G protein-coupled receptor kinase 5

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P43249 (GRK5_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified December 14, 2011. Version 89. History...

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended 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

Organism

Bos taurus (Bovine)

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	590 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Apoptosis Wnt signaling pathway
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Ligand	ATP-binding Lipid-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	Wnt receptor 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
Cellular component	cytoplasm 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 function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW G-protein coupled receptor kinase activity Inferred from electronic annotation. Source: EC lipid binding Inferred from electronic annotation. Source: UniProtKB-KW signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 590

590

G protein-coupled receptor kinase 5

PRO_0000085970

Regions

Domain

53 – 171

119

RGS

Domain

186 – 448

263

Protein kinase

Domain

449 – 514

AGC-kinase C-terminal

Nucleotide binding

192 – 200

ATP By similarity

Region

1 – 185

185

N-terminal

Region

20 – 39

Interaction with calmodulin By similarity

Region

546 – 565

Sufficient for membrane localization By similarity

Motif

388 – 395

Nuclear localization signal By similarity

Sites

Active site

311

Proton acceptor By similarity

Binding site

215

ATP By similarity

Amino acid modifications

Modified residue

484

Phosphoserine; by autocatalysis

Modified residue

485

Phosphothreonine; by autocatalysis

Sequences

Sequence

Length

Mass (Da)

Tools

P43249 [UniParc].

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

590

67,889

        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

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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: 8120045] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 479-491, TISSUE SPECIFICITY, FUNCTION, AUTOPHOSPHORYLATION. Tissue: Tongue epithelium.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U01206 mRNA. Translation: AAA17561.1.
IPI	IPI00698786.
PIR	A54372.
RefSeq	NP_776756.1. NM_174331.2.
UniGene	Bt.4263.
3D structure databases
ProteinModelPortal	P43249.
SMR	P43249. Positions 23-532.
ModBase	Search...
Protein-protein interaction databases
STRING	P43249.
Proteomic databases
PRIDE	P43249.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSBTAT00000010492; ENSBTAP00000010492; ENSBTAG00000007981.
GeneID	281801.
KEGG	bta:281801.
Organism-specific databases
CTD	2869.
Phylogenomic databases
eggNOG	maNOG06237.
GeneTree	ENSGT00550000074318.
HOVERGEN	HBG004532.
InParanoid	P43249.
OrthoDB	EOG4HHP24.
Enzyme and pathway databases
BRENDA	2.7.11.16. 908.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR000239. GPCR_kinase. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR000342. Regulat_G_prot_signal. IPR016137. Regulat_G_prot_signal_superfam. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
KO	K08291.
Pfam	PF00069. Pkinase. 1 hit. PF00615. RGS. 1 hit. [Graphical view]
PRINTS	PR00717. GPCRKINASE.
SMART	SM00315. RGS. 1 hit. SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF48097. Regulat_G_prot_signal_superfam. 1 hit.
PROSITE	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]
ProtoNet	Search...

Entry information

Entry name

GRK5_BOVIN

Accession

Primary (citable) accession number: P43249

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	December 14, 2011
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Family and domain databases

Entry information

Relevant documents