ID   RGR_HUMAN               Reviewed;         291 AA.
AC   P47804; A6NKK7; Q96FC5;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   24-JAN-2024, entry version 189.
DE   RecName: Full=RPE-retinal G protein-coupled receptor;
GN   Name=RGR;
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 / MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Retina;
RX   PubMed=7947717; DOI=10.1021/bi00248a022;
RA   Shen D., Jiang M., Hao W., Tao L., Salazar M., Fong H.K.W.;
RT   "A human opsin-related gene that encodes a retinaldehyde-binding protein.";
RL   Biochemistry 33:13117-13125(1994).
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 MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP   [LARGE SCALE MRNA] OF 1-265 (ISOFORM 3).
RC   TISSUE=Brain;
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   [4]
RP   VARIANT RP44 ARG-66, AND VARIANTS LEU-132; ASN-152; THR-234 AND PHE-241.
RX   PubMed=10581022; DOI=10.1038/70496;
RA   Morimura H., Saindelle-Ribeaudeau F., Berson E.L., Dryja T.P.;
RT   "Mutations in RGR, encoding a light-sensitive opsin homologue, in patients
RT   with retinitis pigmentosa.";
RL   Nat. Genet. 23:393-394(1999).
CC   -!- FUNCTION: Receptor for all-trans- and 11-cis-retinal. Binds
CC       preferentially to the former and may catalyze the isomerization of the
CC       chromophore by a retinochrome-like mechanism.
CC   -!- INTERACTION:
CC       P47804; Q96EK5: KIFBP; NbExp=2; IntAct=EBI-745818, EBI-744150;
CC       P47804-3; P46379-2: BAG6; NbExp=3; IntAct=EBI-25834767, EBI-10988864;
CC       P47804-3; P55212: CASP6; NbExp=3; IntAct=EBI-25834767, EBI-718729;
CC       P47804-3; P06307: CCK; NbExp=3; IntAct=EBI-25834767, EBI-6624398;
CC       P47804-3; P28329-3: CHAT; NbExp=3; IntAct=EBI-25834767, EBI-25837549;
CC       P47804-3; Q8NI60: COQ8A; NbExp=3; IntAct=EBI-25834767, EBI-745535;
CC       P47804-3; P02489: CRYAA; NbExp=3; IntAct=EBI-25834767, EBI-6875961;
CC       P47804-3; G5E9A7: DMWD; NbExp=3; IntAct=EBI-25834767, EBI-10976677;
CC       P47804-3; O14645: DNALI1; NbExp=3; IntAct=EBI-25834767, EBI-395638;
CC       P47804-3; P22607: FGFR3; NbExp=3; IntAct=EBI-25834767, EBI-348399;
CC       P47804-3; Q14957: GRIN2C; NbExp=3; IntAct=EBI-25834767, EBI-8285963;
CC       P47804-3; P06396: GSN; NbExp=3; IntAct=EBI-25834767, EBI-351506;
CC       P47804-3; O00291: HIP1; NbExp=3; IntAct=EBI-25834767, EBI-473886;
CC       P47804-3; O14901: KLF11; NbExp=3; IntAct=EBI-25834767, EBI-948266;
CC       P47804-3; Q92876: KLK6; NbExp=3; IntAct=EBI-25834767, EBI-2432309;
CC       P47804-3; P13473-2: LAMP2; NbExp=3; IntAct=EBI-25834767, EBI-21591415;
CC       P47804-3; Q9BVL2: NUP58; NbExp=3; IntAct=EBI-25834767, EBI-2811583;
CC       P47804-3; D3DTS7: PMP22; NbExp=3; IntAct=EBI-25834767, EBI-25882629;
CC       P47804-3; P62826: RAN; NbExp=3; IntAct=EBI-25834767, EBI-286642;
CC       P47804-3; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-25834767, EBI-5235340;
CC       P47804-3; Q86WV8: TSC1; NbExp=3; IntAct=EBI-25834767, EBI-12806590;
CC       P47804-3; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-25834767, EBI-741480;
CC       P47804-3; Q9Y649; NbExp=3; IntAct=EBI-25834767, EBI-25900580;
CC   -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1; Synonyms=Short;
CC         IsoId=P47804-1; Sequence=Displayed;
CC       Name=2; Synonyms=Long;
CC         IsoId=P47804-2; Sequence=VSP_003773;
CC       Name=3;
CC         IsoId=P47804-3; Sequence=VSP_038387;
CC   -!- TISSUE SPECIFICITY: Preferentially expressed at high levels in the
CC       retinal pigment epithelium (RPE) and Mueller cells of the neural
CC       retina.
CC   -!- PTM: Covalently binds all-trans- and 11-cis-retinal.
