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