GRK5_HUMAN
ID GRK5_HUMAN Reviewed; 590 AA.
AC P34947; D3DRD0; Q5T059;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=G protein-coupled receptor kinase 5;
DE EC=2.7.11.16;
DE AltName: Full=G protein-coupled receptor kinase GRK5;
GN Name=GRK5; Synonyms=GPRK5;
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], AND TISSUE SPECIFICITY.
RX PubMed=7685906; DOI=10.1073/pnas.90.12.5588;
RA Kunapuli P., Benovic J.L.;
RT "Cloning and expression of GRK5: a member of the G protein-coupled receptor
RT kinase family.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:5588-5592(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 [5]
RP INDUCTION.
RX PubMed=8381058; DOI=10.1161/01.cir.87.2.454;
RA Ungerer M., Bohm M., Elce J.S., Erdmann E., Lohse M.J.;
RT "Altered expression of beta-adrenergic receptor kinase and beta 1-
RT adrenergic receptors in the failing human heart.";
RL Circulation 87:454-463(1993).
RN [6]
RP PHOSPHORYLATION AT SER-484 AND THR-485, AND MUTAGENESIS OF SER-484 AND
RP THR-485.
RX PubMed=8144599; DOI=10.1016/s0021-9258(17)34046-2;
RA Kunapuli P., Gurevich V.V., Benovic J.L.;
RT "Phospholipid-stimulated autophosphorylation activates the G protein-
RT coupled receptor kinase GRK5.";
RL J. Biol. Chem. 269:10209-10212(1994).
RN [7]
RP ACTIVITY REGULATION.
RX PubMed=9218466; DOI=10.1074/jbc.272.29.18273;
RA Pronin A.N., Satpaev D.K., Slepak V.Z., Benovic J.L.;
RT "Regulation of G protein-coupled receptor kinases by calmodulin and
RT localization of the calmodulin binding domain.";
RL J. Biol. Chem. 272:18273-18280(1997).
RN [8]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEU-550; LEU-551; LEU-554 AND
RP PHE-555.
RX PubMed=14976207; DOI=10.1074/jbc.m310738200;
RA Thiyagarajan M.M., Stracquatanio R.P., Pronin A.N., Evanko D.S.,
RA Benovic J.L., Wedegaertner P.B.;
RT "A predicted amphipathic helix mediates plasma membrane localization of
RT GRK5.";
RL J. Biol. Chem. 279:17989-17995(2004).
RN [9]
RP SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, AND MUTAGENESIS OF
RP ARG-388; LYS-389; LYS-391; LYS-393 AND ARG-394.
RX PubMed=15542828; DOI=10.1128/mcb.24.23.10169-10179.2004;
RA Johnson L.R., Scott M.G., Pitcher J.A.;
RT "G protein-coupled receptor kinase 5 contains a DNA-binding nuclear
RT localization sequence.";
RL Mol. Cell. Biol. 24:10169-10179(2004).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-484 AND THR-485, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP FUNCTION IN PHOSPHORYLATION OF ARRB1, AND INTERACTION WITH HTR4.
RX PubMed=19661922; DOI=10.1038/emboj.2009.215;
RA Barthet G., Carrat G., Cassier E., Barker B., Gaven F., Pillot M.,
RA Framery B., Pellissier L.P., Augier J., Kang D.S., Claeysen S., Reiter E.,
RA Baneres J.L., Benovic J.L., Marin P., Bockaert J., Dumuis A.;
RT "Beta-arrestin1 phosphorylation by GRK5 regulates G protein-independent 5-
RT HT4 receptor signalling.";
RL EMBO J. 28:2706-2718(2009).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF LRP6.
RX PubMed=19801552; DOI=10.1074/jbc.m109.047456;
RA Chen M., Philipp M., Wang J., Premont R.T., Garrison T.R., Caron M.G.,
RA Lefkowitz R.J., Chen W.;
RT "G Protein-coupled receptor kinases phosphorylate LRP6 in the Wnt
RT pathway.";
RL J. Biol. Chem. 284:35040-35048(2009).
RN [13]
RP FUNCTION IN PHOSPHORYLATION OF TP53, INTERACTION WITH TP53, AND MUTAGENESIS
RP OF LYS-215.
RX PubMed=20124405; DOI=10.1074/jbc.m109.094243;
RA Chen X., Zhu H., Yuan M., Fu J., Zhou Y., Ma L.;
RT "G-protein-coupled receptor kinase 5 phosphorylates p53 and inhibits DNA
RT damage-induced apoptosis.";
RL J. Biol. Chem. 285:12823-12830(2010).
