RAS guanyl-releasing protein 2 (Ca+2 & DAG-regulated guanine nucleotide exchange factor I, CalDAG-GEFI, F25B3.3 kinase-like protein, Cdc25-like protein, HCDC25L, RASGRP2, CDC25L, MCG7)
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Function
- Ca+2- & DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP
- may also activate other GTPases including RRAS, RRAS2, NRAS, KRAS but not HRAS
- functions in aggregation of platelets & adhesion of T-lymphocytes & neutrophils probably through inside-out integrin activation
- may function in the muscarinic acetylcholine receptor M1/ CHRM1 signaling pathway
- forms a signaling complex with RAP1 & BRAF
- interacts with RAP1
- interacts with F-actin
- isoform 1 & isoform 2 are differently regulated by Ca+2 & DAG
- isoform 2 is palmitoylated & myristoylated
Structure
- N-terminal Ras-GEF domain mediates association with F-actin belongs to the RASGRP family
- contains 2 EF-hand domains
- contains 1 N-terminal Ras-GEF domain
- contains 1 phorbol-ester/DAG-type Zn+2 finger
- contains 1 Ras-GEF domain
Compartment
- cytoplasm
- peripheral membrane
- cell junction, synapse, synaptosome
- found both in the cytosol & associated with membranes
- isoform 2 mainly localizes to the cell membrane
- enriched at juxtamenbrane areas & membrane ruffles through association with F-actin
localizes to the cell bodies & axons of striatal neurons (putative)
Alternative splicing
named isoforms=3
Expression
- detected in platelets, neutrophils & T lymphocytes (at protein level)
- expressed in brain, enriched in the striatum
- expressed in the hematopoietic system
- detected in heart, brain, lung, placenta, liver, skeletal muscle & kidney
- expressed in fetal brain, lung, liver & kidney
Pathology
- defects in RASGRP2 are the cause of leukocyte adhesion deficiency-3