ARHG2_MOUSE
ID ARHG2_MOUSE Reviewed; 985 AA.
AC Q60875; E9QNW9; O09115; Q3TBI4; Q3TJ16; Q8CHE1; Q923E0; Q9ESG7;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 4.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Rho guanine nucleotide exchange factor 2;
DE AltName: Full=Guanine nucleotide exchange factor H1;
DE Short=GEF-H1;
DE AltName: Full=LBC'S first cousin;
DE AltName: Full=Lymphoid blast crisis-like 1;
DE AltName: Full=Oncogene LFC;
DE AltName: Full=Rhobin;
GN Name=Arhgef2; Synonyms=Kiaa0651, Lbcl1, Lfc;
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 2).
RC TISSUE=Myeloid;
RX PubMed=7629163; DOI=10.1074/jbc.270.31.18388;
RA Whitehead I., Kirk H., Tognon C., Trigo-Gonzalez G., Kay R.;
RT "Expression cloning of lfc, a novel oncogene with structural similarities
RT to guanine nucleotide exchange factors and to the regulatory region of
RT protein kinase C.";
RL J. Biol. Chem. 270:18388-18395(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC STRAIN=BALB/cJ;
RA Olofsson B.;
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA De Sepulveda P., Rottapel R.;
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Brain;
RX PubMed=12465718; DOI=10.1093/dnares/9.5.179;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Hara Y., Nagase T., Ohara O.,
RA Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: I.
RT The complete nucleotide sequences of 100 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 9:179-188(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 5).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Dendritic cell, and Liver;
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 [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=Czech II; TISSUE=Mammary 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 [8]
RP SUBCELLULAR LOCATION.
RX PubMed=12604587; DOI=10.1083/jcb.200211047;
RA Benais-Pont G., Punn A., Flores-Maldonado C., Eckert J., Raposo G.,
RA Fleming T.P., Cereijido M., Balda M.S., Matter K.;
RT "Identification of a tight junction-associated guanine nucleotide exchange
RT factor that activates Rho and regulates paracellular permeability.";
RL J. Cell Biol. 160:729-740(2003).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain cortex;
RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200;
RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,
RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B.,
RA Panse C., Schlapbach R., Mansuy I.M.;
RT "Qualitative and quantitative analyses of protein phosphorylation in naive
RT and stimulated mouse synaptosomal preparations.";
RL Mol. Cell. Proteomics 6:283-293(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-931 AND SER-959, AND
RP IDENTIFICATION BY 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 [11]
RP REVIEW ON FUNCTION.
RX PubMed=18394899; DOI=10.1016/j.tcb.2008.02.006;
RA Birkenfeld J., Nalbant P., Yoon S.-H., Bokoch G.M.;
RT "Cellular functions of GEF-H1, a microtubule-regulated Rho-GEF: is altered
RT GEF-H1 activity a crucial determinant of disease pathogenesis?";
RL Trends Cell Biol. 18:210-219(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-163; SER-174; SER-646;
RP SER-781; THR-795; SER-885; SER-931; SER-939; SER-940; SER-955 AND SER-959,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-646, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151; SER-163; SER-174;
RP SER-885; SER-939; SER-940; THR-944; SER-946; SER-951; SER-952; SER-955 AND
RP SER-959, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, Spleen,
RC 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).
RN [15]
RP INTERACTION WITH CAPN6.
RX PubMed=21406564; DOI=10.1242/jcs.072561;
RA Tonami K., Kurihara Y., Arima S., Nishiyama K., Uchijima Y., Asano T.,
RA Sorimachi H., Kurihara H.;
RT "Calpain-6, a microtubule-stabilizing protein, regulates Rac1 activity and
RT cell motility through interaction with GEF-H1.";
RL J. Cell Sci. 124:1214-1223(2011).
RN [16]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=28453519; DOI=10.1371/journal.pgen.1006746;
RA Ravindran E., Hu H., Yuzwa S.A., Hernandez-Miranda L.R., Kraemer N.,
RA Ninnemann O., Musante L., Boltshauser E., Schindler D., Huebner A.,
RA Reinecker H.C., Ropers H.H., Birchmeier C., Miller F.D., Wienker T.F.,
RA Huebner C., Kaindl A.M.;
RT "Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-
RT hindbrain malformation.";
RL PLoS Genet. 13:E1006746-E1006746(2017).
