ARBK1_HUMAN
ID ARBK1_HUMAN Reviewed; 689 AA.
AC P25098; B0ZBE1; Q13837; Q6GTT3;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 227.
DE RecName: Full=Beta-adrenergic receptor kinase 1;
DE Short=Beta-ARK-1;
DE EC=2.7.11.15 {ECO:0000269|PubMed:19715378};
DE AltName: Full=G-protein coupled receptor kinase 2 {ECO:0000312|HGNC:HGNC:289};
GN Name=GRK2 {ECO:0000312|HGNC:HGNC:289}; Synonyms=ADRBK1, BARK, BARK1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2037065; DOI=10.1016/0014-5793(91)80568-n;
RA Benovic J.L., Stone W.C., Huebner K., Croce C., Caron M.G., Lefkowitz R.J.;
RT "cDNA cloning and chromosomal localization of the human beta-adrenergic
RT receptor kinase.";
RL FEBS Lett. 283:122-126(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Blood;
RX PubMed=1339451; DOI=10.1016/s0021-9258(19)50511-7;
RA Chuang T.T., Sallese M., Ambrosini G., Parruti G., de Blasi A.;
RT "High expression of beta-adrenergic receptor kinase in human peripheral
RT blood leukocytes. Isoproterenol and platelet activating factor can induce
RT kinase translocation.";
RL J. Biol. Chem. 267:6886-6892(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8195124; DOI=10.1016/s0021-9258(17)36554-7;
RA Penn R.B., Benovic J.L.;
RT "Structure of the human gene encoding the beta-adrenergic receptor
RT kinase.";
RL J. Biol. Chem. 269:14924-14930(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=PNS, and Testis;
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 [6]
RP INTERACTION WITH ARRB1.
RX PubMed=9501202; DOI=10.1073/pnas.95.6.2985;
RA Aragay A.M., Mellado M., Frade J.M., Martin A.M., Jimenez-Sainz M.C.,
RA Martinez-A C., Mayor F. Jr.;
RT "Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization
RT mediated by the G protein-coupled receptor kinase 2.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:2985-2990(1998).
RN [7]
RP INTERACTION WITH CCR5, AND TISSUE SPECIFICITY.
RX PubMed=10085131; DOI=10.1074/jbc.274.13.8875;
RA Oppermann M., Mack M., Proudfoot A.E., Olbrich H.;
RT "Differential effects of CC chemokines on CC chemokine receptor 5 (CCR5)
RT phosphorylation and identification of phosphorylation sites on the CCR5
RT carboxyl terminus.";
RL J. Biol. Chem. 274:8875-8885(1999).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-670, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH ADRB2, SITES REQUIRED FOR
RP RECEPTOR PHOSPHORYLATION, AND MUTAGENESIS OF ASP-3; LEU-4; GLU-5;
RP 7-VAL-ALA-8 AND ASP-10.
RX PubMed=19715378; DOI=10.1021/bi900408g;
RA Pao C.S., Barker B.L., Benovic J.L.;
RT "Role of the amino terminus of G protein-coupled receptor kinase 2 in
RT receptor phosphorylation.";
RL Biochemistry 48:7325-7333(2009).
RN [10]
RP FUNCTION, AND INTERACTION WITH LPAR1; LPAR2 AND RALA.
RX PubMed=19306925; DOI=10.1016/j.cellsig.2009.03.011;
RA Aziziyeh A.I., Li T.T., Pape C., Pampillo M., Chidiac P., Possmayer F.,
RA Babwah A.V., Bhattacharya M.;
RT "Dual regulation of lysophosphatidic acid (LPA1) receptor signalling by Ral
RT and GRK.";
RL Cell. Signal. 21:1207-1217(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-670, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP FUNCTION.
RX PubMed=30284927; DOI=10.1152/ajplung.00135.2018;
RA Yim P.D., Gallos G., Perez-Zoghbi J.F., Zhang Y., Xu D., Wu A.,
RA Berkowitz D.E., Emala C.W.;
RT "Airway smooth muscle photorelaxation via opsin receptor activation.";
RL Am. J. Physiol. 316:L82-L93(2019).
RN [14]
RP STRUCTURE BY NMR OF 552-670.
