MGP Database

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MGP003822

UniProt Annotations

Entry Information
Gene NameRho/Rac guanine nucleotide exchange factor (GEF) 2
Protein EntryARHG2_HUMAN
UniProt IDQ92974
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; IsoId=Q92974-1; Sequence=Displayed; Name=2; IsoId=Q92974-2; Sequence=VSP_039458; Name=3; IsoId=Q92974-3; Sequence=VSP_039457, VSP_039458;
DomainThe DH (DBL-homology) domain interacts with and promotes loading of GTP on RhoA. Promotes tyrosine phosphorylation of RIPK2.
DomainThe PH (pleckstrin-homology) domain is involved in microtubule binding and targeting to tight junctions.
FunctionActivates 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, which was uniquely reported in PubMed:9857026. 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. Required for RHOA and RIP2 dependent NF-kappaB signaling pathways activation upon S.flexneri cell invasion. Involved not only in sensing peptidoglycan (PGN)-derived muropeptides through NOD1 that is independent of its GEF activity, but also in the activation of NF-kappaB by Shigella effector proteins (IpgB2 and OspB) which requires its GEF activity and the activation of RhoA. 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. {ECO:0000269|PubMed:19043560, ECO:0000269|PubMed:21887730, ECO:0000269|PubMed:9857026}.
InductionUp-regulated by bacterial peptidoglycans stimulation, such as muramyl dipeptide and in biopsies from inflamed mucosal areas of Crohn's disease patients. {ECO:0000269|PubMed:21887730}.
InteractionP63104:YWHAZ; NbExp=2; IntAct=EBI-302405, EBI-347088;
PtmPhosphorylation of Ser-886 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. {ECO:0000269|PubMed:14970201, ECO:0000269|PubMed:15827085, ECO:0000269|PubMed:16964243, ECO:0000269|PubMed:17081983, ECO:0000269|PubMed:17488622, ECO:0000269|PubMed:18211802, ECO:0000269|PubMed:18220336, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:19690332, ECO:0000269|PubMed:21406692}.
Sequence CautionSequence=AAC97383.1; Type=Miscellaneous discrepancy; Note=Sequence differs at a large extent from the sequence shown in the paper.; Evidence={ECO:0000305}; Sequence=AAH20567.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAA31626.3; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=CAA33634.1; Type=Frameshift; Positions=887, 984; Evidence={ECO:0000305};
SimilarityContains 1 DH (DBL-homology) domain. {ECO:0000255|PROSITE-ProRule:PRU00062}.
SimilarityContains 1 PH domain. {ECO:0000255|PROSITE- ProRule:PRU00145}.
SimilarityContains 1 phorbol-ester/DAG-type zinc finger. {ECO:0000255|PROSITE-ProRule:PRU00226}.
Subcellular LocationCytoplasm. Cell junction, tight junction. Golgi apparatus. Cytoplasm, cytoskeleton, spindle. Cell projection, ruffle membrane. Cytoplasmic vesicle. Note=Localizes to the tips of cortical microtubules of the mitotic spindle during cell division, and is further released upon microtubule depolymerization. Recruited into membrane ruffles induced by S.flexneri at tight junctions of polarized epithelial cells. Colocalized with NOD2 and RIPK2 in vesicles and with the cytoskeleton.
SubunitFound 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-886. Interacts with the kinases PAK4, AURKA and MAPK1. Interacts with RHOA and RAC1. Interacts with NOD1. Interacts (via the N-terminal zinc finger) with CAPN6 (via domain II) (By similarity). {ECO:0000250}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/ARHGEF2ID43150ch1q22.html";
Web ResourceName=Wikipedia; Note=ARHGEF2 entry; URL="http://en.wikipedia.org/wiki/ARHGEF2";
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