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G protein-coupled receptor kinase 6

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1470

Nomenclature: G protein-coupled receptor kinase 6

Abbreviated Name: GRK6

Family: GRK4 subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 576 5q35.3 GRK6 G protein-coupled receptor kinase 6
Mouse - 576 13 30.06 cM Grk6 G protein-coupled receptor kinase 6
Rat - 576 17p14 Grk6 G protein-coupled receptor kinase 6
Previous and Unofficial Names Click here for help
GPRK6
Database Links Click here for help
Alphafold P43250 (Hs), O70293 (Mm), P97711 (Rn)
BRENDA 2.7.11.16
ChEMBL Target CHEMBL6144 (Hs)
Ensembl Gene ENSG00000198055 (Hs), ENSMUSG00000074886 (Mm), ENSRNOG00000014615 (Rn)
Entrez Gene 2870 (Hs), 26385 (Mm), 59076 (Rn)
Human Protein Atlas ENSG00000198055 (Hs)
KEGG Enzyme 2.7.11.16
KEGG Gene hsa:2870 (Hs), mmu:26385 (Mm), rno:59076 (Rn)
OMIM 600869 (Hs)
Pharos P43250 (Hs)
RefSeq Nucleotide NM_001004105 (Hs), NM_001112711 (Mm), NM_001112712 (Rn)
RefSeq Protein NP_001004105 (Hs), NP_001106182 (Mm), NP_001033107 (Mm), NP_036068 (Mm), NP_001106183 (Rn)
UniProtKB P43250 (Hs), O70293 (Mm), P97711 (Rn)
Wikipedia GRK6 (Hs)
Selected 3D Structures Click here for help
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 Click here for help
EC Number: 2.7.11.16

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
balanol Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.3 pIC50 5
⤷ pIC50 6.3 (IC50 4.9x10-7 M) [5]
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
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 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.4 16.0 0.5
K-252a Small molecule or natural product Hs Inhibitor Inhibition 23.4 36.0 5.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 44.4 90.0 81.0
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 46.3 68.0 17.0
Syk inhibitor Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 47.2 96.0 89.0
JAK inhibitor I Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 48.2 59.0 68.0
indirubin derivative E804 Small molecule or natural product Hs Inhibitor Inhibition 53.1 68.0 72.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 55.6 104.0 101.0
PDK1/Akt/Flt dual pathway inhibitor Small molecule or natural product Hs Inhibitor Inhibition 58.0 104.0 91.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand 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

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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 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1470.