RN [14]
RP FUNCTION IN PHOSPHORYLATION OF ADRB2, AND AUTOPHOSPHORYLATION.
RX PubMed=20038610; DOI=10.1124/mol.109.058115;
RA Baameur F., Morgan D.H., Yao H., Tran T.M., Hammitt R.A., Sabui S.,
RA McMurray J.S., Lichtarge O., Clark R.B.;
RT "Role for the regulator of G-protein signaling homology domain of G
RT protein-coupled receptor kinases 5 and 6 in beta 2-adrenergic receptor and
RT rhodopsin phosphorylation.";
RL Mol. Pharmacol. 77:405-415(2010).
RN [15]
RP FUNCTION IN PHOSPHORYLATION OF ST13, AND INTERACTION WITH ST13.
RX PubMed=21728385; DOI=10.1021/bi2005202;
RA Barker B.L., Benovic J.L.;
RT "G protein-coupled receptor kinase 5 phosphorylation of Hip regulates
RT internalization of the chemokine receptor CXCR4.";
RL Biochemistry 50:6933-6941(2011).
RN [16]
RP VARIANTS [LARGE SCALE ANALYSIS] LEU-41; VAL-119; SER-122; MET-129; ILE-141;
RP GLU-163 AND HIS-304.
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).
RN [17]
RP VARIANT LEU-41, CHARACTERIZATION OF VARIANT LEU-41, POLYMORPHISM, AND
RP POSSIBLE PROTECTIVE ROLE IN THE PROGRESSION OF HEART FAILURE.
RX PubMed=18425130; DOI=10.1038/nm1750;
RA Liggett S.B., Cresci S., Kelly R.J., Syed F.M., Matkovich S.J., Hahn H.S.,
RA Diwan A., Martini J.S., Sparks L., Parekh R.R., Spertus J.A., Koch W.J.,
RA Kardia S.L., Dorn G.W. II;
RT "A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is
RT protective in heart failure.";
RL Nat. Med. 14:510-517(2008).
CC -!- FUNCTION: Serine/threonine kinase that phosphorylates preferentially
CC the activated forms of a variety of G-protein-coupled receptors
CC (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated
CC receptor desensitization, internalization, and signaling events leading
CC to their down-regulation. Phosphorylates a variety of GPCRs, including
CC adrenergic receptors, muscarinic acetylcholine receptors (more
CC specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid
CC receptors. In addition to GPCRs, also phosphorylates various
CC substrates: Hsc70-interacting protein/ST13, TP53/p53, HDAC5, and
CC arrestin-1/ARRB1. Phosphorylation of ARRB1 by GRK5 inhibits G-protein
CC independent MAPK1/MAPK3 signaling downstream of 5HT4-receptors.
CC Phosphorylation of HDAC5, a repressor of myocyte enhancer factor 2
CC (MEF2) leading to nuclear export of HDAC5 and allowing MEF2-mediated
CC transcription. Phosphorylation of TP53/p53, a crucial tumor suppressor,
CC inhibits TP53/p53-mediated apoptosis. Phosphorylation of ST13 regulates
CC internalization of the chemokine receptor. Phosphorylates rhodopsin
CC (RHO) (in vitro) and a non G-protein-coupled receptor, LRP6 during Wnt
CC signaling (in vitro). {ECO:0000269|PubMed:19661922,
CC ECO:0000269|PubMed:19801552, ECO:0000269|PubMed:20038610,
CC ECO:0000269|PubMed:20124405, ECO:0000269|PubMed:21728385}.
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 calmodulin with an IC(50) of 50 nM.
CC Calmodulin inhibits GRK5 association with receptor and phospholipid.
CC {ECO:0000269|PubMed:9218466}.
CC -!- SUBUNIT: Interacts with ST13 (via the C-terminus 303-319 AA)
CC (PubMed:21728385). Interacts with TP53/p53 (PubMed:20124405). Interacts
CC with HTR4 (via C-terminus 330-346 AA); this interaction is promoted by
CC 5-HT (serotonin) (PubMed:19661922). Interacts with HDAC5 (By
CC similarity). Interacts with GIT1 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q62833, ECO:0000250|UniProtKB:Q8VEB1,
CC ECO:0000269|PubMed:19661922, ECO:0000269|PubMed:20124405,
CC ECO:0000269|PubMed:21728385}.
