G protein-coupled receptor kinase 6 | GRK4 subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

Top ▲

G protein-coupled receptor kinase 6

target has curated data in GtoImmuPdb

Target id: 1470

Nomenclature: G protein-coupled receptor kinase 6

Abbreviated Name: GRK6

Family: GRK4 subfamily

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 560 5q35 GRK6 G protein-coupled receptor kinase 6
Mouse - 576 13 B1-3 Grk6 G protein-coupled receptor kinase 6
Rat - 576 17p14 Grk6 G protein-coupled receptor kinase 6
Previous and Unofficial Names
GPRK6
Database Links
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of G protein coupled receptor kinase 6 bound to AMPPNP
PDB Id:  2ACX
Ligand:  AMP-PNP
Resolution:  2.6Å
Species:  Human
References:  3
Enzyme Reaction
EC Number: 2.7.11.16

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
balanol Hs Inhibition 6.3 pIC50 5
pIC50 6.3 (IC50 4.9x10-7 M) [5]
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx


Reference: 1-2

Key to terms and symbols Click column headers to sort
Target used in screen: GRK6/GRK6
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 7.4 16.0 0.5
K-252a Hs Inhibitor Inhibition 23.4 36.0 5.0
Gö 6976 Hs Inhibitor Inhibition 44.4 90.0 81.0
SU11652 Hs Inhibitor Inhibition 46.3 68.0 17.0
Syk inhibitor Hs Inhibitor Inhibition 47.2 96.0 89.0
JAK inhibitor I Hs Inhibitor Inhibition 48.2 59.0 68.0
indirubin derivative E804 Hs Inhibitor Inhibition 53.1 68.0 72.0
SB 218078 Hs Inhibitor Inhibition 55.6 104.0 101.0
PDK1/Akt/Flt dual pathway inhibitor Hs Inhibitor Inhibition 58.0 104.0 91.0
midostaurin Hs Inhibitor Inhibition 60.8 79.0 70.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
GRK6 expression and activity is downregulated in lymphocytes from RA patients [4]

References

Show »

1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1039-45. [PMID:22037377]

2. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem. J., 451 (2): 313-28. [PMID:23398362]

3. Lodowski DT, Tesmer VM, Benovic JL, Tesmer JJ. (2006) The structure of G protein-coupled receptor kinase (GRK)-6 defines a second lineage of GRKs. J. Biol. Chem., 281 (24): 16785-93. [PMID:16613860]

4. Lombardi MS, Kavelaars A, Schedlowski M, Bijlsma JW, Okihara KL, Van de Pol M, Ochsmann S, Pawlak C, Schmidt RE, Heijnen CJ. (1999) Decreased expression and activity of G-protein-coupled receptor kinases in peripheral blood mononuclear cells of patients with rheumatoid arthritis. FASEB J., 13 (6): 715-25. [PMID:10094932]

5. Tesmer JJ, Tesmer VM, Lodowski DT, Steinhagen H, Huber J. (2010) Structure of human G protein-coupled receptor kinase 2 in complex with the kinase inhibitor balanol. J. Med. Chem., 53 (4): 1867-70. [PMID:20128603]

How to cite this page

GRK4 subfamily: G protein-coupled receptor kinase 6. Last modified on 07/12/2016. Accessed on 08/12/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1470.