RX PubMed=9446593; DOI=10.1074/jbc.273.5.2835;
RA Fushman D., Najmabadi-Haske T., Cahill S., Zheng J., Levine H. III,
RA Cowburn D.;
RT "The solution structure and dynamics of the pleckstrin homology domain of G
RT protein-coupled receptor kinase 2 (beta-adrenergic receptor kinase 1). A
RT binding partner of Gbetagamma subunits.";
RL J. Biol. Chem. 273:2835-2843(1998).
RN [15]
RP VARIANTS [LARGE SCALE ANALYSIS] THR-184 AND GLN-578.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Specifically phosphorylates the agonist-occupied form of the
CC beta-adrenergic and closely related receptors, probably inducing a
CC desensitization of them (PubMed:19715378). Key regulator of LPAR1
CC signaling (PubMed:19306925). Competes with RALA for binding to LPAR1
CC thus affecting the signaling properties of the receptor
CC (PubMed:19306925). Desensitizes LPAR1 and LPAR2 in a phosphorylation-
CC independent manner (PubMed:19306925). Positively regulates ciliary
CC smoothened (SMO)-dependent Hedgehog (Hh) signaling pathway by
CC facilitating the trafficking of SMO into the cilium and the stimulation
CC of SMO activity (By similarity). Inhibits relaxation of airway smooth
CC muscle in response to blue light (PubMed:30284927).
CC {ECO:0000250|UniProtKB:P21146, ECO:0000269|PubMed:19306925,
CC ECO:0000269|PubMed:19715378, ECO:0000269|PubMed:30284927}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[beta-adrenergic receptor] + ATP = [beta-adrenergic receptor]-
CC phosphate + ADP + H(+); Xref=Rhea:RHEA:19429, Rhea:RHEA-COMP:11222,
CC Rhea:RHEA-COMP:11223, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43176, ChEBI:CHEBI:68546, ChEBI:CHEBI:456216;
CC EC=2.7.11.15; Evidence={ECO:0000269|PubMed:19715378};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19430;
CC Evidence={ECO:0000305|PubMed:19715378};
CC -!- ACTIVITY REGULATION: In contrast to other AGC family kinases, the
CC catalytic activity is solely regulated by the binding of substrates and
CC ligands, not by phosphorylation of the kinase domain.
CC {ECO:0000250|UniProtKB:P21146}.
CC -!- SUBUNIT: Interacts with the heterodimer formed by GNB1 and GNG2 (By
CC similarity). Interacts with GIT1 (By similarity). Interacts with, and
CC phosphorylates chemokine-stimulated CCR5 (PubMed:10085131). Interacts
CC with ARRB1 (PubMed:9501202). Interacts with LPAR1 and LPAR2
CC (PubMed:19306925). Interacts with RALA in response to LPAR1 activation
CC (PubMed:19306925). ADRBK1 and RALA mutually inhibit each other's
CC binding to LPAR1 (PubMed:19306925). Interacts with ADRB2
CC (PubMed:19715378). {ECO:0000250|UniProtKB:P21146,
CC ECO:0000250|UniProtKB:P26817, ECO:0000269|PubMed:19715378}.
CC -!- INTERACTION:
CC P25098; P05067: APP; NbExp=3; IntAct=EBI-3904795, EBI-77613;
CC P25098; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-3904795, EBI-9087876;
CC P25098; P21860: ERBB3; NbExp=3; IntAct=EBI-3904795, EBI-720706;
CC P25098; P21462: FPR1; NbExp=3; IntAct=EBI-3904795, EBI-2869495;
CC P25098; Q9Y2X7: GIT1; NbExp=5; IntAct=EBI-3904795, EBI-466061;
CC P25098; P35626: GRK3; NbExp=2; IntAct=EBI-3904795, EBI-2875868;
CC P25098; Q00987: MDM2; NbExp=4; IntAct=EBI-3904795, EBI-389668;
CC P25098; P13591: NCAM1; NbExp=3; IntAct=EBI-3904795, EBI-2846607;
CC P25098; P25963: NFKBIA; NbExp=2; IntAct=EBI-3904795, EBI-307386;
CC P25098; Q13635: PTCH1; NbExp=2; IntAct=EBI-3904795, EBI-8775406;
CC P25098; P0CG48: UBC; NbExp=3; IntAct=EBI-3904795, EBI-3390054;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P26817}. Cell
CC membrane {ECO:0000250|UniProtKB:P21146}. Postsynapse
CC {ECO:0000250|UniProtKB:P26817}. Presynapse
CC {ECO:0000250|UniProtKB:P26817}.