CC -!- INTERACTION:
CC P34947; P25963: NFKBIA; NbExp=2; IntAct=EBI-7149314, EBI-307386;
CC P34947; P97288: Htr4; Xeno; NbExp=8; IntAct=EBI-7149314, EBI-7149283;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell membrane; Peripheral
CC membrane protein. Note=Predominantly localized at the plasma membrane;
CC targeted to the cell surface through the interaction with
CC phospholipids. Nucleus localization is regulated in a GPCR and
CC Ca(2+)/calmodulin-dependent fashion.
CC -!- TISSUE SPECIFICITY: Highest levels in heart, placenta, lung > skeletal
CC muscle > brain, liver, pancreas > kidney. {ECO:0000269|PubMed:7685906}.
CC -!- INDUCTION: Overexpressed during heart failure.
CC {ECO:0000269|PubMed:8381058}.
CC -!- PTM: Autophosphorylated. Autophosphorylation may play a critical role
CC in the regulation of GRK5 kinase activity.
CC {ECO:0000269|PubMed:8144599}.
CC -!- POLYMORPHISM: Variant Leu-41 variant is rare in European-Americans
CC individuals but common in African-Americans individuals (40% of the
CC African-American individuals studied carry at least one allele).
CC Variant leu-41 is associated with decreased mortality in African-
CC Americans with heart failure or cardiac ischemia.
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; L15388; AAA58620.1; -; mRNA.
DR EMBL; AL355273; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL355861; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL583824; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49394.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49395.1; -; Genomic_DNA.
DR EMBL; BC064506; AAH64506.1; -; mRNA.
DR CCDS; CCDS7612.1; -.
DR PIR; A48277; A48277.
DR PIR; B48682; B48682.
DR RefSeq; NP_005299.1; NM_005308.2.
DR PDB; 4TNB; X-ray; 2.11 A; A=1-590.
DR PDB; 4TND; X-ray; 1.80 A; A=1-590.
DR PDB; 6PJX; X-ray; 1.96 A; A=1-590.
DR PDBsum; 4TNB; -.
DR PDBsum; 4TND; -.
DR PDBsum; 6PJX; -.
DR AlphaFoldDB; P34947; -.
DR SMR; P34947; -.
DR BioGRID; 109127; 174.
DR DIP; DIP-57457N; -.
DR IntAct; P34947; 5.
DR MINT; P34947; -.
DR STRING; 9606.ENSP00000376609; -.
DR BindingDB; P34947; -.
DR ChEMBL; CHEMBL5678; -.
DR GuidetoPHARMACOLOGY; 1469; -.
DR iPTMnet; P34947; -.
DR PhosphoSitePlus; P34947; -.
DR BioMuta; GRK5; -.
DR DMDM; 462203; -.
DR jPOST; P34947; -.
DR MassIVE; P34947; -.
DR MaxQB; P34947; -.
DR PaxDb; P34947; -.
DR PeptideAtlas; P34947; -.
DR PRIDE; P34947; -.
DR ProteomicsDB; 54958; -.
DR ABCD; P34947; 1 sequenced antibody.
DR Antibodypedia; 18824; 535 antibodies from 39 providers.
DR DNASU; 2869; -.
DR Ensembl; ENST00000392870.3; ENSP00000376609.2; ENSG00000198873.12.
DR GeneID; 2869; -.
DR KEGG; hsa:2869; -.
DR MANE-Select; ENST00000392870.3; ENSP00000376609.2; NM_005308.3; NP_005299.1.
DR UCSC; uc001led.4; human.
DR CTD; 2869; -.
DR DisGeNET; 2869; -.
DR GeneCards; GRK5; -.
DR HGNC; HGNC:4544; GRK5.
DR HPA; ENSG00000198873; Low tissue specificity.
DR MIM; 600870; gene.
DR neXtProt; NX_P34947; -.
DR OpenTargets; ENSG00000198873; -.
DR PharmGKB; PA180; -.
DR VEuPathDB; HostDB:ENSG00000198873; -.
DR eggNOG; KOG0986; Eukaryota.
DR GeneTree; ENSGT00940000160702; -.
DR HOGENOM; CLU_000288_63_41_1; -.
DR InParanoid; P34947; -.
DR OMA; YIVNRIF; -.
DR OrthoDB; 1104340at2759; -.
DR PhylomeDB; P34947; -.
DR TreeFam; TF313940; -.
