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P43249 (GRK5_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
G protein-coupled receptor kinase 5

EC=2.7.11.16
Alternative name(s):
G protein-coupled receptor kinase GRK5
Gene names
Name:GRK5
Synonyms:GPRK5
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos

Protein attributes

Sequence length590 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1

Catalytic activity

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

Enzyme regulation

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

Subunit structure

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

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. Cell membrane; 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.

Tissue specificity

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

Post-translational modification

Autophosphorylated. Autophosphorylation may play a critical role in the regulation of GRK5 kinase activity By similarity. Ref.1

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily.

Contains 1 AGC-kinase C-terminal domain.

Contains 1 protein kinase domain.

Contains 1 RGS domain.

Ontologies

Keywords
   Biological processApoptosis
Wnt signaling pathway
   Cellular componentCell membrane
Cytoplasm
Membrane
Nucleus
   LigandATP-binding
Lipid-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

tachykinin receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

termination of G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

G-protein coupled receptor kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

lipid binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein serine/threonine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 590590G protein-coupled receptor kinase 5
PRO_0000085970

Regions

Domain53 – 171119RGS
Domain186 – 448263Protein kinase
Domain449 – 51466AGC-kinase C-terminal
Nucleotide binding192 – 2009ATP By similarity
Region1 – 185185N-terminal
Region20 – 3920Interaction with calmodulin By similarity
Region546 – 56520Sufficient for membrane localization By similarity
Motif388 – 3958Nuclear localization signal By similarity

Sites

Active site3111Proton acceptor By similarity
Binding site2151ATP By similarity

Amino acid modifications

Modified residue4841Phosphoserine; by autocatalysis
Modified residue4851Phosphothreonine; by autocatalysis

Sequences

Sequence LengthMass (Da)Tools
P43249 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: E8F353697D8BA6E2

FASTA59067,889
        10         20         30         40         50         60 
MELENIVANT VLLKAREGGG GKRKGKSKKW KEILKFPHIN QCEDLRRTID RDYCSLCDKQ 

        70         80         90        100        110        120 
PVGRLLFRQF CETRPGLESY IQFLDSVAEY EVTPDEKLGE KGKEIMTKYL TPKSPVFITQ 

       130        140        150        160        170        180 
VGRDLVSQTE EKLLQKPCKE LFSACVQSVH DYLRGEPFHE YLDSMYFDRF LQWKWLERQP 

       190        200        210        220        230        240 
VTKNTFRQYR VLGKGGFGEV CACQVRATGK MYACKRLEKK RIKKRKGESM ALNEKQILEK 

       250        260        270        280        290        300 
VNSRFVVNLA YAYETKDALC LVLTIMNGGD LKFHIYNMGN PGFEEERALF YAAEILCGLE 

       310        320        330        340        350        360 
DLHHENIVYR DLKPENILLD DYGHIRISDL GLAVKIPEGD LIRGRVGTVG YMAPEVLNNQ 

       370        380        390        400        410        420 
RYGLSPDYWG LGCLIYEMIE GQSPFRGRKE KVKREEVDRR VLETEEVYSH KFSEEAKSIC 

       430        440        450        460        470        480 
KMLLTKDAKQ RLGCQEEGAA EVKRHPFFRN MNFKRLEAGM LDPPFVPDPR AVYCKDVLDI 

       490        500        510        520        530        540 
EQFSTVKGVN LDHTDDDFYS KFSTGSVPIP WQSEMIETEC FKELNVFGPH GTLSPDLNRS 

       550        560        570        580        590 
HPPEPPKKGL LQRLFKRQHQ NNSKSSPNSK TSFNHHINSN HVSSNSTGSS 

« Hide

References

[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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U01206 mRNA. Translation: AAA17561.1.
PIRA54372.
RefSeqNP_776756.1. NM_174331.2.
UniGeneBt.4263.

3D structure databases

ProteinModelPortalP43249.
SMRP43249. Positions 23-532.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9913.ENSBTAP00000010492.

Proteomic databases

PRIDEP43249.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSBTAT00000010492; ENSBTAP00000010492; ENSBTAG00000007981.
GeneID281801.
KEGGbta:281801.

Organism-specific databases

CTD2869.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00730000110512.
HOGENOMHOG000006742.
HOVERGENHBG004532.
InParanoidP43249.
KOK08291.
OMAEMMETEC.
OrthoDBEOG7V1FQK.
TreeFamTF313940.

Enzyme and pathway databases

BRENDA2.7.11.16. 908.

Family and domain databases

InterProIPR000961. 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]
PfamPF00069. Pkinase. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view]
PRINTSPR00717. GPCRKINASE.
SMARTSM00315. RGS. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF48097. SSF48097. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS51285. 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]
ProtoNetSearch...

Other

NextBio20805714.

Entry information

Entry nameGRK5_BOVIN
AccessionPrimary (citable) accession number: P43249
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: February 19, 2014
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families