CC -!- TISSUE SPECIFICITY: Expressed in peripheral blood leukocytes.
CC {ECO:0000269|PubMed:10085131}.
CC -!- DOMAIN: The PH domain binds anionic phospholipids and helps recruiting
CC ADRBK1 from the cytoplasm to plasma membrane close to activated
CC receptors. It mediates binding to G protein beta and gamma subunits,
CC competing with G-alpha subunits and other G-betagamma effectors.
CC {ECO:0000250|UniProtKB:P21146}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. GPRK subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Beta adrenergic receptor kinase
CC entry;
CC URL="https://en.wikipedia.org/wiki/Beta_Adrenergic_Receptor_Kinase";
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DR EMBL; X61157; CAA43470.1; -; mRNA.
DR EMBL; M80776; AAA58391.1; -; mRNA.
DR EMBL; U08438; AAB60689.1; -; Genomic_DNA.
DR EMBL; U08435; AAB60689.1; JOINED; Genomic_DNA.
DR EMBL; U08436; AAB60689.1; JOINED; Genomic_DNA.
DR EMBL; U08437; AAB60689.1; JOINED; Genomic_DNA.
DR EMBL; EU326303; ACA05909.1; -; Genomic_DNA.
DR EMBL; BC037963; AAH37963.1; -; mRNA.
DR EMBL; BC090863; AAH90863.1; -; mRNA.
DR CCDS; CCDS8156.1; -.
DR PIR; A53791; A53791.
DR RefSeq; NP_001610.2; NM_001619.3.
DR PDB; 1BAK; NMR; -; A=556-670.
DR PDB; 3CIK; X-ray; 2.75 A; A=1-689.
DR PDB; 3KRW; X-ray; 2.90 A; A=2-689.
DR PDB; 3KRX; X-ray; 3.10 A; A=2-689.
DR PDB; 3V5W; X-ray; 2.07 A; A=1-689.
DR PDB; 4MK0; X-ray; 2.40 A; A=30-668.
DR PDB; 4PNK; X-ray; 2.56 A; A=1-689.
DR PDB; 5HE1; X-ray; 3.15 A; A=29-670.
DR PDB; 5UKK; X-ray; 2.60 A; A=30-671.
DR PDB; 5UKL; X-ray; 2.15 A; A=30-671.
DR PDB; 5UUU; X-ray; 2.70 A; A=23-538.
DR PDB; 5UVC; X-ray; 2.65 A; A=23-538.
DR PDB; 5WG3; X-ray; 2.90 A; A=1-689.
DR PDB; 5WG4; X-ray; 2.31 A; A=1-689.
DR PDB; 5WG5; X-ray; 3.10 A; A=1-689.
DR PDB; 6C2Y; X-ray; 2.74 A; A=1-689.
DR PDB; 6U7C; X-ray; 2.44 A; A=1-689.
DR PDB; 7K7L; X-ray; 2.54 A; A=30-668.
DR PDB; 7K7Z; X-ray; 2.61 A; A=30-668.
DR PDB; 7PWD; X-ray; 2.60 A; A=1-689.
DR PDBsum; 1BAK; -.
DR PDBsum; 3CIK; -.
DR PDBsum; 3KRW; -.
DR PDBsum; 3KRX; -.
DR PDBsum; 3V5W; -.
DR PDBsum; 4MK0; -.
DR PDBsum; 4PNK; -.
DR PDBsum; 5HE1; -.
DR PDBsum; 5UKK; -.
DR PDBsum; 5UKL; -.
DR PDBsum; 5UUU; -.
DR PDBsum; 5UVC; -.
DR PDBsum; 5WG3; -.
DR PDBsum; 5WG4; -.
DR PDBsum; 5WG5; -.
DR PDBsum; 6C2Y; -.
DR PDBsum; 6U7C; -.
DR PDBsum; 7K7L; -.
DR PDBsum; 7K7Z; -.
DR PDBsum; 7PWD; -.
DR AlphaFoldDB; P25098; -.
DR SMR; P25098; -.
DR BioGRID; 106665; 81.
DR DIP; DIP-42429N; -.
DR IntAct; P25098; 34.
DR MINT; P25098; -.
DR STRING; 9606.ENSP00000312262; -.
DR BindingDB; P25098; -.
DR ChEMBL; CHEMBL4079; -.
DR DrugBank; DB00171; ATP.
DR DrugCentral; P25098; -.
