Tchem GRK2 Beta-adrenergic receptor kinase 1

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Beta-adrenergic Receptor Kinase 1

Protein Summary

Description

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 (By similarity). This gene encodes a member of the G protein-coupled receptor kinase family of proteins. The encoded protein phosphorylates the beta-adrenergic receptor as well as a wide range of other substrates including non-GPCR cell surface receptors, and cytoskeletal, mitochondrial, and transcription factor proteins. Data from rodent models supports a role for this gene in embryonic development, heart function and metabolism. Elevated expression of this gene has been observed in human patients with heart failure and Alzheimer's disease. [provided by RefSeq, Sep 2017]

Uniprot Accession IDs

• P25098
• B0ZBE1
• Q13837
• Q6GTT3
• Beta-ARK-1

Gene Name

• GRK2

Ensembl ID

• ENST00000308595
• ENSP00000312262
• ENSG00000173020

Symbol

• ADRBK1
• BARK
• BARK1
• BARK1
• ADRBK1
• BETA-ARK1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	0
biological term	0
cell line	0
cell type or tissue	0
cellular component	0

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 463.81   (req: < 5)

Gene RIFs: 139   (req: <= 3)

Antibodies: 626   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 463.81   (req: >= 5)

Gene RIFs: 139   (req: > 3)

Antibodies: 626   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 20

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 42

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Active Ligands (42)

Explore Active Ligands

1 – 10 of 42

CHEMBL60254

GRK2Tchem Kinase

IC50: 7.38000011

CHEMBL3732018

GRK2Tchem Kinase

Ki: 8

CHEMBL3728772

GRK2Tchem Kinase

Ki: 8

CHEMBL3729453

GRK2Tchem Kinase

Ki: 8

CHEMBL3093151

GRK2Tchem Kinase

IC50: 6.34000015

CHEMBL3718495

GRK2Tchem Kinase

IC50: 8.11

CHEMBL3717691

GRK2Tchem Kinase

IC50: 8.03

CHEMBL3715563

GRK2Tchem Kinase

IC50: 7.7

CHEMBL3716599

GRK2Tchem Kinase

IC50: 7.92

CHEMBL3716786

GRK2Tchem Kinase

IC50: 8

Protein Data Bank (16)

1 – 5 of 16

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (48)

Reactome (21)

KEGG (6)

PathwayCommons (18)

WikiPathways (3)

Activation of SMO (R-HSA-5635838)

Click on a row in the table to change the structure displayed.

Items per page:

5

1 – 5 of 21

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activation of SMO	18 targets	R-HSA-5635838
Reactome	Ca-dependent events	36 targets	R-HSA-111996
Reactome	CaM pathway	34 targets	R-HSA-111997
Reactome	Calmodulin induced events	34 targets	R-HSA-111933
Reactome	Cargo recognition for clathrin-mediated endocytosis	105 targets	R-HSA-8856825

Name	Explore in Pharos	Explore in Source
Activation of SMO	18 targets	R-HSA-5635838
Ca-dependent events	36 targets	R-HSA-111996
CaM pathway	34 targets	R-HSA-111997
Calmodulin induced events	34 targets	R-HSA-111933
Cargo recognition for clathrin-mediated endocytosis	105 targets	R-HSA-8856825

Gene Ontology Terms (25)

Functions (6)

Components (5)

Processes (14)

Items per page:

10

1 – 6 of 6

GO Term	Evidence	Assigned by
Edg-2 lysophosphatidic acid receptor binding	Inferred from Direct Assay (IDA)	UniProtKB
alpha-2A adrenergic receptor binding	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
G protein-coupled receptor kinase activity	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
protein kinase activity	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
beta-adrenergic receptor kinase activity	Traceable Author Statement (TAS)	Reactome
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (659)

