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Protein

Rho guanine nucleotide exchange factor 2

Gene

Arhgef2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Activates Rho-GTPases by promoting the exchange of GDP for GTP. May be involved in epithelial barrier permeability, cell motility and polarization, dendritic spine morphology, antigen presentation, leukemic cell differentiation, cell cycle regulation, innate immune response, and cancer. Binds Rac-GTPases, but does not seem to promote nucleotide exchange activity toward Rac-GTPases. May stimulate instead the cortical activity of Rac. Inactive toward CDC42, TC10, or Ras-GTPases. Forms an intracellular sensing system along with NOD1 for the detection of microbial effectors during cell invasion by pathogens. Involved in innate immune signaling transduction pathway promoting cytokine IL6/interleukin-6 and TNF-alpha secretion in macrophage upon stimulation by bacterial peptidoglycans; acts as a signaling intermediate between NOD2 receptor and RIPK2 kinase. Contributes to the tyrosine phosphorylation of RIPK2 through Src tyrosine kinase leading to NF-kappaB activation by NOD2 (By similarity).By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri39 – 86Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST48

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Biological processi

Cell cycle, Cell division, Immunity, Innate immunity, Mitosis

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-193648. NRAGE signals death through JNK.
R-RNO-194840. Rho GTPase cycle.
R-RNO-416482. G alpha (12/13) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Rho guanine nucleotide exchange factor 2
Alternative name(s):
Guanine nucleotide exchange factor H1
Short name:
GEF-H1
Gene namesi
Name:Arhgef2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 2

Organism-specific databases

RGDi1304659. Arhgef2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Golgi apparatus, Microtubule, Tight junction

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003456241 – 985Rho guanine nucleotide exchange factor 2Add BLAST985

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei109PhosphoserineBy similarity1
Modified residuei122PhosphoserineBy similarity1
Modified residuei129PhosphoserineBy similarity1
Modified residuei133PhosphoserineBy similarity1
Modified residuei137PhosphoserineBy similarity1
Modified residuei143Phosphoserine; by PAK4By similarity1
Modified residuei151PhosphoserineCombined sources1
Modified residuei163PhosphoserineBy similarity1
Modified residuei172PhosphoserineBy similarity1
Modified residuei174PhosphoserineCombined sources1
Modified residuei177PhosphoserineCombined sources1
Modified residuei354N6-acetyllysineBy similarity1
Modified residuei646PhosphoserineCombined sources1
Modified residuei649PhosphoserineBy similarity1
Modified residuei680Phosphothreonine; by MAPK1 or MAPK3By similarity1
Modified residuei692PhosphoserineBy similarity1
Modified residuei710PhosphoserineBy similarity1
Modified residuei781PhosphoserineBy similarity1
Modified residuei795PhosphothreonineBy similarity1
Modified residuei885PhosphoserineCombined sources1
Modified residuei893PhosphotyrosineBy similarity1
Modified residuei895Phosphoserine; by PAK4By similarity1
Modified residuei931PhosphoserineCombined sources1
Modified residuei939PhosphoserineBy similarity1
Modified residuei940PhosphoserineBy similarity1
Modified residuei944PhosphothreonineBy similarity1
Modified residuei946PhosphoserineBy similarity1
Modified residuei951PhosphoserineBy similarity1
Modified residuei952PhosphoserineBy similarity1
Modified residuei955PhosphoserineCombined sources1
Modified residuei959PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation of Ser-885 by PAK1 induces binding to protein YWHAZ, promoting its relocation to microtubules and the inhibition of its activity. Phosphorylated by AURKA and CDK1 during mitosis, which negatively regulates its activity. Phosphorylation by MAPK1 or MAPK3 increases nucleotide exchange activity. Phosphorylation by PAK4 releases GEF-H1 from the microtubules. Phosphorylated on serine, threonine and tyrosine residues in a RIPK2-dependent manner (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ5FVC2.
PRIDEiQ5FVC2.

PTM databases

iPTMnetiQ5FVC2.
PhosphoSitePlusiQ5FVC2.

Expressioni

Gene expression databases

BgeeiENSRNOG00000020027.
ExpressionAtlasiQ5FVC2. baseline and differential.
GenevisibleiQ5FVC2. RN.

Interactioni

Subunit structurei

Found in a complex composed at least of ARHGEF2, NOD2 and RIPK2. Interacts with RIPK2; the interaction mediates tyrosine phosphorylation of RIPK2 by Src kinase CSK. Interacts with RIPK1 and RIPK3. Interacts with YWHAZ/14-3-3 zeta; when phosphorylated at Ser-885. Interacts with the kinases PAK4, AURKA and MAPK1. Interacts with RHOA and RAC1. Interacts with NOD1 (By similarity). Interacts (via the N- terminal zinc finger) with CAPN6 (via domain II) (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-48721N.
STRINGi10116.ENSRNOP00000027182.

Structurei

3D structure databases

ProteinModelPortaliQ5FVC2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini236 – 433DHPROSITE-ProRule annotationAdd BLAST198
Domaini473 – 572PHPROSITE-ProRule annotationAdd BLAST100

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili591 – 615Sequence analysisAdd BLAST25
Coiled coili797 – 866Sequence analysisAdd BLAST70

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi493 – 496Poly-Leu4

Domaini

The DH (DBL-homology) domain promotes tyrosine phosphorylation of RIPK2 (By similarity). The DH (DBL-homology) domain interacts with and promotes loading of GTP on RhoA.By similarity
The PH (pleckstrin-homology) domain is involved in microtubule binding and targeting to tight junctions.

