GRK4_HUMAN
ID GRK4_HUMAN Reviewed; 578 AA.
AC P32298; O00641; O00642; Q13293; Q13294; Q13295; Q14453; Q14725; Q15313;
AC Q15314; Q15315; Q15316; Q17RH6; Q53EQ8;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 3.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=G protein-coupled receptor kinase 4;
DE EC=2.7.11.16;
DE AltName: Full=G protein-coupled receptor kinase GRK4;
DE AltName: Full=ITI1;
GN Name=GRK4; Synonyms=GPRK2L, GPRK4;
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 [GENOMIC DNA] (ISOFORM 3), AND VARIANT ALA-486.
RX PubMed=1338872; DOI=10.1093/hmg/1.9.697;
RA Ambrose C., James M., Barnes G., Lin C., Bates G., Altherr M., Duyao M.,
RA Groot N., Church D., Wasmuth J.J., Lehrach H., Housman D., Buckler A.J.,
RA Gusella J.F., McDonald M.E.;
RT "A novel G protein-coupled receptor kinase gene cloned from 4p16.3.";
RL Hum. Mol. Genet. 1:697-703(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), AND VARIANT ALA-486.
RC TISSUE=Testis;
RX PubMed=9092566; DOI=10.1074/jbc.272.15.10188;
RA Sallese M., Mariggio S., Collodel G., Moretti E., Piomboni P., Baccetti B.,
RA de Blasi A.;
RT "G protein-coupled receptor kinase GRK4. Molecular analysis of the four
RT isoforms and ultrastructural localization in spermatozoa and germinal
RT cells.";
RL J. Biol. Chem. 272:10188-10195(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING, FUNCTION,
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, PALMITOYLATION, AND VARIANT
RP ALA-486.
RC TISSUE=Testis;
RX PubMed=8626439; DOI=10.1074/jbc.271.11.6403;
RA Premont R.T., Macrae A.D., Stoffel R.H., Chung N., Pitcher J.A.,
RA Ambrose C., Inglese J., MacDonald M.E., Lefkowitz R.J.;
RT "Characterization of the G protein-coupled receptor kinase GRK4.
RT Identification of four splice variants.";
RL J. Biol. Chem. 271:6403-6410(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANT ALA-486.
RC TISSUE=Brain;
RX PubMed=8135832; DOI=10.1006/bbrc.1994.1306;
RA Sallese M., Lombardi M.S., de Blasi A.;
RT "Two isoforms of G protein-coupled receptor kinase 4 identified by
RT molecular cloning.";
RL Biochem. Biophys. Res. Commun. 199:848-854(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Kidney;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-486.
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 [8]
RP TISSUE SPECIFICITY.
RX PubMed=16636192; DOI=10.1161/01.hyp.0000222004.74872.17;
RA Sanada H., Yatabe J., Midorikawa S., Katoh T., Hashimoto S., Watanabe T.,
RA Xu J., Luo Y., Wang X., Zeng C., Armando I., Felder R.A., Jose P.A.;
RT "Amelioration of genetic hypertension by suppression of renal G protein-
RT coupled receptor kinase type 4 expression.";
RL Hypertension 47:1131-1139(2006).
RN [9]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP DRD3.
RX PubMed=19520868; DOI=10.1074/jbc.m109.003665;
RA Villar V.A.M., Jones J.E., Armando I., Palmes-Saloma C., Yu P.,
RA Pascua A.M., Keever L., Arnaldo F.B., Wang Z., Luo Y., Felder R.A.,
RA Jose P.A.;
RT "G protein-coupled receptor kinase 4 (GRK4) regulates the phosphorylation
RT and function of the dopamine D3 receptor.";
RL J. Biol. Chem. 284:21425-21434(2009).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [11]
RP VARIANTS [LARGE SCALE ANALYSIS] LEU-65; THR-116; VAL-142; ILE-247; GLN-383;
RP PRO-425; ILE-473; ALA-486 AND THR-495.
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 activated forms of G protein-
CC coupled receptors. GRK4-alpha can phosphorylate rhodopsin and its
CC activity is inhibited by calmodulin; the other three isoforms do not
CC phosphorylate rhodopsin and do not interact with calmodulin. GRK4-alpha
CC and GRK4-gamma phosphorylate DRD3. Phosphorylates ADRB2.
CC {ECO:0000269|PubMed:19520868, ECO:0000269|PubMed:8626439}.
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 -!- ACTIVITY REGULATION: Inhibited by heparin.
CC {ECO:0000269|PubMed:19520868}.
