GRK2

Chr 11q13.2

G protein-coupled receptor kinase 2

Aliases:: BARK1
MANE:: ENST00000308595.10

OMIM: 109635 ↗NCBI: 156 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

GRK2 · P25098

v62025-08-01

Predicted Aligned Error matrix for GRK2 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

89.9/ 100

Confident

689 residues

Confidence breakdown

Very high(≥ 90)73%
Confident(70–90)18%
Low(50–70)6%
Very low(< 50)3%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Moderate Evidence (Amber)

Skeletal ciliopathies
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

Jeune syndrome
0.48
bone Paget disease
0.24
Jeune syndrome - GRK2-related
0.12
rheumatoid arthritis
0.11
neoplasm
0.10
hepatocellular carcinoma
0.09
response to xenobiotic stimulus
0.09
rheumatic disorder
0.09
pulmonary arterial hypertension
0.09
breast cancer
0.09

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

G protein-coupled receptor kinase 2

Specifically phosphorylates the activated forms of G protein-coupled receptors (PubMed:14976224, PubMed:16179383, PubMed:19306925, PubMed:19715378, PubMed:21799898, PubMed:23077507, PubMed:30284927, PubMed:39138140, PubMed:40384633). Such receptor phosphorylation initiates beta-arrestin-mediated receptor internalization, and signaling events leading to their desensitization (PubMed:14976224, PubMed:16179383, PubMed:19306925, PubMed:19715378, PubMed:21799898, PubMed:23077507, PubMed:30284927, PubMed:39138140, PubMed:40384633). Phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them (PubMed:19715378). Phosphorylates catecholamine-activated ADRB2 to regulate physiological cardiomyocyte contraction rate responses (By similarity). Also phosphorylates ligand-bound C3a and C5a anaphylatoxin receptors (C3AR1 and C5AR1, respectively), leading to receptor desensitization (PubMed:21799898, PubMed:23077507). Positively regulates ciliary smoothened (SMO) signaling pathway by mediating phosphorylation of SMO, facilitating SMO trafficking into the cilium and the stimulation of SMO activity (PubMed:39138140). Also positively regulates SMO signaling by mediating phosphorylation of GPR161, a key inhibitor SMO signaling, promoting ciliary export of GPR161 (PubMed:40384633). Key regulator of LPAR1 signaling (PubMed:19306925). Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor (PubMed:19306925). Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner (PubMed:19306925). Inhibits relaxation of airway smooth muscle in response to blue light (PubMed:30284927)