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Protein

G protein-coupled receptor kinase 5

Gene

GRK5

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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 (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 similarity1 Publication

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)DescriptionActionsGraphical viewLength
Binding sitei215ATPPROSITE-ProRule annotation1
Active sitei311Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi192 – 200ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

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. 908.
ReactomeiR-BTA-418555. G alpha (s) 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
Proteomesi
  • UP000009136 Componenti: 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

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000859701 – 590G protein-coupled receptor kinase 5Add BLAST590

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei484Phosphoserine; by autocatalysis1 Publication1
Modified residuei485Phosphothreonine; by autocatalysis1 Publication1
Modified residuei579PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP43249.
PRIDEiP43249.

PTM databases

iPTMnetiP43249.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSBTAG00000007981.

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

Secondary structure

1590
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi30 – 33Combined sources4
Helixi39 – 42Combined sources4
Helixi43 – 47Combined sources5
Helixi53 – 57Combined sources5
Helixi61 – 72Combined sources12
Turni75 – 77Combined sources3
Helixi78 – 91Combined sources14
Helixi98 – 109Combined sources12
Beta strandi111 – 113Combined sources3
Helixi123 – 135Combined sources13
Helixi143 – 153Combined sources11
Helixi156 – 163Combined sources8
Helixi165 – 177Combined sources13
Helixi183 – 185Combined sources3
Beta strandi186 – 194Combined sources9
Beta strandi196 – 205Combined sources10
Turni206 – 208Combined sources3
Beta strandi211 – 218Combined sources8
Helixi219 – 224Combined sources6
Helixi228 – 240Combined sources13
Beta strandi249 – 254Combined sources6
Beta strandi256 – 263Combined sources8
Helixi271 – 275Combined sources5
Beta strandi277 – 280Combined sources4
Helixi285 – 304Combined sources20
Helixi314 – 316Combined sources3
Beta strandi317 – 319Combined sources3
Beta strandi325 – 327Combined sources3
Helixi354 – 357Combined sources4
Beta strandi362 – 364Combined sources3
Helixi365 – 380Combined sources16
Beta strandi381 – 383Combined sources3
Helixi394 – 403Combined sources10
Helixi414 – 423Combined sources10
Helixi428 – 430Combined sources3
Turni436 – 438Combined sources3
Helixi439 – 443Combined sources5
Helixi446 – 448Combined sources3
Helixi453 – 457Combined sources5
Helixi494 – 502Combined sources9
Helixi508 – 517Combined sources10
Helixi520 – 524Combined sources5
Beta strandi529 – 531Combined sources3
Helixi535 – 537Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4WNKX-ray2.42A1-590[»]
ProteinModelPortaliP43249.
SMRiP43249.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini53 – 171RGSPROSITE-ProRule annotationAdd BLAST119
Domaini186 – 448Protein kinasePROSITE-ProRule annotationAdd BLAST263
Domaini449 – 514AGC-kinase C-terminalAdd BLAST66

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 185N-terminalAdd BLAST185
Regioni20 – 39Interaction with calmodulinBy similarityAdd BLAST20
Regioni546 – 565Sufficient for membrane localizationBy similarityAdd BLAST20

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi388 – 395Nuclear localization signalBy similarity8

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

eggNOGiKOG0986. Eukaryota.
ENOG410YRQZ. LUCA.
GeneTreeiENSGT00860000133699.
HOGENOMiHOG000006742.
HOVERGENiHBG004532.
InParanoidiP43249.
KOiK08291.
OMAiEFENSMY.
OrthoDBiEOG091G062G.
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. RGS.
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

        10         20         30         40         50
MELENIVANT VLLKAREGGG GKRKGKSKKW KEILKFPHIN QCEDLRRTID
60 70 80 90 100
RDYCSLCDKQ PVGRLLFRQF CETRPGLESY IQFLDSVAEY EVTPDEKLGE
110 120 130 140 150
KGKEIMTKYL TPKSPVFITQ VGRDLVSQTE EKLLQKPCKE LFSACVQSVH
160 170 180 190 200
DYLRGEPFHE YLDSMYFDRF LQWKWLERQP VTKNTFRQYR VLGKGGFGEV
210 220 230 240 250
CACQVRATGK MYACKRLEKK RIKKRKGESM ALNEKQILEK VNSRFVVNLA
260 270 280 290 300
YAYETKDALC LVLTIMNGGD LKFHIYNMGN PGFEEERALF YAAEILCGLE
310 320 330 340 350
DLHHENIVYR DLKPENILLD DYGHIRISDL GLAVKIPEGD LIRGRVGTVG
360 370 380 390 400
YMAPEVLNNQ RYGLSPDYWG LGCLIYEMIE GQSPFRGRKE KVKREEVDRR
410 420 430 440 450
VLETEEVYSH KFSEEAKSIC KMLLTKDAKQ RLGCQEEGAA EVKRHPFFRN
460 470 480 490 500
MNFKRLEAGM LDPPFVPDPR AVYCKDVLDI EQFSTVKGVN LDHTDDDFYS
510 520 530 540 550
KFSTGSVPIP WQSEMIETEC FKELNVFGPH GTLSPDLNRS HPPEPPKKGL
560 570 580 590
LQRLFKRQHQ NNSKSSPNSK TSFNHHINSN HVSSNSTGSS
Length:590
Mass (Da):67,889
Last modified:November 1, 1995 - v1
Checksum:iE8F353697D8BA6E2
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
Links Updated
U01206 mRNA. Translation: AAA17561.1.
PIRiA54372.
RefSeqiNP_776756.1. NM_174331.2.
UniGeneiBt.4263.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4WNKX-ray2.42A1-590[»]
ProteinModelPortaliP43249.
SMRiP43249.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-60782N.
STRINGi9913.ENSBTAP00000010492.

PTM databases

iPTMnetiP43249.

Proteomic databases

PaxDbiP43249.
PRIDEiP43249.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2869.

Phylogenomic databases

eggNOGiKOG0986. Eukaryota.
ENOG410YRQZ. LUCA.
GeneTreeiENSGT00860000133699.
HOGENOMiHOG000006742.
HOVERGENiHBG004532.
InParanoidiP43249.
KOiK08291.
OMAiEFENSMY.
OrthoDBiEOG091G062G.
TreeFamiTF313940.

Enzyme and pathway databases

BRENDAi2.7.11.16. 908.
ReactomeiR-BTA-418555. G alpha (s) signalling events.

Gene expression databases

BgeeiENSBTAG00000007981.

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. RGS.
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]
ProtoNetiSearch...

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: November 30, 2016
This is version 124 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.