Explore Interacting Targets

1 – 10 of 659

• See Interactions on String-DB

GRK3

Tchem

Family: Kinase

Novelty: 0.0229797

p_int: 0.999999999

p_wrong: 1e-9

Score: 0.967

Data Source: BioPlex,STRINGDB

PPP1R16B

Tbio

Family: Enzyme

Novelty: 0.09294561

p_int: 0.999991127

p_ni: 0.000008867

p_wrong: 6e-9

Score: 0.361

Data Source: BioPlex,STRINGDB

TBC1D14

Tbio

Novelty: 0.30090271

p_int: 0.999595419

p_ni: 0.000404581

Score: 0.239

Data Source: BioPlex,STRINGDB

GNG2

Tbio

Novelty: 0.08273543

Score: 0.995

Data Source: STRINGDB

GNB1

Tbio

Novelty: 0.04716243

Score: 0.994

Data Source: STRINGDB

SMO

Tclin

Family: GPCR

Novelty: 0.04792829

Score: 0.99

Data Source: Reactome,STRINGDB

ARRB1

Tbio

Novelty: 0.00194842

Score: 0.987

Data Source: STRINGDB

ARRB2

Tbio

Novelty: 0.00180049

Score: 0.982

Data Source: STRINGDB

ADRB2

Tclin

Family: GPCR

Novelty: 0.00038334

Score: 0.981

Data Source: Reactome,STRINGDB

AGTR1

Tclin

Family: GPCR

Novelty: 0.00032594

Score: 0.98

Data Source: STRINGDB

Publication Statistics

PubMed Score  463.81

PubMed score by year

Reset Zoom

PubTator Score  470.2

PubTator score by year

Reset Zoom

Patents

Reset Zoom

Amino Acid Sequence

Residue Counts

Sequence

MADLEAVLADVSYLMAMEKSKATPAARASKKILLPEPSIRSVMQKYLEDRGEVTFEKIFSQKLGYLLFRD

1-70

FCLNHLEEARPLVEFYEEIKKYEKLETEEERVARSREIFDSYIMKELLACSHPFSKSATEHVQGHLGKKQ

70-140

VPPDLFQPYIEEICQNLRGDVFQKFIESDKFTRFCQWKNVELNIHLTMNDFSVHRIIGRGGFGEVYGCRK

140-210

ADTGKMYAMKCLDKKRIKMKQGETLALNERIMLSLVSTGDCPFIVCMSYAFHTPDKLSFILDLMNGGDLH

210-280

YHLSQHGVFSEADMRFYAAEIILGLEHMHNRFVVYRDLKPANILLDEHGHVRISDLGLACDFSKKKPHAS

280-350

VGTHGYMAPEVLQKGVAYDSSADWFSLGCMLFKLLRGHSPFRQHKTKDKHEIDRMTLTMAVELPDSFSPE

350-420

LRSLLEGLLQRDVNRRLGCLGRGAQEVKESPFFRSLDWQMVFLQKYPPPLIPPRGEVNAADAFDIGSFDE

420-490

EDTKGIKLLDSDQELYRNFPLTISERWQQEVAETVFDTINAETDRLEARKKAKNKQLGHEEDYALGKDCI

490-560

MHGYMSKMGNPFLTQWQRRYFYLFPNRLEWRGEGEAPQSLLTMEEIQSVEETQIKERKCLLLKIRGGKQF

560-630

ILQCDSDPELVQWKKELRDAYREAQQLVQRVPKMKNKPRSPVVELSKVPLVQRGSANGL

630-689

MADLEAVLADVSYLMAMEKSKATPAARASKKILLPEPSIRSVMQKYLEDRGEVTFEKIFSQKLGYLLFRDFCLNHLEEARPLVEFYEEIKKYEKLETEEERVARSREIFDSYIMKELLACSHPFSKSATEHVQGHLGKKQVPPDLFQPYIEEICQNLRGDVFQKFIESDKFTRFCQWKNVELNIHLTMNDFSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLDKKRIKMKQGETLALNERIMLSLVSTGDCPFIVCMSYAFHTPDKLSFILDLMNGGDLHYHLSQHGVFSEADMRFYAAEIILGLEHMHNRFVVYRDLKPANILLDEHGHVRISDLGLACDFSKKKPHASVGTHGYMAPEVLQKGVAYDSSADWFSLGCMLFKLLRGHSPFRQHKTKDKHEIDRMTLTMAVELPDSFSPELRSLLEGLLQRDVNRRLGCLGRGAQEVKESPFFRSLDWQMVFLQKYPPPLIPPRGEVNAADAFDIGSFDEEDTKGIKLLDSDQELYRNFPLTISERWQQEVAETVFDTINAETDRLEARKKAKNKQLGHEEDYALGKDCIMHGYMSKMGNPFLTQWQRRYFYLFPNRLEWRGEGEAPQSLLTMEEIQSVEETQIKERKCLLLKIRGGKQFILQCDSDPELVQWKKELRDAYREAQQLVQRVPKMKNKPRSPVVELSKVPLVQRGSANGL

Find similar targets by:

Uniprot Keyword

3D-structure
ATP-binding
Cell membrane
Complete proteome
Cytoplasm
Kinase
Membrane
Nucleotide-binding
Phosphoprotein
Polymorphism