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    Grk6 G protein-coupled receptor kinase 6 [ Mus musculus (house mouse) ]

    Gene ID: 26385, updated on 9-Dec-2024

    Summary

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    Official Symbol
    Grk6provided by MGI
    Official Full Name
    G protein-coupled receptor kinase 6provided by MGI
    Primary source
    MGI:MGI:1347078
    See related
    Ensembl:ENSMUSG00000074886 AllianceGenome:MGI:1347078
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    Gprk6
    Summary
    Predicted to enable G protein-coupled receptor kinase activity and beta-adrenergic receptor kinase activity. Predicted to be involved in desensitization of G protein-coupled receptor signaling pathway. Predicted to be located in membrane. Predicted to be active in cytoplasm. Is expressed in several structures, including genitourinary system; liver; lung; spleen; and submandibular gland primordium. Human ortholog(s) of this gene implicated in Parkinson's disease. Orthologous to human GRK6 (G protein-coupled receptor kinase 6). [provided by Alliance of Genome Resources, Dec 2024]
    Expression
    Ubiquitous expression in spleen adult (RPKM 77.5), thymus adult (RPKM 59.5) and 27 other tissues See more
    Orthologs
    human all
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    Genomic context

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    See Grk6 in Genome Data Viewer
    Location:
    13 B1; 13 30.06 cM
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 13 NC_000079.7 (55592865..55608740)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 13 NC_000079.6 (55445072..55460927)

    Chromosome 13 - NC_000079.7Genomic Context describing neighboring genes Neighboring gene solute carrier family 34 (sodium phosphate), member 1 Neighboring gene profilin 3 Neighboring gene coagulation factor XII (Hageman factor) Neighboring gene STARR-seq mESC enhancer starr_34617 Neighboring gene STARR-positive B cell enhancer ABC_E8892 Neighboring gene STARR-positive B cell enhancer ABC_E212 Neighboring gene STARR-positive B cell enhancer ABC_E4072 Neighboring gene microRNA 6943 Neighboring gene proline rich 7 (synaptic) Neighboring gene drebrin 1 Neighboring gene microRNA 6944

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. G protein-coupled receptor kinase 6 (GRK6) regulates insulin processing and secretion via effects on proinsulin conversion to insulin. Varney MJ, et al. J Biol Chem, 2022 Oct. PMID 36030052, Free PMC Article
    2. Role of GRK6 in the Regulation of Platelet Activation through Selective G Protein-Coupled Receptor (GPCR) Desensitization. Chaudhary PK, et al. Int J Mol Sci, 2020 May 30. PMID 32486261, Free PMC Article
    3. GRK6, a gatekeeper of visceral hyperalgesia. Murga C, et al. Brain Behav Immun, 2009 Jan. PMID 18977289
    4. Morphine-induced physiological and behavioral responses in mice lacking G protein-coupled receptor kinase 6. Raehal KM, et al. Drug Alcohol Depend, 2009 Oct 1. PMID 19497686, Free PMC Article
    5. The variable C-terminal extension of G-protein-coupled receptor kinase 6 constitutes an accessorial autoregulatory domain. Vatter P, et al. FEBS J, 2005 Dec. PMID 16302968

