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O70293

- GRK6_MOUSE

UniProt

O70293 - GRK6_MOUSE

Protein

G protein-coupled receptor kinase 6

Gene

Grk6

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 137 (01 Oct 2014)
      Sequence version 1 (01 Aug 1998)
      Previous versions | rss
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    Functioni

    Specifically phosphorylates the activated forms of G protein-coupled receptors. Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their desensitization. Seems to be involved in the desensitization of D2-like dopamine receptors in striatum and chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis By similarity. Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor, LRP6 during Wnt signaling (in vitro) By similarity.By similarity

    Catalytic activityi

    ATP + [G-protein-coupled receptor] = ADP + [G-protein-coupled receptor] phosphate.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei215 – 2151ATPPROSITE-ProRule annotation
    Active sitei311 – 3111Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi192 – 2009ATPPROSITE-ProRule annotation
    Nucleotide bindingi264 – 2707ATPPROSITE-ProRule annotation
    Nucleotide bindingi315 – 3184ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. G-protein coupled receptor kinase activity Source: UniProtKB-EC
    3. protein binding Source: IntAct

    GO - Biological processi

    1. termination of G-protein coupled receptor signaling pathway Source: InterPro
    2. Wnt signaling pathway Source: UniProtKB-KW

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Wnt signaling pathway

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    G protein-coupled receptor kinase 6 (EC:2.7.11.16)
    Alternative name(s):
    G protein-coupled receptor kinase GRK6
    Gene namesi
    Name:Grk6
    Synonyms:Gprk6
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 13

    Organism-specific databases

    MGIiMGI:1347078. Grk6.

    Subcellular locationi

    GO - Cellular componenti

    1. membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Disruption phenotypei

    Deficient mice show significant altered central dopamine receptors regulation, deficient lymphocyte chemotaxis and increased acute inflammation and neutrophil chemotaxis.3 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 576576G protein-coupled receptor kinase 6PRO_0000085975Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei484 – 4841Phosphoserine; by autocatalysisBy similarity
    Modified residuei485 – 4851Phosphothreonine; by autocatalysisBy similarity
    Lipidationi561 – 5611S-palmitoyl cysteineBy similarity
    Lipidationi562 – 5621S-palmitoyl cysteineBy similarity
    Lipidationi565 – 5651S-palmitoyl cysteineBy similarity

    Keywords - PTMi

    Lipoprotein, Palmitate, Phosphoprotein

    Proteomic databases

    PaxDbiO70293.
    PRIDEiO70293.

    PTM databases

    PhosphoSiteiO70293.

    Expressioni

    Tissue specificityi

    Expressed in the brain in striatal neurons.1 Publication

    Gene expression databases

    ArrayExpressiO70293.
    BgeeiO70293.
    CleanExiMM_GRK6.
    GenevestigatoriO70293.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    SLC9A3R1Q286195EBI-7073604,EBI-7073613From a different organism.

    Protein-protein interaction databases

    IntActiO70293. 3 interactions.
    MINTiMINT-1793102.

    Structurei

    3D structure databases

    ProteinModelPortaliO70293.
    SMRiO70293. Positions 2-557.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini53 – 171119RGSPROSITE-ProRule annotationAdd
    BLAST
    Domaini186 – 448263Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini449 – 51466AGC-kinase C-terminalAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 185185N-terminalAdd
    BLAST

    Sequence similaritiesi

    Contains 1 AGC-kinase C-terminal domain.Curated
    Contains 1 protein kinase domain.PROSITE-ProRule annotation
    Contains 1 RGS domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00730000110512.
    HOGENOMiHOG000006742.
    HOVERGENiHBG004532.
    InParanoidiQ6DI67.
    KOiK08291.
    OMAiMLEPPFK.
    OrthoDBiEOG7V1FQK.
    PhylomeDBiO70293.
    TreeFamiTF313940.

