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 24-JAN-2024, entry version 209. 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}. 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; 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; 29. 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; 9606-ENSP00000381129; -. DR PeptideAtlas; P32298; -. DR ProteomicsDB; 54861; -. [P32298-1] DR ProteomicsDB; 54862; -. [P32298-2] DR ProteomicsDB; 54863; -. [P32298-3] DR ProteomicsDB; 54864; -. [P32298-4] DR Antibodypedia; 3832; 301 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 AGR; HGNC:4543; -. DR CTD; 2868; -. DR DisGeNET; 2868; -. DR GeneCards; GRK4; -. DR HGNC; HGNC:4543; GRK4. DR HPA; ENSG00000125388; Tissue enhanced (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; PFRPDPN; -. DR OrthoDB; 2906348at2759; -. 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 1173 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 112 other cell types or tissues. DR ExpressionAtlas; P32298; baseline and differential. 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:0004672; F:protein kinase activity; IBA:GO_Central. DR GO; GO:0050254; F:rhodopsin kinase activity; TAS:Reactome. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. 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 CDD; cd05631; STKc_GRK4; 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:SF14; G PROTEIN-COUPLED RECEPTOR KINASE 4; 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. DR Genevisible; P32298; HS. 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 //