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GRK6 G protein-coupled receptor kinase 6 [ Homo sapiens (human) ]

Gene ID: 2870, updated on 3-Apr-2024

Summary

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Official Symbol
GRK6provided by HGNC
Official Full Name
G protein-coupled receptor kinase 6provided by HGNC
Primary source
HGNC:HGNC:4545
See related
Ensembl:ENSG00000198055 MIM:600869; AllianceGenome:HGNC:4545
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
GPRK6
Summary
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. Several transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]
Expression
Broad expression in bone marrow (RPKM 27.2), lymph node (RPKM 19.5) and 23 other tissues See more
Orthologs
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Genomic context

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Location:
5q35.3
Exon count:
18
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (177425523..177442891)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (177968774..177986142)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (176853677..176869892)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:176828971-176829828 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:176830685-176831542 Neighboring gene profilin 3 Neighboring gene coagulation factor XII Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23717 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:176853351-176853890 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23718 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23719 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:176867639-176868335 Neighboring gene PRR7 antisense RNA 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:176874472-176875100 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:176876138-176876638 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:176876639-176877139 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16688 Neighboring gene proline rich 7, synaptic Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:176881361-176882061 Neighboring gene Sharpr-MPRA regulatory region 1974 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16691 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16692 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:176884168-176884868 Neighboring gene drebrin 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:176894101-176894646 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr5:176895193-176895738 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr5:176895739-176896284 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:176897377-176897922 Neighboring gene hESC enhancers GRCh37_chr5:176899493-176899996 and GRCh37_chr5:176899997-176900498

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
  • 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. The Role of G Protein-Coupled Receptor Kinase 6 Regulation in Inflammation and Pain. Stegen M, et al. Int J Mol Sci, 2022 Dec 14. PMID 36555521, Free PMC Article
  2. Characterization of the G protein-coupled receptor kinase 6 promoter reveals a functional CREB binding site. Stegen M, et al. PLoS One, 2021. PMID 33600497, Free PMC Article
  3. Overexpression of G Protein-Coupled Receptor Kinase 6 (GRK6) Is Associated with Progression and Poor Prognosis of Papillary Thyroid Carcinoma. Che X, et al. Med Sci Monit, 2018 May 28. PMID 29805156, Free PMC Article
  4. Prognostic value of decreased GRK6 expression in lung adenocarcinoma. Yao S, et al. J Cancer Res Clin Oncol, 2016 Dec. PMID 27601164
  5. Aberrant GRK6 promoter methylation is associated with poor prognosis in hypopharyngeal squamous cell carcinoma. Qiu X, et al. Oncol Rep, 2016 Feb. PMID 26718636

See all (83) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The Role of G Protein-Coupled Receptor Kinase 6 Regulation in Inflammation and Pain.
    Title: The Role of G Protein-Coupled Receptor Kinase 6 Regulation in Inflammation and Pain.
  2. M2 macrophages-derived exosomal miR-3917 promotes the progression of lung cancer via targeting GRK6.
    Title: M2 macrophages-derived exosomal miR-3917 promotes the progression of lung cancer via targeting GRK6.
  3. Multisite NHERF1 phosphorylation controls GRK6A regulation of hormone-sensitive phosphate transport.
    Title: Multisite NHERF1 phosphorylation controls GRK6A regulation of hormone-sensitive phosphate transport.
  4. Characterization of the G protein-coupled receptor kinase 6 promoter reveals a functional CREB binding site.
    Title: Characterization of the G protein-coupled receptor kinase 6 promoter reveals a functional CREB binding site.
  5. GRK6 S-nitrosylation at cys 474 enhances its kinase activity toward alpha-syn phosphorylation at S129.
    Title: S-Nitrosylation of G protein-coupled receptor kinase 6 and Casein kinase 2 alpha modulates their kinase activity toward alpha-synuclein phosphorylation in an animal model of Parkinson's disease.
  6. MiR-19b-3p attenuates IL-1beta induced extracellular matrix degradation and inflammatory injury in chondrocytes by targeting GRK6.
    Title: MiR-19b-3p attenuates IL-1β induced extracellular matrix degradation and inflammatory injury in chondrocytes by targeting GRK6.
  7. Hypermethylation of the GRK6 gene promoter suppressed binding of C/EBPalpha, thereby contributing to the promotion of cell migration and invasion.
    Title: Hypermethylation of the G protein-coupled receptor kinase 6 (GRK6) promoter inhibits binding of C/EBPα, and GRK6 knockdown promotes cell migration and invasion in lung adenocarcinoma cells.
  8. GRK6 overexpression can significantly enhance tumor proliferation and invasion, which was consistent with clinical findings.
    Title: Overexpression of G Protein-Coupled Receptor Kinase 6 (GRK6) Is Associated with Progression and Poor Prognosis of Papillary Thyroid Carcinoma.
  9. demonstrate for the first time exosomal enrichment of G-protein-coupled receptor kinase (GRK) 5 and GRK6, both of which regulate Src and IGF-IR signaling and have been implicated in cancer.
    Title: c-Src, Insulin-Like Growth Factor I Receptor, G-Protein-Coupled Receptor Kinases and Focal Adhesion Kinase are Enriched Into Prostate Cancer Cell Exosomes.
  10. Genetic variation in OXTR and GRK6 is associated with the amount of oxytocin required as well as the duration of labor and risk for cesarean delivery among women undergoing induction of labor near term.
    Title: The association of single-nucleotide polymorphisms in the oxytocin receptor and G protein-coupled receptor kinase 6 (GRK6) genes with oxytocin dosing requirements and labor outcomes.
Submit: New GeneRIF Correction See all GeneRIFs (31)