CC -!- FUNCTION: Activates Rho-GTPases by promoting the exchange of GDP for
CC GTP. May be involved in epithelial barrier permeability, cell motility
CC and polarization, dendritic spine morphology, antigen presentation,
CC leukemic cell differentiation, cell cycle regulation, innate immune
CC response, and cancer. Binds Rac-GTPases, but does not seem to promote
CC nucleotide exchange activity toward Rac-GTPases. May stimulate instead
CC the cortical activity of Rac. Inactive toward CDC42, TC10, or Ras-
CC GTPases. Forms an intracellular sensing system along with NOD1 for the
CC detection of microbial effectors during cell invasion by pathogens.
CC Involved in innate immune signaling transduction pathway promoting
CC cytokine IL6/interleukin-6 and TNF-alpha secretion in macrophage upon
CC stimulation by bacterial peptidoglycans; acts as a signaling
CC intermediate between NOD2 receptor and RIPK2 kinase. Contributes to the
CC tyrosine phosphorylation of RIPK2 through Src tyrosine kinase leading
CC to NF-kappaB activation by NOD2. Overexpression activates Rho-, but not
CC Rac-GTPases, and increases paracellular permeability (By similarity).
CC Involved in neuronal progenitor cell division and differentiation
CC (PubMed:28453519). Involved in the migration of precerebellar neurons
CC (PubMed:28453519). {ECO:0000250|UniProtKB:Q865S3,
CC ECO:0000250|UniProtKB:Q92974, ECO:0000269|PubMed:28453519}.
CC -!- SUBUNIT: Found in a complex composed at least of ARHGEF2, NOD2 and
CC RIPK2. Interacts with RIPK2; the interaction mediates tyrosine
CC phosphorylation of RIPK2 by Src kinase CSK. Interacts with RIPK1 and
CC RIPK3. Interacts with YWHAZ/14-3-3 zeta; when phosphorylated at Ser-
CC 885. Interacts with the kinases PAK4, AURKA and MAPK1. Interacts with
CC RHOA and RAC1. Interacts with NOD1 (By similarity). Interacts (via the
CC N- terminal zinc finger) with CAPN6 (via domain II). Interacts with
CC DYNLT1. {ECO:0000250, ECO:0000250|UniProtKB:Q865S3,
CC ECO:0000269|PubMed:21406564}.
CC -!- INTERACTION:
CC Q60875; Q61097: Ksr1; NbExp=5; IntAct=EBI-772191, EBI-1536336;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q865S3, ECO:0000250|UniProtKB:Q92974}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q865S3, ECO:0000250|UniProtKB:Q92974}. Cell
CC junction, tight junction {ECO:0000269|PubMed:12604587}. Golgi apparatus
CC {ECO:0000250|UniProtKB:Q92974}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000250|UniProtKB:Q865S3, ECO:0000250|UniProtKB:Q92974}.
CC Cytoplasmic vesicle {ECO:0000250|UniProtKB:Q92974}. Note=Localizes to
CC the tips of cortical microtubules of the mitotic spindle during cell
CC division, and is further released upon microtubule depolymerization (By
CC similarity). Colocalized with NOD2 and RIPK2 in vesicles and with the
CC cytoskeleton (By similarity). Associated with apical intercellular
CC junctions in the trophectoderm of the blastocyst (PubMed:12604587).
CC {ECO:0000250|UniProtKB:Q92974, ECO:0000269|PubMed:12604587}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q60875-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q60875-2; Sequence=VSP_022641;
CC Name=3;
CC IsoId=Q60875-3; Sequence=VSP_022640, VSP_022642, VSP_022643;
CC Name=4;
CC IsoId=Q60875-4; Sequence=VSP_034962;
CC Name=5;
CC IsoId=Q60875-5; Sequence=VSP_034962, VSP_034963;
CC -!- TISSUE SPECIFICITY: Ubiquitous, with the exception of liver tissue.
CC Levels are high in hemopoietic tissues (thymus, spleen, bone marrow) as
CC well as in kidney and lung. Expressed in the germinal zones of both the
CC neocortex and the cerebellum and in the pontine gray nuclei
CC (PubMed:28453519). {ECO:0000269|PubMed:28453519}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the neuroepithelium of telencephalon,
CC diencephalon and rhombencephalon at 11 dpc (PubMed:28453519).
