Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

GRK5 (P34947) - Overview - Molecular Target Synopsis

Protein


GRK5, G protein-coupled receptor kinase 5
Enzyme Classification 2.7.11.16
UniProt P34947

Also Known as GRK5_HUMAN, GRK5, GPRK5

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). Interacts with ST13 (via the C-terminus 303-319 AA). Interacts with TP53/p53. Interacts with HTR4 (via C-terminus 330-346 AA); this interaction is promoted by 5-HT (serotonin). Interacts with HDAC5.

4TND
CRYSTAL STRUCTURE OF G PROTEIN-COUPLED RECEPTOR KINASE 5 IN COMPLEX WITH AMP-PNP
RCSB/PDB
Inspect Structure
See all 3D Structures for GRK5

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
590ENSG00000198873ENST00000392870ENSP00000376609P34947-1
485ENSG00000198873ENST00000369108ENSP00000358104

Sub-cellular localization


UniProt: GRK5 is active in the following subcellular-locations: cell membrane, cytoplasm, nucleus.
GO terms: GRK5 is active in the following subcellular-locations: cytoplasm, cytosol, nuclear membrane, nuclear speck, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project GRK5 has gain in 1 cell-lines, loss in 0 cell-lines and no signal in 1003 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SK_MEL_28, HS578T, M14

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: Hs 675.T, A-673, SK-N-DZ

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, AG445, HSMM

(see details)

RNA Interference


GRK5 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: MDAMB436, MHM. (see details)

3D Structures


For GRK5 there are:
2 structures (2 chains) solved
2 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


GRK5 has been screened with 324 compounds (494 bioactivities), 11 compounds have bioactivities that show binding affinity of <= 500nM (11 bioactivities). (see details)