CC -!- SUBUNIT: Interacts with DRD3. {ECO:0000269|PubMed:19520868}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cell cortex. Note=Both at
CC the cell surface and dispersed in the cytoplasm under basal conditions.
CC Receptor stimulation results in the internalization of GRK4 to the
CC perinuclear area, where colocalization with DRD3 is observed strongly
CC at 5 and 15 minutes. DRD3 and GRK4 colocalize in lipid rafts of renal
CC proximal tubule cells.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=GRK4-alpha, GRK4D;
CC IsoId=P32298-1; Sequence=Displayed;
CC Name=2; Synonyms=GRK4-beta, GRK4C;
CC IsoId=P32298-2; Sequence=VSP_004936;
CC Name=3; Synonyms=GRK4-delta, GRK4A;
CC IsoId=P32298-3; Sequence=VSP_004936, VSP_004937;
CC Name=4; Synonyms=GRK4-gamma, GRK4B;
CC IsoId=P32298-4; Sequence=VSP_004937;
CC -!- TISSUE SPECIFICITY: Isoform 1, isoform 2, isoform 3, and isoform 4 are
CC expressed in testis. Isoform 4 is expressed in myometrium.
CC {ECO:0000269|PubMed:16636192, ECO:0000269|PubMed:8626439}.
CC -!- PTM: Palmitoylated. {ECO:0000269|PubMed:8626439}.
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; L03718; AAB04045.1; -; Genomic_DNA.
DR EMBL; X97879; CAA66468.1; -; mRNA.
DR EMBL; X97880; CAA66469.1; -; mRNA.
DR EMBL; X97881; CAA66470.1; -; mRNA.
DR EMBL; U33054; AAC50406.1; -; mRNA.
DR EMBL; U33055; AAC50407.1; -; mRNA.
DR EMBL; U33056; AAC50408.1; -; mRNA.
DR EMBL; U33168; AAC50409.1; -; Genomic_DNA.
DR EMBL; U33153; AAC50409.1; JOINED; Genomic_DNA.
DR EMBL; U33155; AAC50409.1; JOINED; Genomic_DNA.
DR EMBL; U33156; AAC50409.1; JOINED; Genomic_DNA.
DR EMBL; U33157; AAC50409.1; JOINED; Genomic_DNA.
DR EMBL; U33158; AAC50409.1; JOINED; Genomic_DNA.
DR EMBL; U33159; AAC50409.1; JOINED; Genomic_DNA.
DR EMBL; U33160; AAC50409.1; JOINED; Genomic_DNA.
DR EMBL; U33161; AAC50409.1; JOINED; Genomic_DNA.
DR EMBL; U33162; AAC50409.1; JOINED; Genomic_DNA.
DR EMBL; U33163; AAC50409.1; JOINED; Genomic_DNA.
DR EMBL; U33164; AAC50409.1; JOINED; Genomic_DNA.
DR EMBL; U33165; AAC50409.1; JOINED; Genomic_DNA.
DR EMBL; U33166; AAC50409.1; JOINED; Genomic_DNA.
DR EMBL; U33167; AAC50409.1; JOINED; Genomic_DNA.
DR EMBL; U33168; AAC50410.1; -; Genomic_DNA.
DR EMBL; U33153; AAC50410.1; JOINED; Genomic_DNA.
DR EMBL; U33154; AAC50410.1; JOINED; Genomic_DNA.
DR EMBL; U33155; AAC50410.1; JOINED; Genomic_DNA.
DR EMBL; U33156; AAC50410.1; JOINED; Genomic_DNA.
DR EMBL; U33157; AAC50410.1; JOINED; Genomic_DNA.
DR EMBL; U33158; AAC50410.1; JOINED; Genomic_DNA.
DR EMBL; U33159; AAC50410.1; JOINED; Genomic_DNA.
DR EMBL; U33160; AAC50410.1; JOINED; Genomic_DNA.
DR EMBL; U33161; AAC50410.1; JOINED; Genomic_DNA.
DR EMBL; U33162; AAC50410.1; JOINED; Genomic_DNA.
DR EMBL; U33163; AAC50410.1; JOINED; Genomic_DNA.
DR EMBL; U33164; AAC50410.1; JOINED; Genomic_DNA.
DR EMBL; U33165; AAC50410.1; JOINED; Genomic_DNA.
DR EMBL; U33166; AAC50410.1; JOINED; Genomic_DNA.
DR EMBL; U33167; AAC50410.1; JOINED; Genomic_DNA.
DR EMBL; U33168; AAC50411.1; -; Genomic_DNA.
DR EMBL; U33153; AAC50411.1; JOINED; Genomic_DNA.
