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O70293 (GRK6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
G protein-coupled receptor kinase 6

EC=2.7.11.16
Alternative name(s):
G protein-coupled receptor kinase GRK6
Gene names
Name:Grk6
Synonyms:Gprk6
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length576 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4 Ref.5 Ref.6

Catalytic activity

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

Subcellular location

Membrane; Lipid-anchor.

Tissue specificity

Expressed in the brain in striatal neurons. Ref.6

Disruption phenotype

Deficient mice show significant altered central dopamine receptors regulation, deficient lymphocyte chemotaxis and increased acute inflammation and neutrophil chemotaxis. Ref.4 Ref.5 Ref.6

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

Binary interactions

With

Entry

#Exp.

IntAct

Notes

SLC9A3R1Q286195EBI-7073604,EBI-7073613From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform GRK6A (identifier: O70293-1)

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.
Isoform GRK6B (identifier: O70293-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 576576G protein-coupled receptor kinase 6
PRO_0000085975

Regions

Domain53 – 171119RGS
Domain186 – 448263Protein kinase
Domain449 – 51466AGC-kinase C-terminal
Nucleotide binding192 – 2009ATP By similarity
Nucleotide binding264 – 2707ATP By similarity
Nucleotide binding315 – 3184ATP By similarity
Region1 – 185185N-terminal

Sites

Active site3111Proton acceptor By similarity
Binding site2151ATP By similarity

Amino acid modifications

Modified residue4841Phosphoserine; by autocatalysis By similarity
Modified residue4851Phosphothreonine; by autocatalysis By similarity
Lipidation5611S-palmitoyl cysteine By similarity
Lipidation5621S-palmitoyl cysteine By similarity
Lipidation5651S-palmitoyl cysteine By similarity

Natural variations

Alternative sequence560 – 57617DCCGN…LPTRL → RIAVGTAATVRKSSPPASSP QAEAPTGGWR in isoform GRK6B.
VSP_004939

Experimental info

Sequence conflict981R → Q in AAC09265. Ref.1
Sequence conflict5711E → K in AAC09265. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform GRK6A [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: 91EEC2028CAF4B91

FASTA57665,979
        10         20         30         40         50         60 
MELENIVANT VLLKAREGGG GNRKGKSKKW RQMLQFPHIS QCEELRLSLE RDYHSLCERQ 

        70         80         90        100        110        120 
PIGRLLFREF CATRPELTRC TAFLDGVSEY EVTPDEKRKA CGRRLMQNFL SHTGPDLIPE 

       130        140        150        160        170        180 
VPRQLVSNCA QRLEQGPCKD LFQELTRLTH EYLSTAPFAD YLDSIYFNRF LQWKWLERQP 

       190        200        210        220        230        240 
VTKNTFRQYR VLGKGGFGEV CACQVRATGK MYACKKLEKK RIKKRKGEAM ALNEKQILEK 

       250        260        270        280        290        300 
VNSRFVVSLA YAYETKDALC LVLTLMNGGD LKFHIYHMGQ AGFPEARAVF YAAEICCGLE 

       310        320        330        340        350        360 
DLHRERIVYR DLKPENILLD DHGHIRISDL GLAVHVPEGQ TIKGRVGTVG YMAPEVVRNE 

       370        380        390        400        410        420 
RYTFSPDWWA LGCLLYEMIA GQSPFQQRKK KIKREEVERL VKEVAEEYTD RFSSQARSLC 

       430        440        450        460        470        480 
SQLLSKDPAE RLGCRGGGAR EVKEHPLFKK LNFKRLGAGM LEPPFKPDPQ AIYCKDVLDI 

       490        500        510        520        530        540 
EQFSTVKGVD LEPTDQDFYQ KFATGSVSIP WQNEMVETEC FQELNVFGLD GSVPPDLDWK 

       550        560        570 
GQPTAPPKKG LLQRLFSRQD CCGNCSDSEE ELPTRL 

« Hide

Isoform GRK6B [UniParc].

Checksum: C08443E7CB2B714D
Show »

FASTA58967,115

References

« Hide 'large scale' references
[1]"The GRK4 subfamily of G protein-coupled receptor kinases. Alternative splicing, gene organization, and sequence conservation."
Premont R.T., Macrae A.D., Aparicio S.A., Kendall H.E., Welch J.E., Lefkowitz R.J.
J. Biol. Chem. 274:29381-29389(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS GRK6A AND GRK6B).
Strain: 129/SvJ.
[2]"Primary structure of murine G-protein-coupled receptor kinase 6 splice variants predict differential regulation by posttranslational modifications."
Moepps B., Vatter P., Frode R., Waechter F., Gierschik P.
Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS GRK6A AND GRK6B).
Strain: 129/SvJ and C57BL/6J.
Tissue: Thymus.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GRK6B).
Strain: 129.
Tissue: Mammary gland.
[4]"Defective lymphocyte chemotaxis in beta-arrestin2- and GRK6-deficient mice."
Fong A.M., Premont R.T., Richardson R.M., Yu Y.R., Lefkowitz R.J., Patel D.D.
Proc. Natl. Acad. Sci. U.S.A. 99:7478-7483(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[5]"Increased acute inflammation, leukotriene B4-induced chemotaxis, and signaling in mice deficient for G protein-coupled receptor kinase 6."
Kavelaars A., Vroon A., Raatgever R.P., Fong A.M., Premont R.T., Patel D.D., Lefkowitz R.J., Heijnen C.J.
J. Immunol. 171:6128-6134(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[6]"Dopaminergic supersensitivity in G protein-coupled receptor kinase 6-deficient mice."
Gainetdinov R.R., Bohn L.M., Sotnikova T.D., Cyr M., Laakso A., Macrae A.D., Torres G.E., Kim K.M., Lefkowitz R.J., Caron M.G., Premont R.T.
Neuron 38:291-303(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001033107.1. NM_001038018.4.
NP_001106182.1. NM_001112711.2.
NP_001272992.1. NM_001286063.1.
NP_001272993.1. NM_001286064.1.
NP_001272994.1. NM_001286065.1.
NP_036068.2. NM_011938.4.
UniGeneMm.10193.

3D structure databases

ProteinModelPortalO70293.
SMRO70293. Positions 2-557.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActO70293. 3 interactions.
MINTMINT-1793102.

PTM databases

PhosphoSiteO70293.

Proteomic databases

PaxDbO70293.
PRIDEO70293.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000001115; ENSMUSP00000001115; ENSMUSG00000074886. [O70293-2]
GeneID26385.
KEGGmmu:26385.
UCSCuc007qqw.1. mouse. [O70293-1]

Organism-specific databases

CTD2870.
MGIMGI:1347078. Grk6.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00730000110512.
HOGENOMHOG000006742.
HOVERGENHBG004532.
InParanoidQ6DI67.
KOK08291.
OMAMLEPPFK.
OrthoDBEOG7V1FQK.
PhylomeDBO70293.
TreeFamTF313940.

Gene expression databases

ArrayExpressO70293.
BgeeO70293.
CleanExMM_GRK6.
GenevestigatorO70293.

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

NextBio304313.
PROO70293.
SOURCESearch...

Entry information

Entry nameGRK6_MOUSE
AccessionPrimary (citable) accession number: O70293
Secondary accession number(s): O70294, O70295, Q6DI67
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: August 1, 1998
Last modified: April 16, 2014
This is version 133 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

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot