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GRK3 G protein-coupled receptor kinase 3 [ Homo sapiens (human) ]

Gene ID: 157, updated on 2-Nov-2024

Summary

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Official Symbol
GRK3provided by HGNC
Official Full Name
G protein-coupled receptor kinase 3provided by HGNC
Primary source
HGNC:HGNC:290
See related
Ensembl:ENSG00000100077 MIM:109636; AllianceGenome:HGNC:290
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
BARK2; ADRBK2
Summary
The beta-adrenergic receptor kinase specifically phosphorylates the agonist-occupied form of the beta-adrenergic and related G protein-coupled receptors. Overall, the beta adrenergic receptor kinase 2 has 85% amino acid similarity with beta adrenergic receptor kinase 1, with the protein kinase catalytic domain having 95% similarity. These data suggest the existence of a family of receptor kinases which may serve broadly to regulate receptor function. [provided by RefSeq, Jul 2008]
Expression
Broad expression in fat (RPKM 17.4), spleen (RPKM 8.7) and 22 other tissues See more
Orthologs
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Genomic context

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See GRK3 in Genome Data Viewer
Location:
22q12.1
Exon count:
24
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (25564675..25729294)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (26025826..26190440)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (25960642..26125261)

Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene conserved acetylation island sequence 2 enhancer Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:25868192-25868692 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:25868693-25869193 Neighboring gene uncharacterized LOC124905094 Neighboring gene crystallin beta B2 pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18786 Neighboring gene microRNA 6817 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13561 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13562 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr22:25961339-25961854 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18787 Neighboring gene GRK3 antisense RNA 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:26001784-26002284 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:26015847-26016633 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13563 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13564 Neighboring gene YES1 pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18788 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr22:26099534-26100733 Neighboring gene RNA, 5S ribosomal pseudogene 494 Neighboring gene Sharpr-MPRA regulatory region 14204 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18789 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:26150305-26150816 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:26150817-26151326 Neighboring gene Sharpr-MPRA regulatory region 2919 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:26173086-26173586 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:26173587-26174087 Neighboring gene myosin XVIIIB Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:26242211-26242711 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18790 Neighboring gene MYO18B antisense RNA 1 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:26331174-26331797 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:26338651-26339188 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:26339189-26339725 Neighboring gene RN7SK pseudogene 169

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Evidence that a single nucleotide polymorphism in the promoter of the G protein receptor kinase 3 gene is associated with bipolar disorder. Barrett TB, et al. Mol Psychiatry, 2003 May. PMID 12808434
  2. beta-Adrenoceptor and GRK3 expression in human lymphocytes is related to blood pressure and urinary albumin excretion. Oliver E, et al. J Hypertens, 2010 Jun. PMID 20216086
  3. Association analysis of GRK3 gene promoter variants in cocaine abuse. Guindalini C, et al. Psychiatr Genet, 2007 Aug. PMID 17621168
  4. Molecular cloning, functional expression and mRNA analysis of human beta-adrenergic receptor kinase 2. Parruti G, et al. Biochem Biophys Res Commun, 1993 Jan 29. PMID 8427589
  5. Suppression of G-protein-coupled receptor kinase 3 expression is a feature of classical GBM that is required for maximal growth. Woerner BM, et al. Mol Cancer Res, 2012 Jan. PMID 22086906, Free PMC Article

See all (64) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. A novel GRK3-HDAC2 regulatory pathway is a key direct link between neuroendocrine differentiation and angiogenesis in prostate cancer progression.
    Title: A novel GRK3-HDAC2 regulatory pathway is a key direct link between neuroendocrine differentiation and angiogenesis in prostate cancer progression.
  2. Aged G Protein-Coupled Receptor Kinase 3 (Grk3)-Deficient Mice Exhibit Enhanced Osteoclastogenesis and Develop Bone Lesions Analogous to Human Paget's Disease of Bone.
    Title: Aged G Protein-Coupled Receptor Kinase 3 (Grk3)-Deficient Mice Exhibit Enhanced Osteoclastogenesis and Develop Bone Lesions Analogous to Human Paget's Disease of Bone.
  3. TEAD3 inhibits the proliferation and metastasis of prostate cancer via suppressing ADRBK2.
    Title: TEAD3 inhibits the proliferation and metastasis of prostate cancer via suppressing ADRBK2.
  4. Dissecting the roles of GRK2 and GRK3 in mu-opioid receptor internalization and beta-arrestin2 recruitment using CRISPR/Cas9-edited HEK293 cells.
    Title: Dissecting the roles of GRK2 and GRK3 in μ-opioid receptor internalization and β-arrestin2 recruitment using CRISPR/Cas9-edited HEK293 cells.
  5. RKIP has several binding sites within the N-termini of GRK3.The N-termini of GRK3 binds to beta2-adrenoceptors.
    Title: The N-termini of GRK2 and GRK3 simulate the stimulating effects of RKIP on β-adrenoceptors.
  6. Study found that GRK3 was significantly overexpressed in 162 pairs of colon cancer tissues than in the matched noncancerous mucosa. These data show that aberrant expression of GRK3 plays an important role in promoting colon cancer progression through enhanced proliferation and reduced apoptosis.
    Title: Overexpression of GRK3, Promoting Tumor Proliferation, Is Predictive of Poor Prognosis in Colon Cancer.
  7. hat expression of GRK3 was down-regulated in pancreatic ductal adenocarcinoma and was an independent prognostic factor
    Title: High expression of GRK3 is associated with favorable prognosis in pancreatic ductal adenocarcinoma.
  8. GRK3 is a new critical activator of neuroendocrine phenotypes and mediator of CREB activation in promoting neuroendocrine differentiation of prostate cancer cells.
    Title: GRK3 is a direct target of CREB activation and regulates neuroendocrine differentiation of prostate cancer cells.
  9. effects of GRK3 modulation appear to be specific to chemokine-mediated migration behaviors without influencing tumor cell proliferation or survival
    Title: G Protein Coupled Receptor Kinase 3 Regulates Breast Cancer Migration, Invasion, and Metastasis.
  10. data are consistent with the possibility that oncogenes can induce cellular stiffness via an HDAC6-induced reorganization of the vimentin intermediate filament network
    Title: GRK3 is essential for metastatic cells and promotes prostate tumor progression.
Submit: New GeneRIF Correction See all GeneRIFs (26)

