Ras-specific guanine nucleotide-releasing factor 2 (Ras-GRF2, guanine nucleotide-releasing factor 2, Ras guanine nucleotide exchange factor 2, RASGRF2, GRF2)

Function: - Ca⁺²-regulated nucleotide exchange factor activating both Ras & RAC1 through the exchange of bound GDP for GTP - preferentially activates HRAS in vivo compared to RRAS based on their different types of prenylation - role in synaptic plasticity by contributing to the induction of long term potentiation - homooligomer & heterooligomer with RASGRF1 - interacts with Ras & RAC1 - interacts (Ca⁺²-dependent) with calmodulin (putative) - interacts with CDK5R1 & EPB49 - interacts with the AMPA receptor through GRIA1 (putative) - interacts with microtubules (putative) - phosphorylated by CDK5, down-regulates RASGRF2-mediated RAC1 activation - ubiquitinated upon interaction with Ras - ubiquitination leads to degradation through the 26S proteasome (putative) Structure: - Ras-GEF domain & the N-terminal Ras-GEF domain form a Ras-binding site & mediate Ras activation (putative) - IQ domain mediates the Ca⁺²-dependent interaction with calmodulin but is dispensable for the Ras-GEF activity - DH (DBL-homology) domain mediates interaction with RASGRF1 & EPB49 & is required for RAC1 activation - contains 1 DH (DBL-homology) domain - contains 1 IQ domain - contains 1 N-terminal Ras-GEF domain - contains 2 PH domains - contains 1 Ras-GEF domain Compartment: - cytoplasm, cell membrane, endoplasmic reticulum - translocates to membranes when activated - found both at cell periphery & along the axon of neurons Expression: - widely expressed - expressed in brain > heart, lung, pancreas & kidney - detected in placenta - expressed in brain & lung (at protein level)

General

guanine nucleotide exchange factor (GDP/GTP dissociation stimulator, guanine nucleotide-releasing factor/protein, GNEF, GNDS, GDS) phosphoprotein

Properties

SIZE: entity length = 1237 aa MW = 141 kD COMPARTMENT: cytoplasm endoplasmic reticulum MOTIF: PH domain {22-133} coiled coil {155-193} IQ motif {205-234} Dbl homology domain {243-429} PH domain {470-588} guanine nucleotide exchange domain NAME: guanine nucleotide exchange domain SITE: 635-756 MOTIF: Ser phosphorylation site {S737} Regulates proteasomal degradation {744-752} guanine nucleotide exchange domain NAME: guanine nucleotide exchange domain SITE: 1002-1234 MOTIF: Responsible of the affinity for farnesylated versus geranylgeranylated Ras {1099-1128}

Database Correlations

OMIM 606614 UniProt O14827 PFAM correlations

References

UniProt :accession O14827