GRK6_MOUSE
ID GRK6_MOUSE Reviewed; 576 AA.
AC O70293; O70294; O70295; Q6DI67;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=G protein-coupled receptor kinase 6;
DE EC=2.7.11.16;
DE AltName: Full=G protein-coupled receptor kinase GRK6;
GN Name=Grk6; Synonyms=Gprk6;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS GRK6A AND GRK6B).
RC STRAIN=129/SvJ;
RX PubMed=10506199; DOI=10.1074/jbc.274.41.29381;
RA Premont R.T., Macrae A.D., Aparicio S.A., Kendall H.E., Welch J.E.,
RA Lefkowitz R.J.;
RT "The GRK4 subfamily of G protein-coupled receptor kinases. Alternative
RT splicing, gene organization, and sequence conservation.";
RL J. Biol. Chem. 274:29381-29389(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS GRK6A AND GRK6B).
RC STRAIN=129/SvJ, and C57BL/6J; TISSUE=Thymus;
RA Moepps B., Vatter P., Frode R., Waechter F., Gierschik P.;
RT "Primary structure of murine G-protein-coupled receptor kinase 6 splice
RT variants predict differential regulation by posttranslational
RT modifications.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GRK6B).
RC STRAIN=129; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=12032308; DOI=10.1073/pnas.112198299;
RA Fong A.M., Premont R.T., Richardson R.M., Yu Y.R., Lefkowitz R.J.,
RA Patel D.D.;
RT "Defective lymphocyte chemotaxis in beta-arrestin2- and GRK6-deficient
RT mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:7478-7483(2002).
RN [5]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=14634128; DOI=10.4049/jimmunol.171.11.6128;
RA Kavelaars A., Vroon A., Raatgever R.P., Fong A.M., Premont R.T.,
RA Patel D.D., Lefkowitz R.J., Heijnen C.J.;
RT "Increased acute inflammation, leukotriene B4-induced chemotaxis, and
RT signaling in mice deficient for G protein-coupled receptor kinase 6.";
RL J. Immunol. 171:6128-6134(2003).
RN [6]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=12718862; DOI=10.1016/s0896-6273(03)00192-2;
RA Gainetdinov R.R., Bohn L.M., Sotnikova T.D., Cyr M., Laakso A.,
RA Macrae A.D., Torres G.E., Kim K.M., Lefkowitz R.J., Caron M.G.,
RA Premont R.T.;
RT "Dopaminergic supersensitivity in G protein-coupled receptor kinase 6-
RT deficient mice.";
RL Neuron 38:291-303(2003).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-484; THR-485; SER-566 AND
RP SER-568, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-578 (ISOFORM GRK6B),
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Specifically phosphorylates the activated forms of G protein-
CC coupled receptors. Such receptor phosphorylation initiates beta-
CC arrestin-mediated receptor desensitization, internalization, and
CC signaling events leading to their desensitization. Seems to be involved
CC in the desensitization of D2-like dopamine receptors in striatum and
CC chemokine receptor CXCR4 which is critical for CXCL12-induced cell
CC chemotaxis (By similarity). Phosphorylates rhodopsin (RHO) (in vitro)
CC and a non G-protein-coupled receptor, LRP6 during Wnt signaling (in
CC vitro) (By similarity). {ECO:0000250, ECO:0000269|PubMed:12032308,
CC ECO:0000269|PubMed:12718862, ECO:0000269|PubMed:14634128}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[G-protein-coupled receptor] + ATP = [G-protein-coupled
CC receptor]-phosphate + ADP + H(+); Xref=Rhea:RHEA:12008, Rhea:RHEA-
CC COMP:11260, Rhea:RHEA-COMP:11261, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43176, ChEBI:CHEBI:68546,
CC ChEBI:CHEBI:456216; EC=2.7.11.16;
CC -!- SUBUNIT: Interacts with GIT1. {ECO:0000250|UniProtKB:P97711}.
