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Regulator of G protein signaling 3 (RGS3)
- Target
- RGS3
- Molecular classification
- Signal transduction protein, GTPase-activating protein (GAP), Member of RGS (Regulator of G-protein signaling) family, Protein containing C2, PDZ, and RGS domains
01
Overview
Regulator of G protein signaling 3 is a member of the RGS family, serving as a GTPase-activating protein that accelerates the deactivation of G alpha subunits, thus terminating their signaling activity. It interacts with heterotrimeric G proteins to inhibit signaling pathways downstream of G protein-coupled receptors (GPCRs) and plays roles in cell signaling, Wnt pathway modulation, epithelial-mesenchymal transition, and apoptosis. Multiple isoforms exist, some cytosolic and plasma membrane-associated, others nuclear. Mutations and altered expression in RGS3 are associated with cancer, cardiac, and neurological disease risk.
- Other names
- RGP3PDZ-RGS3C2PAFLJ20370regulator of G-protein signalling 3
02
Mechanism of action
Drugs/agents affecting RGS3 typically: Inhibit or enhance its expression (e.g., via miRNA); Affect G-protein signaling indirectly by modulating RGS3 activity
03
Biological functions
Signal transductionNegative regulation of G-protein-mediated signalingInhibition of inositol phosphate formation and MAP kinase activationInvolvement in Wnt signaling and epithelial-mesenchymal transitionInduction of apoptosis (specific isoforms)Control of cellular response to sensory stimuli
04
Disease associations
Cancer (especially in breast tumors and triple-negative breast cancer)Cardiovascular diseases (mutation is linked to abnormalities in cardiac structure and function)Non-syndromic X-linked intellectual disabilityHypertension-associated bladder dysfunction
05
Safety considerations
Therapeutic targeting is challenging due to broad tissue expression and essential role in normal GPCR signalingOff-target effects may result from disruption of essential signaling pathways
06
Interacting drugs
There are no approved drugs directly targeting RGS3 as of the 2024 literature, but gene expression modulation and indirect targeting (e.g., miRNA-126-3p inhibition in cancer) are reported
07
Biomarkers
RGS3 upregulation in p53-mutated breast tumors (predictor for response to docetaxel)rs144636307 mutation as a candidate marker for cardiac abnormalities
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