CC   -!- DISEASE: Retinitis pigmentosa 44 (RP44) [MIM:613769]: A retinal
CC       dystrophy belonging to the group of pigmentary retinopathies. Retinitis
CC       pigmentosa is characterized by retinal pigment deposits visible on
CC       fundus examination and primary loss of rod photoreceptor cells followed
CC       by secondary loss of cone photoreceptors. Patients typically have night
CC       vision blindness and loss of midperipheral visual field. As their
CC       condition progresses, they lose their far peripheral visual field and
CC       eventually central vision as well. {ECO:0000269|PubMed:10581022}.
CC       Note=The disease is caused by variants affecting the gene represented
CC       in this entry.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. Opsin
CC       subfamily. {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC   -!- WEB RESOURCE: Name=Mutations of the RGR gene; Note=Retina
CC       International's Scientific Newsletter;
CC       URL="https://www.retina-international.org/files/sci-news/rgrmut.htm";
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DR   EMBL; U15790; AAB92384.1; -; Genomic_DNA.
DR   EMBL; U14911; AAB92384.1; JOINED; Genomic_DNA.
DR   EMBL; U15785; AAB92384.1; JOINED; Genomic_DNA.
DR   EMBL; U15786; AAB92384.1; JOINED; Genomic_DNA.
DR   EMBL; U15787; AAB92384.1; JOINED; Genomic_DNA.
DR   EMBL; U15788; AAB92384.1; JOINED; Genomic_DNA.
DR   EMBL; U15789; AAB92384.1; JOINED; Genomic_DNA.
DR   EMBL; U14910; AAA56748.1; -; mRNA.
DR   EMBL; AC022389; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BG912392; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; BC011349; AAH11349.1; -; mRNA.
DR   CCDS; CCDS41543.1; -. [P47804-3]
DR   CCDS; CCDS7374.1; -. [P47804-2]
DR   CCDS; CCDS91288.1; -. [P47804-1]
DR   PIR; A55980; A55980.
DR   PIR; B55980; B55980.
DR   RefSeq; NP_001012738.1; NM_001012720.1. [P47804-1]
DR   RefSeq; NP_001012740.1; NM_001012722.1. [P47804-3]
DR   RefSeq; NP_002912.2; NM_002921.3. [P47804-2]
DR   AlphaFoldDB; P47804; -.
DR   SMR; P47804; -.
DR   BioGRID; 111927; 10.
DR   IntAct; P47804; 26.
DR   MINT; P47804; -.
DR   STRING; 9606.ENSP00000352427; -.
DR   GlyCosmos; P47804; 1 site, No reported glycans.
DR   GlyGen; P47804; 1 site.
DR   iPTMnet; P47804; -.
DR   PhosphoSitePlus; P47804; -.
DR   BioMuta; RGR; -.
DR   DMDM; 1350592; -.
DR   MassIVE; P47804; -.
DR   PaxDb; 9606-ENSP00000352427; -.
DR   PeptideAtlas; P47804; -.
DR   ProteomicsDB; 55796; -. [P47804-1]
DR   ProteomicsDB; 55797; -. [P47804-2]
DR   ProteomicsDB; 55798; -. [P47804-3]
DR   Antibodypedia; 15900; 236 antibodies from 28 providers.
DR   DNASU; 5995; -.
DR   Ensembl; ENST00000358110.7; ENSP00000350823.5; ENSG00000148604.15. [P47804-3]
DR   Ensembl; ENST00000359452.9; ENSP00000352427.4; ENSG00000148604.15. [P47804-2]
DR   Ensembl; ENST00000652092.2; ENSP00000498299.1; ENSG00000148604.15. [P47804-1]
DR   GeneID; 5995; -.
DR   KEGG; hsa:5995; -.
DR   MANE-Select; ENST00000652092.2; ENSP00000498299.1; NM_001012720.2; NP_001012738.1.
DR   UCSC; uc001kdd.2; human. [P47804-1]
DR   AGR; HGNC:9990; -.
DR   CTD; 5995; -.
DR   DisGeNET; 5995; -.
DR   GeneCards; RGR; -.
DR   GeneReviews; RGR; -.
DR   HGNC; HGNC:9990; RGR.
DR   HPA; ENSG00000148604; Tissue enriched (retina).
DR   MalaCards; RGR; -.
DR   MIM; 600342; gene.
DR   MIM; 613769; phenotype.
DR   neXtProt; NX_P47804; -.
DR   OpenTargets; ENSG00000148604; -.
DR   Orphanet; 791; Retinitis pigmentosa.
DR   PharmGKB; PA34360; -.
DR   VEuPathDB; HostDB:ENSG00000148604; -.
DR   eggNOG; KOG3656; Eukaryota.
DR   GeneTree; ENSGT01090000260051; -.
DR   HOGENOM; CLU_009579_3_2_1; -.
