Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Rho guanine nucleotide exchange factor 2

Gene

Arhgef2

Organism
Mus musculus (Mouse)
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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri39 – 8648Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
BLAST

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-MMU-193648. NRAGE signals death through JNK.
R-MMU-194840. Rho GTPase cycle.
R-MMU-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
LBC'S first cousin
Lymphoid blast crisis-like 1
Oncogene LFC
Rhobin
Gene namesi
Name:Arhgef2
Synonyms:Kiaa0651, Lbcl1, Lfc
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:103264. 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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 985985Rho guanine nucleotide exchange factor 2PRO_0000080910Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei109 – 1091PhosphoserineBy similarity
Modified residuei122 – 1221PhosphoserineBy similarity
Modified residuei129 – 1291PhosphoserineBy similarity
Modified residuei133 – 1331PhosphoserineBy similarity
Modified residuei137 – 1371PhosphoserineBy similarity
Modified residuei143 – 1431Phosphoserine; by PAK4By similarity
Modified residuei151 – 1511PhosphoserineCombined sources
Modified residuei163 – 1631PhosphoserineCombined sources
Modified residuei172 – 1721PhosphoserineBy similarity
Modified residuei174 – 1741PhosphoserineCombined sources
Modified residuei177 – 1771PhosphoserineBy similarity
Modified residuei354 – 3541N6-acetyllysineBy similarity
Modified residuei646 – 6461PhosphoserineCombined sources
Modified residuei649 – 6491PhosphoserineBy similarity
Modified residuei680 – 6801Phosphothreonine; by MAPK1 or MAPK3By similarity
Modified residuei692 – 6921PhosphoserineBy similarity
Modified residuei710 – 7101PhosphoserineBy similarity
Modified residuei781 – 7811PhosphoserineCombined sources
Modified residuei795 – 7951PhosphothreonineCombined sources
Modified residuei885 – 8851PhosphoserineCombined sources
Modified residuei893 – 8931PhosphotyrosineBy similarity
Modified residuei895 – 8951Phosphoserine; by PAK4By similarity
Modified residuei931 – 9311PhosphoserineCombined sources
Modified residuei939 – 9391PhosphoserineCombined sources
Modified residuei940 – 9401PhosphoserineCombined sources
Modified residuei944 – 9441PhosphothreonineCombined sources
Modified residuei946 – 9461PhosphoserineCombined sources
Modified residuei951 – 9511PhosphoserineCombined sources
Modified residuei952 – 9521PhosphoserineCombined sources
Modified residuei955 – 9551PhosphoserineCombined sources
Modified residuei959 – 9591PhosphoserineCombined sources

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

MaxQBiQ60875.
PaxDbiQ60875.
PeptideAtlasiQ60875.
PRIDEiQ60875.

PTM databases

iPTMnetiQ60875.
PhosphoSiteiQ60875.
SwissPalmiQ60875.

Expressioni

Tissue specificityi

Ubiquitous, with the exception of liver tissue. Levels are high in hemopoietic tissues (thymus, spleen, bone marrow) as well as in kidney and lung.

Gene expression databases

BgeeiENSMUSG00000028059.
ExpressionAtlasiQ60875. baseline and differential.
GenevisibleiQ60875. MM.

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 similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Ksr1Q610975EBI-772191,EBI-1536336

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201114. 5 interactions.
IntActiQ60875. 8 interactions.
MINTiMINT-2982807.
STRINGi10090.ENSMUSP00000029694.

Structurei

3D structure databases

ProteinModelPortaliQ60875.
SMRiQ60875. Positions 211-571.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini236 – 433198DHPROSITE-ProRule annotationAdd
BLAST
Domaini473 – 572100PHPROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili591 – 61929Sequence analysisAdd
BLAST
Coiled coili797 – 86670Sequence analysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi493 – 4964Poly-Leu

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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri39 – 8648Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IR0Y. Eukaryota.
ENOG410XT68. LUCA.
GeneTreeiENSGT00760000119193.
HOVERGENiHBG050566.
InParanoidiQ60875.
KOiK12791.
OMAiQSVRICP.
OrthoDBiEOG091G00G7.
TreeFamiTF325887.

