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

    Gene ID: 2870, updated on 27-Nov-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
    mouse all
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    Genomic context

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    See GRK6 in Genome Data Viewer
    Location:
    5q35.3
    Exon count:
    18
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (177425523..177442891)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (177968774..177986142)
    RS_2024_09 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. Overexpression of wild-type and catalytically inactive forms of GRK2 and GRK6 fails to alter the agonist-induced phosphorylation of the C5a receptor (CD88): evidence that GRK6 is autophosphorylated in COS-7 cells. Milcent MD, et al. Biochem Biophys Res Commun, 1999 May 27. PMID 10334944
    2. Association study of common variants within the G protein-coupled receptor kinase 6 gene and schizophrenia susceptibility in Han Chinese. Tang W, et al. Hum Psychopharmacol, 2014 Jan. PMID 24302161
    3. GRK6 expression in patients with hepatocellular carcinoma. Li YP. Asian Pac J Trop Med, 2013 Mar. PMID 23375037
    4. Aberrant GRK6 promoter methylation is associated with poor prognosis in hypopharyngeal squamous cell carcinoma. Qiu X, et al. Oncol Rep, 2016 Feb. PMID 26718636
    5. The structure of G protein-coupled receptor kinase (GRK)-6 defines a second lineage of GRKs. Lodowski DT, et al. J Biol Chem, 2006 Jun 16. PMID 16613860

    See all (88) 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)

    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 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_2024_08

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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