GRK7_HUMAN
ID GRK7_HUMAN Reviewed; 553 AA.
AC Q8WTQ7;
DT 27-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Rhodopsin kinase GRK7;
DE EC=2.7.11.14 {ECO:0000269|PubMed:15946941};
DE AltName: Full=G protein-coupled receptor kinase 7;
DE AltName: Full=G protein-coupled receptor kinase GRK7;
DE Flags: Precursor;
GN Name=GRK7; Synonyms=GPRK7;
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.
RC TISSUE=Retina;
RX PubMed=11754336;
RA Chen C.-K., Zhang K., Church-Kopish J., Huang W., Zhang H., Chen Y.-J.,
RA Frederick J.M., Baehr W.;
RT "Characterization of human GRK7 as a potential cone opsin kinase.";
RL Mol. Vis. 7:305-313(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RX PubMed=11717351; DOI=10.1523/jneurosci.21-23-09175.2001;
RA Weiss E.R., Ducceschi M.H., Horner T.J., Li A., Craft C.M., Osawa S.;
RT "Species-specific differences in expression of G-protein-coupled receptor
RT kinase (GRK) 7 and GRK1 in mammalian cone photoreceptor cells: implications
RT for cone cell phototransduction.";
RL J. Neurosci. 21:9175-9184(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, FUNCTION IN
RP PHOSPHORYLATION OF RHO, ACTIVITY REGULATION, AUTOPHOSPHORYLATION, AND
RP MUTAGENESIS OF SER-23 AND SER-36.
RX PubMed=15946941; DOI=10.1074/jbc.m505117200;
RA Horner T.J., Osawa S., Schaller M.D., Weiss E.R.;
RT "Phosphorylation of GRK1 and GRK7 by cAMP-dependent protein kinase
RT attenuates their enzymatic activities.";
RL J. Biol. Chem. 280:28241-28250(2005).
RN [5]
RP TISSUE SPECIFICITY, AND PHOSPHORYLATION AT SER-36.
RX PubMed=18803695; DOI=10.1111/j.1471-4159.2008.05691.x;
RA Osawa S., Jo R., Weiss E.R.;
RT "Phosphorylation of GRK7 by PKA in cone photoreceptor cells is regulated by
RT light.";
RL J. Neurochem. 107:1314-1324(2008).
RN [6]
RP VARIANTS [LARGE SCALE ANALYSIS] HIS-81; TRP-113; CYS-115; THR-127; GLY-196;
RP MET-196; TRP-226; PHE-253; GLN-309; ILE-313; GLY-443 AND THR-460.
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: Retina-specific kinase involved in the shutoff of the
CC photoresponse and adaptation to changing light conditions via cone
CC opsin phosphorylation, including rhodopsin (RHO).
CC {ECO:0000269|PubMed:15946941}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[rhodopsin] = ADP + H(+) + O-phospho-L-
CC threonyl-[rhodopsin]; Xref=Rhea:RHEA:56552, Rhea:RHEA-COMP:14596,
CC Rhea:RHEA-COMP:14597, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.14; Evidence={ECO:0000269|PubMed:15946941};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[rhodopsin] = ADP + H(+) + O-phospho-L-seryl-
CC [rhodopsin]; Xref=Rhea:RHEA:23356, Rhea:RHEA-COMP:14594, Rhea:RHEA-
CC COMP:14595, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.14;
CC Evidence={ECO:0000269|PubMed:15946941};
CC -!- ACTIVITY REGULATION: Inhibited by phosphorylation of Ser-36.
CC {ECO:0000250}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.9 uM for rhodopsin {ECO:0000269|PubMed:15946941};
CC KM=21.4 uM for ATP {ECO:0000269|PubMed:15946941};
CC Vmax=915 nmol/min/mg enzyme {ECO:0000269|PubMed:15946941};
CC -!- SUBUNIT: Interacts (when prenylated) with PDE6D; this promotes release
CC from membranes. {ECO:0000250|UniProtKB:Q8WMV0}.
