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Q62833

- GRK5_RAT

UniProt

Q62833 - GRK5_RAT

Protein

G protein-coupled receptor kinase 5

Gene

Grk5

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 105 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    Functioni

    Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein-coupled receptors (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their down-regulation. Phosphorylates a variety of GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid receptors. In addition to GPCRs, also phosphorylates various substrates: Hsc70-interacting protein/ST13, TP53/p53, HDAC5, and arrestin-1/ARRB1. Phosphorylation of ARRB1 by GRK5 inhibits G-protein independent MAPK1/MAPK3 signaling downstream of 5HT4-receptors. Phosphorylation of HDAC5, a repressor of myocyte enhancer factor 2 (MEF2) leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription. Phosphorylation of TP53/p53, a crucial tumor suppressor, inhibits TP53/p53-mediated apoptosis. Phosphorylation of ST13 regulates internalization of the chemokine receptor 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.

    Enzyme regulationi

    Inhibited by calmodulin with an IC50 of 50 nM. Calmodulin inhibits GRK5 association with receptor and phospholipid By similarity.By similarity

    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

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. G-protein coupled receptor kinase activity Source: RGD
    3. lipid binding Source: UniProtKB-KW
    4. protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. desensitization of G-protein coupled receptor protein signaling pathway Source: RGD
    3. negative regulation of apoptotic process Source: UniProtKB
    4. protein autophosphorylation Source: UniProtKB
    5. regulation of G-protein coupled receptor protein signaling pathway Source: RGD
    6. response to drug Source: RGD
    7. termination of G-protein coupled receptor signaling pathway Source: InterPro
    8. Wnt signaling pathway Source: UniProtKB-KW

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Apoptosis, Wnt signaling pathway

    Keywords - Ligandi

    ATP-binding, Lipid-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.11.16. 5301.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    G protein-coupled receptor kinase 5 (EC:2.7.11.16)
    Alternative name(s):
    G protein-coupled receptor kinase GRK5
    Gene namesi
    Name:Grk5
    Synonyms:Gprk5
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi61985. Grk5.

    Subcellular locationi

    Cytoplasm 1 Publication. Nucleus 1 Publication. Cell membrane By similarity; Peripheral membrane protein By similarity
    Note: Predominantly localized at the plasma membrane, targeted to the cell surface through the interaction with phospholipids. Nucleus localization is regulated in a GPCR and Ca2+/calmodulin-dependent fashion By similarity.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB-SubCell
    3. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 590590G protein-coupled receptor kinase 5PRO_0000085973Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei484 – 4841Phosphoserine; by autocatalysisBy similarity
    Modified residuei485 – 4851Phosphothreonine; by autocatalysisBy similarity

    Post-translational modificationi

    Autophosphorylated. Autophosphorylation may play a critical role in the regulation of GRK5 kinase activity.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiQ62833.
    PRIDEiQ62833.

    PTM databases

    PhosphoSiteiQ62833.

    Expressioni

    Tissue specificityi

    Not expressed ubiquitously in brain but is mainly localize in limbic brain regions with a very prominent expression in the lateral septal area.1 Publication

    Inductioni

    By cocaine in the lateral septum. Up-regulated in the failing heart.2 Publications

    Gene expression databases

    GenevestigatoriQ62833.

    Interactioni

    Subunit structurei

    Interacts with ST13 (via the C-terminus 303-319 AA). Interacts with TP53/p53. Interacts with HTR4 (via C-terminus 330-346 AA); this interaction is promoted by 5-HT (serotonin). Interacts with HDAC5.By similarity

    Protein-protein interaction databases

    MINTiMINT-220922.
    STRINGi10116.ENSRNOP00000015687.

    Structurei

    3D structure databases

    ProteinModelPortaliQ62833.
    SMRiQ62833. Positions 23-532.
    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
    Regioni20 – 3920Interaction with calmodulinBy similarityAdd
    BLAST
    Regioni546 – 56520Sufficient for membrane localizationBy similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi388 – 3958Nuclear localization signalBy similarity

    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.
    HOGENOMiHOG000006742.
    HOVERGENiHBG004532.
    InParanoidiQ62833.
    KOiK08291.
    PhylomeDBiQ62833.