    Family and domain databases

    InterProiIPR000961. AGC-kinase_C.
    IPR000239. GPCR_kinase.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR016137. Regulat_G_prot_signal_superfam.
    IPR000342. RGS_dom.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PfamiPF00069. Pkinase. 1 hit.
    PF00615. RGS. 1 hit.
    [Graphical view]
    PRINTSiPR00717. GPCRKINASE.
    SMARTiSM00315. RGS. 1 hit.
    SM00133. S_TK_X. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF48097. SSF48097. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    PS50132. RGS. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform GRK6A (identifier: O70293-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MELENIVANT VLLKAREGGG GNRKGKSKKW RQMLQFPHIS QCEELRLSLE    50
    RDYHSLCERQ PIGRLLFREF CATRPELTRC TAFLDGVSEY EVTPDEKRKA 100
    CGRRLMQNFL SHTGPDLIPE VPRQLVSNCA QRLEQGPCKD LFQELTRLTH 150
    EYLSTAPFAD YLDSIYFNRF LQWKWLERQP VTKNTFRQYR VLGKGGFGEV 200
    CACQVRATGK MYACKKLEKK RIKKRKGEAM ALNEKQILEK VNSRFVVSLA 250
    YAYETKDALC LVLTLMNGGD LKFHIYHMGQ AGFPEARAVF YAAEICCGLE 300
    DLHRERIVYR DLKPENILLD DHGHIRISDL GLAVHVPEGQ TIKGRVGTVG 350
    YMAPEVVRNE RYTFSPDWWA LGCLLYEMIA GQSPFQQRKK KIKREEVERL 400
    VKEVAEEYTD RFSSQARSLC SQLLSKDPAE RLGCRGGGAR EVKEHPLFKK 450
    LNFKRLGAGM LEPPFKPDPQ AIYCKDVLDI EQFSTVKGVD LEPTDQDFYQ 500
    KFATGSVSIP WQNEMVETEC FQELNVFGLD GSVPPDLDWK GQPTAPPKKG 550
    LLQRLFSRQD CCGNCSDSEE ELPTRL 576
    Length:576
    Mass (Da):65,979
    Last modified:August 1, 1998 - v1
    Checksum:i91EEC2028CAF4B91
    GO
    Isoform GRK6B (identifier: O70293-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         560-576: DCCGNCSDSEEELPTRL → RIAVGTAATVRKSSPPASSPQAEAPTGGWR

    Show »
    Length:589
    Mass (Da):67,115
    Checksum:iC08443E7CB2B714D
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti98 – 981R → Q in AAC09265. (PubMed:10506199)Curated
    Sequence conflicti571 – 5711E → K in AAC09265. (PubMed:10506199)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei560 – 57617DCCGN…LPTRL → RIAVGTAATVRKSSPPASSP QAEAPTGGWR in isoform GRK6B. 3 PublicationsVSP_004939Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF040747 mRNA. Translation: AAC09268.1.
    AF040748 mRNA. Translation: AAC09269.1.
    AF040749 mRNA. Translation: AAC09270.1.
    AF040754 Genomic DNA. Translation: AAC09265.1.
    Y17967 Genomic DNA. Translation: CAA76975.1.
    Y17967 Genomic DNA. Translation: CAA76976.1.
    Y15798 mRNA. Translation: CAA75789.1.
    Y15799 mRNA. Translation: CAA75790.1.
    BC075719 mRNA. Translation: AAH75719.1.
    CCDSiCCDS49272.1. [O70293-2]
    RefSeqiNP_001033107.1. NM_001038018.4. [O70293-2]
    NP_001106182.1. NM_001112711.2. [O70293-1]
    NP_001272992.1. NM_001286063.1.
    NP_001272993.1. NM_001286064.1.
    NP_001272994.1. NM_001286065.1.
    NP_036068.2. NM_011938.4.
    UniGeneiMm.10193.

    Genome annotation databases

    EnsembliENSMUST00000001115; ENSMUSP00000001115; ENSMUSG00000074886. [O70293-2]
    GeneIDi26385.
    KEGGimmu:26385.
    UCSCiuc007qqw.1. mouse. [O70293-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF040747 mRNA. Translation: AAC09268.1 .
    AF040748 mRNA. Translation: AAC09269.1 .
    AF040749 mRNA. Translation: AAC09270.1 .
    AF040754 Genomic DNA. Translation: AAC09265.1 .
    Y17967 Genomic DNA. Translation: CAA76975.1 .
    Y17967 Genomic DNA. Translation: CAA76976.1 .
    Y15798 mRNA. Translation: CAA75789.1 .
    Y15799 mRNA. Translation: CAA75790.1 .
    BC075719 mRNA. Translation: AAH75719.1 .
    CCDSi CCDS49272.1. [O70293-2 ]
    RefSeqi NP_001033107.1. NM_001038018.4. [O70293-2 ]
    NP_001106182.1. NM_001112711.2. [O70293-1 ]
    NP_001272992.1. NM_001286063.1.
    NP_001272993.1. NM_001286064.1.
    NP_001272994.1. NM_001286065.1.
    NP_036068.2. NM_011938.4.
    UniGenei Mm.10193.