CC -!- INTERACTION:
CC O70293-1; Q28619: SLC9A3R1; Xeno; NbExp=5; IntAct=EBI-7073604, EBI-7073613;
CC -!- SUBCELLULAR LOCATION: Membrane; Lipid-anchor.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=GRK6A;
CC IsoId=O70293-1; Sequence=Displayed;
CC Name=GRK6B;
CC IsoId=O70293-2; Sequence=VSP_004939;
CC -!- TISSUE SPECIFICITY: Expressed in the brain in striatal neurons.
CC {ECO:0000269|PubMed:12718862}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice show significant altered central
CC dopamine receptors regulation, deficient lymphocyte chemotaxis and
CC increased acute inflammation and neutrophil chemotaxis.
CC {ECO:0000269|PubMed:12032308, ECO:0000269|PubMed:12718862,
CC ECO:0000269|PubMed:14634128}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. GPRK subfamily. {ECO:0000305}.
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DR EMBL; AF040747; AAC09268.1; -; mRNA.
DR EMBL; AF040748; AAC09269.1; -; mRNA.
DR EMBL; AF040749; AAC09270.1; -; mRNA.
DR EMBL; AF040754; AAC09265.1; -; Genomic_DNA.
DR EMBL; Y17967; CAA76975.1; -; Genomic_DNA.
DR EMBL; Y17967; CAA76976.1; -; Genomic_DNA.
DR EMBL; Y15798; CAA75789.1; -; mRNA.
DR EMBL; Y15799; CAA75790.1; -; mRNA.
DR EMBL; BC075719; AAH75719.1; -; mRNA.
DR CCDS; CCDS88457.1; -. [O70293-1]
DR RefSeq; NP_001033107.1; NM_001038018.4. [O70293-2]
DR RefSeq; NP_001106182.1; NM_001112711.2. [O70293-1]
DR RefSeq; NP_001272992.1; NM_001286063.1.
DR RefSeq; NP_001272993.1; NM_001286064.1.
DR RefSeq; NP_001272994.1; NM_001286065.1.
DR RefSeq; NP_036068.2; NM_011938.4.
DR AlphaFoldDB; O70293; -.
DR SMR; O70293; -.
DR BioGRID; 204943; 2.
DR CORUM; O70293; -.
DR IntAct; O70293; 2.
DR MINT; O70293; -.
DR STRING; 10090.ENSMUSP00000001115; -.
DR iPTMnet; O70293; -.
DR PhosphoSitePlus; O70293; -.
DR SwissPalm; O70293; -.
DR EPD; O70293; -.
DR jPOST; O70293; -.
DR MaxQB; O70293; -.
DR PaxDb; O70293; -.
DR PeptideAtlas; O70293; -.
DR PRIDE; O70293; -.
DR ProteomicsDB; 271166; -. [O70293-1]
DR ProteomicsDB; 271167; -. [O70293-2]
DR ABCD; O70293; 2 sequenced antibodies.
DR Antibodypedia; 17408; 396 antibodies from 37 providers.
DR DNASU; 26385; -.
DR Ensembl; ENSMUST00000001115; ENSMUSP00000001115; ENSMUSG00000074886. [O70293-2]
DR Ensembl; ENSMUST00000224118; ENSMUSP00000152968; ENSMUSG00000074886. [O70293-1]
DR GeneID; 26385; -.
DR KEGG; mmu:26385; -.
DR UCSC; uc007qqw.2; mouse. [O70293-2]
DR UCSC; uc011yzt.2; mouse. [O70293-1]
DR CTD; 2870; -.
DR MGI; MGI:1347078; Grk6.
DR VEuPathDB; HostDB:ENSMUSG00000074886; -.
DR eggNOG; KOG0986; Eukaryota.
DR GeneTree; ENSGT00940000158544; -.
DR InParanoid; O70293; -.
DR OrthoDB; 1104340at2759; -.
