ID   GRK1_RAT                Reviewed;         564 AA.
AC   Q63651;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 1.
DT   08-NOV-2023, entry version 164.
DE   RecName: Full=Rhodopsin kinase GRK1;
DE            Short=RK;
DE            EC=2.7.11.14 {ECO:0000250|UniProtKB:Q9WVL4};
DE   AltName: Full=G protein-coupled receptor kinase 1 {ECO:0000312|RGD:619712};
DE   Flags: Precursor;
GN   Name=Grk1 {ECO:0000312|RGD:619712}; Synonyms=Rhok;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Sprague-Dawley; TISSUE=Retina;
RX   PubMed=9147475; DOI=10.1017/s0952523800011366;
RA   Zhao X., Haeseleer F., Fariss R.N., Huang J., Baehr W., Milam A.H.,
RA   Palczewski K.;
RT   "Molecular cloning and localization of rhodopsin kinase in the mammalian
RT   pineal.";
RL   Vis. Neurosci. 14:225-232(1997).
RN   [2]
RP   TISSUE SPECIFICITY.
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   PROTEIN SEQUENCE OF 20-31, IDENTIFICATION BY MASS SPECTROMETRY,
RP   PHOSPHORYLATION AT SER-21, AND TISSUE SPECIFICITY.
RX   PubMed=21504899; DOI=10.1074/jbc.m111.230904;
RA   Osawa S., Jo R., Xiong Y., Reidel B., Tserentsoodol N., Arshavsky V.Y.,
RA   Iuvone P.M., Weiss E.R.;
RT   "Phosphorylation of G protein-coupled receptor kinase 1 (GRK1) is regulated
RT   by light but independent of phototransduction in rod photoreceptors.";
RL   J. Biol. Chem. 286:20923-20929(2011).
CC   -!- FUNCTION: Retina-specific kinase involved in the signal turnoff via
CC       phosphorylation of rhodopsin (RHO), the G protein- coupled receptor
CC       that initiates the phototransduction cascade (By similarity). This
CC       rapid desensitization is essential for scotopic vision and permits
CC       rapid adaptation to changes in illumination (By similarity). May play a
CC       role in the maintenance of the outer nuclear layer in the retina (By
CC       similarity). {ECO:0000250|UniProtKB:Q9WVL4}.
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:0000250|UniProtKB:Q9WVL4};
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:0000250|UniProtKB:Q9WVL4};
CC   -!- ACTIVITY REGULATION: Inhibited by RCVRN, which prevents the interaction
CC       between GRK1 and RHO (By similarity). Inhibition is calcium-dependent
CC       (By similarity). {ECO:0000250|UniProtKB:P28327}.
CC   -!- SUBUNIT: Interacts (via N-terminus) with RCVRN (via C-terminus); the
CC       interaction is Ca(2+)-dependent (By similarity). Interacts (when
CC       prenylated) with PDE6D; this promotes release from membranes (By
CC       similarity). May form a complex composed of RHO, GRK1 and RCVRN in a
CC       Ca(2+)-dependent manner; RCVRN prevents the interaction between GRK1
CC       and RHO (By similarity). {ECO:0000250|UniProtKB:P28327}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P28327}; Lipid-
CC       anchor {ECO:0000250|UniProtKB:P28327}. Cell projection, cilium,
CC       photoreceptor outer segment {ECO:0000250|UniProtKB:Q9WVL4}.
CC       Note=Subcellular location is not affected by light or dark conditions.
CC       {ECO:0000250|UniProtKB:Q9WVL4}.
CC   -!- TISSUE SPECIFICITY: Detected in retina (at protein level)
CC       (PubMed:21504899). Retina-specific. Expressed in rod and cone
CC       photoreceptor cells. {ECO:0000269|PubMed:11717351,
CC       ECO:0000269|PubMed:21504899}.
CC   -!- PTM: Autophosphorylated, Ser-21 is a minor site of autophosphorylation
CC       compared to Ser-491 and Thr-492 (By similarity). Phosphorylation at
CC       Ser-21 is regulated by light and activated by cAMP. {ECO:0000250,
CC       ECO:0000269|PubMed:21504899}.
CC   -!- PTM: Farnesylation is required for full activity.
CC       {ECO:0000250|UniProtKB:P28327}.
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; U63971; AAB05930.1; -; mRNA.
DR   RefSeq; NP_112358.1; NM_031096.1.
DR   AlphaFoldDB; Q63651; -.
DR   SMR; Q63651; -.
DR   STRING; 10116.ENSRNOP00000024999; -.
DR   iPTMnet; Q63651; -.
DR   PhosphoSitePlus; Q63651; -.
DR   PaxDb; 10116-ENSRNOP00000024999; -.
DR   GeneID; 81760; -.
DR   KEGG; rno:81760; -.
DR   UCSC; RGD:619712; rat.
DR   AGR; RGD:619712; -.
DR   CTD; 6011; -.
DR   RGD; 619712; Grk1.
