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O70293

- GRK6_MOUSE

UniProt

O70293 - GRK6_MOUSE

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Protein

G protein-coupled receptor kinase 6

Gene

Grk6

Organism
Mus musculus (Mouse)
Status
Reviewed - 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 similarity

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei215 – 2151ATPPROSITE-ProRule annotation
Active sitei311 – 3111Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi192 – 2009ATPPROSITE-ProRule annotation
Nucleotide bindingi264 – 2707ATPPROSITE-ProRule annotation
Nucleotide bindingi315 – 3184ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. G-protein coupled receptor kinase activity Source: UniProtKB-EC

GO - Biological processi

  1. termination of G-protein coupled receptor signaling pathway Source: InterPro
  2. Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Wnt signaling pathway

Keywords - Ligandi

ATP-binding, Nucleotide-binding

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
ProteomesiUP000000589: Chromosome 13

Organism-specific databases

MGIiMGI:1347078. Grk6.

Subcellular locationi

GO - Cellular componenti

  1. membrane Source: UniProtKB-KW
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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 576576G protein-coupled receptor kinase 6PRO_0000085975Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei484 – 4841Phosphoserine; by autocatalysisBy similarity
Modified residuei485 – 4851Phosphothreonine; by autocatalysisBy similarity
Lipidationi561 – 5611S-palmitoyl cysteineBy similarity
Lipidationi562 – 5621S-palmitoyl cysteineBy similarity
Lipidationi565 – 5651S-palmitoyl cysteineBy similarity

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

MaxQBiO70293.
PaxDbiO70293.
PRIDEiO70293.

PTM databases

PhosphoSiteiO70293.

Expressioni

Tissue specificityi

Expressed in the brain in striatal neurons.1 Publication

Gene expression databases

BgeeiO70293.
CleanExiMM_GRK6.
ExpressionAtlasiO70293. baseline and differential.
GenevestigatoriO70293.

Interactioni

Binary interactionsi

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

Protein-protein interaction databases

IntActiO70293. 3 interactions.
MINTiMINT-1793102.

Structurei

3D structure databases

ProteinModelPortaliO70293.
SMRiO70293. Positions 2-557.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini53 – 171119RGSPROSITE-ProRule annotationAdd
BLAST
Domaini186 – 448263Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini449 – 51466AGC-kinase C-terminalAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 185185N-terminalAdd
BLAST

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

eggNOGiCOG0515.
GeneTreeiENSGT00770000120493.
HOGENOMiHOG000006742.
HOVERGENiHBG004532.
InParanoidiO70293.
KOiK08291.
OMAiMLEPPFK.
OrthoDBiEOG7V1FQK.
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. Regulat_G_prot_signal_superfam.
IPR000342. RGS_dom.
IPR002290. Ser/Thr_dual-sp_kinase.
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. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti98 – 981R → Q in AAC09265. (PubMed:10506199)Curated
Sequence conflicti571 – 5711E → K in AAC09265. (PubMed:10506199)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei560 – 57617DCCGN…LPTRL → RIAVGTAATVRKSSPPASSP QAEAPTGGWR in isoform GRK6B. 3 PublicationsVSP_004939Add
BLAST

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.1. 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 .
CCDSi CCDS49272.1. [O70293-2 ]
RefSeqi NP_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.
UniGenei Mm.10193.

3D structure databases

ProteinModelPortali O70293.
SMRi O70293. Positions 2-557.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi O70293. 3 interactions.
MINTi MINT-1793102.

PTM databases

PhosphoSitei O70293.

Proteomic databases

MaxQBi O70293.
PaxDbi O70293.
PRIDEi O70293.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000001115 ; ENSMUSP00000001115 ; ENSMUSG00000074886 . [O70293-2 ]
GeneIDi 26385.
KEGGi mmu:26385.
UCSCi uc007qqw.1. mouse. [O70293-1 ]

Organism-specific databases

CTDi 2870.
MGIi MGI:1347078. Grk6.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00770000120493.
HOGENOMi HOG000006742.
HOVERGENi HBG004532.
InParanoidi O70293.
KOi K08291.
OMAi MLEPPFK.
OrthoDBi EOG7V1FQK.
PhylomeDBi O70293.
TreeFami TF313940.

Miscellaneous databases

NextBioi 304313.
PROi O70293.
SOURCEi Search...

Gene expression databases

Bgeei O70293.
CleanExi MM_GRK6.
ExpressionAtlasi O70293. baseline and differential.
Genevestigatori O70293.

Family and domain databases

InterProi IPR000961. 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.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view ]
PRINTSi PR00717. GPCRKINASE.
SMARTi SM00315. RGS. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF48097. SSF48097. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi 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 ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

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 26, 2014
This is version 139 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

External Data

Dasty 3