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Rho guanine nucleotide exchange factor 2; guanine nucleotide exchange factor H1; GEF-H1; microtubule-regulated Rho-GEF; proliferating cell nucleolar antigen p40 (ARHGEF2, KIAA0651, LFP40)

Function: - activates Rho-GTPases by promoting the exchange of GDP for GTP - may be involved in - epithelial barrier permeability - cell motility & polarization - dendritic spine morphology - antigen presentation - leukemic cell differentiation - cell cycle regulation - cancer - binds Rac-GTPases, but does not seem to promote nucleotide exchange activity toward Rac-GTPases - may stimulate the cortical activity of Rac - inactive toward CDC42, TC10, or Ras-GTPases - forms an intracellular sensing system along with NOD1 for detection of microbial effectors during cell invasion by pathogens - required for RHOA & RIP2 dependent NF-kappaB signaling upon S flexneri cell invasion - role in sensing peptidoglycan (PGN)-derived muropeptides through NOD1 independent of its GEF activity - role in activation of NF-kappaB by Shigella effector proteins (IpgB2 & OspB) which requires its GEF activity & activation of RhoA - phosphorylation of Ser-886 by PAK1 induces binding to protein 14-3-3 zeta, promoting its relocation to microtubules & inhibition of its activity - phosphorylated by AURKA & 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 - interacts with 14-3-3 zeta when phosphorylated at Ser-886 - interacts with the kinases PAK4, AURKA & MAPK1 - interacts with RHOA & RAC1 - interacts with NOD1 - interacts (via the N-terminal Zn+2 finger) with CAPN6 (via domain II) (putative) Structure: - the DH (DBL-homology) domain interacts with & promotes loading of GTP on RhoA - the PH (pleckstrin-homology) domain is involved in - microtubule binding & targeting to tight junctions - contains 1 DH (DBL-homology) domain - contains 1 PH domain - contains 1 phorbol-ester/DAG-type Zn+2 finger Compartment: - cytoplasm - cell junction, tight junction - Golgi - cytoskeleton, spindle - cell projection, ruffle membrane - localizes to the tips of cortical microtubules of the mitotic spindle during cell division, & is released upon microtubule depolymerization - recruited into membrane ruffles induced by S flexneri at tight junctions of polarized epithelial cells Alternative splicing: named isoforms=3

General

phosphoprotein rho guanine nucleotide exchange factor zinc finger protein

Properties

SIZE: entity length = 986 aa MW = 112 kD COMPARTMENT: cytoplasm golgi MOTIF: Zinc finger NAME: Zinc finger SITE: 39-86 EFFECTOR-BOUND: Zn+2 Ser phosphorylation site {S143} Ser phosphorylation site {S149} Ser phosphorylation site {S151} Thr phosphorylation site {T152} Thr phosphorylation site {T153} Ser phosphorylation site {S163} Ser phosphorylation site {S172} Ser phosphorylation site {S174} Ser phosphorylation site {S177} Dbl homology domain {235-432} PH domain {472-571} coiled coil {587-611} Ser phosphorylation site {S645} Ser phosphorylation site {S648} Thr phosphorylation site {T679} Ser phosphorylation site {S691} Ser phosphorylation site {S696} Ser phosphorylation site {S782} coiled coil {798-867} Ser phosphorylation site {S886} Tyr phosphorylation site {Y894} Ser phosphorylation site {S896} Ser phosphorylation site {S932} Ser phosphorylation site {S940} Ser phosphorylation site {S941} Thr phosphorylation site {T945} Ser phosphorylation site {S947} Ser phosphorylation site {S953} Ser phosphorylation site {S956} Ser phosphorylation site {S960}

Database Correlations

OMIM 607560 UniProt Q92974 PFAM correlations Entrez Gene 9181 Kegg hsa:9181

References

  1. UniProt :accession Q92974
  2. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/ARHGEF2ID43150ch1q22.html
  3. Wikipedia; Note: ARHGEF2 entry http://en.wikipedia.org/wiki/ARHGEF2