Family and domain databases

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]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q60875-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« 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 HTRFLNQLLE
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
RILQNSHGVE EEYQDLASAL GLVKELLSNV DQDVHELEKE ARLQEIYNRM
460 470 480 490 500
DPRAQTPVPG KGPFGRDELL RRKLIHEGCL 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 KNVELFAEMV HFQALKAGFV GMPPPALPRG LFRLESFESL
660 670 680 690 700
RGERLLKDAL REVEGLKDLL LGPCVDLPMT SREPALPLDS DSGSCPGVTA
710 720 730 740 750
NGEARTFNGS IELCRADSDS SQKDRNGNQL RSPQEEVLQP LINLYGLLHG
760 770 780 790 800
LQAVVVQQER LMEALFPEGP ERWEKLSRAN SRDGEAGRAA VASVTPEKQA
810 820 830 840 850
TELALLQRQH TLLQEELRRC QRLGEERATE AGSLEARLRE SEQARALLER
860 870 880 890 900
EAEEIRRQLA ALGQNEPLPA EAPWARRPLD PRRRSLPAGD ALYLSFNPPQ
910 920 930 940 950
PSRGHDRLDL PVTVRSLHRP FDDREAQELG SPEDRLQDSS DPDTGSEEEV
960 970 980
SSRLSPPHSP RDFTRMQDIP EETESRDGEP TASES
Length:985
Mass (Da):111,974
Last modified:July 27, 2011 - v4
Checksum:i1A5EAB73F95005D1
GO
Isoform 2 (identifier: Q60875-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     574-985: Missing.

Show »
Length:573
Mass (Da):65,836
Checksum:i6BB5C323B6FE355A
GO
Isoform 3 (identifier: Q60875-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: MSRIESLTRARIDRSKEQATK → MSGNRRQPSRRGQ
     596-596: T → S
     597-985: Missing.

Show »
Length:588
Mass (Da):67,638
Checksum:i7224EA3E1C9EDCCB
GO
Isoform 4 (identifier: Q60875-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-27: Missing.

Show »
Length:958
Mass (Da):108,744
Checksum:i2C38027E3BB226B7
GO
Isoform 5 (identifier: Q60875-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-27: Missing.
     112-113: Missing.

Show »
Length:956
Mass (Da):108,528
Checksum:i07B245CA6CA2EF2D
GO

Sequence cautioni

The sequence BAC41438 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti156 – 1561A → V in CAA65067 (Ref. 2) Curated
Sequence conflicti539 – 5391M → V in AAG09271 (Ref. 3) Curated
Sequence conflicti679 – 6791M → T in AAG09271 (Ref. 3) Curated
Sequence conflicti679 – 6791M → T in BAC41438 (PubMed:12465718).Curated
Sequence conflicti679 – 6791M → T in AAH06589 (PubMed:15489334).Curated
Sequence conflicti810 – 8101H → Y in BAE42325 (PubMed:16141072).Curated
Sequence conflicti941 – 9411D → G in AAG09271 (Ref. 3) Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2727Missing in isoform 4 and isoform 5. 2 PublicationsVSP_034962Add
BLAST
Alternative sequencei1 – 2121MSRIE…EQATK → MSGNRRQPSRRGQ in isoform 3. 1 PublicationVSP_022640Add
BLAST
Alternative sequencei112 – 1132Missing in isoform 5. 1 PublicationVSP_034963
Alternative sequencei574 – 985412Missing in isoform 2. 1 PublicationVSP_022641Add
BLAST
Alternative sequencei596 – 5961T → S in isoform 3. 1 PublicationVSP_022642
Alternative sequencei597 – 985389Missing in isoform 3. 1 PublicationVSP_022643Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U28495 mRNA. Translation: AAC52234.1.
X95761 mRNA. Translation: CAA65067.1.
AF177032 mRNA. Translation: AAG09271.1.
AB093254 mRNA. Translation: BAC41438.1. Different initiation.
AK167628 mRNA. Translation: BAE39679.1.
AK171223 mRNA. Translation: BAE42325.1.
AC145168 Genomic DNA. No translation available.
BC006589 mRNA. Translation: AAH06589.1.
CCDSiCCDS17481.1. [Q60875-1]
CCDS57221.1. [Q60875-5]
CCDS57222.1. [Q60875-4]
PIRiI49342.
RefSeqiNP_001185840.1. NM_001198911.1.
NP_001185841.1. NM_001198912.1. [Q60875-4]
NP_001185842.1. NM_001198913.1. [Q60875-5]
NP_032513.3. NM_008487.3. [Q60875-1]
XP_006501130.1. XM_006501067.2. [Q60875-4]
UniGeneiMm.239329.
Mm.482396.