DR BRENDA; 2.7.11.16; 2681.
DR PathwayCommons; P34947; -.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR SignaLink; P34947; -.
DR SIGNOR; P34947; -.
DR BioGRID-ORCS; 2869; 14 hits in 1109 CRISPR screens.
DR ChiTaRS; GRK5; human.
DR GeneWiki; GRK5; -.
DR GenomeRNAi; 2869; -.
DR Pharos; P34947; Tchem.
DR PRO; PR:P34947; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P34947; protein.
DR Bgee; ENSG00000198873; Expressed in saphenous vein and 195 other tissues.
DR Genevisible; P34947; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0047696; F:beta-adrenergic receptor kinase activity; IMP:CACAO.
DR GO; GO:0004703; F:G protein-coupled receptor kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0005543; F:phospholipid binding; TAS:ProtInc.
DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR GO; GO:0005080; F:protein kinase C binding; TAS:ProtInc.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0045444; P:fat cell differentiation; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:CACAO.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:CACAO.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central.
DR GO; GO:0007217; P:tachykinin receptor signaling pathway; IDA:BHF-UCL.
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 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; PS50132; RGS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; ATP-binding; Cell membrane; Cytoplasm; Kinase;
KW Lipid-binding; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Wnt signaling pathway.
FT CHAIN 1..590
FT /note="G protein-coupled receptor kinase 5"
FT /id="PRO_0000085971"
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 REGION 20..39
FT /note="Interaction with calmodulin"
FT REGION 531..590
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 546..565
FT /note="Sufficient for membrane localization"
FT MOTIF 388..395
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:15542828"
FT COMPBIAS 555..590
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 311
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
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 MOD_RES 484
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:8144599,
FT ECO:0007744|PubMed:18669648"
FT MOD_RES 485
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:8144599,
FT ECO:0007744|PubMed:18669648"
FT MOD_RES 579
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VEB1"
FT VARIANT 41
FT /note="Q -> L (exerts a protective effect in heart failure
FT and ischemia; dbSNP:rs2230345)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:18425130"
FT /id="VAR_040517"
FT VARIANT 119
FT /note="A -> V (in dbSNP:rs55980792)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040518"
FT VARIANT 122
FT /note="G -> S (in dbSNP:rs55902633)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040519"
FT VARIANT 129
FT /note="T -> M (in dbSNP:rs34679178)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040520"
FT VARIANT 141
FT /note="L -> I (in dbSNP:rs56254855)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040521"
FT VARIANT 163
FT /note="D -> E (in a lung neuroendocrine carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040522"
FT VARIANT 304
FT /note="R -> H (in dbSNP:rs2230349)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040523"
FT MUTAGEN 215
FT /note="K->R: Failed to phosphorylate p53/TP53."
FT /evidence="ECO:0000269|PubMed:20124405"
FT MUTAGEN 388
FT /note="R->A: Nuclear exclusion; when associated with A-389;
FT A-391; A-393 and A-394."
FT /evidence="ECO:0000269|PubMed:15542828"
FT MUTAGEN 389
FT /note="K->A: Nuclear exclusion; when associated with A-388;
FT A-391; A-393 and A-394."
FT /evidence="ECO:0000269|PubMed:15542828"
FT MUTAGEN 391
FT /note="K->A: Nuclear exclusion; when associated with A-388;
FT A-389; A-393 and A-394."
FT /evidence="ECO:0000269|PubMed:15542828"
FT MUTAGEN 393
FT /note="K->A: Nuclear exclusion; when associated with A-388;
FT A-389; A-391 and A-394."
FT /evidence="ECO:0000269|PubMed:15542828"
FT MUTAGEN 394
FT /note="R->A: Nuclear exclusion; when associated with A-388;
FT A-389; A-391 and A-393."
FT /evidence="ECO:0000269|PubMed:15542828"
FT MUTAGEN 484
FT /note="S->A: 15-20 fold defects in kinase activity; when
FT associated with A-485."
FT /evidence="ECO:0000269|PubMed:8144599"
FT MUTAGEN 485
FT /note="T->A: 15-20 fold defects in kinase activity; when
FT associated with A-484."
FT /evidence="ECO:0000269|PubMed:8144599"
FT MUTAGEN 550
FT /note="L->A: No detectable plasma membrane localization;
FT when associated with A-551; A-554; and A-555."
FT /evidence="ECO:0000269|PubMed:14976207"
FT MUTAGEN 551
FT /note="L->A: No detectable plasma membrane localization;
FT when associated with A-550; A-554; and A-555."