    3D structure databases

    ProteinModelPortali O70293.
    SMRi O70293. Positions 2-557.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi O70293. 3 interactions.
    MINTi MINT-1793102.

    PTM databases

    PhosphoSitei O70293.

    Proteomic databases

    PaxDbi O70293.
    PRIDEi O70293.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000001115 ; ENSMUSP00000001115 ; ENSMUSG00000074886 . [O70293-2 ]
    GeneIDi 26385.
    KEGGi mmu:26385.
    UCSCi uc007qqw.1. mouse. [O70293-1 ]

    Organism-specific databases

    CTDi 2870.
    MGIi MGI:1347078. Grk6.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00730000110512.
    HOGENOMi HOG000006742.
    HOVERGENi HBG004532.
    InParanoidi Q6DI67.
    KOi K08291.
    OMAi MLEPPFK.
    OrthoDBi EOG7V1FQK.
    PhylomeDBi O70293.
    TreeFami TF313940.

    Miscellaneous databases

    NextBioi 304313.
    PROi O70293.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O70293.
    Bgeei O70293.
    CleanExi MM_GRK6.
    Genevestigatori O70293.

    Family and domain databases

    InterProi IPR000961. AGC-kinase_C.
    IPR000239. GPCR_kinase.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR016137. Regulat_G_prot_signal_superfam.
    IPR000342. RGS_dom.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00069. Pkinase. 1 hit.
    PF00615. RGS. 1 hit.
    [Graphical view ]
    PRINTSi PR00717. GPCRKINASE.
    SMARTi SM00315. RGS. 1 hit.
    SM00133. S_TK_X. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48097. SSF48097. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS51285. AGC_KINASE_CTER. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    PS50132. RGS. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The GRK4 subfamily of G protein-coupled receptor kinases. Alternative splicing, gene organization, and sequence conservation."
      Premont R.T., Macrae A.D., Aparicio S.A., Kendall H.E., Welch J.E., Lefkowitz R.J.
      J. Biol. Chem. 274:29381-29389(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS GRK6A AND GRK6B).
      Strain: 129/SvJ.
    2. "Primary structure of murine G-protein-coupled receptor kinase 6 splice variants predict differential regulation by posttranslational modifications."
      Moepps B., Vatter P., Frode R., Waechter F., Gierschik P.
      Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS GRK6A AND GRK6B).
      Strain: 129/SvJ and C57BL/6J.
      Tissue: Thymus.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GRK6B).
      Strain: 129.
      Tissue: Mammary gland.
    4. "Defective lymphocyte chemotaxis in beta-arrestin2- and GRK6-deficient mice."
      Fong A.M., Premont R.T., Richardson R.M., Yu Y.R., Lefkowitz R.J., Patel D.D.
      Proc. Natl. Acad. Sci. U.S.A. 99:7478-7483(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    5. "Increased acute inflammation, leukotriene B4-induced chemotaxis, and signaling in mice deficient for G protein-coupled receptor kinase 6."
      Kavelaars A., Vroon A., Raatgever R.P., Fong A.M., Premont R.T., Patel D.D., Lefkowitz R.J., Heijnen C.J.
      J. Immunol. 171:6128-6134(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    6. "Dopaminergic supersensitivity in G protein-coupled receptor kinase 6-deficient mice."
      Gainetdinov R.R., Bohn L.M., Sotnikova T.D., Cyr M., Laakso A., Macrae A.D., Torres G.E., Kim K.M., Lefkowitz R.J., Caron M.G., Premont R.T.
      Neuron 38:291-303(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiGRK6_MOUSE
    AccessioniPrimary (citable) accession number: O70293
    Secondary accession number(s): O70294, O70295, Q6DI67
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: August 1, 1998
    Last modified: October 1, 2014
    This is version 137 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3