Sequence similaritiesi

Contains 1 DH (DBL-homology) domain.PROSITE-ProRule annotation
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 phorbol-ester/DAG-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri39 – 86Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST48

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IR0Y. Eukaryota.
ENOG410XT68. LUCA.
GeneTreeiENSGT00760000119193.
HOGENOMiHOG000236361.
HOVERGENiHBG050566.
InParanoidiQ5FVC2.
KOiK12791.
PhylomeDBiQ5FVC2.
TreeFamiTF325887.

Family and domain databases

CDDicd00029. C1. 1 hit.
Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR000219. DH-domain.
IPR002219. PE/DAG-bd.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00109. C1. 1 hit.
SM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q5FVC2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSRIESLTRA RIDRSKEQAT KTREKEKMKE AKDARYTNGH LFTTISVSGM
60 70 80 90 100
TMCYACNKSI TAKEALICPT CNVTIHNRCK DTLANCTKVK QKQQKAALLR
110 120 130 140 150
NNTALQSVSL RSKTTTRERP TSAIYPSDSF RQSLLGSRRG LSSLSLAKSV
160 170 180 190 200
STTNIAGHFN DESPLGLRQI LSQSTDSLNM RNRTLSVESL IDEGVEVFYN
210 220 230 240 250
ELMSDFEMDE KDFEADSWSL AVDSSFLQQH KKEVMKKQDV IYELIQTELH
260 270 280 290 300
HVRTLKIMTR LFRTGMLEEL QMEPEVVQGL FPCVDELSDI HTRFLSQLLE
310 320 330 340 350
RRRQALCPGS TRNFVIHRLG DLLISQFSGS NAEQMRKTYS EFCSRHTKAL
360 370 380 390 400
KLYKELYARD KRFQQFIRKM TRSAVLKRHG VQECILLVTQ RITKYPVLIN
410 420 430 440 450
RILQNSHGIE EEYQDLAAAL GLVKELLSNV DQDVHELEKE ARLQEIYNRM
460 470 480 490 500
DPRAQTPVPG KGPFGRDELL RRKLIHDGCL LWKTATGRFK DVLLLLMTDV
510 520 530 540 550
LVFLQEKDQK YIFTSLDKPS VVSLQNLIVR DIANQAKGMF LISSGPPEMY
560 570 580 590 600
EVHAASRDDR TTWIRVIQQS VRLCPSREDF PLIETEDKAY LRRIKTKLQQ
610 620 630 640 650
KNQALVELLQ MNVELFAEMV HFQALKAGFI GMPPPTLPRG LFRLESFESL
660 670 680 690 700
RGERLLKDAL REVEGLKDLL LGPCVDLPLT AREPALPVEA DSGSCPGVTA
710 720 730 740 750
NGEARTFNGS IELCRADSDS SQKDRNGNQL RSPQEEALQP LVNLYGLLQG
760 770 780 790 800
LQAVVVQQER LMEALFPEGP ERWEKLSRAN SRDGEAGRAA VASVTPEKQA
810 820 830 840 850
TELALLQRQH SLLQEELRRC QRLGEERATE AGSLEARLRE SEQARALLER
860 870 880 890 900
EAEEIRRQLA ALGQNEPLPA EAPWARRPLD PRRRSLPAGD ALYLSFNPPQ
910 920 930 940 950
PSRGHDRLDL PVTVRSLHRP FDDREAQELG SPEDRLQDSS DPDTCSEEEV
960 970 980
SSRLSPPHSP RDFTRMQDIP EETESRDGEP TASES
Length:985
Mass (Da):111,909
Last modified:March 1, 2005 - v1
Checksum:i73684403A04B9242
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC090078 mRNA. Translation: AAH90078.1.
RefSeqiNP_001012079.1. NM_001012079.1.
UniGeneiRn.12255.

Genome annotation databases

EnsembliENSRNOT00000027182; ENSRNOP00000027182; ENSRNOG00000020027.
GeneIDi310635.
KEGGirno:310635.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC090078 mRNA. Translation: AAH90078.1.
RefSeqiNP_001012079.1. NM_001012079.1.
UniGeneiRn.12255.

3D structure databases

ProteinModelPortaliQ5FVC2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-48721N.
STRINGi10116.ENSRNOP00000027182.

PTM databases

iPTMnetiQ5FVC2.
PhosphoSitePlusiQ5FVC2.

Proteomic databases

PaxDbiQ5FVC2.
PRIDEiQ5FVC2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000027182; ENSRNOP00000027182; ENSRNOG00000020027.
GeneIDi310635.
KEGGirno:310635.

Organism-specific databases

CTDi9181.
RGDi1304659. Arhgef2.

Phylogenomic databases

eggNOGiENOG410IR0Y. Eukaryota.
ENOG410XT68. LUCA.
GeneTreeiENSGT00760000119193.
HOGENOMiHOG000236361.
HOVERGENiHBG050566.
InParanoidiQ5FVC2.
KOiK12791.
PhylomeDBiQ5FVC2.
TreeFamiTF325887.

Enzyme and pathway databases

ReactomeiR-RNO-193648. NRAGE signals death through JNK.
R-RNO-194840. Rho GTPase cycle.
R-RNO-416482. G alpha (12/13) signalling events.

Miscellaneous databases

PROiQ5FVC2.

Gene expression databases

BgeeiENSRNOG00000020027.
ExpressionAtlasiQ5FVC2. baseline and differential.
GenevisibleiQ5FVC2. RN.

Family and domain databases

CDDicd00029. C1. 1 hit.
Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR000219. DH-domain.
IPR002219. PE/DAG-bd.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00109. C1. 1 hit.
SM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiARHG2_RAT
AccessioniPrimary (citable) accession number: Q5FVC2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 22, 2008
Last sequence update: March 1, 2005
Last modified: November 30, 2016
This is version 106 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.