    See all (58) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. G protein-coupled receptor kinase 6 (GRK6) regulates insulin processing and secretion via effects on proinsulin conversion to insulin.
      Title: G protein-coupled receptor kinase 6 (GRK6) regulates insulin processing and secretion via effects on proinsulin conversion to insulin.
    2. Role of GRK6 in the Regulation of Platelet Activation through Selective G Protein-Coupled Receptor (GPCR) Desensitization.
      Title: Role of GRK6 in the Regulation of Platelet Activation through Selective G Protein-Coupled Receptor (GPCR) Desensitization.
    3. These data indicate that GRK2, GRK5 and GRK6 redundantly modulate Smo-GATA crosstalk in fetal mouse hearts, orchestrating transcriptional pathways previously linked to clinical and experimental atrioventricular canal defects
      Title: G-protein receptor kinases 2, 5 and 6 redundantly modulate Smoothened-GATA transcriptional crosstalk in fetal mouse hearts.
    4. findings show that chemerin-activated CMKLR1 regulation in inflammatory macrophages is largely GRK6 and beta-arrestin mediated, which may impact innate immunity and have therapeutic implications in rheumatic disease.
      Title: Chemerin-activated functions of CMKLR1 are regulated by G protein-coupled receptor kinase 6 (GRK6) and β-arrestin 2 in inflammatory macrophages.
    5. Conditions for optimal dendritic cells guidance are perfectly provided by the CCL21 gradients measured in vivo. Furthermore, CCR7 signal termination by the G-protein-coupled receptor kinase 6 (GRK6) is crucial for haptotactic but dispensable for chemotactic CCL21 gradient sensing in vitro and confirm those observations in vivo.
      Title: Dendritic Cells Interpret Haptotactic Chemokine Gradients in a Manner Governed by Signal-to-Noise Ratio and Dependent on GRK6.
    6. These studies suggest a previously unrecognized and novel role for GRK6 in neutrophil migration specific to pulmonary tissue during bacterial infection.
      Title: Role of G protein-coupled receptor kinase-6 in Escherichia coli lung infection model in mice.
    7. Silencing of GRK6 expression by siRNA impairs CXCR4-serine 339 phosphorylation and migration of cardiac stem cellss caused by SCF. In vivo, knockdown of GRK6 impairs the ability of CSCs to migrate into peri-infarcted areas.
      Title: SCF/c-kit transactivates CXCR4-serine 339 phosphorylation through G protein-coupled receptor kinase 6 and regulates cardiac stem cell migration.
    8. This work demonstrates the importance of GRK6 in regulation of hematopoietic stem cell self-renewal and reveals its potential role in participation of stress response.
      Title: GRK6 regulates ROS response and maintains hematopoietic stem cell self-renewal.
    9. GRK6-mediated OXTR desensitization in labor is necessary for normal uterine contractile patterns and optimal fetal outcome.
      Title: Enhanced Uterine Contractility and Stillbirth in Mice Lacking G Protein-Coupled Receptor Kinase 6 (GRK6): Implications for Oxytocin Receptor Desensitization.
    10. It regulates apoptotic engulfment in phagocytes. (review)
      Title: [Research on Molecular Mechanisms of Engulfment of Apoptotic Cells].
    Submit: New GeneRIF Correction See all GeneRIFs (24)

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)
    • Endonuclease-mediated (2) 
    • Gene trapped (1) 
    • Targeted (2)  1 citation

    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 MGI

    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 G protein-coupled receptor kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables G protein-coupled receptor kinase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables beta-adrenergic receptor kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables beta-adrenergic receptor kinase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in Wnt signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in desensitization of G protein-coupled receptor signaling pathway ISO
    Inferred from Sequence Orthology
    more info
    		  
    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 IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    G protein-coupled receptor kinase 6
    Names
    g protein-coupled receptor kinase GRK6
    NP_001033107.1
    NP_001106182.1
    NP_001272992.1
    NP_001272993.1
    NP_001272994.1
    NP_001272995.1
    NP_001364005.1
    NP_001364006.1
    NP_036068.2

    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_001038018.5 → NP_001033107.1  G protein-coupled receptor kinase 6 isoform a

      See identical proteins and their annotated locations for NP_001033107.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
      Source sequence(s)
      AK051405, AW048460, CT009762, Y15799
      UniProtKB/TrEMBL
      O70296
      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_001112711.2 → NP_001106182.1  G protein-coupled receptor kinase 6 isoform c

      See identical proteins and their annotated locations for NP_001106182.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) uses an alternate splice site in the 3' coding region, which results in a frameshift, compared to variant 1. The encoded isoform (c) has a shorter and distinct C-terminus, compared to isoform a.
      Source sequence(s)
      AK051405, AW048460, CT009762, Y15799
      Consensus CDS
      CCDS88457.1
      UniProtKB/Swiss-Prot
      O70293, O70294, O70295, Q6DI67
      UniProtKB/TrEMBL
      Q792R0
      Related
      ENSMUSP00000152968.2, ENSMUST00000224118.2
      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

