ARHG2_RAT
ID ARHG2_RAT Reviewed; 985 AA.
AC Q5FVC2;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Rho guanine nucleotide exchange factor 2;
DE AltName: Full=Guanine nucleotide exchange factor H1;
DE Short=GEF-H1;
GN Name=Arhgef2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [2]
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151; SER-174; SER-177;
RP SER-646; SER-885; SER-931; SER-955 AND SER-959, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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. Involved in
CC neuronal progenitor cell division and differentiation. Involved in the
CC migration of precerebellar neurons. {ECO:0000250|UniProtKB:Q60875,
CC ECO:0000250|UniProtKB:Q865S3}.
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 (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q865S3}.
CC -!- INTERACTION:
CC Q5FVC2; P19490: Gria1; NbExp=4; IntAct=EBI-15756732, EBI-371642;
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:0000250|UniProtKB:Q865S3,
CC ECO:0000250|UniProtKB:Q92974}. 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.
CC Colocalized with NOD2 and RIPK2 in vesicles and with the cytoskeleton.
CC {ECO:0000250|UniProtKB:Q92974}.
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 ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC090078; AAH90078.1; -; mRNA.
DR RefSeq; NP_001012079.1; NM_001012079.1.
DR AlphaFoldDB; Q5FVC2; -.
DR SMR; Q5FVC2; -.
DR BioGRID; 259684; 2.
DR DIP; DIP-48721N; -.
DR IntAct; Q5FVC2; 2.
DR STRING; 10116.ENSRNOP00000027182; -.
DR iPTMnet; Q5FVC2; -.
DR PhosphoSitePlus; Q5FVC2; -.
DR jPOST; Q5FVC2; -.
DR PaxDb; Q5FVC2; -.
DR PRIDE; Q5FVC2; -.
DR Ensembl; ENSRNOT00000027182; ENSRNOP00000027182; ENSRNOG00000020027.
DR GeneID; 310635; -.
DR KEGG; rno:310635; -.
DR CTD; 9181; -.
DR RGD; 1304659; Arhgef2.
DR eggNOG; KOG3520; Eukaryota.
DR GeneTree; ENSGT00940000158341; -.
DR HOGENOM; CLU_002466_1_1_1; -.
DR InParanoid; Q5FVC2; -.
DR PhylomeDB; Q5FVC2; -.
DR TreeFam; TF325887; -.
DR Reactome; R-RNO-193648; NRAGE signals death through JNK.
DR Reactome; R-RNO-416482; G alpha (12/13) signalling events.
DR Reactome; R-RNO-8980692; RHOA GTPase cycle.
DR Reactome; R-RNO-9013026; RHOB GTPase cycle.
DR PRO; PR:Q5FVC2; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000020027; Expressed in lung and 19 other tissues.
DR ExpressionAtlas; Q5FVC2; baseline and differential.
DR Genevisible; Q5FVC2; RN.
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; ISO:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
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; ISO:RGD.
DR GO; GO:0002102; C:podosome; ISO:RGD.
DR GO; GO:0014069; C:postsynaptic density; ISO:RGD.
DR GO; GO:0099092; C:postsynaptic density, intracellular component; IDA:SynGO.
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; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; ISS:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; ISS:UniProtKB.
DR GO; GO:0055059; P:asymmetric neuroblast division; ISS:UniProtKB.
DR GO; GO:0000902; P:cell morphogenesis; ISS:UniProtKB.
DR GO; GO:0071225; P:cellular response to muramyl dipeptide; ISS:UniProtKB.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0071802; P:negative regulation of podosome assembly; ISO:RGD.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB.
DR GO; GO:2001224; P:positive regulation of neuron migration; ISS: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; ISO:RGD.
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 Acetylation; Cell cycle; Cell division; Cell junction; Coiled coil;
KW Cytoplasm; Cytoplasmic vesicle; Cytoskeleton; Developmental protein;
KW Differentiation; Golgi apparatus; Guanine-nucleotide releasing factor;
KW Immunity; Innate immunity; Metal-binding; Microtubule; Mitosis;
KW Neurogenesis; Phosphoprotein; Proto-oncogene; Reference proteome;
KW Tight junction; Zinc; Zinc-finger.
FT CHAIN 1..985
FT /note="Rho guanine nucleotide exchange factor 2"
FT /id="PRO_0000345624"
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..615
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:22673903"
FT MOD_RES 163
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
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:22673903"
FT MOD_RES 177
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
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:22673903"
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:0000250|UniProtKB:Q60875"
FT MOD_RES 795
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q60875"
FT MOD_RES 885
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
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:22673903"
FT MOD_RES 939
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 940
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 944
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 946
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 951
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60875"
FT MOD_RES 952
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92974"
FT MOD_RES 955
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 959
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 985 AA; 111909 MW; 73684403A04B9242 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 HTRFLSQLLE
RRRQALCPGS TRNFVIHRLG DLLISQFSGS NAEQMRKTYS EFCSRHTKAL KLYKELYARD
KRFQQFIRKM TRSAVLKRHG VQECILLVTQ RITKYPVLIN RILQNSHGIE EEYQDLAAAL
GLVKELLSNV DQDVHELEKE ARLQEIYNRM DPRAQTPVPG KGPFGRDELL RRKLIHDGCL
LWKTATGRFK DVLLLLMTDV LVFLQEKDQK YIFTSLDKPS VVSLQNLIVR DIANQAKGMF
LISSGPPEMY EVHAASRDDR TTWIRVIQQS VRLCPSREDF PLIETEDKAY LRRIKTKLQQ
KNQALVELLQ MNVELFAEMV HFQALKAGFI GMPPPTLPRG LFRLESFESL RGERLLKDAL
REVEGLKDLL LGPCVDLPLT AREPALPVEA DSGSCPGVTA NGEARTFNGS IELCRADSDS
SQKDRNGNQL RSPQEEALQP LVNLYGLLQG LQAVVVQQER LMEALFPEGP ERWEKLSRAN
SRDGEAGRAA VASVTPEKQA TELALLQRQH SLLQEELRRC QRLGEERATE AGSLEARLRE
SEQARALLER EAEEIRRQLA ALGQNEPLPA EAPWARRPLD PRRRSLPAGD ALYLSFNPPQ
PSRGHDRLDL PVTVRSLHRP FDDREAQELG SPEDRLQDSS DPDTCSEEEV SSRLSPPHSP
RDFTRMQDIP EETESRDGEP TASES
