Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Combined Automated Annotation using Multiple IEA Methods
Characterization of p190RhoGEF, a RhoA-specific guanine nucleotide exchange factor that interacts with microtubules.
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The p190RhoGEF DH/PH module activates RhoA but not Rac1 or Cdc42.
"Here we show that the isolated tandem Dbl homology/pleckstrin homology domain of p190RhoGEF activates RhoA in vitro, but not Rac1 or Cdc42, as determined by GDP release and protein binding assays."
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Endogenous p190RhoGEF is cytosolic, on microtubules and at the plasma membrane.
"Immunofluorescence studies show that endogenous p190RhoGEF localizes to distinct RhoA-containing regions at the plasma membrane, to the cytosol and along microtubules."
p190RhoGEF exchanges GTP for GDP on RHOA, activating it
Recruitment of p190RhoGEF to p-FAK
Rgnef (p190RhoGEF) knockout inhibits RhoA activity, focal adhesion establishment, and cell motility downstream of integrins.
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Rgnef knockout impairs integrin-stimulated RhoA activation and migration.
"loss of Rgnef significantly inhibited haptotaxis migration, wound closure motility, focal adhesion number, and RhoA GTPase activation after fibronectin-integrin stimulation."
A non-canonical role for Rgnef in promoting integrin-stimulated focal adhesion kinase activation.
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Rgnef scaffolds FAK at early adhesions independently of GEF activity.
"These results support a scaffolding role for Rgnef in FAK localization and activation at early adhesions in a PH-domain-dependent but GEF-activity-independent manner."
Direct regulation of p190RhoGEF by activated Rho and Rac GTPases.
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Active RhoA and Rac1 bind the p190RhoGEF PH domain and stimulate exchange on RhoA.
"Both activated RhoA and Rac1 can stimulate exchange of nucleotide on RhoA by localization of p190RhoGEF to its substrate, RhoA·GDP, in vitro."
UniProt entry Q8N1W1 (ARG28_HUMAN)
PTHR13944 PAINT annotations
Affinage mechanistic annotation for ARHGEF28 (human)