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

GRK6 (P43250) - Overview - Molecular Target Synopsis

Protein


GRK6, G protein-coupled receptor kinase 6
Enzyme Classification 2.7.11.16
UniProt P43250

Also Known as GRK6_HUMAN, GRK6, GPRK6

Specifically phosphorylates the activated forms of G protein-coupled receptors. Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their desensitization. Seems to be involved in the desensitization of D2-like dopamine receptors in striatum and chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis (By similarity). Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor: LRP6 during Wnt signaling (in vitro).

3NYN
CRYSTAL STRUCTURE OF G PROTEIN-COUPLED RECEPTOR KINASE 6 IN COMPLEX WITH SANGIVAMYCIN
RCSB/PDB
Inspect Structure
See all 3D Structures for GRK6

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: GRK6 is active in the following subcellular-locations: membrane.
GO terms: GRK6 is active in the following subcellular-locations: membrane, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project GRK6 has gain in 2 cell-lines, loss in 2 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HL_60, K_562, MOLT_4

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H929, HEL, Jurkat, Clone E6-1

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: SK-N-SH, K562, A549

(see details)

RNA Interference


GRK6 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: SUM44, SKGT4. (see details)

3D Structures


For GRK6 there are:
3 structures (6 chains) solved
3 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

GRK6 is solved in complex with the approved drug(s):

AMP/ADENOSINE PHOSPHATE (3NYO_A, 3NYO_B).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


GRK6 has been screened with 728 compounds (1269 bioactivities), 3 compounds have bioactivities that show binding affinity of <= 500nM (3 bioactivities). (see details)