CC -!- INTERACTION:
CC Q8WTQ7; P08238: HSP90AB1; NbExp=2; IntAct=EBI-6423032, EBI-352572;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q8WMV0}; Lipid-
CC anchor {ECO:0000250|UniProtKB:Q8WMV0}.
CC -!- TISSUE SPECIFICITY: Retinal cones, outer and inner segments.
CC {ECO:0000269|PubMed:11754336, ECO:0000269|PubMed:18803695}.
CC -!- PTM: Autophosphorylated in vitro at Ser-490. Phosphorylation at Ser-36
CC is regulated by light and activated by cAMP.
CC {ECO:0000269|PubMed:18803695}.
CC -!- MISCELLANEOUS: Although the protein is present in a diversity of
CC vertebrates ranging from bony fish to mammals, the mouse and rat
CC orthologous proteins do not exist.
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; AF439409; AAL48216.1; -; mRNA.
DR EMBL; AF282269; AAL33880.1; -; mRNA.
DR EMBL; AC112504; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS3120.1; -.
DR RefSeq; NP_631948.1; NM_139209.2.
DR RefSeq; XP_016861206.1; XM_017005717.1.
DR AlphaFoldDB; Q8WTQ7; -.
DR SMR; Q8WTQ7; -.
DR BioGRID; 126297; 9.
DR IntAct; Q8WTQ7; 14.
DR STRING; 9606.ENSP00000264952; -.
DR BindingDB; Q8WTQ7; -.
DR ChEMBL; CHEMBL1075133; -.
DR DrugCentral; Q8WTQ7; -.
DR GuidetoPHARMACOLOGY; 1471; -.
DR iPTMnet; Q8WTQ7; -.
DR PhosphoSitePlus; Q8WTQ7; -.
DR BioMuta; GRK7; -.
DR DMDM; 21263659; -.
DR MassIVE; Q8WTQ7; -.
DR PaxDb; Q8WTQ7; -.
DR PeptideAtlas; Q8WTQ7; -.
DR PRIDE; Q8WTQ7; -.
DR ProteomicsDB; 74583; -.
DR Antibodypedia; 33484; 222 antibodies from 27 providers.
DR DNASU; 131890; -.
DR Ensembl; ENST00000264952.2; ENSP00000264952.2; ENSG00000114124.3.
DR Ensembl; ENST00000682958.1; ENSP00000508022.1; ENSG00000114124.3.
DR GeneID; 131890; -.
DR KEGG; hsa:131890; -.
DR MANE-Select; ENST00000682958.1; ENSP00000508022.1; NM_139209.3; NP_631948.1.
DR UCSC; uc011bnd.3; human.
DR CTD; 131890; -.
DR DisGeNET; 131890; -.
DR GeneCards; GRK7; -.
DR HGNC; HGNC:17031; GRK7.
DR HPA; ENSG00000114124; Tissue enriched (retina).
DR MIM; 606987; gene.
DR neXtProt; NX_Q8WTQ7; -.
DR OpenTargets; ENSG00000114124; -.
DR PharmGKB; PA38433; -.
DR VEuPathDB; HostDB:ENSG00000114124; -.
DR eggNOG; KOG0986; Eukaryota.
DR GeneTree; ENSGT00940000160511; -.
DR HOGENOM; CLU_000288_63_41_1; -.
DR InParanoid; Q8WTQ7; -.
DR OMA; VFEMQPV; -.
DR OrthoDB; 1104340at2759; -.
DR PhylomeDB; Q8WTQ7; -.
DR TreeFam; TF313940; -.
DR BRENDA; 2.7.11.14; 2681.
DR PathwayCommons; Q8WTQ7; -.
DR Reactome; R-HSA-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR SABIO-RK; Q8WTQ7; -.
DR SignaLink; Q8WTQ7; -.
DR SIGNOR; Q8WTQ7; -.
DR BioGRID-ORCS; 131890; 9 hits in 1077 CRISPR screens.
DR ChiTaRS; GRK7; human.
DR GenomeRNAi; 131890; -.
DR Pharos; Q8WTQ7; Tchem.
DR PRO; PR:Q8WTQ7; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q8WTQ7; protein.
DR Bgee; ENSG00000114124; Expressed in buccal mucosa cell and 29 other tissues.