Genome annotation databases

EnsembliENSMUST00000029694; ENSMUSP00000029694; ENSMUSG00000028059. [Q60875-1]
ENSMUST00000107510; ENSMUSP00000103134; ENSMUSG00000028059. [Q60875-4]
ENSMUST00000170653; ENSMUSP00000127843; ENSMUSG00000028059. [Q60875-5]
ENSMUST00000175911; ENSMUSP00000135428; ENSMUSG00000028059. [Q60875-3]
GeneIDi16800.
KEGGimmu:16800.
UCSCiuc008pvw.2. mouse. [Q60875-1]
uc008pvy.2. mouse. [Q60875-5]
uc008pwa.1. mouse. [Q60875-3]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U28495 mRNA. Translation: AAC52234.1.
X95761 mRNA. Translation: CAA65067.1.
AF177032 mRNA. Translation: AAG09271.1.
AB093254 mRNA. Translation: BAC41438.1. Different initiation.
AK167628 mRNA. Translation: BAE39679.1.
AK171223 mRNA. Translation: BAE42325.1.
AC145168 Genomic DNA. No translation available.
BC006589 mRNA. Translation: AAH06589.1.
CCDSiCCDS17481.1. [Q60875-1]
CCDS57221.1. [Q60875-5]
CCDS57222.1. [Q60875-4]
PIRiI49342.
RefSeqiNP_001185840.1. NM_001198911.1.
NP_001185841.1. NM_001198912.1. [Q60875-4]
NP_001185842.1. NM_001198913.1. [Q60875-5]
NP_032513.3. NM_008487.3. [Q60875-1]
XP_006501130.1. XM_006501067.2. [Q60875-4]
UniGeneiMm.239329.
Mm.482396.

3D structure databases

ProteinModelPortaliQ60875.
SMRiQ60875. Positions 211-571.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201114. 5 interactions.
IntActiQ60875. 8 interactions.
MINTiMINT-2982807.
STRINGi10090.ENSMUSP00000029694.

PTM databases

iPTMnetiQ60875.
PhosphoSiteiQ60875.
SwissPalmiQ60875.

Proteomic databases

MaxQBiQ60875.
PaxDbiQ60875.
PeptideAtlasiQ60875.
PRIDEiQ60875.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000029694; ENSMUSP00000029694; ENSMUSG00000028059. [Q60875-1]
ENSMUST00000107510; ENSMUSP00000103134; ENSMUSG00000028059. [Q60875-4]
ENSMUST00000170653; ENSMUSP00000127843; ENSMUSG00000028059. [Q60875-5]
ENSMUST00000175911; ENSMUSP00000135428; ENSMUSG00000028059. [Q60875-3]
GeneIDi16800.
KEGGimmu:16800.
UCSCiuc008pvw.2. mouse. [Q60875-1]
uc008pvy.2. mouse. [Q60875-5]
uc008pwa.1. mouse. [Q60875-3]

Organism-specific databases

CTDi9181.
MGIiMGI:103264. Arhgef2.
RougeiSearch...

Phylogenomic databases

eggNOGiENOG410IR0Y. Eukaryota.
ENOG410XT68. LUCA.
GeneTreeiENSGT00760000119193.
HOVERGENiHBG050566.
InParanoidiQ60875.
KOiK12791.
OMAiQSVRICP.
OrthoDBiEOG091G00G7.
TreeFamiTF325887.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiArhgef2. mouse.
PROiQ60875.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028059.
ExpressionAtlasiQ60875. baseline and differential.
GenevisibleiQ60875. MM.

Family and domain databases

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_MOUSE
AccessioniPrimary (citable) accession number: Q60875
Secondary accession number(s): E9QNW9
, O09115, Q3TBI4, Q3TJ16, Q8CHE1, Q923E0, Q9ESG7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 27, 2011
Last modified: September 7, 2016
This is version 146 of the entry and version 4 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.