    3. NM_001286063.2 → NP_001272992.1  G protein-coupled receptor kinase 6 isoform d

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (d) has a shorter N-terminus, compared to isoform a.
      Source sequence(s)
      AK051405, AW048460, CT009762, Y15799
      UniProtKB/TrEMBL
      A0A286YDZ5, O70296
      Related
      ENSMUSP00000153623.2, ENSMUST00000224653.2
      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

    4. NM_001286064.2 → NP_001272993.1  G protein-coupled receptor kinase 6 isoform e

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5) uses an alternate in-frame splice site in the central coding region, compared to variant 1. The encoded isoform (e) is shorter, compared to isoform a.
      Source sequence(s)
      AK051405, AW048460, CT009762, Y15799
      UniProtKB/TrEMBL
      A0A286YDA5, O70296
      Conserved Domains (3) summary
      smart00220
      Location:186 → 443
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd05630
      Location:185 → 464
      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

    5. NM_001286065.1 → NP_001272994.1  G protein-coupled receptor kinase 6 isoform f

      Status: VALIDATED

      Description
      Transcript Variant: This variant (6) uses an alternate in-frame splice site in the central coding region, and uses an alternate splice site in the 3' coding region, which results in a frameshift, compared to variant 1. The encoded isoform (f) is shorter and has a distinct C-terminus, compared to isoform a.
      Source sequence(s)
      AK051405, AW048460, CT009762, Y15799
      Consensus CDS
      CCDS88458.1
      UniProtKB/TrEMBL
      A0A286YE10, Q3UK88
      Related
      ENSMUSP00000153668.2, ENSMUST00000225925.2
      Conserved Domains (3) summary
      smart00220
      Location:186 → 414
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl02565
      Location:35 → 179
      RGS; Regulator of G protein signaling (RGS) domain superfamily
      cl21453
      Location:185 → 435
      PKc_like; Protein Kinases, catalytic domain

    6. NM_001286066.2 → NP_001272995.1  G protein-coupled receptor kinase 6 isoform g

      Status: VALIDATED

      Description
      Transcript Variant: This variant (7) has multiple differences compared to variant 1. These differences result in a distinct 5' UTR, 3' UTR, and 3' coding region, and cause translation initiation from a downstream start codon. The encoded isoform (g) has a shorter N-terminus and a distinct and shorter C-terminus, compared to isoform a.
      Source sequence(s)
      CT009762
      UniProtKB/TrEMBL
      Q9EP84
      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

    7. NM_001377076.1 → NP_001364005.1  G protein-coupled receptor kinase 6 isoform h

      Status: VALIDATED

      Source sequence(s)
      CT009762
      UniProtKB/TrEMBL
      Q792R0
      Conserved Domains (2) summary
      cd05630
      Location:180 → 464
      STKc_GRK6; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6
      cl02565
      Location:30 → 174
      RGS; Regulator of G protein signaling (RGS) domain superfamily

    8. NM_001377077.1 → NP_001364006.1  G protein-coupled receptor kinase 6 isoform i

      Status: VALIDATED

      Source sequence(s)
      CT009762
      Conserved Domains (1) summary
      cl21453
      Location:1 → 204
      PKc_like; Protein Kinases, catalytic domain

    9. NM_011938.5 → NP_036068.2  G protein-coupled receptor kinase 6 isoform b

      See identical proteins and their annotated locations for NP_036068.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (b) has a shorter and distinct C-terminus, compared to isoform a.
      Source sequence(s)
      CT009762
      Consensus CDS
      CCDS36676.1
      UniProtKB/TrEMBL
      Q792R0, Q9EP84
      Related
      ENSMUSP00000097081.4, ENSMUST00000099482.5
      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_000001635.27-RS_2024_02

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

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000079.7 Reference GRCm39 C57BL/6J

      Range
      55592865..55608740
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O70293.1 GenPept UniProtKB/Swiss-Prot:O70293

    Gene LinkOut

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

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