GRK1_MOUSE
ID GRK1_MOUSE Reviewed; 564 AA.
AC Q9WVL4;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Rhodopsin kinase GRK1;
DE Short=RK;
DE EC=2.7.11.14 {ECO:0000269|PubMed:10097103};
DE AltName: Full=G protein-coupled receptor kinase 1 {ECO:0000312|MGI:MGI:1345146};
DE Flags: Precursor;
GN Name=Grk1 {ECO:0000312|MGI:MGI:1345146}; Synonyms=Rhok;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], DISRUPTION PHENOTYPE, FUNCTION, CATALYTIC
RP ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=10097103; DOI=10.1073/pnas.96.7.3718;
RA Chen C.K., Burns M.E., Spencer M., Niemi G.A., Chen J., Hurley J.B.,
RA Baylor D.A., Simon M.I.;
RT "Abnormal photoresponses and light-induced apoptosis in rods lacking
RT rhodopsin kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:3718-3722(1999).
RN [2]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10704496; DOI=10.1523/jneurosci.20-06-02209.2000;
RA Lyubarsky A.L., Chen C., Simon M.I., Pugh E.N. Jr.;
RT "Mice lacking G-protein receptor kinase 1 have profoundly slowed recovery
RT of cone-driven retinal responses.";
RL J. Neurosci. 20:2209-2217(2000).
RN [3]
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 [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15961391; DOI=10.1074/jbc.m501789200;
RA Strissel K.J., Lishko P.V., Trieu L.H., Kennedy M.J., Hurley J.B.,
RA Arshavsky V.Y.;
RT "Recoverin undergoes light-dependent intracellular translocation in rod
RT photoreceptors.";
RL J. Biol. Chem. 280:29250-29255(2005).
RN [5]
RP TISSUE SPECIFICITY, AND PHOSPHORYLATION AT SER-21.
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).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF LEU-363.
RX PubMed=26427409; DOI=10.1007/978-3-319-17121-0_24;
RA Charette J.R., Samuels I.S., Yu M., Stone L., Hicks W., Shi L.Y.,
RA Krebs M.P., Naggert J.K., Nishina P.M., Peachey N.S.;
RT "A Chemical Mutagenesis Screen Identifies Mouse Models with ERG Defects.";
RL Adv. Exp. Med. Biol. 854:177-183(2016).
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 (PubMed:10097103,
CC PubMed:10704496, PubMed:26427409). This rapid desensitization is
CC essential for scotopic vision and permits rapid adaptation to changes
CC in illumination (PubMed:10097103, PubMed:10704496). May play a role in
CC the maintenance of the outer nuclear layer in the retina
CC (PubMed:26427409). {ECO:0000269|PubMed:10097103,
CC ECO:0000269|PubMed:10704496, ECO:0000269|PubMed:26427409}.
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:10097103};
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:10097103};
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:0000269|PubMed:15961391}.
CC Note=Subcellular location is not affected by light or dark conditions.
CC {ECO:0000269|PubMed:15961391}.
CC -!- TISSUE SPECIFICITY: Expressed in the retina; primarily located in rod
CC outer segments of retina photoreceptor cells (at protein level)
CC (PubMed:11717351, PubMed:15961391, PubMed:21504899). Also detected in
CC cone photoreceptor cells (at protein level) (PubMed:10704496).
CC {ECO:0000269|PubMed:10704496, ECO:0000269|PubMed:11717351,
CC ECO:0000269|PubMed:15961391, ECO:0000269|PubMed:21504899}.
CC -!- PTM: Autophosphorylated, Ser-21 is a minor site of autophosphorylation
CC compared to Ser-491 and Thr-492. Phosphorylation at Ser-21 is regulated
CC by light and activated by cAMP. {ECO:0000250}.
CC -!- PTM: Farnesylation is required for full activity.
CC {ECO:0000250|UniProtKB:P28327}.
CC -!- DISRUPTION PHENOTYPE: In rod photoreceptor cells, the light-induced ion
CC currents do not decay rapidly, but are greatly prolonged, contrary to
CC what is observed with wild-type mice. The retina photoreceptor layer
CC appears normal when mutant mice are kept in constant darkness, but
CC exposure to light causes apoptosis in retina photoreceptor cells.