DR GuidetoPHARMACOLOGY; 1466; -.
DR iPTMnet; P25098; -.
DR PhosphoSitePlus; P25098; -.
DR BioMuta; GRK2; -.
DR DMDM; 126302521; -.
DR EPD; P25098; -.
DR jPOST; P25098; -.
DR MassIVE; P25098; -.
DR MaxQB; P25098; -.
DR PaxDb; P25098; -.
DR PeptideAtlas; P25098; -.
DR PRIDE; P25098; -.
DR ProteomicsDB; 54254; -.
DR Antibodypedia; 16429; 728 antibodies from 42 providers.
DR DNASU; 156; -.
DR Ensembl; ENST00000308595.10; ENSP00000312262.5; ENSG00000173020.11.
DR GeneID; 156; -.
DR KEGG; hsa:156; -.
DR MANE-Select; ENST00000308595.10; ENSP00000312262.5; NM_001619.5; NP_001610.2.
DR UCSC; uc009yrn.2; human.
DR CTD; 156; -.
DR DisGeNET; 156; -.
DR GeneCards; GRK2; -.
DR HGNC; HGNC:289; GRK2.
DR HPA; ENSG00000173020; Tissue enhanced (bone).
DR MIM; 109635; gene.
DR neXtProt; NX_P25098; -.
DR OpenTargets; ENSG00000173020; -.
DR PharmGKB; PA40; -.
DR VEuPathDB; HostDB:ENSG00000173020; -.
DR eggNOG; KOG0986; Eukaryota.
DR GeneTree; ENSGT00940000161626; -.
DR InParanoid; P25098; -.
DR OMA; FIQRSPN; -.
DR OrthoDB; 1104340at2759; -.
DR PhylomeDB; P25098; -.
DR TreeFam; TF313940; -.
DR BRENDA; 2.7.11.15; 2681.
DR PathwayCommons; P25098; -.
DR Reactome; R-HSA-111933; Calmodulin induced events.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-5635838; Activation of SMO.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR SignaLink; P25098; -.
DR SIGNOR; P25098; -.
DR BioGRID-ORCS; 156; 59 hits in 1121 CRISPR screens.
DR ChiTaRS; GRK2; human.
DR EvolutionaryTrace; P25098; -.
DR GeneWiki; Beta_adrenergic_receptor_kinase; -.
DR GenomeRNAi; 156; -.
DR Pharos; P25098; Tchem.
DR PRO; PR:P25098; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P25098; protein.
DR Bgee; ENSG00000173020; Expressed in granulocyte and 149 other tissues.
DR ExpressionAtlas; P25098; baseline and differential.
DR Genevisible; P25098; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005929; C:cilium; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098794; C:postsynapse; IEA:UniProtKB-SubCell.
DR GO; GO:0098793; C:presynapse; IEA:UniProtKB-SubCell.
DR GO; GO:0031694; F:alpha-2A adrenergic receptor binding; ISS:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0047696; F:beta-adrenergic receptor kinase activity; TAS:Reactome.
DR GO; GO:0031755; F:Edg-2 lysophosphatidic acid receptor binding; IDA:UniProtKB.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IBA:GO_Central.
DR GO; GO:0004703; F:G protein-coupled receptor kinase activity; IMP:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; ISS:BHF-UCL.
DR GO; GO:0060048; P:cardiac muscle contraction; IMP:BHF-UCL.
DR GO; GO:0002029; P:desensitization of G protein-coupled receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0007213; P:G protein-coupled acetylcholine receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:1901081; P:negative regulation of relaxation of smooth muscle; IMP:UniProtKB.
DR GO; GO:0045988; P:negative regulation of striated muscle contraction; IMP:BHF-UCL.
DR GO; GO:0003108; P:negative regulation of the force of heart contraction by chemical signal; IMP:BHF-UCL.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:BHF-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IEA:Ensembl.
DR GO; GO:0033605; P:positive regulation of catecholamine secretion; ISS:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0031623; P:receptor internalization; IDA:UniProtKB.
DR GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central.
DR GO; GO:0002026; P:regulation of the force of heart contraction; IBA:GO_Central.
DR GO; GO:0007217; P:tachykinin receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0046718; P:viral entry into host cell; IMP:CACAO.
DR GO; GO:0019079; P:viral genome replication; IMP:CACAO.
DR Gene3D; 1.10.167.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR000239; GPCR_kinase.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
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; PF00169; PH; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00615; RGS; 1.