DR EMBL; U33154; AAC50411.1; JOINED; Genomic_DNA.
DR EMBL; U33155; AAC50411.1; JOINED; Genomic_DNA.
DR EMBL; U33156; AAC50411.1; JOINED; Genomic_DNA.
DR EMBL; U33157; AAC50411.1; JOINED; Genomic_DNA.
DR EMBL; U33158; AAC50411.1; JOINED; Genomic_DNA.
DR EMBL; U33159; AAC50411.1; JOINED; Genomic_DNA.
DR EMBL; U33160; AAC50411.1; JOINED; Genomic_DNA.
DR EMBL; U33161; AAC50411.1; JOINED; Genomic_DNA.
DR EMBL; U33162; AAC50411.1; JOINED; Genomic_DNA.
DR EMBL; U33163; AAC50411.1; JOINED; Genomic_DNA.
DR EMBL; U33164; AAC50411.1; JOINED; Genomic_DNA.
DR EMBL; U33165; AAC50411.1; JOINED; Genomic_DNA.
DR EMBL; U33166; AAC50411.1; JOINED; Genomic_DNA.
DR EMBL; U33168; AAC50412.1; -; Genomic_DNA.
DR EMBL; U33153; AAC50412.1; JOINED; Genomic_DNA.
DR EMBL; U33155; AAC50412.1; JOINED; Genomic_DNA.
DR EMBL; U33156; AAC50412.1; JOINED; Genomic_DNA.
DR EMBL; U33157; AAC50412.1; JOINED; Genomic_DNA.
DR EMBL; U33158; AAC50412.1; JOINED; Genomic_DNA.
DR EMBL; U33159; AAC50412.1; JOINED; Genomic_DNA.
DR EMBL; U33160; AAC50412.1; JOINED; Genomic_DNA.
DR EMBL; U33161; AAC50412.1; JOINED; Genomic_DNA.
DR EMBL; U33162; AAC50412.1; JOINED; Genomic_DNA.
DR EMBL; U33163; AAC50412.1; JOINED; Genomic_DNA.
DR EMBL; U33164; AAC50412.1; JOINED; Genomic_DNA.
DR EMBL; U33165; AAC50412.1; JOINED; Genomic_DNA.
DR EMBL; U33166; AAC50412.1; JOINED; Genomic_DNA.
DR EMBL; AK223581; BAD97301.1; -; mRNA.
DR EMBL; X98118; CAA66802.1; -; mRNA.
DR EMBL; X75897; CAA53506.1; -; mRNA.
DR EMBL; Z68192; CAA92341.1; -; Genomic_DNA.
DR EMBL; BC117320; AAI17321.1; -; mRNA.
DR CCDS; CCDS33946.1; -. [P32298-1]
DR CCDS; CCDS33947.1; -. [P32298-4]
DR CCDS; CCDS47002.1; -. [P32298-2]
DR CCDS; CCDS68656.1; -. [P32298-3]
DR PIR; I54326; I54326.
DR PIR; JC2127; JC2127.
DR RefSeq; NP_001004056.1; NM_001004056.1. [P32298-2]
DR RefSeq; NP_001004057.1; NM_001004057.1. [P32298-4]
DR RefSeq; NP_005298.2; NM_005307.2. [P32298-3]
DR RefSeq; NP_892027.2; NM_182982.2. [P32298-1]
DR PDB; 4YHJ; X-ray; 2.60 A; A/B=1-578.
DR PDBsum; 4YHJ; -.
DR AlphaFoldDB; P32298; -.
DR SMR; P32298; -.
DR BioGRID; 109126; 14.
DR IntAct; P32298; 18.
DR STRING; 9606.ENSP00000381129; -.
DR BindingDB; P32298; -.
DR ChEMBL; CHEMBL5861; -.
DR DrugCentral; P32298; -.
DR GuidetoPHARMACOLOGY; 1468; -.
DR iPTMnet; P32298; -.
DR PhosphoSitePlus; P32298; -.
DR BioMuta; GRK4; -.
DR DMDM; 143811400; -.
DR jPOST; P32298; -.
DR MassIVE; P32298; -.
DR MaxQB; P32298; -.
DR PaxDb; P32298; -.
DR PeptideAtlas; P32298; -.
DR PRIDE; P32298; -.
DR ProteomicsDB; 54861; -. [P32298-1]
DR ProteomicsDB; 54862; -. [P32298-2]
DR ProteomicsDB; 54863; -. [P32298-3]
DR ProteomicsDB; 54864; -. [P32298-4]
DR Antibodypedia; 3832; 281 antibodies from 29 providers.