CC {ECO:0000269|PubMed:10097103, ECO:0000269|PubMed:10704496}.
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; AF085240; AAD40189.1; -; mRNA.
DR CCDS; CCDS22112.1; -.
DR AlphaFoldDB; Q9WVL4; -.
DR SMR; Q9WVL4; -.
DR STRING; 10090.ENSMUSP00000033827; -.
DR iPTMnet; Q9WVL4; -.
DR PhosphoSitePlus; Q9WVL4; -.
DR MaxQB; Q9WVL4; -.
DR PaxDb; Q9WVL4; -.
DR PRIDE; Q9WVL4; -.
DR ProteomicsDB; 255155; -.
DR MGI; MGI:1345146; Grk1.
DR eggNOG; KOG0986; Eukaryota.
DR InParanoid; Q9WVL4; -.
DR PhylomeDB; Q9WVL4; -.
DR Reactome; R-MMU-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR ChiTaRS; Grk1; mouse.
DR PRO; PR:Q9WVL4; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9WVL4; protein.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001750; C:photoreceptor outer segment; IDA:MGI.
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; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IMP:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:MGI.
DR GO; GO:0016310; P:phosphorylation; IMP:MGI.
DR GO; GO:0008594; P:photoreceptor cell morphogenesis; IMP:MGI.
DR GO; GO:0042327; P:positive regulation of phosphorylation; IMP:MGI.
DR GO; GO:0060060; P:post-embryonic retina morphogenesis in camera-type eye; IMP:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
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; IMP:MGI.
DR GO; GO:0097473; P:retinal rod cell apoptotic process; IMP:MGI.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR CDD; cd05608; STKc_GRK1; 1.
DR Gene3D; 1.10.167.10; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR000239; GPCR_kinase.
DR InterPro; IPR032965; GRK1.
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:SF11; PTHR24355:SF11; 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; 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; Cell projection; Kinase; Lipoprotein; Membrane; Methylation;
KW Nucleotide-binding; Phosphoprotein; Prenylation; Reference proteome;
KW Sensory transduction; Serine/threonine-protein kinase; Transferase; Vision.
FT CHAIN 1..561
FT /note="Rhodopsin kinase GRK1"
FT /id="PRO_0000024377"
FT PROPEP 562..564
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000024378"
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"
FT MUTAGEN 363
FT /note="L->P: Defects in photoreceptor light response and
FT loss of photoreceptors by one year of age."
FT /evidence="ECO:0000269|PubMed:26427409"
SQ SEQUENCE 564 AA; 63837 MW; EF0795FAE42BA5DB CRC64;
MDFGSLETVV ANSAFIAARG SFDGSSTPSS RDKKYLAKLR LPPLSKCEGL RDNLSLEFES
LCSEQPIGKR LFQQFLKTDE RHVPALELWK DIEDYDTADD DLRPQKAQAI LAEYLDPQGT
LFCNFLDQGM VTRVKEGPTG SQDGLFQPLL QATMEHLSQA PFQEYLESLY FLRFLQWKWL
EAQPIGEDWF LDFRVLGKGG FGEVSACQMK ATGKMYACKK LNKKRLKKKK GYQGAIVEKR
ILTKVHSRFI VSLAYAFETK TDLCLVMTIM NGGDVRYHIY NVDEDNPGFS EPRAIYYTAQ
IISGLEHLHQ RRIVYRDLKP ENVLLDNDGN IRISDLGLAV ELKEGQNKTK GYAGTPGFMA
PELLRGEEYD FSVDYFALGV TLYEMIAARG PFRARGEKVE NKELKQRIIS EPVKYPEKFS
QASKDFCEQL LEKDPEKRLG FRDGTCDALR ANVLFKDISW RQLEAGMLIP PFIPDSRTVY
AKNIQDVGAF STVKGVVFDK ADTEFFQEFA SGNCSIPWQE EMIETGLFGD LNVWRADGQM
PDDMKGITTE EAAPTAKSGM CLIS
