The DH (DBL-homology) domain interacts with and promotes loading of GTP on RhoA. Promotes tyrosine phosphorylation of RIPK2.
The PH domain has no affinity for phosphoinositides suggesting that it does not interact directly with membranes.
The phorbol-ester/DAG-type zinc-finger and the C-terminal coiled-coil domains (606-986) are both important for association with microtubules.
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. Overexpression activates Rho-, but not Rac-GTPases, and increases paracellular permeability (By similarity). Involved in neuronal progenitor cell division and differentiation (PubMed:28453519). Involved in the migration of precerebellar neurons (By similarity).
Neurodevelopmental disorder with midbrain and hindbrain malformations
NEDMHM
An autosomal recessive neurodevelopmental disorder characterized by intellectual disability, speech delay, mild microcephaly, midbrain-hindbrain malformations, and variable dysmorphic features.
None
The disease is caused by variants affecting the gene represented in this entry.
Phosphorylation 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.
KIAA0651, LFP40, ARHGEF2, Rho guanine nucleotide exchange factor 2, Guanine nucleotide exchange factor H1, Microtubule-regulated Rho-GEF, Proliferating cell nucleolar antigen p40, GEF-H1
Proteins
Oncology
111543Da
We found 1 product in 1 category