FT /evidence="ECO:0000269|PubMed:14976207"
FT MUTAGEN 554
FT /note="L->A: No detectable plasma membrane localization;
FT when associated with A-550; A-551; and A-555."
FT /evidence="ECO:0000269|PubMed:14976207"
FT MUTAGEN 555
FT /note="F->A: No detectable plasma membrane localization;
FT when associated with A-550; A-551; and A-554."
FT /evidence="ECO:0000269|PubMed:14976207"
FT HELIX 3..16
FT /evidence="ECO:0007829|PDB:6PJX"
FT TURN 17..20
FT /evidence="ECO:0007829|PDB:6PJX"
FT HELIX 22..25
FT /evidence="ECO:0007829|PDB:6PJX"
FT HELIX 30..33
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 39..42
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 43..48
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 53..57
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 61..71
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 75..91
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 98..109
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 123..134
FT /evidence="ECO:0007829|PDB:4TND"
FT TURN 139..142
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 143..153
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 156..162
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 165..177
FT /evidence="ECO:0007829|PDB:4TND"
FT STRAND 185..195
FT /evidence="ECO:0007829|PDB:4TND"
FT STRAND 198..205
FT /evidence="ECO:0007829|PDB:4TND"
FT TURN 206..208
FT /evidence="ECO:0007829|PDB:4TND"
FT STRAND 211..218
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 219..224
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 228..240
FT /evidence="ECO:0007829|PDB:4TND"
FT STRAND 249..254
FT /evidence="ECO:0007829|PDB:4TND"
FT STRAND 256..263
FT /evidence="ECO:0007829|PDB:4TND"
FT STRAND 268..270
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 271..277
FT /evidence="ECO:0007829|PDB:4TND"
FT STRAND 278..280
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 285..304
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 314..316
FT /evidence="ECO:0007829|PDB:4TND"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:4TND"
FT STRAND 325..327
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 330..332
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 354..357
FT /evidence="ECO:0007829|PDB:4TND"
FT STRAND 362..364
FT /evidence="ECO:0007829|PDB:6PJX"
FT HELIX 366..380
FT /evidence="ECO:0007829|PDB:4TND"
FT STRAND 384..386
FT /evidence="ECO:0007829|PDB:6PJX"
FT HELIX 394..403
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 414..423
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 428..430
FT /evidence="ECO:0007829|PDB:4TND"
FT TURN 436..438
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 439..443
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 446..448
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 453..457
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 477..479
FT /evidence="ECO:0007829|PDB:6PJX"
FT STRAND 489..491
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 494..502
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 508..517
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 520..524
FT /evidence="ECO:0007829|PDB:4TND"
FT STRAND 529..531
FT /evidence="ECO:0007829|PDB:4TND"
FT HELIX 535..537
FT /evidence="ECO:0007829|PDB:4TND"
SQ SEQUENCE 590 AA; 67787 MW; D363567ECFF5CF21 CRC64;
MELENIVANT VLLKAREGGG GKRKGKSKKW KEILKFPHIS QCEDLRRTID RDYCSLCDKQ
PIGRLLFRQF CETRPGLECY IQFLDSVAEY EVTPDEKLGE KGKEIMTKYL TPKSPVFIAQ
VGQDLVSQTE EKLLQKPCKE LFSACAQSVH EYLRGEPFHE YLDSMFFDRF LQWKWLERQP
VTKNTFRQYR VLGKGGFGEV CACQVRATGK MYACKRLEKK RIKKRKGESM ALNEKQILEK
VNSQFVVNLA YAYETKDALC LVLTIMNGGD LKFHIYNMGN PGFEEERALF YAAEILCGLE
DLHRENTVYR DLKPENILLD DYGHIRISDL GLAVKIPEGD LIRGRVGTVG YMAPEVLNNQ
RYGLSPDYWG LGCLIYEMIE GQSPFRGRKE KVKREEVDRR VLETEEVYSH KFSEEAKSIC
KMLLTKDAKQ RLGCQEEGAA EVKRHPFFRN MNFKRLEAGM LDPPFVPDPR AVYCKDVLDI
EQFSTVKGVN LDHTDDDFYS KFSTGSVSIP WQNEMIETEC FKELNVFGPN GTLPPDLNRN
HPPEPPKKGL LQRLFKRQHQ NNSKSSPSSK TSFNHHINSN HVSSNSTGSS