DR DNASU; 2868; -.
DR Ensembl; ENST00000345167.10; ENSP00000264764.8; ENSG00000125388.20. [P32298-2]
DR Ensembl; ENST00000398051.8; ENSP00000381128.4; ENSG00000125388.20. [P32298-3]
DR Ensembl; ENST00000398052.9; ENSP00000381129.4; ENSG00000125388.20. [P32298-1]
DR Ensembl; ENST00000504933.1; ENSP00000427445.1; ENSG00000125388.20. [P32298-4]
DR GeneID; 2868; -.
DR KEGG; hsa:2868; -.
DR MANE-Select; ENST00000398052.9; ENSP00000381129.4; NM_182982.3; NP_892027.2.
DR UCSC; uc003ggn.2; human. [P32298-1]
DR CTD; 2868; -.
DR DisGeNET; 2868; -.
DR GeneCards; GRK4; -.
DR HGNC; HGNC:4543; GRK4.
DR HPA; ENSG00000125388; Tissue enhanced (brain, testis).
DR MIM; 137026; gene.
DR neXtProt; NX_P32298; -.
DR OpenTargets; ENSG00000125388; -.
DR PharmGKB; PA28941; -.
DR VEuPathDB; HostDB:ENSG00000125388; -.
DR eggNOG; KOG0986; Eukaryota.
DR GeneTree; ENSGT00940000160151; -.
DR HOGENOM; CLU_000288_63_41_1; -.
DR InParanoid; P32298; -.
DR OMA; EVCFKSD; -.
DR OrthoDB; 1104340at2759; -.
DR PhylomeDB; P32298; -.
DR TreeFam; TF313940; -.
DR BRENDA; 2.7.11.16; 2681.
DR PathwayCommons; P32298; -.
DR Reactome; R-HSA-2514859; Inactivation, recovery and regulation of the phototransduction cascade. [P32298-1]
DR SignaLink; P32298; -.
DR SIGNOR; P32298; -.
DR BioGRID-ORCS; 2868; 7 hits in 1095 CRISPR screens.
DR ChiTaRS; GRK4; human.
DR GeneWiki; GRK4; -.
DR GenomeRNAi; 2868; -.
DR Pharos; P32298; Tchem.
DR PRO; PR:P32298; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P32298; protein.
DR Bgee; ENSG00000125388; Expressed in left testis and 110 other tissues.
DR ExpressionAtlas; P32298; baseline and differential.
DR Genevisible; P32298; HS.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0097381; C:photoreceptor disc membrane; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004703; F:G protein-coupled receptor kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR GO; GO:0050254; F:rhodopsin kinase activity; TAS:Reactome.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0031623; P:receptor internalization; IDA:UniProtKB.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0022400; P:regulation of rhodopsin mediated signaling pathway; TAS:Reactome.
DR GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
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 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cytoplasm;
KW Kinase; Lipoprotein; Nucleotide-binding; Palmitate; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..578
FT /note="G protein-coupled receptor kinase 4"
FT /id="PRO_0000085967"
FT DOMAIN 52..172
FT /note="RGS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT DOMAIN 187..449
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 450..515
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 1..154
FT /note="N-terminal"
FT ACT_SITE 312
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 193..201
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 216
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22223895"
FT MOD_RES 485
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70507"
FT VAR_SEQ 18..49
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:8135832,
FT ECO:0000303|PubMed:9092566, ECO:0000303|Ref.5"
FT /id="VSP_004936"
FT VAR_SEQ 516..561
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:9092566, ECO:0000303|Ref.5"
FT /id="VSP_004937"
FT VARIANT 65
FT /note="R -> L (in dbSNP:rs2960306)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_024573"
FT VARIANT 95
FT /note="D -> H (in dbSNP:rs13305979)"
FT /id="VAR_051621"
FT VARIANT 116
FT /note="A -> T (in dbSNP:rs34857805)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046043"
FT VARIANT 142
FT /note="A -> V (in dbSNP:rs1024323)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_024574"
FT VARIANT 183
FT /note="T -> R (in dbSNP:rs45538934)"
FT /id="VAR_051622"
FT VARIANT 247
FT /note="V -> I (in dbSNP:rs1140085)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_007806"
FT VARIANT 383
FT /note="H -> Q (in dbSNP:rs55852353)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046044"
FT VARIANT 425
FT /note="L -> P"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040516"
FT VARIANT 440
