GRK3 (G Protein-Coupled Receptor Kinase 3)
A key regulator of GPCR desensitization and signaling in cardiovascular and neurological systems
Gene Information Card
| Symbol | GRK3 |
|---|---|
| Full Name | G Protein-Coupled Receptor Kinase 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 22q12.1 |
| NCBI Gene ID | 157 ncbi.nlm.nih.gov/gene/157 |
| Ensembl ID | ENSG00000100077 |
| UniProt ID | P35626 |
| OMIM ID | 109636 |
| HGNC ID | 4613 |
| Aliases | ADRBK2, BARK2, GPRK3 |
Description
GRK3 (G protein-coupled receptor kinase 3) encodes a member of the G protein-coupled receptor kinase (GRK) subfamily of the AGC (protein kinase A, G, C) protein kinase family. GRK3 specifically phosphorylates agonist-occupied G protein-coupled receptors (GPCRs), initiating homologous desensitization. It is highly expressed in brain, heart, and immune tissues, and plays critical roles in regulating neurotransmitter, hormone, and chemokine signaling. Dysregulation of GRK3 is implicated in cardiovascular diseases, psychiatric disorders, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Heart failure | GRK3 upregulation leads to enhanced desensitization of beta-adrenergic receptors, reducing cardiac contractility | PMID: 10880451 |
| Bipolar disorder | GRK3 polymorphisms associated with altered dopamine receptor desensitization | PMID: 12508121 |
| Schizophrenia | GRK3 expression changes linked to dopamine and glutamate receptor signaling | PMID: 16936799 |
| Hypertension | GRK3-mediated desensitization of angiotensin II receptors contributes to blood pressure dysregulation | PMID: 15374818 |
| Cancer (breast, prostate) | GRK3 overexpression promotes GPCR-driven tumor growth and metastasis | PMID: 23563491 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Heart (left ventricle) | 8.3 | Low |
| Lung | 6.1 | Low |
| Liver | 2.4 | Not detected |
| Kidney | 4.7 | Low |
| Spleen | 3.9 | Low |
| Testis | 15.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | High expression in embryonic kidney cells |
| SH-SY5Y | 14.3 | Neuroblastoma cell line, high expression |
| MCF7 | 7.8 | Breast cancer cell line, moderate expression |
| HepG2 | 3.2 | Hepatocellular carcinoma, low expression |
| Jurkat | 5.6 | T-cell leukemia, moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1012C>T (p.Arg338Trp) | Missense | <0.01% | Reduced kinase activity, altered GPCR desensitization |
| c.1456G>A (p.Glu486Lys) | Missense | <0.01% | Impaired receptor phosphorylation |
| c.1789_1791del (p.Lys597del) | In-frame deletion | <0.01% | Loss of C-terminal domain, reduced membrane localization |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., p.Arg338Trp) reduce catalytic activity, impairing GPCR desensitization.
Gain of Function (GOF)
Not well documented; overexpression in cancer may act as a functional gain.
Dominant Negative (DN)
C-terminal truncations (e.g., p.Lys597del) can interfere with wild-type GRK3 localization.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor kinase activity (GO:0004703) | • G protein-coupled receptor internalization (GO:0002031) |
| • beta-adrenergic receptor kinase activity (GO:0004704) | • protein serine/threonine kinase activity (GO:0004674) |
| • receptor phosphorylation (GO:0018105) | • desensitization of G protein-coupled receptor signaling (GO:0002029) |
Pathways
• GPCR downstream signaling (Reactome: R-HSA-388396)
• Beta-adrenergic receptor signaling (Reactome: R-HSA-418594)
• Class A/1 (Rhodopsin-like) receptors (Reactome: R-HSA-375276)
• G alpha (s) signaling events (Reactome: R-HSA-418555)
Protein Summary
GRK3 is a 688-amino acid serine/threonine kinase (UniProt P35626) that phosphorylates agonist-bound GPCRs, initiating arrestin-mediated desensitization and internalization. It contains an N-terminal RGS-like domain, a central kinase domain, and a C-terminal lipid-binding domain for membrane targeting. GRK3 is highly expressed in brain and heart, where it regulates neurotransmitter and adrenergic signaling. Alternative splicing produces multiple isoforms with distinct tissue distributions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GRK3 Knockout HEK293 Cell Line | EDJ-KQ901 | Human | 157 | Details Get a Quote |
| GRK3 Knockout A-549 Cell Line | EDJ-KQ19749 | Human | 157 | Details Get a Quote |
| GRK3 Knockout HCT 116 Cell Line | EDJ-KQ19750 | Human | 157 | Details Get a Quote |
| GRK3 Knockout HeLa Cell Line | EDJ-KQ52573 | Human | 157 | Details Get a Quote |
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