Tchem GRK5 G protein-coupled receptor kinase 5

Protein Summary

Description

Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein-coupled receptors (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their down-regulation. Phosphorylates a variety of GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid receptors. In addition to GPCRs, also phosphorylates various substrates: Hsc70-interacting protein/ST13, TP53/p53, HDAC5, and arrestin-1/ARRB1. Phosphorylation of ARRB1 by GRK5 inhibits G-protein independent MAPK1/MAPK3 signaling downstream of 5HT4-receptors. Phosphorylation of HDAC5, a repressor of myocyte enhancer factor 2 (MEF2) leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription. Phosphorylation of TP53/p53, a crucial tumor suppressor, inhibits TP53/p53-mediated apoptosis. Phosphorylation of ST13 regulates internalization of the chemokine receptor. Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor, LRP6 during Wnt signaling (in vitro). This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating their deactivation. It has also been shown to play a role in regulating the motility of polymorphonuclear leukocytes (PMNs). [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P34947
• D3DRD0
• Q5T059

Gene Name

• GRK5

Ensembl ID

• ENST00000392870
• ENSP00000376609
• ENSG00000198873

Symbol

• GPRK5
• GPRK5
• FP2025

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.98
disease perturbation	0.95
protein domain	0.92
transcription factor binding site profile	0.86
chemical bioactivity profile	0.71

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / G Protein-coupled Receptor Kinase 5

DTO Classes

Protein / Kinase / Protein Kinase / Agc Group / Grk Family / Grk Subfamily / G Protein-coupled Receptor Kinase 5

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 119.07   (req: < 5)

Gene RIFs: 75   (req: <= 3)

Antibodies: 473   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 119.07   (req: >= 5)

Gene RIFs: 75   (req: > 3)

Antibodies: 473   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 17

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 11

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0