DEP domain-containing protein 2 (phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2, PtdIns(3,4,5)-dependent Rac exchanger 2, P-Rex2, DEPDC2, PREX2)
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Function
- RAC1 guanine nucleotide exchange factor (GEF)
- activates Rac proteins by exchanging bound GDP for free GTP
- synergistically activated by PIP3 & the beta gamma subunits of heterotrimeric G protein
- mediates activation of RAC1 in a PI3K-dependent manner
- role in Rac signaling
- acts downstream of both G protein-coupled receptors & phosphoinositide 3-kinase
- interacts with RAC1
Structure
- PH domain confers substrate specificity & recognition able to discriminate between RAC1, RHOA, CDC42
- DH domain alone was unable to confer substrate specificity & recognition
- contains 2 DEP domains
- contains 1 DH domain (DBL-homology domain)
- contains 2 PDZ domain (DHR domains)
- contains 1 PH domain
Alternative splicing
named isoforms=3
Expression
- isoform 1: highly expressed in skeletal muscle, heart, placenta, absent from peripheral blood leukocytes
- isoform 2 is expressed in skeletal muscle, kidney, small intestine, placenta
- isoform 3 is expressed in the heart