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Protein

G protein-coupled receptor kinase 6

Gene

Grk6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Specifically phosphorylates the activated forms of G protein-coupled receptors. Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their desensitization. Seems to be involved in the desensitization of D2-like dopamine receptors in striatum and chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis (By similarity). Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor, LRP6 during Wnt signaling (in vitro) (By similarity).By similarity3 Publications

Catalytic activityi

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

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
Nucleotide bindingi264 – 270ATPPROSITE-ProRule annotation7
Nucleotide bindingi315 – 318ATPPROSITE-ProRule annotation4

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Wnt signaling pathway

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.16. 3474.
ReactomeiR-MMU-418555. G alpha (s) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
G protein-coupled receptor kinase 6 (EC:2.7.11.16)
Alternative name(s):
G protein-coupled receptor kinase GRK6
Gene namesi
Name:Grk6
Synonyms:Gprk6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:1347078. Grk6.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Disruption phenotypei

Deficient mice show significant altered central dopamine receptors regulation, deficient lymphocyte chemotaxis and increased acute inflammation and neutrophil chemotaxis.3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000859751 – 576G protein-coupled receptor kinase 6Add BLAST576

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei484PhosphoserineCombined sources1
Modified residuei485PhosphothreonineCombined sources1
Lipidationi561S-palmitoyl cysteineBy similarity1
Lipidationi562S-palmitoyl cysteineBy similarity1
Lipidationi565S-palmitoyl cysteineBy similarity1
Modified residuei566PhosphoserineCombined sources1
Modified residuei568PhosphoserineCombined sources1
Isoform GRK6B (identifier: O70293-2)
Modified residuei578PhosphoserineCombined sources1

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

MaxQBiO70293.
PaxDbiO70293.
PeptideAtlasiO70293.
PRIDEiO70293.

PTM databases

iPTMnetiO70293.
PhosphoSitePlusiO70293.
SwissPalmiO70293.

Expressioni

Tissue specificityi

Expressed in the brain in striatal neurons.1 Publication

Gene expression databases

BgeeiENSMUSG00000074886.
CleanExiMM_GRK6.
ExpressionAtlasiO70293. baseline and differential.
GenevisibleiO70293. MM.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
SLC9A3R1Q286195EBI-7073604,EBI-7073613From a different organism.

Protein-protein interaction databases

IntActiO70293. 3 interactors.
MINTiMINT-1793102.
STRINGi10090.ENSMUSP00000001115.

Structurei

3D structure databases

ProteinModelPortaliO70293.
SMRiO70293.
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

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.
InParanoidiO70293.
KOiK08291.
OMAiMLEPPFK.
OrthoDBiEOG091G062G.
PhylomeDBiO70293.
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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform GRK6A (identifier: O70293-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MELENIVANT VLLKAREGGG GNRKGKSKKW RQMLQFPHIS QCEELRLSLE
60 70 80 90 100
RDYHSLCERQ PIGRLLFREF CATRPELTRC TAFLDGVSEY EVTPDEKRKA
110 120 130 140 150
CGRRLMQNFL SHTGPDLIPE VPRQLVSNCA QRLEQGPCKD LFQELTRLTH
160 170 180 190 200
EYLSTAPFAD YLDSIYFNRF LQWKWLERQP VTKNTFRQYR VLGKGGFGEV
210 220 230 240 250
CACQVRATGK MYACKKLEKK RIKKRKGEAM ALNEKQILEK VNSRFVVSLA
260 270 280 290 300
YAYETKDALC LVLTLMNGGD LKFHIYHMGQ AGFPEARAVF YAAEICCGLE
310 320 330 340 350
DLHRERIVYR DLKPENILLD DHGHIRISDL GLAVHVPEGQ TIKGRVGTVG
360 370 380 390 400
YMAPEVVRNE RYTFSPDWWA LGCLLYEMIA GQSPFQQRKK KIKREEVERL
410 420 430 440 450
VKEVAEEYTD RFSSQARSLC SQLLSKDPAE RLGCRGGGAR EVKEHPLFKK
460 470 480 490 500
LNFKRLGAGM LEPPFKPDPQ AIYCKDVLDI EQFSTVKGVD LEPTDQDFYQ
510 520 530 540 550
KFATGSVSIP WQNEMVETEC FQELNVFGLD GSVPPDLDWK GQPTAPPKKG
560 570
LLQRLFSRQD CCGNCSDSEE ELPTRL
Length:576
Mass (Da):65,979
Last modified:August 1, 1998 - v1
Checksum:i91EEC2028CAF4B91
GO
Isoform GRK6B (identifier: O70293-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     560-576: DCCGNCSDSEEELPTRL → RIAVGTAATVRKSSPPASSPQAEAPTGGWR