CC {ECO:0000269|PubMed:28453519}.
CC -!- DOMAIN: The DH (DBL-homology) domain promotes tyrosine phosphorylation
CC of RIPK2 (By similarity). The DH (DBL-homology) domain interacts with
CC and promotes loading of GTP on RhoA. {ECO:0000250}.
CC -!- DOMAIN: The PH domain has no affinity for phosphoinositides suggesting
CC that it does not interact directly with membranes.
CC {ECO:0000250|UniProtKB:Q92974}.
CC -!- DOMAIN: The phorbol-ester/DAG-type zinc-finger and the C-terminal
CC coiled-coil domains (606-986) are both important for association with
CC microtubules. {ECO:0000250|UniProtKB:Q92974}.
CC -!- PTM: Phosphorylation of Ser-885 by PAK1 induces binding to protein
CC YWHAZ, promoting its relocation to microtubules and the inhibition of
CC its activity. Phosphorylated by AURKA and CDK1 during mitosis, which
CC negatively regulates its activity. Phosphorylation by MAPK1 or MAPK3
CC increases nucleotide exchange activity. Phosphorylation by PAK4
CC releases GEF-H1 from the microtubules. Phosphorylated on serine,
CC threonine and tyrosine residues in a RIPK2-dependent manner (By
CC similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice show reduced volume of the total brain, the
CC cerebellum and the brainstem. Show complete lack of precerebellar
CC pontin gray and reticulotegmental nuclei. Show impaired precerebellar
CC neuron migration. {ECO:0000269|PubMed:28453519}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC41438.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U28495; AAC52234.1; -; mRNA.
DR EMBL; X95761; CAA65067.1; -; mRNA.
DR EMBL; AF177032; AAG09271.1; -; mRNA.
DR EMBL; AB093254; BAC41438.1; ALT_INIT; mRNA.
DR EMBL; AK167628; BAE39679.1; -; mRNA.
DR EMBL; AK171223; BAE42325.1; -; mRNA.
DR EMBL; AC145168; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006589; AAH06589.1; -; mRNA.
DR CCDS; CCDS17481.1; -. [Q60875-1]
DR CCDS; CCDS57221.1; -. [Q60875-5]
DR CCDS; CCDS57222.1; -. [Q60875-4]
DR PIR; I49342; I49342.
DR RefSeq; NP_001185840.1; NM_001198911.1.
DR RefSeq; NP_001185841.1; NM_001198912.1. [Q60875-4]
DR RefSeq; NP_001185842.1; NM_001198913.1. [Q60875-5]
DR RefSeq; NP_032513.3; NM_008487.3. [Q60875-1]
DR RefSeq; XP_006501130.1; XM_006501067.3. [Q60875-4]
DR PDB; 5WI4; X-ray; 2.00 A; A/B/C=139-164.
DR PDBsum; 5WI4; -.
DR AlphaFoldDB; Q60875; -.
DR SMR; Q60875; -.
DR BioGRID; 201114; 61.
DR IntAct; Q60875; 18.
DR MINT; Q60875; -.
DR STRING; 10090.ENSMUSP00000029694; -.
DR iPTMnet; Q60875; -.
DR PhosphoSitePlus; Q60875; -.
DR SwissPalm; Q60875; -.
DR EPD; Q60875; -.
DR jPOST; Q60875; -.
DR MaxQB; Q60875; -.
DR PaxDb; Q60875; -.
DR PeptideAtlas; Q60875; -.
DR PRIDE; Q60875; -.
DR ProteomicsDB; 283214; -. [Q60875-1]
DR ProteomicsDB; 283215; -. [Q60875-2]
DR ProteomicsDB; 283216; -. [Q60875-3]
DR ProteomicsDB; 283217; -. [Q60875-4]
DR ProteomicsDB; 283218; -. [Q60875-5]
DR Antibodypedia; 20425; 452 antibodies from 33 providers.
DR DNASU; 16800; -.
