InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ARHGEF2

Summary

InnateDB Protein

IDBP-103342.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

ARHGEF2

Protein Name

Rho/Rac guanine nucleotide exchange factor (GEF) 2

Synonyms

GEF; GEF-H1; GEFH1; LFP40; P40;

Species

Homo sapiens

Ensembl Protein

ENSP00000315325

InnateDB Gene

IDBG-103338 (ARHGEF2)

Protein Structure

UniProt Annotation

Function

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, 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:0000269PubMed:19043560, ECO:0000269PubMed:21887730, ECO:0000269PubMed:9857026}.

Subcellular Localization

Cytoplasm. 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.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 52 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.

Experimentally validated
Total	52 [view]
Protein-Protein	52 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005089	Rho guanyl-nucleotide exchange factor activity
GO:0005515	protein binding
GO:0008017	microtubule binding
GO:0008134	transcription factor binding
GO:0008270	zinc ion binding
GO:0017048	Rho GTPase binding
GO:0030676	Rac guanyl-nucleotide exchange factor activity
GO:0048365	Rac GTPase binding

Biological Process

GO:0000902	cell morphogenesis
GO:0006886	intracellular protein transport
GO:0007015	actin filament organization
GO:0007026	negative regulation of microtubule depolymerization
GO:0007067	mitotic nuclear division
GO:0007264	small GTPase mediated signal transduction
GO:0032321	positive regulation of Rho GTPase activity
GO:0032755	positive regulation of interleukin-6 production
GO:0032760	positive regulation of tumor necrosis factor production
GO:0032855	positive regulation of Rac GTPase activity
GO:0035023	regulation of Rho protein signal transduction
GO:0035556	intracellular signal transduction
GO:0042127	regulation of cell proliferation
GO:0043065	positive regulation of apoptotic process
GO:0045087	innate immune response
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0050731	positive regulation of peptidyl-tyrosine phosphorylation
GO:0051056	regulation of small GTPase mediated signal transduction
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0060546	negative regulation of necroptotic process
GO:0071225	cellular response to muramyl dipeptide
GO:0071356	cellular response to tumor necrosis factor
GO:0071474	cellular hyperosmotic response
GO:0097190	apoptotic signaling pathway
GO:1902042	negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:1902219	negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress

Cellular Component

GO:0005737	cytoplasm
GO:0005794	Golgi apparatus
GO:0005819	spindle
GO:0005829	cytosol
GO:0005856	cytoskeleton
GO:0005874	microtubule
GO:0005923	tight junction
GO:0016023	cytoplasmic membrane-bounded vesicle
GO:0031982	vesicle
GO:0032587	ruffle membrane
GO:0043234	protein complex