DR PRINTS; PR00717; GPCRKINASE.
DR SMART; SM00233; PH; 1.
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; PS50003; PH_DOMAIN; 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 3D-structure; ATP-binding; Cell membrane; Cell projection; Cytoplasm;
KW Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Synapse; Transferase.
FT CHAIN 1..689
FT /note="Beta-adrenergic receptor kinase 1"
FT /id="PRO_0000085627"
FT DOMAIN 54..175
FT /note="RGS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT DOMAIN 191..453
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 454..521
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT DOMAIN 558..652
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 1..190
FT /note="N-terminal"
FT ACT_SITE 317
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 197..205
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 220
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 3
FT /note="Required for receptor phosphorylation"
FT /evidence="ECO:0000269|PubMed:19715378"
FT SITE 4
FT /note="Required for receptor phosphorylation"
FT /evidence="ECO:0000269|PubMed:19715378"
FT SITE 10
FT /note="Required for receptor phosphorylation"
FT /evidence="ECO:0000269|PubMed:19715378"
FT MOD_RES 670
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:23186163"
FT VARIANT 184
FT /note="I -> T (in dbSNP:rs55696045)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040378"
FT VARIANT 578
FT /note="R -> Q (in a colorectal adenocarcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040379"
FT MUTAGEN 3
FT /note="D->A: 85% reduction in phosphorylation of G-protein
FT coupled receptor rhodopsin."
FT /evidence="ECO:0000269|PubMed:19715378"
FT MUTAGEN 3
FT /note="D->K: 95% reduction in phosphorylation of G-protein
FT coupled receptor rhodopsin. 60% reduction in
FT phosphorylation of beta-2 adrenergic receptor ADRB2. Does
FT not affect binding to ADRB2. Not activated by receptor
FT binding. No effect on phosphorylation of the non-receptor
FT substrate tubulin."
FT /evidence="ECO:0000269|PubMed:19715378"
FT MUTAGEN 3
FT /note="D->N: 60% reduction in phosphorylation of G-protein
FT coupled receptor rhodopsin."
FT /evidence="ECO:0000269|PubMed:19715378"
FT MUTAGEN 4
FT /note="L->A: 95% reduction in phosphorylation of G-protein
FT coupled receptor rhodopsin. 90% reduction in
FT phosphorylation of beta-2 adrenergic receptor ADRB2. Does
FT not affect binding to ADRB2. Not activated by receptor
FT binding. No effect on phosphorylation of the non-receptor
FT substrate tubulin."
FT /evidence="ECO:0000269|PubMed:19715378"
FT MUTAGEN 4
FT /note="L->K: 95% reduction in phosphorylation of G-protein
FT coupled receptor rhodopsin."
FT /evidence="ECO:0000269|PubMed:19715378"
FT MUTAGEN 5
FT /note="E->A: 50% reduction in phosphorylation of G-protein
FT coupled receptor rhodopsin."
FT /evidence="ECO:0000269|PubMed:19715378"
FT MUTAGEN 7..8
FT /note="VL->AA: 95% reduction in phosphorylation of G-
FT protein coupled receptor rhodopsin."
FT /evidence="ECO:0000269|PubMed:19715378"
FT MUTAGEN 10
FT /note="D->A: 95% reduction in phosphorylation of G-protein
FT coupled receptor rhodopsin and beta-2 adrenergic receptor
FT ADRB2. Does not affect binding to ADRB2. Not activated by
FT receptor binding. No effect on phosphorylation of the non-
FT receptor substrate tubulin."