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

EBI GWAS Catalog

Description
Genetic associations for activated partial thromboplastin time and prothrombin time, their gene expression profiles, and risk of coronary artery disease.
EBI GWAS Catalog
New loci associated with kidney function and chronic kidney disease.
EBI GWAS Catalog
Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis.
EBI GWAS Catalog

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

Clone Names

  • FLJ32135

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables G protein-coupled receptor kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables beta-adrenergic receptor kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables beta-adrenergic receptor kinase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables beta-adrenergic receptor kinase activity TAS
Traceable Author Statement
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in G protein-coupled receptor signaling pathway TAS
Traceable Author Statement
more info
  
involved_in Wnt signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in phosphorylation IEA
Inferred from Electronic Annotation
more info
  
involved_in protein phosphorylation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of G protein-coupled receptor signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in membrane HDA PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
G protein-coupled receptor kinase 6
NP_001004105.1
NP_001004106.1
NP_001351093.1
NP_002073.2
XP_006714921.1
XP_006714922.1
XP_011532840.1
XP_047273082.1
XP_054208434.1
XP_054208435.1
XP_054208436.1
XP_054208437.1

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.

Genomic

  1. NG_031981.1 RefSeqGene

    Range
    4991..21206
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001004105.3 → NP_001004105.1  G protein-coupled receptor kinase 6 isoform C

    See identical proteins and their annotated locations for NP_001004105.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains an alternate 3' terminal exon, compared to variant 2, resulting in a shorter isoform (C) with a distinct C-terminus compared to isoform B.
    Source sequence(s)
    AC145098, AF040752, BC009277, BI258860
    Consensus CDS
    CCDS43406.1
    UniProtKB/TrEMBL
    Q96AD6
    Related
    ENSP00000348230.5, ENST00000355958.9
    Conserved Domains (3) summary
    smart00220
    Location:186 → 448
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd05630
    Location:185 → 469
    STKc_GRK6; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6
    cl02565
    Location:35 → 179
    RGS; Regulator of G protein signaling (RGS) domain superfamily

  2. NM_001004106.3 → NP_001004106.1  G protein-coupled receptor kinase 6 isoform A

    See identical proteins and their annotated locations for NP_001004106.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) uses an alternate acceptor splice site in the last exon, compared to variant 2, resulting in a shorter isoform (A) compared to isoform B.
    Source sequence(s)
    AC145098, BC009277, BI258860
    Consensus CDS
    CCDS34303.1
    UniProtKB/Swiss-Prot
    O60541, P43250, Q13652
    UniProtKB/TrEMBL
    F8W9W2
    Related
    ENSP00000347655.5, ENST00000355472.10
    Conserved Domains (2) summary
    cd05630
    Location:185 → 469
    STKc_GRK6; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6
    cl02565
    Location:35 → 179
    RGS; Regulator of G protein signaling (RGS) domain superfamily

  3. NM_001364164.2 → NP_001351093.1  G protein-coupled receptor kinase 6 isoform D

    Status: REVIEWED

    Source sequence(s)
    AC145098
    Conserved Domains (1) summary
    cl21453
    Location:1 → 259
    PKc_like; Protein Kinases, catalytic domain

  4. NM_002082.4 → NP_002073.2  G protein-coupled receptor kinase 6 isoform B

    See identical proteins and their annotated locations for NP_002073.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) represents the longest transcript and encodes the longest isoform (B).
    Source sequence(s)
    AC145098, AF040751, BC009277, BI258860
    UniProtKB/TrEMBL
    Q96AD6
    Conserved Domains (3) summary
    smart00220
    Location:186 → 448
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd05630
    Location:185 → 469
    STKc_GRK6; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6
    cl02565
    Location:35 → 179
    RGS; Regulator of G protein signaling (RGS) domain superfamily

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    177425523..177442891
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047417126.1 → XP_047273082.1  G protein-coupled receptor kinase 6 isoform X3

  2. XM_006714859.3 → XP_006714922.1  G protein-coupled receptor kinase 6 isoform X2

    UniProtKB/TrEMBL
    Q96AD6
    Conserved Domains (3) summary
    smart00220
    Location:154 → 416
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd05630
    Location:153 → 437
    STKc_GRK6; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6
    cl02565
    Location:3 → 147
    RGS; Regulator of G protein signaling (RGS) domain superfamily

  3. XM_006714858.4 → XP_006714921.1  G protein-coupled receptor kinase 6 isoform X1

    See identical proteins and their annotated locations for XP_006714921.1

    UniProtKB/TrEMBL
    B3KPS5, Q96AD6
    Conserved Domains (3) summary
    smart00220
    Location:156 → 418
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd05630
    Location:155 → 439
    STKc_GRK6; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6
    cl02565
    Location:20 → 149
    RGS; Regulator of G protein signaling (RGS) domain superfamily

  4. XM_011534538.2 → XP_011532840.1  G protein-coupled receptor kinase 6 isoform X4

    Conserved Domains (2) summary
    smart00220
    Location:1 → 183
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cl21453
    Location:1 → 204
    PKc_like; Protein Kinases, catalytic domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    177968774..177986142
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054352461.1 → XP_054208436.1  G protein-coupled receptor kinase 6 isoform X3

  2. XM_054352460.1 → XP_054208435.1  G protein-coupled receptor kinase 6 isoform X2

  3. XM_054352459.1 → XP_054208434.1  G protein-coupled receptor kinase 6 isoform X1

    UniProtKB/TrEMBL
    B3KPS5

  4. XM_054352462.1 → XP_054208437.1  G protein-coupled receptor kinase 6 isoform X4

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P43250.2 GenPept UniProtKB/Swiss-Prot:P43250

Gene LinkOut

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