DR   InParanoid; P47804; -.
DR   OMA; KYRMIPA; -.
DR   OrthoDB; 5355595at2759; -.
DR   PhylomeDB; P47804; -.
DR   TreeFam; TF324998; -.
DR   PathwayCommons; P47804; -.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   Reactome; R-HSA-419771; Opsins.
DR   SignaLink; P47804; -.
DR   BioGRID-ORCS; 5995; 11 hits in 1140 CRISPR screens.
DR   ChiTaRS; RGR; human.
DR   GeneWiki; Retinal_G_protein_coupled_receptor; -.
DR   GenomeRNAi; 5995; -.
DR   Pharos; P47804; Tbio.
DR   PRO; PR:P47804; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; P47804; Protein.
DR   Bgee; ENSG00000148604; Expressed in pigmented layer of retina and 119 other cell types or tissues.
DR   ExpressionAtlas; P47804; baseline and differential.
DR   GO; GO:0005886; C:plasma membrane; TAS:ProtInc.
DR   GO; GO:0008020; F:G protein-coupled photoreceptor activity; IBA:GO_Central.
DR   GO; GO:0004930; F:G protein-coupled receptor activity; TAS:ProtInc.
DR   GO; GO:0071482; P:cellular response to light stimulus; IBA:GO_Central.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0007602; P:phototransduction; IBA:GO_Central.
DR   GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR   CDD; cd15072; 7tmA_Retinal_GPR; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   InterPro; IPR027430; Retinal_BS.
DR   InterPro; IPR001793; RPE_GPCR.
DR   PANTHER; PTHR24240; OPSIN; 1.
DR   PANTHER; PTHR24240:SF90; RPE-RETINAL G PROTEIN-COUPLED RECEPTOR; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   PRINTS; PR00667; RPERETINALR.
DR   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR   PROSITE; PS00238; OPSIN; 1.
DR   Genevisible; P47804; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Chromophore; Disease variant; Disulfide bond;
KW   G-protein coupled receptor; Glycoprotein; Membrane; Photoreceptor protein;
KW   Receptor; Reference proteome; Retinal protein; Retinitis pigmentosa;
KW   Sensory transduction; Transducer; Transmembrane; Transmembrane helix;
KW   Vision.
FT   CHAIN           1..291
FT                   /note="RPE-retinal G protein-coupled receptor"
FT                   /id="PRO_0000197822"
FT   TOPO_DOM        1..15
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        16..36
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        37..52
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        53..73
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        74..91
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        92..112
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        113..130
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        131..151
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        152..175
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        176..196
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        197..219
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        220..240
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        241..247
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        248..268
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        269..291
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         255
FT                   /note="N6-(retinylidene)lysine"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        172
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        88..162
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT   VAR_SEQ         78
FT                   /note="L -> LRVSH (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:7947717"
FT                   /id="VSP_003773"
FT   VAR_SEQ         211..248
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_038387"
FT   VARIANT         66
FT                   /note="S -> R (in RP44; dbSNP:rs104894187)"
FT                   /evidence="ECO:0000269|PubMed:10581022"
FT                   /id="VAR_017034"
FT   VARIANT         132
FT                   /note="V -> L (in dbSNP:rs370808520)"
FT                   /evidence="ECO:0000269|PubMed:10581022"
FT                   /id="VAR_017055"
FT   VARIANT         152
FT                   /note="H -> N (in dbSNP:rs150808273)"
FT                   /evidence="ECO:0000269|PubMed:10581022"
FT                   /id="VAR_017056"
FT   VARIANT         234
FT                   /note="A -> T (in dbSNP:rs377043137)"
FT                   /evidence="ECO:0000269|PubMed:10581022"
FT                   /id="VAR_017058"
FT   VARIANT         241
FT                   /note="S -> F (in dbSNP:rs61730895)"
FT                   /evidence="ECO:0000269|PubMed:10581022"
FT                   /id="VAR_017057"
SQ   SEQUENCE   291 AA;  31874 MW;  85AB087E09719E88 CRC64;
     MAETSALPTG FGELEVLAVG MVLLVEALSG LSLNTLTIFS FCKTPELRTP CHLLVLSLAL
     ADSGISLNAL VAATSSLLRR WPYGSDGCQA HGFQGFVTAL ASICSSAAIA WGRYHHYCTR
     SQLAWNSAVS LVLFVWLSSA FWAALPLLGW GHYDYEPLGT CCTLDYSKGD RNFTSFLFTM
     SFFNFAMPLF ITITSYSLME QKLGKSGHLQ VNTTLPARTL LLGWGPYAIL YLYAVIADVT
     SISPKLQMVP ALIAKMVPTI NAINYALGNE MVCRGIWQCL SPQKREKDRT K
//