FT /evidence="ECO:0000269|PubMed:19715378"
FT CONFLICT 168..185
FT /note="SDKFTRFCQWKNVELNIH -> RISSHGFASGRMWSSTST (in Ref. 3;
FT AAB60689)"
FT /evidence="ECO:0000305"
FT CONFLICT 211
FT /note="A -> R (in Ref. 1; CAA43470 and 3; AAB60689)"
FT /evidence="ECO:0000305"
FT CONFLICT 422
FT /note="R -> H (in Ref. 1; CAA43470 and 3; AAB60689)"
FT /evidence="ECO:0000305"
FT CONFLICT 465
FT /note="K -> R (in Ref. 1; CAA43470)"
FT /evidence="ECO:0000305"
FT HELIX 39..49
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 55..59
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 62..75
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 80..93
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 98..109
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 112..118
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 119..122
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 126..137
FT /evidence="ECO:0007829|PDB:3V5W"
FT TURN 143..146
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 147..157
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 160..167
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 169..181
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 191..199
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 201..210
FT /evidence="ECO:0007829|PDB:3V5W"
FT TURN 211..213
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 216..223
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 224..229
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 233..246
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:3KRW"
FT STRAND 257..262
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 264..271
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 276..278
FT /evidence="ECO:0007829|PDB:5HE1"
FT HELIX 279..286
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 291..309
FT /evidence="ECO:0007829|PDB:3V5W"
FT TURN 310..312
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 320..322
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 323..325
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 327..329
FT /evidence="ECO:0007829|PDB:5WG4"
FT STRAND 331..333
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 336..338
FT /evidence="ECO:0007829|PDB:3CIK"
FT STRAND 343..345
FT /evidence="ECO:0007829|PDB:5WG4"
FT HELIX 354..356
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 359..362
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 363..365
FT /evidence="ECO:0007829|PDB:7K7L"
FT HELIX 371..386
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 390..392
FT /evidence="ECO:0007829|PDB:5WG5"
FT HELIX 393..395
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 399..408
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 415..417
FT /evidence="ECO:0007829|PDB:3KRW"
FT HELIX 419..428
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 433..435
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 440..442
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 444..447
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 451..453
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 458..462
FT /evidence="ECO:0007829|PDB:3V5W"
FT TURN 477..480
FT /evidence="ECO:0007829|PDB:5UKL"
FT TURN 492..495
FT /evidence="ECO:0007829|PDB:5UUU"
FT HELIX 500..503
FT /evidence="ECO:0007829|PDB:3V5W"
FT TURN 504..508
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 514..522
FT /evidence="ECO:0007829|PDB:3V5W"
FT TURN 523..525
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 526..546
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 555..557
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 561..568
FT /evidence="ECO:0007829|PDB:3V5W"
FT TURN 571..573
FT /evidence="ECO:0007829|PDB:5UKL"
FT STRAND 577..584
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 587..591
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 593..595
FT /evidence="ECO:0007829|PDB:4MK0"
FT STRAND 599..602
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 603..605
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 606..616
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 618..624
FT /evidence="ECO:0007829|PDB:3V5W"
FT TURN 625..627
FT /evidence="ECO:0007829|PDB:3V5W"
FT STRAND 628..633
FT /evidence="ECO:0007829|PDB:3V5W"
FT HELIX 637..658
FT /evidence="ECO:0007829|PDB:3V5W"
FT TURN 662..664
FT /evidence="ECO:0007829|PDB:3V5W"
SQ SEQUENCE 689 AA; 79574 MW; 4DB68F62841AFA7D CRC64;
MADLEAVLAD VSYLMAMEKS KATPAARASK KILLPEPSIR SVMQKYLEDR GEVTFEKIFS
QKLGYLLFRD FCLNHLEEAR PLVEFYEEIK KYEKLETEEE RVARSREIFD SYIMKELLAC
SHPFSKSATE HVQGHLGKKQ VPPDLFQPYI EEICQNLRGD VFQKFIESDK FTRFCQWKNV
ELNIHLTMND FSVHRIIGRG GFGEVYGCRK ADTGKMYAMK CLDKKRIKMK QGETLALNER
IMLSLVSTGD CPFIVCMSYA FHTPDKLSFI LDLMNGGDLH YHLSQHGVFS EADMRFYAAE
IILGLEHMHN RFVVYRDLKP ANILLDEHGH VRISDLGLAC DFSKKKPHAS VGTHGYMAPE
VLQKGVAYDS SADWFSLGCM LFKLLRGHSP FRQHKTKDKH EIDRMTLTMA VELPDSFSPE
LRSLLEGLLQ RDVNRRLGCL GRGAQEVKES PFFRSLDWQM VFLQKYPPPL IPPRGEVNAA
DAFDIGSFDE EDTKGIKLLD SDQELYRNFP LTISERWQQE VAETVFDTIN AETDRLEARK
KAKNKQLGHE EDYALGKDCI MHGYMSKMGN PFLTQWQRRY FYLFPNRLEW RGEGEAPQSL
LTMEEIQSVE ETQIKERKCL LLKIRGGKQF ILQCDSDPEL VQWKKELRDA YREAQQLVQR
VPKMKNKPRS PVVELSKVPL VQRGSANGL