    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.
    [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.
    PS50132. RGS. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q62833-1 [UniParc]FASTAAdd to Basket

    « Hide

    MELENIVANT VLLKAREGGG GKRKGKSKKW KEILKFPHIN QCEDLRRTID    50
    RDYYSLCDKQ PIGRLLFRQF CETRPGLECY IQFLDLVAEY EITPDENLGA 100
    KGKEIMTKYL SPKSPVFIAQ VGQDLVSQTE KKLLQSPCKE LFSACAQSVH 150
    DYLKGDPFHE YLDSMYFDRF LQWKWLERQP VTKNTFRQYR VLGKGGFGEV 200
    CACQVRATGK MYACKRLEKK RIKKRKGESM ALNEKQILEK VNSQFVVNLA 250
    YAYETKDALC LVLTIMNGGD LKFHIYNMGN PGFEEERALF YAAEILCGLE 300
    DLHRENTVYR DLKPENILLD DYGHIRISDL GLAVKIPEGD LIRGRVGTVG 350
    YMAPEVLNNQ RYGLSPDYWG LGCLIYEMIE GQSPFRGRKE KVKREEVDRR 400
    VLETEEVYSP KFSEEAKSIC NMLLTKDSKQ RLGCQEEGAA EVKRHPFFRN 450
    MNFKRLEAGM LDPPFVPDPR AVYCKDVLDI EQFSTVKGVN LDHTDDDFYS 500
    KFSTGSVPIP WQNEMIETEC FKELNVFGPN GTLSPDLNRS QPPEPPKKGL 550
    FHRLFRRQHQ NNSKSSPTPK TSCNHRINSN HINSNSTGSS 590
    Length:590
    Mass (Da):67,783
    Last modified:November 1, 1996 - v1
    Checksum:iDCAE0C00B1247AFA
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U34841 mRNA. Translation: AAC52536.1.
    RefSeqiNP_110456.1. NM_030829.1.
    UniGeneiRn.6500.

    Genome annotation databases

    GeneIDi59075.
    KEGGirno:59075.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U34841 mRNA. Translation: AAC52536.1 .
    RefSeqi NP_110456.1. NM_030829.1.
    UniGenei Rn.6500.

    3D structure databases

    ProteinModelPortali Q62833.
    SMRi Q62833. Positions 23-532.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    MINTi MINT-220922.
    STRINGi 10116.ENSRNOP00000015687.

    PTM databases

    PhosphoSitei Q62833.

    Proteomic databases

    PaxDbi Q62833.
    PRIDEi Q62833.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 59075.
    KEGGi rno:59075.

    Organism-specific databases

    CTDi 2869.
    RGDi 61985. Grk5.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000006742.
    HOVERGENi HBG004532.
    InParanoidi Q62833.
    KOi K08291.
    PhylomeDBi Q62833.

    Enzyme and pathway databases

    BRENDAi 2.7.11.16. 5301.

    Miscellaneous databases

    NextBioi 611692.

    Gene expression databases

    Genevestigatori Q62833.

    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.
    [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.
    PS50132. RGS. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Involvement of G protein-coupled receptor kinase 5 in homologous desensitization of the thyrotropin receptor."
      Nagayama Y., Tanaka K., Hara T., Namba H., Yamashita S., Taniyama K., Niwa M.
      J. Biol. Chem. 271:10143-10148(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Differential regulation of dopamine D1A receptor responsiveness by various G protein-coupled receptor kinases."
      Tiberi M., Nash S.R., Bertrand L., Lefkowitz R.J., Caron M.G.
      J. Biol. Chem. 271:3771-3778(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    3. "Myocardial distribution and regulation of GRK and beta-arrestin isoforms in congestive heart failure in rats."
      Vinge L.E., Oie E., Andersson Y., Grogaard H.K., Andersen G., Attramadal H.
      Am. J. Physiol. 281:H2490-H2499(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    4. "Distribution of G-protein-coupled receptor kinase (GRK) isoforms 2, 3, 5 and 6 mRNA in the rat brain."
      Erdtmann-Vourliotis M., Mayer P., Ammon S., Riechert U., Hollt V.
      Brain Res. Mol. Brain Res. 95:129-137(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY, INDUCTION.
    5. "Myocyte redistribution of GRK2 and GRK5 in hypertensive, heart-failure-prone rats."
      Yi X.P., Gerdes A.M., Li F.
      Hypertension 39:1058-1063(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.

    Entry informationi

    Entry nameiGRK5_RAT
    AccessioniPrimary (citable) accession number: Q62833
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 105 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3