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G protein-coupled receptor kinase 6 (EC 2.7.11.16) (G protein-coupled receptor kinase GRK6)

 GRK6_MOUSE              Reviewed;         576 AA.
O70293; O70294; O70295; Q6DI67;
30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
01-AUG-1998, sequence version 1.
12-SEP-2018, entry version 169.
RecName: Full=G protein-coupled receptor kinase 6;
EC=2.7.11.16;
AltName: Full=G protein-coupled receptor kinase GRK6;
Name=Grk6; Synonyms=Gprk6;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS GRK6A AND GRK6B).
STRAIN=129/SvJ;
PubMed=10506199; DOI=10.1074/jbc.274.41.29381;
Premont R.T., Macrae A.D., Aparicio S.A., Kendall H.E., Welch J.E.,
Lefkowitz R.J.;
"The GRK4 subfamily of G protein-coupled receptor kinases. Alternative
splicing, gene organization, and sequence conservation.";
J. Biol. Chem. 274:29381-29389(1999).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS GRK6A AND GRK6B).
STRAIN=129/SvJ, and C57BL/6J; TISSUE=Thymus;
Moepps B., Vatter P., Frode R., Waechter F., Gierschik P.;
"Primary structure of murine G-protein-coupled receptor kinase 6
splice variants predict differential regulation by posttranslational
modifications.";
Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GRK6B).
STRAIN=129; TISSUE=Mammary gland;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
DISRUPTION PHENOTYPE, AND FUNCTION.
PubMed=12032308; DOI=10.1073/pnas.112198299;
Fong A.M., Premont R.T., Richardson R.M., Yu Y.R., Lefkowitz R.J.,
Patel D.D.;
"Defective lymphocyte chemotaxis in beta-arrestin2- and GRK6-deficient
mice.";
Proc. Natl. Acad. Sci. U.S.A. 99:7478-7483(2002).
[5]
DISRUPTION PHENOTYPE, AND FUNCTION.
PubMed=14634128; DOI=10.4049/jimmunol.171.11.6128;
Kavelaars A., Vroon A., Raatgever R.P., Fong A.M., Premont R.T.,
Patel D.D., Lefkowitz R.J., Heijnen C.J.;
"Increased acute inflammation, leukotriene B4-induced chemotaxis, and
signaling in mice deficient for G protein-coupled receptor kinase 6.";
J. Immunol. 171:6128-6134(2003).
[6]
DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
PubMed=12718862; DOI=10.1016/S0896-6273(03)00192-2;
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.;
"Dopaminergic supersensitivity in G protein-coupled receptor kinase 6-
deficient mice.";
Neuron 38:291-303(2003).
[7]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-484; THR-485; SER-566
AND SER-568, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-578
(ISOFORM GRK6B), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
ANALYSIS].
TISSUE=Brain, Kidney, Lung, Spleen, and Testis;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and
expression.";
Cell 143:1174-1189(2010).
-!- 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).
{ECO:0000250, ECO:0000269|PubMed:12032308,
ECO:0000269|PubMed:12718862, ECO:0000269|PubMed:14634128}.
-!- CATALYTIC ACTIVITY: ATP + [G-protein-coupled receptor] = ADP + [G-
protein-coupled receptor] phosphate.
-!- INTERACTION:
Q28619:SLC9A3R1 (xeno); NbExp=5; IntAct=EBI-7073604, EBI-7073613;
-!- SUBCELLULAR LOCATION: Membrane; Lipid-anchor.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=GRK6A;
IsoId=O70293-1; Sequence=Displayed;
Name=GRK6B;
IsoId=O70293-2; Sequence=VSP_004939;
Note=Contains a phosphoserine at position 578.
{ECO:0000244|PubMed:21183079};
-!- TISSUE SPECIFICITY: Expressed in the brain in striatal neurons.
{ECO:0000269|PubMed:12718862}.
-!- DISRUPTION PHENOTYPE: Deficient mice show significant altered
central dopamine receptors regulation, deficient lymphocyte
chemotaxis and increased acute inflammation and neutrophil
chemotaxis. {ECO:0000269|PubMed:12032308,
ECO:0000269|PubMed:12718862, ECO:0000269|PubMed:14634128}.
-!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
protein kinase family. GPRK subfamily. {ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; AF040747; AAC09268.1; -; mRNA.
EMBL; AF040748; AAC09269.1; -; mRNA.
EMBL; AF040749; AAC09270.1; -; mRNA.
EMBL; AF040754; AAC09265.1; -; Genomic_DNA.
EMBL; Y17967; CAA76975.1; -; Genomic_DNA.
EMBL; Y17967; CAA76976.1; -; Genomic_DNA.
EMBL; Y15798; CAA75789.1; -; mRNA.
EMBL; Y15799; CAA75790.1; -; mRNA.
EMBL; BC075719; AAH75719.1; -; mRNA.
CCDS; CCDS49272.1; -. [O70293-2]
RefSeq; NP_001033107.1; NM_001038018.4. [O70293-2]
RefSeq; NP_001106182.1; NM_001112711.2. [O70293-1]
RefSeq; NP_001272992.1; NM_001286063.1.
