GRK2 G protein-coupled receptor kinase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GRK2provided by HGNC
Official Full Name: G protein-coupled receptor kinase 2provided by HGNC
Primary source: HGNC:HGNC:289
See related: Ensembl:ENSG00000173020 MIM:109635; AllianceGenome:HGNC:289
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: BARK1; ADRBK1; BETA-ARK1
Summary: 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]
Expression: Broad expression in bone marrow (RPKM 91.8), spleen (RPKM 61.9) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q13.2

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (67266473..67286556)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (67260429..67280532)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (67033944..67054027)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

GRK2-YAP signaling is implicated in pulmonary arterial hypertension development.
Title: GRK2-YAP signaling is implicated in pulmonary arterial hypertension development.
Exploring the potential biological function of GRK2 in colorectal cancer.
Title: Exploring the potential biological function of GRK2 in colorectal cancer.
G Protein-Coupled Receptor Kinase 2 Selectively Enhances beta-Arrestin Recruitment to the D2 Dopamine Receptor through Mechanisms That Are Independent of Receptor Phosphorylation.
Title: G Protein-Coupled Receptor Kinase 2 Selectively Enhances β-Arrestin Recruitment to the D(2) Dopamine Receptor through Mechanisms That Are Independent of Receptor Phosphorylation.
CXCL9, 10, 11/CXCR3 Axis Contributes to the Progress of Primary Sjogren's Syndrome by Activating GRK2 to Promote T Lymphocyte Migration.
Title: CXCL9, 10, 11/CXCR3 Axis Contributes to the Progress of Primary Sjogren's Syndrome by Activating GRK2 to Promote T Lymphocyte Migration.
Gender differences in GRK2 in cardiovascular diseases and its interactions with estrogen.
Title: Gender differences in GRK2 in cardiovascular diseases and its interactions with estrogen.
Targeted inhibition of the GRK2/HIF-1alpha pathway is an effective strategy to alleviate synovial hypoxia and inflammation.
Title: Targeted inhibition of the GRK2/HIF-1α pathway is an effective strategy to alleviate synovial hypoxia and inflammation.
GRK2 in cardiovascular disease and its potential as a therapeutic target.
Title: GRK2 in cardiovascular disease and its potential as a therapeutic target.
The tyrosine phosphorylation of GRK2 is responsible for activated D2R-mediated insulin resistance.
Title: The tyrosine phosphorylation of GRK2 is responsible for activated D(2)R-mediated insulin resistance.
GRK2 selectively attenuates the neutrophil NADPH-oxidase response triggered by beta-arrestin recruiting GPR84 agonists.
Title: GRK2 selectively attenuates the neutrophil NADPH-oxidase response triggered by β-arrestin recruiting GPR84 agonists.
Mdm2-Mediated Downmodulation of GRK2 Restricts Centrosome Separation for Proper Chromosome Congression.
Title: Mdm2-Mediated Downmodulation of GRK2 Restricts Centrosome Separation for Proper Chromosome Congression.

Submit: New GeneRIF Correction See all GeneRIFs (167)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of adrenergic, beta, receptor kinase 1 (ADRBK1) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1	PubMed
Knockdown of adrenergic, beta, receptor kinase 1 (ADRBK1) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

ADRBK1 (e-PCR)
- UniSTS:480056

MARC_15697-15698:1013523581:1 (e-PCR)
- UniSTS:267871

adrbk1sts1 (e-PCR)
- UniSTS:256645

WI-15244 (e-PCR)
- UniSTS:64509

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables Edg-2 lysophosphatidic acid receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables G protein-coupled receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables G protein-coupled receptor kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables G protein-coupled receptor kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables G protein-coupled receptor kinase activity	ISS Inferred from Sequence or Structural Similarity more info
enables alpha-2A adrenergic receptor binding	ISS Inferred from Sequence or Structural Similarity more info
enables beta-adrenergic receptor kinase activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein kinase activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in G protein-coupled acetylcholine receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info
involved_in cardiac muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in desensitization of G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in desensitization of G protein-coupled receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in desensitization of G protein-coupled receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in heart development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of relaxation of smooth muscle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of striated muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of the force of heart contraction by chemical signal	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptidyl-serine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of catecholamine secretion	ISS Inferred from Sequence or Structural Similarity more info
involved_in receptor internalization	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of the force of heart contraction	IBA Inferred from Biological aspect of Ancestor more info
involved_in symbiont entry into host cell	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in tachykinin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in viral genome replication	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cilium	TAS Traceable Author Statement more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic side of mitochondrial outer membrane	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in membrane	HDA more info	PubMed
located_in membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynapse	IEA Inferred from Electronic Annotation more info
located_in presynapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: beta-adrenergic receptor kinase 1

Names: adrenergic beta receptor kinase 1; beta-ARK-1

NP_001610.2

EC 2.7.11.15

XP_011543075.1

EC 2.7.11.15

XP_054223794.1

EC 2.7.11.15

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001619.5 → NP_001610.2 beta-adrenergic receptor kinase 1

See identical proteins and their annotated locations for NP_001610.2

Status: REVIEWED

Source sequence(s)

BC090863

Consensus CDS

CCDS8156.1

UniProtKB/Swiss-Prot

B0ZBE1, P25098, Q13837, Q6GTT3

UniProtKB/TrEMBL

A0A0S2Z392, A0A0S2Z3I6

Related

ENSP00000312262.5, ENST00000308595.10

Conserved Domains (3) summary

cd08747
Location:30 → 186

RGS_GRK2_GRK3; Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase 2 (GRK2) and G protein-coupled receptor kinase 3 (GRK3)

cd01240
Location:553 → 670

PH_GRK2_subgroup; G Protein-Coupled Receptor Kinase 2 subgroup pleckstrin homology (PH) domain

cd14223
Location:190 → 510

STKc_GRK2; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

67266473..67286556

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011544773.2 → XP_011543075.1 beta-adrenergic receptor kinase 1 isoform X1

See identical proteins and their annotated locations for XP_011543075.1

UniProtKB/TrEMBL

A0A0S2Z3I6

Conserved Domains (5) summary

cd08747
Location:8 → 156

RGS_GRK2_GRK3; Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase 2 (GRK2) and G protein-coupled receptor kinase 3 (GRK3)

cd01240
Location:523 → 640

PH_GRK2_subgroup; G Protein-Coupled Receptor Kinase 2 subgroup pleckstrin homology (PH) domain

cd14223
Location:160 → 480

STKc_GRK2; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2

pfam00069
Location:161 → 423

Pkinase; Protein kinase domain

pfam00169
Location:530 → 620

PH; PH domain