DR   eggNOG; KOG0986; Eukaryota.
DR   InParanoid; Q63651; -.
DR   OrthoDB; 2906348at2759; -.
DR   PhylomeDB; Q63651; -.
DR   BRENDA; 2.7.11.14; 5301.
DR   Reactome; R-RNO-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR   PRO; PR:Q63651; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0001750; C:photoreceptor outer segment; ISO:RGD.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0050254; F:rhodopsin kinase activity; IDA:RGD.
DR   GO; GO:0006915; P:apoptotic process; ISO:RGD.
DR   GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
DR   GO; GO:0016310; P:phosphorylation; ISO:RGD.
DR   GO; GO:0008594; P:photoreceptor cell morphogenesis; ISO:RGD.
DR   GO; GO:0042327; P:positive regulation of phosphorylation; ISO:RGD.
DR   GO; GO:0060060; P:post-embryonic retina morphogenesis in camera-type eye; ISO:RGD.
DR   GO; GO:0022400; P:regulation of rhodopsin mediated signaling pathway; ISS:UniProtKB.
DR   GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central.
DR   GO; GO:0009416; P:response to light stimulus; IEP:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR   GO; GO:0097473; P:retinal rod cell apoptotic process; ISO:RGD.
DR   GO; GO:0016056; P:rhodopsin mediated signaling pathway; TAS:RGD.
DR   GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR   CDD; cd05608; STKc_GRK1; 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; IPR037716; GRK1_dom.
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; G PROTEIN-COUPLED RECEPTOR KINASE/RIBOSOMAL PROTEIN S6 KINASE; 1.
DR   PANTHER; PTHR24355:SF11; RHODOPSIN KINASE GRK1; 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.
PE   1: Evidence at protein level;
KW   ATP-binding; Cell projection; Direct protein sequencing; Kinase;
KW   Lipoprotein; Membrane; Methylation; Nucleotide-binding; Phosphoprotein;
KW   Prenylation; Reference proteome; Sensory transduction;
KW   Serine/threonine-protein kinase; Transferase; Vision.
FT   CHAIN           1..561
FT                   /note="Rhodopsin kinase GRK1"
FT                   /id="PRO_0000024379"
FT   PROPEP          562..564
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000024380"
FT   DOMAIN          58..175
FT                   /note="RGS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT   DOMAIN          190..455
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   DOMAIN          456..521
FT                   /note="AGC-kinase C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT   REGION          1..189
FT                   /note="N-terminal"
FT   REGION          1..15
FT                   /note="Interaction with RCVRN"
FT                   /evidence="ECO:0000250|UniProtKB:P28327"
FT   REGION          456..564
FT                   /note="C-terminal"
FT   ACT_SITE        317
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         196..204
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         219
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         5
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P28327"
FT   MOD_RES         8
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P28327"
FT   MOD_RES         21
FT                   /note="Phosphoserine; by PKA and autocatalysis"
FT                   /evidence="ECO:0000305|PubMed:21504899"
FT   MOD_RES         491
FT                   /note="Phosphoserine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:P28327"
FT   MOD_RES         492
FT                   /note="Phosphothreonine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:P28327"
FT   MOD_RES         561
FT                   /note="Cysteine methyl ester"
FT                   /evidence="ECO:0000250|UniProtKB:P28327"
FT   LIPID           561
FT                   /note="S-farnesyl cysteine"
FT                   /evidence="ECO:0000250|UniProtKB:P28327"
SQ   SEQUENCE   564 AA;  63769 MW;  17E05784E6D1ED00 CRC64;
     MDFGSLETVV ANSAFIAARG SFDGSSTPSS RDKKYLAKLR LPPLSKCEGL RDSISLEFDN
     LCSEQPIGKR LFQQFLKTDE RHVPALELWK DIEDYDTADD DLRPQKAQAI LAEYLDPQGT
     LFCNFLDQGM VARVKEGPTG SQDGLFQPLL QATLEHLSQG PFQEYLGSLY FLRFLQWKWL
     EAQPIGEDWF LDFRVLGKGG FGEVSACQMK ATGKMYACKK LNKKRLKKRK GYQGAIVEKR
     ILAKVHSRFI VSLAYAFETK TDLCLVMTIM NGGDVRYHIY NVDEENPGFP EPRAIYYTAQ
     IISGLEHLHQ RRIVYRDLKP ENVLLDNDGN IRISDLGLAV ELKEGQNKTK GYAGTPGFMA
     PELLRGEEYD FSVDYFALGV TLYEMIAARG PFRARGEKVE NKELKQRIIS EPVKYPEKFS
     QASKDFCEQL LEKDPEKRLG FRDGTCDALR ANVLFKDISW RQLEAGMLIP PFIPDSRTVY
     AKNIQDVGAF STVKGVVFDK ADTEFFQEFA SGNCSIPWQE EMIETGFFGD LNVWRPDGQM
     PDDMKGITVE EAAPTAKSGM CLIS
//