ID:ARHG2_HUMAN DESCRIPTION: RecName: Full=Rho guanine nucleotide exchange factor 2; AltName: Full=Guanine nucleotide exchange factor H1; Short=GEF-H1; AltName: Full=Microtubule-regulated Rho-GEF; AltName: Full=Proliferating cell nucleolar antigen p40; 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, 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. SUBUNIT: Interacts with 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). SUBCELLULAR LOCATION: Cytoplasm. Cell junction, tight junction. Golgi apparatus. Cytoplasm, cytoskeleton, spindle. Cell projection, ruffle membrane. 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. DOMAIN: The DH (DBL-homology) domain interacts with and promotes loading of GTP on RhoA. DOMAIN: The PH (pleckstrin-homology) domain is involved in microtubule binding and targeting to tight junctions. PTM: Phosphorylation of Ser-886 by PAK1 induces binding to protein 14-3-3 zeta, 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. SIMILARITY: Contains 1 DH (DBL-homology) domain. SIMILARITY: Contains 1 PH domain. SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. SEQUENCE CAUTION: Sequence=AAC97383.1; Type=Miscellaneous discrepancy; Note=Sequence differs at a large extent from the sequence shown in the paper; Sequence=AAH20567.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=BAA31626.3; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAA33634.1; Type=Frameshift; Positions=887, 984; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/ARHGEF2ID43150ch1q22.html"; WEB RESOURCE: Name=Wikipedia; Note=ARHGEF2 entry; URL="http://en.wikipedia.org/wiki/ARHGEF2";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q92974
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000132 establishment of mitotic spindle orientation GO:0000902 cell morphogenesis GO:0002376 immune system process GO:0006886 intracellular protein transport GO:0007015 actin filament organization GO:0007026 negative regulation of microtubule depolymerization GO:0007049 cell cycle GO:0007186 G-protein coupled receptor signaling pathway GO:0007275 multicellular organism development GO:0007399 nervous system development GO:0030154 cell differentiation GO:0032755 positive regulation of interleukin-6 production GO:0032760 positive regulation of tumor necrosis factor production 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:0045666 positive regulation of neuron differentiation GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation GO:0050768 negative regulation of neurogenesis GO:0051056 regulation of small GTPase mediated signal transduction GO:0051092 positive regulation of NF-kappaB transcription factor activity GO:0051301 cell division GO:0055059 asymmetric neuroblast division 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:0071802 negative regulation of podosome assembly 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 GO:2001224 positive regulation of neuron migration
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