DR Genevisible; Q8WTQ7; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0097381; C:photoreceptor disc membrane; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004703; F:G protein-coupled receptor kinase activity; IEA:InterPro.
DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR GO; GO:0050254; F:rhodopsin kinase activity; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
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 GO; GO:0007601; P:visual perception; 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 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 ATP-binding; Kinase; Lipoprotein; Membrane; Methylation;
KW Nucleotide-binding; Phosphoprotein; Prenylation; Reference proteome;
KW Sensory transduction; Serine/threonine-protein kinase; Transferase; Vision.
FT CHAIN 1..550
FT /note="Rhodopsin kinase GRK7"
FT /id="PRO_0000024332"
FT PROPEP 551..553
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000024333"
FT DOMAIN 56..176
FT /note="RGS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT DOMAIN 191..454
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 455..520
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ACT_SITE 316
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 MOD_RES 36
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:18803695"
FT MOD_RES 550
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000255"
FT LIPID 550
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000255"
FT VARIANT 81
FT /note="R -> H (in dbSNP:rs34429284)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040527"
FT VARIANT 113
FT /note="C -> W (in dbSNP:rs56070798)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040528"
FT VARIANT 115
FT /note="S -> C (in dbSNP:rs34769632)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040529"
FT VARIANT 127
FT /note="S -> T (in dbSNP:rs35318124)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040530"
FT VARIANT 196
FT /note="V -> G (in dbSNP:rs55707760)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040531"
FT VARIANT 196
FT /note="V -> M (in dbSNP:rs56019094)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040532"
FT VARIANT 226
FT /note="R -> W (in dbSNP:rs35566288)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040533"
FT VARIANT 253
FT /note="S -> F (in a metastatic melanoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040534"
FT VARIANT 309
FT /note="E -> Q (in dbSNP:rs55824414)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040535"
FT VARIANT 313
FT /note="V -> I (in dbSNP:rs56076641)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040536"
FT VARIANT 443
FT /note="E -> G (in dbSNP:rs36009541)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040537"
FT VARIANT 460
FT /note="P -> T (in dbSNP:rs33928105)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040538"
FT VARIANT 461
FT /note="R -> C (in dbSNP:rs36004830)"
FT /id="VAR_051624"
FT MUTAGEN 23
FT /note="S->A: No effect on kinase activity. Increase kinase
FT activity; when associated with A-36."
FT /evidence="ECO:0000269|PubMed:15946941"
FT MUTAGEN 36
FT /note="S->A: No effect on kinase activity. Increase kinase
FT activity; when associated with A-23."
FT /evidence="ECO:0000269|PubMed:15946941"
SQ SEQUENCE 553 AA; 62212 MW; C502E301CF8EB688 CRC64;
MVDMGALDNL IANTAYLQAR KPSDCDSKEL QRRRRSLALP GLQGCAELRQ KLSLNFHSLC
EQQPIGRRLF RDFLATVPTF RKAATFLEDV QNWELAEEGP TKDSALQGLV ATCASAPAPG
NPQPFLSQAV ATKCQAATTE EERVAAVTLA KAEAMAFLQE QPFKDFVTSA FYDKFLQWKL
FEMQPVSDKY FTEFRVLGKG GFGEVCAVQV KNTGKMYACK KLDKKRLKKK GGEKMALLEK
EILEKVSSPF IVSLAYAFES KTHLCLVMSL MNGGDLKFHI YNVGTRGLDM SRVIFYSAQI
ACGMLHLHEL GIVYRDMKPE NVLLDDLGNC RLSDLGLAVE MKGGKPITQR AGTNGYMAPE
ILMEKVSYSY PVDWFAMGCS IYEMVAGRTP FKDYKEKVSK EDLKQRTLQD EVKFQHDNFT
EEAKDICRLF LAKKPEQRLG SREKSDDPRK HHFFKTINFP RLEAGLIEPP FVPDPSVVYA
KDIAEIDDFS EVRGVEFDDK DKQFFKNFAT GAVPIAWQEE IIETGLFEEL NDPNRPTGCE
EGNSSKSGVC LLL