DR PhylomeDB; O70293; -.
DR TreeFam; TF313940; -.
DR BRENDA; 2.7.11.16; 3474.
DR Reactome; R-MMU-418555; G alpha (s) signalling events.
DR BioGRID-ORCS; 26385; 5 hits in 76 CRISPR screens.
DR ChiTaRS; Grk6; mouse.
DR PRO; PR:O70293; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; O70293; protein.
DR Bgee; ENSMUSG00000074886; Expressed in peripheral lymph node and 249 other tissues.
DR ExpressionAtlas; O70293; baseline and differential.
DR Genevisible; O70293; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0047696; F:beta-adrenergic receptor kinase activity; ISO:MGI.
DR GO; GO:0004703; F:G protein-coupled receptor kinase activity; ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR GO; GO:0002029; P:desensitization of G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0010360; P:negative regulation of anion channel activity; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 1.10.167.10; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR000239; GPCR_kinase.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR016137; RGS.
DR InterPro; IPR036305; RGS_sf.
DR InterPro; IPR044926; RGS_subdomain_2.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00615; RGS; 1.
DR PRINTS; PR00717; GPCRKINASE.
DR SMART; SM00315; RGS; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF48097; SSF48097; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50132; RGS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Kinase; Lipoprotein; Membrane;
KW Nucleotide-binding; Palmitate; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Wnt signaling pathway.
FT CHAIN 1..576
FT /note="G protein-coupled receptor kinase 6"
FT /id="PRO_0000085975"
FT DOMAIN 53..171
FT /note="RGS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT DOMAIN 186..448
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 449..514
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 1..185
FT /note="N-terminal"
FT ACT_SITE 311
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 192..200
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 215
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 264..270
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 315..318
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 484
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 485
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 566
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 568
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT LIPID 561
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 562
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 565
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 560..576
FT /note="DCCGNCSDSEEELPTRL -> RIAVGTAATVRKSSPPASSPQAEAPTGGWR
FT (in isoform GRK6B)"
FT /evidence="ECO:0000303|PubMed:10506199,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2"
FT /id="VSP_004939"
FT CONFLICT 98
FT /note="R -> Q (in Ref. 1; AAC09265)"
FT /evidence="ECO:0000305"
FT CONFLICT 571
FT /note="E -> K (in Ref. 1; AAC09265)"
FT /evidence="ECO:0000305"
FT MOD_RES O70293-2:578
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 576 AA; 65979 MW; 91EEC2028CAF4B91 CRC64;
MELENIVANT VLLKAREGGG GNRKGKSKKW RQMLQFPHIS QCEELRLSLE RDYHSLCERQ
PIGRLLFREF CATRPELTRC TAFLDGVSEY EVTPDEKRKA CGRRLMQNFL SHTGPDLIPE
VPRQLVSNCA QRLEQGPCKD LFQELTRLTH EYLSTAPFAD YLDSIYFNRF LQWKWLERQP
VTKNTFRQYR VLGKGGFGEV CACQVRATGK MYACKKLEKK RIKKRKGEAM ALNEKQILEK
VNSRFVVSLA YAYETKDALC LVLTLMNGGD LKFHIYHMGQ AGFPEARAVF YAAEICCGLE
DLHRERIVYR DLKPENILLD DHGHIRISDL GLAVHVPEGQ TIKGRVGTVG YMAPEVVRNE
RYTFSPDWWA LGCLLYEMIA GQSPFQQRKK KIKREEVERL VKEVAEEYTD RFSSQARSLC
SQLLSKDPAE RLGCRGGGAR EVKEHPLFKK LNFKRLGAGM LEPPFKPDPQ AIYCKDVLDI
EQFSTVKGVD LEPTDQDFYQ KFATGSVSIP WQNEMVETEC FQELNVFGLD GSVPPDLDWK
GQPTAPPKKG LLQRLFSRQD CCGNCSDSEE ELPTRL