RefSeq; NP_001272993.1; NM_001286064.1.
RefSeq; NP_001272994.1; NM_001286065.1.
RefSeq; NP_036068.2; NM_011938.4.
UniGene; Mm.10193; -.
ProteinModelPortal; O70293; -.
SMR; O70293; -.
CORUM; O70293; -.
IntAct; O70293; 3.
MINT; O70293; -.
STRING; 10090.ENSMUSP00000001115; -.
iPTMnet; O70293; -.
PhosphoSitePlus; O70293; -.
SwissPalm; O70293; -.
MaxQB; O70293; -.
PaxDb; O70293; -.
PeptideAtlas; O70293; -.
PRIDE; O70293; -.
Ensembl; ENSMUST00000001115; ENSMUSP00000001115; ENSMUSG00000074886. [O70293-2]
Ensembl; ENSMUST00000224118; ENSMUSP00000152968; ENSMUSG00000074886. [O70293-1]
GeneID; 26385; -.
KEGG; mmu:26385; -.
UCSC; uc007qqw.2; mouse. [O70293-2]
UCSC; uc011yzt.2; mouse. [O70293-1]
CTD; 2870; -.
MGI; MGI:1347078; Grk6.
eggNOG; KOG0986; Eukaryota.
eggNOG; ENOG410YRQZ; LUCA.
GeneTree; ENSGT00860000133699; -.
HOGENOM; HOG000006742; -.
HOVERGEN; HBG004532; -.
InParanoid; O70293; -.
KO; K08291; -.
OMA; NFKRLGA; -.
OrthoDB; EOG091G062G; -.
PhylomeDB; O70293; -.
TreeFam; TF313940; -.
BRENDA; 2.7.11.16; 3474.
Reactome; R-MMU-418555; G alpha (s) signalling events.
PRO; PR:O70293; -.
Proteomes; UP000000589; Chromosome 13.
Bgee; ENSMUSG00000074886; Expressed in 279 organ(s), highest expression level in spleen.
CleanEx; MM_GRK6; -.
ExpressionAtlas; O70293; baseline and differential.
Genevisible; O70293; MM.
GO; GO:0005829; C:cytosol; ISO:MGI.
GO; GO:0005886; C:plasma membrane; ISO:MGI.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0047696; F:beta-adrenergic receptor kinase activity; ISO:MGI.
GO; GO:0004703; F:G-protein coupled receptor kinase activity; ISO:MGI.
GO; GO:0002029; P:desensitization of G-protein coupled receptor protein signaling pathway; ISO:MGI.
GO; GO:0010360; P:negative regulation of anion channel activity; ISO:MGI.
GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
InterPro; IPR000961; AGC-kinase_C.
InterPro; IPR000239; GPCR_kinase.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR016137; RGS.
InterPro; IPR036305; RGS_sf.
InterPro; IPR008271; Ser/Thr_kinase_AS.
Pfam; PF00069; Pkinase; 1.
Pfam; PF00615; RGS; 1.
PRINTS; PR00717; GPCRKINASE.
SMART; SM00315; RGS; 1.
SMART; SM00133; S_TK_X; 1.
SMART; SM00220; S_TKc; 1.
SUPFAM; SSF48097; SSF48097; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS51285; AGC_KINASE_CTER; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PROSITE; PS50132; RGS; 1.
1: Evidence at protein level;
Alternative splicing; ATP-binding; Complete proteome; Kinase;
Lipoprotein; Membrane; Nucleotide-binding; Palmitate; Phosphoprotein;
Reference proteome; Serine/threonine-protein kinase; Transferase;
Wnt signaling pathway.
CHAIN 1 576 G protein-coupled receptor kinase 6.
/FTId=PRO_0000085975.
DOMAIN 53 171 RGS. {ECO:0000255|PROSITE-
ProRule:PRU00171}.
DOMAIN 186 448 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
DOMAIN 449 514 AGC-kinase C-terminal.
NP_BIND 192 200 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
NP_BIND 264 270 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
NP_BIND 315 318 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
REGION 1 185 N-terminal.
ACT_SITE 311 311 Proton acceptor. {ECO:0000255|PROSITE-
ProRule:PRU00159, ECO:0000255|PROSITE-
ProRule:PRU10027}.
BINDING 215 215 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
MOD_RES 484 484 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 485 485 Phosphothreonine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 566 566 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 568 568 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
LIPID 561 561 S-palmitoyl cysteine. {ECO:0000250}.
LIPID 562 562 S-palmitoyl cysteine. {ECO:0000250}.
LIPID 565 565 S-palmitoyl cysteine. {ECO:0000250}.
VAR_SEQ 560 576 DCCGNCSDSEEELPTRL -> RIAVGTAATVRKSSPPASSP
QAEAPTGGWR (in isoform GRK6B).
{ECO:0000303|PubMed:10506199,
ECO:0000303|PubMed:15489334,
ECO:0000303|Ref.2}.
/FTId=VSP_004939.
CONFLICT 98 98 R -> Q (in Ref. 1; AAC09265).
{ECO:0000305}.
CONFLICT 571 571 E -> K (in Ref. 1; AAC09265).
{ECO:0000305}.
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


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