Show »
Length:589
Mass (Da):67,115
Checksum:iC08443E7CB2B714D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti98R → Q in AAC09265 (PubMed:10506199).Curated1
Sequence conflicti571E → K in AAC09265 (PubMed:10506199).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004939560 – 576DCCGN…LPTRL → RIAVGTAATVRKSSPPASSP QAEAPTGGWR in isoform GRK6B. 3 PublicationsAdd BLAST17

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF040747 mRNA. Translation: AAC09268.1.
AF040748 mRNA. Translation: AAC09269.1.
AF040749 mRNA. Translation: AAC09270.1.
AF040754 Genomic DNA. Translation: AAC09265.1.
Y17967 Genomic DNA. Translation: CAA76975.1.
Y17967 Genomic DNA. Translation: CAA76976.1.
Y15798 mRNA. Translation: CAA75789.1.
Y15799 mRNA. Translation: CAA75790.1.
BC075719 mRNA. Translation: AAH75719.1.
CCDSiCCDS49272.1. [O70293-2]
RefSeqiNP_001033107.1. NM_001038018.4. [O70293-2]
NP_001106182.1. NM_001112711.2. [O70293-1]
NP_001272992.1. NM_001286063.1.
NP_001272993.1. NM_001286064.1.
NP_001272994.1. NM_001286065.1.
NP_036068.2. NM_011938.4.
UniGeneiMm.10193.

Genome annotation databases

EnsembliENSMUST00000001115; ENSMUSP00000001115; ENSMUSG00000074886. [O70293-2]
GeneIDi26385.
KEGGimmu:26385.
UCSCiuc007qqw.2. mouse. [O70293-2]
uc011yzt.2. mouse. [O70293-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF040747 mRNA. Translation: AAC09268.1.
AF040748 mRNA. Translation: AAC09269.1.
AF040749 mRNA. Translation: AAC09270.1.
AF040754 Genomic DNA. Translation: AAC09265.1.
Y17967 Genomic DNA. Translation: CAA76975.1.
Y17967 Genomic DNA. Translation: CAA76976.1.
Y15798 mRNA. Translation: CAA75789.1.
Y15799 mRNA. Translation: CAA75790.1.
BC075719 mRNA. Translation: AAH75719.1.
CCDSiCCDS49272.1. [O70293-2]
RefSeqiNP_001033107.1. NM_001038018.4. [O70293-2]
NP_001106182.1. NM_001112711.2. [O70293-1]
NP_001272992.1. NM_001286063.1.
NP_001272993.1. NM_001286064.1.
NP_001272994.1. NM_001286065.1.
NP_036068.2. NM_011938.4.
UniGeneiMm.10193.

3D structure databases

ProteinModelPortaliO70293.
SMRiO70293.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO70293. 3 interactors.
MINTiMINT-1793102.
STRINGi10090.ENSMUSP00000001115.

PTM databases

iPTMnetiO70293.
PhosphoSitePlusiO70293.
SwissPalmiO70293.

Proteomic databases

MaxQBiO70293.
PaxDbiO70293.
PeptideAtlasiO70293.
PRIDEiO70293.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000001115; ENSMUSP00000001115; ENSMUSG00000074886. [O70293-2]
GeneIDi26385.
KEGGimmu:26385.
UCSCiuc007qqw.2. mouse. [O70293-2]
uc011yzt.2. mouse. [O70293-1]

Organism-specific databases

CTDi2870.
MGIiMGI:1347078. Grk6.

Phylogenomic databases

eggNOGiKOG0986. Eukaryota.
ENOG410YRQZ. LUCA.
GeneTreeiENSGT00860000133699.
HOGENOMiHOG000006742.
HOVERGENiHBG004532.
InParanoidiO70293.
KOiK08291.
OMAiMLEPPFK.
OrthoDBiEOG091G062G.
PhylomeDBiO70293.
TreeFamiTF313940.

Enzyme and pathway databases

BRENDAi2.7.11.16. 3474.
ReactomeiR-MMU-418555. G alpha (s) signalling events.

Miscellaneous databases

PROiO70293.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000074886.
CleanExiMM_GRK6.
ExpressionAtlasiO70293. baseline and differential.
GenevisibleiO70293. MM.

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 nameiGRK6_MOUSE
AccessioniPrimary (citable) accession number: O70293
Secondary accession number(s): O70294, O70295, Q6DI67
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: August 1, 1998
Last modified: November 30, 2016
This is version 159 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. 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.