DR Ensembl; ENSMUST00000029694; ENSMUSP00000029694; ENSMUSG00000028059. [Q60875-1]
DR Ensembl; ENSMUST00000107510; ENSMUSP00000103134; ENSMUSG00000028059. [Q60875-4]
DR Ensembl; ENSMUST00000170653; ENSMUSP00000127843; ENSMUSG00000028059. [Q60875-5]
DR Ensembl; ENSMUST00000175911; ENSMUSP00000135428; ENSMUSG00000028059. [Q60875-3]
DR GeneID; 16800; -.
DR KEGG; mmu:16800; -.
DR UCSC; uc008pvw.2; mouse. [Q60875-1]
DR UCSC; uc008pvy.2; mouse. [Q60875-5]
DR UCSC; uc008pwa.1; mouse. [Q60875-3]
DR CTD; 9181; -.
DR MGI; MGI:103264; Arhgef2.
DR VEuPathDB; HostDB:ENSMUSG00000028059; -.
DR eggNOG; KOG3520; Eukaryota.
DR GeneTree; ENSGT00940000158341; -.
DR HOGENOM; CLU_002466_1_2_1; -.
DR InParanoid; Q60875; -.
DR OMA; FIAAKEC; -.
DR OrthoDB; 69816at2759; -.
DR PhylomeDB; Q60875; -.
DR TreeFam; TF325887; -.
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 BioGRID-ORCS; 16800; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Arhgef2; mouse.
DR PRO; PR:Q60875; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q60875; protein.
DR Bgee; ENSMUSG00000028059; Expressed in spermatid and 237 other tissues.
DR ExpressionAtlas; Q60875; baseline and differential.
DR Genevisible; Q60875; MM.
DR GO; GO:0005923; C:bicellular tight junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; ISS:UniProtKB.
DR GO; GO:0043198; C:dendritic shaft; IDA:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005874; C:microtubule; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IDA:MGI.
DR GO; GO:0002102; C:podosome; IDA:MGI.
DR GO; GO:0014069; C:postsynaptic density; IDA:MGI.
DR GO; GO:0099092; C:postsynaptic density, intracellular component; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; ISS:UniProtKB.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR GO; GO:0031982; C:vesicle; ISS:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008017; F:microtubule binding; IDA:MGI.
DR GO; GO:0031267; F:small GTPase binding; ISS:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; IPI:MGI.
DR GO; GO:0055059; P:asymmetric neuroblast division; IMP:UniProtKB.
DR GO; GO:0000902; P:cell morphogenesis; IDA:MGI.
DR GO; GO:0071225; P:cellular response to muramyl dipeptide; ISS:UniProtKB.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0007026; P:negative regulation of microtubule depolymerization; ISS:UniProtKB.
DR GO; GO:0050768; P:negative regulation of neurogenesis; IMP:UniProtKB.
DR GO; GO:0071802; P:negative regulation of podosome assembly; IMP:MGI.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IMP:UniProtKB.
DR GO; GO:2001224; P:positive regulation of neuron migration; IMP:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:UniProtKB.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IDA:MGI.
DR CDD; cd00029; C1; 1.
DR CDD; cd13393; PH_ARHGEF2; 1.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR037806; ARHGEF2_PH.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR041020; PH_16.
DR InterPro; IPR001849; PH_domain.
DR Pfam; PF17838; PH_16; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR SMART; SM00109; C1; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; Cell division;
KW Cell junction; Coiled coil; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton;
KW Developmental protein; Differentiation; Golgi apparatus;
KW Guanine-nucleotide releasing factor; Immunity; Innate immunity;
KW Metal-binding; Microtubule; Mitosis; Neurogenesis; Phosphoprotein;
KW Proto-oncogene; Reference proteome; Tight junction; Zinc; Zinc-finger.
