Tchem GRK5 G protein-coupled receptor kinase 5

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / G Protein-coupled Receptor Kinase 5

DTO Classes

Protein / Kinase / Protein Kinase / Agc Group / Grk Family / Grk Subfamily / G Protein-coupled Receptor Kinase 5

Protein Summary

Description

Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein-coupled receptors (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their down-regulation. Phosphorylates a variety of GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid receptors. In addition to GPCRs, also phosphorylates various substrates: Hsc70-interacting protein/ST13, TP53/p53, HDAC5, and arrestin-1/ARRB1. Phosphorylation of ARRB1 by GRK5 inhibits G-protein independent MAPK1/MAPK3 signaling downstream of 5HT4-receptors. Phosphorylation of HDAC5, a repressor of myocyte enhancer factor 2 (MEF2) leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription. Phosphorylation of TP53/p53, a crucial tumor suppressor, inhibits TP53/p53-mediated apoptosis. Phosphorylation of ST13 regulates internalization of the chemokine receptor. Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor, LRP6 during Wnt signaling (in vitro). This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating their deactivation. It has also been shown to play a role in regulating the motility of polymorphonuclear leukocytes (PMNs). [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P34947
• D3DRD0
• Q5T059

Gene Name

• GRK5

Ensembl ID

• ENST00000392870
• ENSP00000376609
• ENSG00000198873

Symbol

• GPRK5
• GPRK5
• FP2025

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.98
disease perturbation	0.95
protein domain	0.92
transcription factor binding site profile	0.86
chemical bioactivity profile	0.71

Related Tools

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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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: 106.5   (req: < 5)

Gene RIFs: 60   (req: <= 3)

Antibodies: 473   (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: 106.5   (req: >= 5)

Gene RIFs: 60   (req: > 3)

Antibodies: 473   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 17

Tchem

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

Active Ligand: 1

Tclin

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

Active Drug: 0

Active Ligands (1)

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1 – 1 of 1

CHEMBL3093151

GRK5Tchem Kinase

IC50 : 7.23000002

GWAS Traits (9)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 9

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
platelet aggregation	GO_0070527	1	1	1		97.1
venous thromboembolism	EFO_0004286	3	1	1	1.1	91.8
mean platelet volume	EFO_0004584	3	1	3		83.3
lymphocyte count	EFO_0004587	2	1	2		68.2
type II diabetes mellitus	EFO_0001360	1	1	0	1.1	43.5

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
platelet aggregation	GO_0070527	1		97.1
venous thromboembolism	EFO_0004286	1	1.1	91.8
mean platelet volume	EFO_0004584	3		83.3
lymphocyte count	EFO_0004587	2		68.2
type II diabetes mellitus	EFO_0001360	0	1.1	43.5

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Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	G protein-coupled receptor kinase 5	VGNC:4700	466217
Macaque	G protein-coupled receptor kinase 5		100427251
Mouse	G protein-coupled receptor kinase 5	MGI:109161	14773
Rat	G protein-coupled receptor kinase 5	RGD:61985	59075
Dog	G protein-coupled receptor kinase 5	VGNC:41505	486915

Species	Name	OMA	EggNOG	Inparanoid
Chimp	G protein-coupled receptor kinase 5
Macaque	G protein-coupled receptor kinase 5
Mouse	G protein-coupled receptor kinase 5
Rat	G protein-coupled receptor kinase 5
Dog	G protein-coupled receptor kinase 5

Protein Structure (2 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-P34947-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 2 of 2

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (21)

Reactome (5)

KEGG (3)

PathwayCommons (10)

WikiPathways (3)

G alpha (q) signalling events (R-HSA-416476)

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Find Similar Targets

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	G alpha (q) signalling events	219 targets	R-HSA-416476
Reactome	G alpha (s) signalling events	577 targets	R-HSA-418555
Reactome	GPCR downstream signalling	1152 targets	R-HSA-388396
Reactome	Signal Transduction	2704 targets	R-HSA-162582
Reactome	Signaling by GPCR	1212 targets	R-HSA-372790

Name	Explore in Pharos	Explore in Source
G alpha (q) signalling events	219 targets	R-HSA-416476
G alpha (s) signalling events	577 targets	R-HSA-418555
GPCR downstream signalling	1152 targets	R-HSA-388396
Signal Transduction	2704 targets	R-HSA-162582
Signaling by GPCR	1212 targets	R-HSA-372790

Gene Ontology Terms (22)

Functions (6)

Components (5)

Processes (11)

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10

1 – 6 of 6

GO Term	Evidence	Assigned by
protein serine/threonine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
beta-adrenergic receptor kinase activity	Inferred from Mutant Phenotype (IMP)	CACAO
phospholipid binding	Traceable Author Statement (TAS)	ProtInc
protein kinase C binding	Traceable Author Statement (TAS)	ProtInc
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
G protein-coupled receptor kinase activity	Inferred from Electronic Annotation (IEA)	UniProtKB-EC

Protein-Protein Interactions (223)

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1 – 10 of 223

• See Interactions on String-DB

GRK6

Tchem

Family: Kinase

Novelty: 0.02740874

p_int: 1

Score: 0.939

Data Source: BioPlex,STRINGDB

ARRB1

Tbio

Novelty: 0.00262758

Score: 0.989

Data Source: STRINGDB

AGTR1

Tclin

Family: GPCR

Novelty: 0.00033439

Score: 0.979

Data Source: STRINGDB

ADRB2

Tclin

Family: GPCR

Novelty: 0.00041821

Score: 0.975

Data Source: Reactome,STRINGDB

ARRB2

Tbio

Novelty: 0.00148149

Score: 0.968

Data Source: STRINGDB

SNCA

Tchem

Novelty: 0.00012042

Score: 0.964

Data Source: STRINGDB

TRHR

Tclin

Family: GPCR

Novelty: 0.01143992

Score: 0.961

Data Source: STRINGDB

NTSR1

Tchem

Family: GPCR

Novelty: 0.00067612

Score: 0.957

Data Source: STRINGDB

LRP6

Tbio

Novelty: 0.00305615

Score: 0.951

Data Source: STRINGDB

GNRHR

Tclin

Family: GPCR

Novelty: 0.00203671

Score: 0.949

Data Source: STRINGDB

Publication Statistics

PubMed Score  106.50

PubMed score by year

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PubTator Score  123.63

PubTator score by year

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Patents

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Amino Acid Sequence

Residue Counts

Protein Sequence

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Ortholog Sequence Conservation

WebLogo Color Code

PolarG S T Y C

NeutralQ N

BasicK R H

AcidicD E

HydrophobicA V L I P W F M

Compare across kinases on ProKinO

Structural Annotations

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UniProt Keyword Find Similar Targets

3D-structure
Apoptosis
ATP-binding
Cell membrane
Complete proteome
Cytoplasm
Kinase
Lipid-binding
Membrane
Nucleotide-binding

GWAS Trait Find Similar Targets

lymphocyte count
lymphocyte percentage of leukocytes
mean platelet volume
monocyte count
neutrophil percentage of leukocytes
platelet aggregation
platelet count
type II diabetes mellitus
venous thromboembolism

MGI Phenotype Find Similar Targets

behavior/neurological phenotype
cardiovascular system phenotype
digestive/alimentary phenotype
endocrine/exocrine gland phenotype
homeostasis/metabolism phenotype
integument phenotype
muscle phenotype
nervous system phenotype
respiratory system phenotype