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

    Gene ID: 157, updated on 10-Dec-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
    mouse all
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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
    • 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)

    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 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

      UniProtKB/TrEMBL
      A8K869

    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

      UniProtKB/TrEMBL
      A8K869

    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

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

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