FT CHAIN 1..985
FT /note="Rho guanine nucleotide exchange factor 2"
FT /id="PRO_0000080910"
FT DOMAIN 236..433
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 473..572
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 39..86
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 131..161
FT /note="Interaction with DYNLT1"
FT /evidence="ECO:0000250|UniProtKB:Q865S3"
FT REGION 890..909
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 918..985
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 591..619
FT /evidence="ECO:0000255"
FT COILED 797..866
FT /evidence="ECO:0000255"
FT COMPBIAS 918..948
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 964..985
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 109
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 122
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 129
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 133
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 137
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 143
FT /note="Phosphoserine; by PAK4"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 151
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 163
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 172
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 174
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 177
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 354
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 646
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19131326,
FT ECO:0007744|PubMed:19144319"
FT MOD_RES 649
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 680
FT /note="Phosphothreonine; by MAPK1 or MAPK3"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 692
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 710
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 781
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 795
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 885
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 893
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 895
FT /note="Phosphoserine; by PAK4"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 931
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19144319"
FT MOD_RES 939
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 940
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 944
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 946
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 951
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 952
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 955
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 959
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..27
FT /note="Missing (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:12465718,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_034962"
FT VAR_SEQ 1..21
FT /note="MSRIESLTRARIDRSKEQATK -> MSGNRRQPSRRGQ (in isoform
FT 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_022640"
FT VAR_SEQ 112..113
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_034963"
FT VAR_SEQ 574..985
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7629163"
FT /id="VSP_022641"
FT VAR_SEQ 596
FT /note="T -> S (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_022642"
FT VAR_SEQ 597..985
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_022643"
FT CONFLICT 156
FT /note="A -> V (in Ref. 2; CAA65067)"
FT /evidence="ECO:0000305"
FT CONFLICT 539
FT /note="M -> V (in Ref. 3; AAG09271)"
FT /evidence="ECO:0000305"
FT CONFLICT 679
FT /note="M -> T (in Ref. 3; AAG09271, 4; BAC41438 and 7;
FT AAH06589)"
FT /evidence="ECO:0000305"
FT CONFLICT 810
FT /note="H -> Y (in Ref. 5; BAE42325)"
FT /evidence="ECO:0000305"
FT CONFLICT 941
FT /note="D -> G (in Ref. 3; AAG09271)"
FT /evidence="ECO:0000305"
FT HELIX 140..143
FT /evidence="ECO:0007829|PDB:5WI4"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:5WI4"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:5WI4"
SQ SEQUENCE 985 AA; 111974 MW; 1A5EAB73F95005D1 CRC64;
MSRIESLTRA RIDRSKEQAT KTREKEKMKE AKDARYTNGH LFTTISVSGM TMCYACNKSI
TAKEALICPT CNVTIHNRCK DTLANCTKVK QKQQKAALLR NNTALQSVSL RSKTTTRERP
TSAIYPSDSF RQSLLGSRRG LSSLSLAKSV STTNIAGHFN DESPLGLRQI LSQSTDSLNM
RNRTLSVESL IDEGVEVFYN ELMSDFEMDE KDFEADSWSL AVDSSFLQQH KKEVMKKQDV
IYELIQTELH HVRTLKIMTR LFRTGMLEEL QMEPEVVQGL FPCVDELSDI HTRFLNQLLE
RRRQALCPGS TRNFVIHRLG DLLISQFSGS NAEQMRKTYS EFCSRHTKAL KLYKELYARD
KRFQQFIRKM TRSAVLKRHG VQECILLVTQ RITKYPVLIN RILQNSHGVE EEYQDLASAL
GLVKELLSNV DQDVHELEKE ARLQEIYNRM DPRAQTPVPG KGPFGRDELL RRKLIHEGCL
LWKTATGRFK DVLLLLMTDV LVFLQEKDQK YIFTSLDKPS VVSLQNLIVR DIANQAKGMF
LISSGPPEMY EVHAASRDDR TTWIRVIQQS VRLCPSREDF PLIETEDKAY LRRIKTKLQQ
KNQALVELLQ KNVELFAEMV HFQALKAGFV GMPPPALPRG LFRLESFESL RGERLLKDAL
REVEGLKDLL LGPCVDLPMT SREPALPLDS DSGSCPGVTA NGEARTFNGS IELCRADSDS
SQKDRNGNQL RSPQEEVLQP LINLYGLLHG LQAVVVQQER LMEALFPEGP ERWEKLSRAN
SRDGEAGRAA VASVTPEKQA TELALLQRQH TLLQEELRRC QRLGEERATE AGSLEARLRE
SEQARALLER EAEEIRRQLA ALGQNEPLPA EAPWARRPLD PRRRSLPAGD ALYLSFNPPQ
PSRGHDRLDL PVTVRSLHRP FDDREAQELG SPEDRLQDSS DPDTGSEEEV SSRLSPPHSP
RDFTRMQDIP EETESRDGEP TASES
