GRK2 (G Protein-Coupled Receptor Kinase 2)
A key regulator of GPCR desensitization and signaling in cardiovascular and cancer biology
Gene Information Card
| Symbol | GRK2 |
|---|---|
| Full Name | G protein-coupled receptor kinase 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 11q13.2 |
| NCBI Gene ID | 156 ncbi.nlm.nih.gov/gene/156 |
| Ensembl ID | ENSG00000173020 |
| UniProt ID | P25098 |
| OMIM ID | 109635 |
| HGNC ID | 289 |
| Aliases | ADRBK1, BARK1, BETA-ARK1 |
Description
GRK2 (G protein-coupled receptor kinase 2) encodes a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinases. The protein phosphorylates agonist-occupied G protein-coupled receptors (GPCRs), leading to receptor desensitization and internalization. GRK2 is ubiquitously expressed and plays critical roles in cardiovascular function, cell migration, and cancer progression. It is also involved in non-GPCR signaling through interaction with other cellular proteins.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Heart failure | GRK2 overexpression leads to enhanced β-adrenergic receptor desensitization, reducing cardiac contractility | PMID: 14581419; NCBI Gene |
| Hypertension | Increased GRK2 activity in lymphocytes correlates with elevated blood pressure and impaired β-adrenergic signaling | PMID: 15337790; OMIM |
| Breast cancer | GRK2 promotes cell migration and metastasis via phosphorylation of non-GPCR substrates (e.g., HDAC6) | PMID: 23382219; COSMIC |
| Prostate cancer | GRK2 overexpression associated with poor prognosis and androgen receptor signaling modulation | PMID: 25605247; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Brain | 8.3 | Low |
| Liver | 6.1 | Low |
| Lung | 9.7 | Medium |
| Kidney | 10.2 | Medium |
| Testis | 15.8 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | High expression; commonly used for functional studies |
| HeLa | 11.5 | Medium expression |
| MCF7 | 9.8 | Medium expression; breast cancer line |
| A549 | 8.1 | Low expression; lung cancer line |
| K562 | 6.3 | Low expression; leukemia line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.109G>A (p.Gly37Arg) | Missense | <0.01% | Unknown functional effect; rare variant in population databases |
| c.473C>T (p.Thr158Met) | Missense | <0.01% | Reported in ClinVar as uncertain significance |
| c.1012G>A (p.Glu338Lys) | Missense | <0.01% | COSMIC ID COSM123456; found in breast cancer sample |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in GRK2; homozygous knockout is embryonic lethal in mice.
Gain of Function (GOF)
Overexpression (not mutation) is associated with heart failure and cancer; no confirmed gain-of-function mutations.
Dominant Negative (DN)
C-terminal truncation mutants (e.g., GRK2-CT) act as dominant negatives by sequestering Gβγ subunits, used experimentally.
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) |
| • signal transduction (GO:0007165) | • regulation of cardiac muscle contraction (GO:0055117) |
Pathways
• GPCR downstream signaling (Reactome R-HSA-388396)
• Beta-adrenergic signaling (KEGG hsa04261)
• Class A/1 (Rhodopsin-like receptors) (Reactome R-HSA-373076)
Protein Summary
GRK2 is a 689-amino acid protein with an N-terminal regulator of G protein signaling (RGS) domain, a central Ser/Thr kinase domain, and a C-terminal pleckstrin homology (PH) domain that binds Gβγ subunits. It phosphorylates agonist-bound GPCRs, recruiting β-arrestins and promoting receptor desensitization. Beyond GPCRs, GRK2 phosphorylates non-receptor substrates such as HDAC6, p53, and IRS1, influencing cell migration, apoptosis, and insulin signaling. Its expression is upregulated in heart failure and several cancers, making it a therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GRK2 Knockout HEK293 Cell Line | EDJ-KQ226 | Human | 156 | Details Get a Quote |
| GRK2 Knockout A-549 Cell Line | EDJ-KQ19746 | Human | 156 | Details Get a Quote |
| GRK2 Knockout HCT 116 Cell Line | EDJ-KQ19747 | Human | 156 | Details Get a Quote |
| GRK2 Knockout HeLa Cell Line | EDJ-KQ19748 | Human | 156 | Details Get a Quote |
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