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)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
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 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 TAS
Traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
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 desensitization of G protein-coupled receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein phosphorylation IEA
Inferred from Electronic Annotation
more info
  
involved_in receptor internalization IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in signal transduction TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in cell projection IEA
Inferred from Electronic Annotation
more info
  
located_in cytosol TAS
Traceable Author Statement
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
G protein-coupled receptor kinase 3
Names
adrenergic, beta, receptor kinase 2
beta-ARK-2
beta-adrenergic receptor kinase 2
NP_001349707.1
NP_005151.2
XP_011528277.1
XP_047297122.1
XP_047297123.1
XP_054181163.1
XP_054181164.1
XP_054181165.1

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)

  1. NM_001362778.2 → NP_001349707.1  G protein-coupled receptor kinase 3 isoform 2

    Status: REVIEWED

    Source sequence(s)
    AL022329, BC029563
    UniProtKB/TrEMBL
    A8K869
    Conserved Domains (3) summary
    cd01240
    Location:440 → 557
    PH_GRK2_subgroup; G Protein-Coupled Receptor Kinase 2 subgroup pleckstrin homology (PH) domain
    cd05633
    Location:72 → 417
    STKc_GRK3; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3
    cl02565
    Location:1 → 73
    RGS; Regulator of G protein signaling (RGS) domain superfamily

  2. NM_005160.4 → NP_005151.2  G protein-coupled receptor kinase 3 isoform 1

    See identical proteins and their annotated locations for NP_005151.2

    Status: REVIEWED

    Source sequence(s)
    AL022329, BC036797, BC063545, BX387339
    Consensus CDS
    CCDS13832.1
    UniProtKB/Swiss-Prot
    P35626, Q9UGW9
    UniProtKB/TrEMBL
    A8K869
    Related
    ENSP00000317578.4, ENST00000324198.11
    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
    cd05633
    Location:185 → 530
    STKc_GRK3; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3

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

  1. NC_000022.11 Reference GRCh38.p14 Primary Assembly

    Range
    25564675..25729294
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047441167.1 → XP_047297123.1  G protein-coupled receptor kinase 3 isoform X3

    UniProtKB/TrEMBL
    Q8N433

  2. XM_047441166.1 → XP_047297122.1  G protein-coupled receptor kinase 3 isoform X1

  3. XM_011529975.3 → XP_011528277.1  G protein-coupled receptor kinase 3 isoform X2

    Conserved Domains (5) summary
    cd01240
    Location:388 → 505
    PH_GRK2_subgroup; G Protein-Coupled Receptor Kinase 2 subgroup pleckstrin homology (PH) domain
    cd05633
    Location:20 → 365
    STKc_GRK3; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3
    pfam00069
    Location:26 → 288
    Pkinase; Protein kinase domain
    pfam00169
    Location:395 → 484
    PH; PH domain
    cl02565
    Location:1 → 21
    RGS; Regulator of G protein signaling (RGS) domain superfamily

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060946.1 Alternate T2T-CHM13v2.0

    Range
    26025826..26190440
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054325190.1 → XP_054181165.1  G protein-coupled receptor kinase 3 isoform X3

    UniProtKB/TrEMBL
    Q8N433

  2. XM_054325188.1 → XP_054181163.1  G protein-coupled receptor kinase 3 isoform X1

  3. XM_054325189.1 → XP_054181164.1  G protein-coupled receptor kinase 3 isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P35626.2 GenPept UniProtKB/Swiss-Prot:P35626

Gene LinkOut

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