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 24-JAN-2024, entry version 151. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Y09365; CAA70542.1; -; mRNA. DR AlphaFoldDB; P97711; -. DR SMR; P97711; -. DR STRING; 10116.ENSRNOP00000073781; -. DR iPTMnet; P97711; -. DR PhosphoSitePlus; P97711; -. DR PaxDb; 10116-ENSRNOP00000050134; -. DR ABCD; P97711; 1 sequenced antibody. DR UCSC; RGD:61986; rat. DR AGR; RGD:61986; -. 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:0016020; C:membrane; IEA:UniProtKB-SubCell. 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: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:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central. DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW. DR CDD; cd05630; STKc_GRK6; 1. DR Gene3D; 6.10.250.2260; -; 1. DR Gene3D; 1.10.167.10; Regulator of G-protein Signalling 4, domain 2; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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 PANTHER; PTHR24355:SF15; G PROTEIN-COUPLED RECEPTOR KINASE 6; 1. DR PANTHER; PTHR24355; G PROTEIN-COUPLED RECEPTOR KINASE/RIBOSOMAL PROTEIN S6 KINASE; 1. 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; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF48097; Regulator of G-protein signaling, RGS; 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 //