; KOG0689; Eukaryota.
DR InParanoid; Q9CWR0; -.
DR OrthoDB; 301115at2759; -.
DR PhylomeDB; Q9CWR0; -.
DR Reactome; R-MMU-416476; G alpha (q) 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 BioGRID-ORCS; 52666; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Arhgef25; mouse.
DR PRO; PR:Q9CWR0; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9CWR0; protein.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0019898; C:extrinsic component of membrane; IBA:GO_Central.
DR GO; GO:0030016; C:myofibril; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0030017; C:sarcomere; IEA:UniProtKB-SubCell.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IEA:InterPro.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR030738; ARHGEF25.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR PANTHER; PTHR22826:SF117; PTHR22826:SF117; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasm;
KW Guanine-nucleotide releasing factor; Membrane; Reference proteome.
FT CHAIN 1..618
FT /note="Rho guanine nucleotide exchange factor 25"
FT /id="PRO_0000322133"
FT DOMAIN 199..375
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 387..505
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 26..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 169..193
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 317..338
FT /note="Important for binding to Rho GTPases"
FT /evidence="ECO:0000250"
FT REGION 506..532
FT /note="Sufficient to bind activated GNAQ"
FT /evidence="ECO:0000250"
FT REGION 521..556
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 584..604
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 584..602
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..33
FT /note="MKPPDRPTPGRTDRILGVMGGMLRACAVPGQEG -> MEQSQGSINSVTRAI
FT CQVLVDAFR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_031876"
FT CONFLICT 148
FT /note="G -> E (in Ref. 2; BAE34610)"
FT /evidence="ECO:0000305"
FT CONFLICT 215
FT /note="E -> V (in Ref. 2; BAE34610)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 618 AA; 68262 MW; F5D016FACE96D3DB CRC64;
MKPPDRPTPG RTDRILGVMG GMLRACAVPG QEGPPERDPL GPGSTKTESD CIEEDQTGQR
EPEVLAWAPQ PESYSIAVSE GSMSASAVSG LAALSGPSSG LSSDPCSPIP PGPVTGLRRW
LDHSKHCLSV ETEAESGQTG QCENWTLGPT LTTGQELPEL TLLTTLLEGP GDKAQPAEEE
TLSQAPKNEE EQKKMALERS MFVLGELVET ERTYEDDLGQ IVEGYMATMA TQGVPESLRG
RDRIVFGNIQ QIYEWHRDYF LQELQQCLKD PDWLAQLFIK HERRLHMYVV YCQNKPKSEH
VLSEFGDSYF EELRQQLGHR LQLNDLLIKP VQRIMKYQLL LKDFLKYYRR AGKDTEELEQ
AVEVMCFVPK RCNDMMSLGR LRGFEGKLTA QGKLLGQDTF LVTEPEAGGL LSSRGRERRV
FLFEQIIIFS EALGGGGRGG AQPGYVYKNS IKVSCLGLEG NLQGNPCRFA LTSRGPEGGI
QRYVLQASDP AVSQAWIKQV AQILESQRDF LNALQSPIEY QRRESQTNSL GRPGGPWVGS
PGRMRPGDLA QASMHTPING SLPSLLLLPR GEVSRVLLPL DTQALSDTPQ TPHDSPALPT
VNTPPCQARL AKLDEDEL
