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

GRK2 (P25098) - Overview - Molecular Target Synopsis

Protein


GRK2, Beta-adrenergic receptor kinase 1
Enzyme Classification 2.7.11.15
UniProt P25098

Also Known as ARBK1_HUMAN, GRK2, ADRBK1, BARK, BARK1

Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them. Key regulator of LPAR1 signaling. Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor. Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner (PubMed:19306925, PubMed:19715378). Positively regulates ciliary smoothened (SMO)-dependent Hedgehog (Hh) signaling pathway by faciltating the trafficking of SMO into the cilium and the stimulation of SMO activity. Interacts with GIT1 (By similarity). Interacts with, and phosphorylates chemokine-stimulated CCR5 (PubMed:10085131). Interacts with ARRB1 (PubMed:9501202). Interacts with LPAR1 and LPAR2 (PubMed:19306925). Interacts with RALA in response to LPAR1 activation (PubMed:19306925). ADRBK1 and RALA mutually inhibit each other's binding to LPAR1 (PubMed:19306925). Interacts with ADRB2 (PubMed:19715378).

6C2Y
HUMAN GRK2 IN COMPLEX WITH GBETAGAMMA SUBUNITS AND CCG257142
RCSB/PDB
Inspect Structure
See all 3D Structures for GRK2

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
689ENSG00000173020ENST00000308595ENSP00000312262P25098-1
408ENSG00000173020ENST00000526285ENSP00000434126

Sub-cellular localization


UniProt: GRK2 is active in the following subcellular-locations: cell membrane, cytoplasm.
GO terms: GRK2 is active in the following subcellular-locations: cilium, cytoplasm, cytosol, membrane, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project GRK2 has gain in 11 cell-lines, loss in 0 cell-lines and no signal in 994 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are:

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are:

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:

(see details)

RNA Interference


GRK2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: COV362, HCC70. (see details)

3D Structures


For GRK2 there are:
16 structures (16 chains) solved
14 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

GRK2 is solved in complex with the approved drug(s):

8PR/PAROXETINE (3V5W_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


GRK2 has been screened with 259 compounds (278 bioactivities), 73 compounds have bioactivities that show binding affinity of <= 500nM (74 bioactivities). (see details)