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P43249

- GRK5_BOVIN

UniProt

P43249 - GRK5_BOVIN

Protein

G protein-coupled receptor kinase 5

Gene

GRK5

Organism
Bos taurus (Bovine)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 106 (01 Oct 2014)
      Sequence version 1 (01 Nov 1995)
      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 (Beta-2 adrenergic receptor), 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. 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: UniProtKB-EC
    3. lipid binding Source: UniProtKB-KW
    4. protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. negative regulation of apoptotic process Source: UniProtKB
    3. protein autophosphorylation Source: UniProtKB
    4. tachykinin receptor signaling pathway Source: Ensembl
    5. termination of G-protein coupled receptor signaling pathway Source: InterPro
    6. 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. 908.
    ReactomeiREACT_209521. G alpha (q) signalling events.

    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
    OrganismiBos taurus (Bovine)
    Taxonomic identifieri9913 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
    ProteomesiUP000009136: Chromosome 26

    Subcellular locationi

    Cytoplasm By similarity. Nucleus By similarity. 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_0000085970Add
    BLAST

    Amino acid modifications

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

    Post-translational modificationi

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

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PRIDEiP43249.

    Expressioni

    Tissue specificityi

    Highest levels in lung, heart, retina, lingual epithelium. Very little in brain, liver, kidney.1 Publication

    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

    DIPiDIP-60782N.
    STRINGi9913.ENSBTAP00000010492.

    Structurei

    3D structure databases

    ProteinModelPortaliP43249.
    SMRiP43249. 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.
    GeneTreeiENSGT00730000110512.
    HOGENOMiHOG000006742.
    HOVERGENiHBG004532.
    InParanoidiP43249.
    KOiK08291.
    OMAiEMMETEC.
    OrthoDBiEOG7V1FQK.
    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]

    Sequencei

    Sequence statusi: Complete.

    P43249-1 [UniParc]FASTAAdd to Basket

    « Hide

    MELENIVANT VLLKAREGGG GKRKGKSKKW KEILKFPHIN QCEDLRRTID    50
    RDYCSLCDKQ PVGRLLFRQF CETRPGLESY IQFLDSVAEY EVTPDEKLGE 100
    KGKEIMTKYL TPKSPVFITQ VGRDLVSQTE EKLLQKPCKE LFSACVQSVH 150
    DYLRGEPFHE YLDSMYFDRF LQWKWLERQP VTKNTFRQYR VLGKGGFGEV 200
    CACQVRATGK MYACKRLEKK RIKKRKGESM ALNEKQILEK VNSRFVVNLA 250
    YAYETKDALC LVLTIMNGGD LKFHIYNMGN PGFEEERALF YAAEILCGLE 300
    DLHHENIVYR DLKPENILLD DYGHIRISDL GLAVKIPEGD LIRGRVGTVG 350
    YMAPEVLNNQ RYGLSPDYWG LGCLIYEMIE GQSPFRGRKE KVKREEVDRR 400
    VLETEEVYSH KFSEEAKSIC KMLLTKDAKQ RLGCQEEGAA EVKRHPFFRN 450
    MNFKRLEAGM LDPPFVPDPR AVYCKDVLDI EQFSTVKGVN LDHTDDDFYS 500
    KFSTGSVPIP WQSEMIETEC FKELNVFGPH GTLSPDLNRS HPPEPPKKGL 550
    LQRLFKRQHQ NNSKSSPNSK TSFNHHINSN HVSSNSTGSS 590
    Length:590
    Mass (Da):67,889
    Last modified:November 1, 1995 - v1
    Checksum:iE8F353697D8BA6E2
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U01206 mRNA. Translation: AAA17561.1.
    PIRiA54372.
    RefSeqiNP_776756.1. NM_174331.2.
    UniGeneiBt.4263.

    Genome annotation databases

    EnsembliENSBTAT00000010492; ENSBTAP00000010492; ENSBTAG00000007981.
    GeneIDi281801.
    KEGGibta:281801.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U01206 mRNA. Translation: AAA17561.1 .
    PIRi A54372.
    RefSeqi NP_776756.1. NM_174331.2.
    UniGenei Bt.4263.

    3D structure databases

    ProteinModelPortali P43249.
    SMRi P43249. Positions 23-532.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-60782N.
    STRINGi 9913.ENSBTAP00000010492.

    Proteomic databases

    PRIDEi P43249.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSBTAT00000010492 ; ENSBTAP00000010492 ; ENSBTAG00000007981 .
    GeneIDi 281801.
    KEGGi bta:281801.

    Organism-specific databases

    CTDi 2869.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00730000110512.
    HOGENOMi HOG000006742.
    HOVERGENi HBG004532.
    InParanoidi P43249.
    KOi K08291.
    OMAi EMMETEC.
    OrthoDBi EOG7V1FQK.
    TreeFami TF313940.

    Enzyme and pathway databases

    BRENDAi 2.7.11.16. 908.
    Reactomei REACT_209521. G alpha (q) signalling events.

    Miscellaneous databases

    NextBioi 20805714.

    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. "Identification, purification, and characterization of GRK5, a member of the family of G protein-coupled receptor kinases."
      Premont R.T., Koch W.J., Inglese J., Lefkowitz R.J.
      J. Biol. Chem. 269:6832-6841(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 479-491, TISSUE SPECIFICITY, FUNCTION, AUTOPHOSPHORYLATION.
      Tissue: Tongue epithelium.

    Entry informationi

    Entry nameiGRK5_BOVIN
    AccessioniPrimary (citable) accession number: P43249
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: November 1, 1995
    Last modified: October 1, 2014
    This is version 106 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, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3