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Q62833

- GRK5_RAT

UniProt

Q62833 - GRK5_RAT

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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

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
Complete GO annotation...

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-KW
  2. nucleus Source: UniProtKB-KW
  3. plasma membrane Source: UniProtKB
Complete GO annotation...

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.
[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

        10         20         30         40         50
MELENIVANT VLLKAREGGG GKRKGKSKKW KEILKFPHIN QCEDLRRTID
60 70 80 90 100
RDYYSLCDKQ PIGRLLFRQF CETRPGLECY IQFLDLVAEY EITPDENLGA
110 120 130 140 150
KGKEIMTKYL SPKSPVFIAQ VGQDLVSQTE KKLLQSPCKE LFSACAQSVH
160 170 180 190 200
DYLKGDPFHE YLDSMYFDRF LQWKWLERQP VTKNTFRQYR VLGKGGFGEV
210 220 230 240 250
CACQVRATGK MYACKRLEKK RIKKRKGESM ALNEKQILEK VNSQFVVNLA
260 270 280 290 300
YAYETKDALC LVLTIMNGGD LKFHIYNMGN PGFEEERALF YAAEILCGLE
310 320 330 340 350
DLHRENTVYR DLKPENILLD DYGHIRISDL GLAVKIPEGD LIRGRVGTVG
360 370 380 390 400
YMAPEVLNNQ RYGLSPDYWG LGCLIYEMIE GQSPFRGRKE KVKREEVDRR
410 420 430 440 450
VLETEEVYSP KFSEEAKSIC NMLLTKDSKQ RLGCQEEGAA EVKRHPFFRN
460 470 480 490 500
MNFKRLEAGM LDPPFVPDPR AVYCKDVLDI EQFSTVKGVN LDHTDDDFYS
510 520 530 540 550
KFSTGSVPIP WQNEMIETEC FKELNVFGPN GTLSPDLNRS QPPEPPKKGL
560 570 580 590
FHRLFRRQHQ NNSKSSPTPK TSCNHRINSN HINSNSTGSS
Length:590
Mass (Da):67,783
Last modified:November 1, 1996 - v1
Checksum:iDCAE0C00B1247AFA
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.
[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 29, 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, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3