FT /note="A -> V (in dbSNP:rs747003103)"
FT /id="VAR_051623"
FT VARIANT 473
FT /note="V -> I (in dbSNP:rs35024854)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046045"
FT VARIANT 486
FT /note="V -> A (in dbSNP:rs1801058)"
FT /evidence="ECO:0000269|PubMed:1338872,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:8135832, ECO:0000269|PubMed:8626439,
FT ECO:0000269|PubMed:9092566"
FT /id="VAR_024575"
FT VARIANT 495
FT /note="A -> T (in dbSNP:rs35463176)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046046"
FT CONFLICT 562
FT /note="G -> D (in Ref. 1; CAA66468/CAA66802)"
FT /evidence="ECO:0000305"
FT HELIX 30..33
FT /evidence="ECO:0007829|PDB:4YHJ"
FT TURN 39..42
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 43..48
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 53..57
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 61..71
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 75..91
FT /evidence="ECO:0007829|PDB:4YHJ"
FT TURN 95..97
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 98..109
FT /evidence="ECO:0007829|PDB:4YHJ"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 123..132
FT /evidence="ECO:0007829|PDB:4YHJ"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:4YHJ"
FT TURN 140..143
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 144..154
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 157..162
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 166..178
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 184..186
FT /evidence="ECO:0007829|PDB:4YHJ"
FT STRAND 187..195
FT /evidence="ECO:0007829|PDB:4YHJ"
FT STRAND 197..206
FT /evidence="ECO:0007829|PDB:4YHJ"
FT TURN 207..209
FT /evidence="ECO:0007829|PDB:4YHJ"
FT STRAND 212..219
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 220..226
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 229..241
FT /evidence="ECO:0007829|PDB:4YHJ"
FT STRAND 250..255
FT /evidence="ECO:0007829|PDB:4YHJ"
FT STRAND 257..264
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 272..276
FT /evidence="ECO:0007829|PDB:4YHJ"
FT TURN 277..279
FT /evidence="ECO:0007829|PDB:4YHJ"
FT STRAND 280..283
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 286..304
FT /evidence="ECO:0007829|PDB:4YHJ"
FT TURN 305..307
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 315..317
FT /evidence="ECO:0007829|PDB:4YHJ"
FT STRAND 318..320
FT /evidence="ECO:0007829|PDB:4YHJ"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:4YHJ"
FT STRAND 341..343
FT /evidence="ECO:0007829|PDB:4YHJ"
FT TURN 350..352
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 355..358
FT /evidence="ECO:0007829|PDB:4YHJ"
FT STRAND 363..365
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 366..381
FT /evidence="ECO:0007829|PDB:4YHJ"
FT STRAND 382..384
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 395..403
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 415..424
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 429..431
FT /evidence="ECO:0007829|PDB:4YHJ"
FT TURN 433..438
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 439..444
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 447..449
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 454..458
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 494..500
FT /evidence="ECO:0007829|PDB:4YHJ"
FT STRAND 505..507
FT /evidence="ECO:0007829|PDB:4YHJ"
FT HELIX 509..518
FT /evidence="ECO:0007829|PDB:4YHJ"
FT TURN 519..524
FT /evidence="ECO:0007829|PDB:4YHJ"
SQ SEQUENCE 578 AA; 66583 MW; 72FCF94ED551F2D0 CRC64;
MELENIVANS LLLKARQGGY GKKSGRSKKW KEILTLPPVS QCSELRHSIE KDYSSLCDKQ
PIGRRLFRQF CDTKPTLKRH IEFLDAVAEY EVADDEDRSD CGLSILDRFF NDKLAAPLPE
IPPDVVTECR LGLKEENPSK KAFEECTRVA HNYLRGEPFE EYQESSYFSQ FLQWKWLERQ
PVTKNTFRHY RVLGKGGFGE VCACQVRATG KMYACKKLQK KRIKKRKGEA MALNEKRILE
KVQSRFVVSL AYAYETKDAL CLVLTIMNGG DLKFHIYNLG NPGFDEQRAV FYAAELCCGL
EDLQRERIVY RDLKPENILL DDRGHIRISD LGLATEIPEG QRVRGRVGTV GYMAPEVVNN
EKYTFSPDWW GLGCLIYEMI QGHSPFKKYK EKVKWEEVDQ RIKNDTEEYS EKFSEDAKSI
CRMLLTKNPS KRLGCRGEGA AGVKQHPVFK DINFRRLEAN MLEPPFCPDP HAVYCKDVLD
IEQFSVVKGI YLDTADEDFY ARFATGCVSI PWQNEMIESG CFKDINKSES EEALPLDLDK
NIHTPVSRPN RGFFYRLFRR GGCLTMVPSE KEVEPKQC
