GRK6_RAT
ID GRK6_RAT Reviewed; 576 AA.
AC P97711;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 143.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9387888; DOI=10.1016/s0169-328x(97)00186-1;
RA Fehr C., Fickova M., Hiemke C., Reuss S., Dahmen N.;
RT "Molecular cloning of rat G-protein-coupled receptor kinase 6 (GRK6) from
RT brain tissue, and its mRNA expression in different brain regions and
RT peripheral tissues.";
RL Brain Res. Mol. Brain Res. 49:278-282(1997).
RN [2]
RP INTERACTION WITH GIT1.
RX PubMed=9826657; DOI=10.1073/pnas.95.24.14082;
RA Premont R.T., Claing A., Vitale N., Freeman J.L.R., Pitcher J.A.,
RA Patton W.A., Moss J., Vaughan M., Lefkowitz R.J.;
RT "Beta2-adrenergic receptor regulation by GIT1, a G protein-coupled receptor
RT kinase-associated ADP ribosylation factor GTPase-activating protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:14082-14087(1998).
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}.
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:0000269|PubMed:9826657}.
CC -!- SUBCELLULAR LOCATION: Membrane; Lipid-anchor.
CC -!- TISSUE SPECIFICITY: Widely expressed. Detectable in all brain areas
CC examined. {ECO:0000269|PubMed:9387888}.
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; Y09365; CAA70542.1; -; mRNA.
DR AlphaFoldDB; P97711; -.
DR SMR; P97711; -.
DR STRING; 10116.ENSRNOP00000050134; -.
DR iPTMnet; P97711; -.
DR PhosphoSitePlus; P97711; -.
DR PaxDb; P97711; -.
DR PRIDE; P97711; -.
DR ABCD; P97711; 1 sequenced antibody.
DR UCSC; RGD:61986; rat.
DR RGD; 61986; Grk6.
DR eggNOG; KOG0986; Eukaryota.
DR InParanoid; P97711; -.
DR PhylomeDB; P97711; -.
DR BRENDA; 2.7.11.16; 5301.
DR Reactome; R-RNO-418555; G alpha (s) signalling events.
DR PRO; PR:P97711; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0047696; F:beta-adrenergic receptor kinase activity; ISO:RGD.
DR GO; GO:0004703; F:G protein-coupled receptor kinase activity; IDA:RGD.
DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0002029; P:desensitization of G protein-coupled receptor signaling pathway; IDA:RGD.
DR GO; GO:0010360; P:negative regulation of anion channel activity; IMP:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
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 ATP-binding; Kinase; Lipoprotein; Membrane; Nucleotide-binding; Palmitate;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Wnt signaling pathway.
FT CHAIN 1..576
FT /note="G protein-coupled receptor kinase 6"
FT /id="PRO_0000085976"
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; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P43250"
FT MOD_RES 485
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P43250"
FT MOD_RES 566
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70293"
FT MOD_RES 568
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70293"
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"
SQ SEQUENCE 576 AA; 65963 MW; 0089AC9EE231F5C9 CRC64;
MELENIVANT VLLKAREGGG GNRKGKSKKW RQMLQFPHIS QCEELRLSLE RDYHSLCERQ
PIGRLLFREF CATRPELTRC TAFLDGVAEY EVTPDEKRKA CGCRLMQNFL SHTGPDLIPE
VPRQLVSNCA QRLEQGPCKD LFQELTRLTH EYLSMAPFAD YLDSIYFNRF LQWKWLERQP
VTKNTFRQYR VLGKGGFGEV CACQVRATGK MYACKKLEKK RIKKRKGEAM ALNEKQILEK
VNSRFVVSLA YAYETKDALC LVLTLMNGGD LKFHIYHMGQ AGFPEARAVF YAAEICCGLE
DLHRERIVYR DLKPENILLD DHGHIRISDL GLTVHVPEGQ TIKGRVGTVG YMAPEVVKNE
RYTFSPDWWA LGCLLYEMIA GQSPFQQRKK KIKREEVERL VKEVAEEYTD RFSPQARSLC
SQLPNKDPAE RLGCRGGGAR EVKEHPLFKK LNFKRLGAGM LEPPFKPDPQ AIYCKDVLDI
EQFSTVKGVD LEPTDQDFYQ KFATGSVSIP WQNEMVETEC FQELNVFGLD GSVPPDLDWK
GQPTAPPKKG LLQRLFSRQD CCGNCSDSEE ELPTRL
