RPE65_RAT
ID RPE65_RAT Reviewed; 533 AA.
AC O70276; F1M8Q2;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 11-DEC-2013, sequence version 4.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Retinoid isomerohydrolase;
DE EC=3.1.1.64 {ECO:0000250|UniProtKB:Q28175};
DE AltName: Full=All-trans-retinyl-palmitate hydrolase;
DE AltName: Full=Lutein isomerase;
DE AltName: Full=Meso-zeaxanthin isomerase;
DE EC=5.3.3.22 {ECO:0000250|UniProtKB:Q16518};
DE AltName: Full=Retinal pigment epithelium-specific 65 kDa protein;
DE AltName: Full=Retinol isomerase;
GN Name=Rpe65;
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=Wistar; TISSUE=Retina;
RX PubMed=9512345; DOI=10.1016/s0014-5793(98)00081-7;
RA Manes G., Leducq R., Kucharczak J., Pages A., Schmitt-Bernard C.F.,
RA Hamel C.P.;
RT "Rat messenger RNA for the retinal pigment epithelium-specific protein
RT RPE65 gradually accumulates in two weeks from late embryonic days.";
RL FEBS Lett. 423:133-137(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Critical isomerohydrolase in the retinoid cycle involved in
CC regeneration of 11-cis-retinal, the chromophore of rod and cone opsins.
CC Catalyzes the cleavage and isomerization of all-trans-retinyl fatty
CC acid esters to 11-cis-retinol which is further oxidized by 11-cis
CC retinol dehydrogenase to 11-cis-retinal for use as visual chromophore.
CC Essential for the production of 11-cis retinal for both rod and cone
CC photoreceptors. Also capable of catalyzing the isomerization of lutein
CC to meso-zeaxanthin an eye-specific carotenoid. The soluble form binds
CC vitamin A (all-trans-retinol), making it available for LRAT processing
CC to all-trans-retinyl ester. The membrane form, palmitoylated by LRAT,
CC binds all-trans-retinyl esters, making them available for IMH
CC (isomerohydrolase) processing to all-cis-retinol. The soluble form is
CC regenerated by transferring its palmitoyl groups onto 11-cis-retinol, a
CC reaction catalyzed by LRAT. {ECO:0000250|UniProtKB:Q16518,
CC ECO:0000250|UniProtKB:Q28175}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an all-trans-retinyl ester + H2O = 11-cis-retinol + a fatty
CC acid + H(+); Xref=Rhea:RHEA:31771, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16302, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:63410; EC=3.1.1.64;
CC Evidence={ECO:0000250|UniProtKB:Q28175};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lutein = (3R,3'S)-zeaxanthin; Xref=Rhea:RHEA:12729,
CC ChEBI:CHEBI:28838, ChEBI:CHEBI:138919; EC=5.3.3.22;
CC Evidence={ECO:0000250|UniProtKB:Q16518};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinyl hexadecanoate + H2O = 11-cis-retinol + H(+)
CC + hexadecanoate; Xref=Rhea:RHEA:31775, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16302,
CC ChEBI:CHEBI:17616; EC=3.1.1.64;
CC Evidence={ECO:0000250|UniProtKB:Q16518};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000250|UniProtKB:Q28175};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:Q28175};
CC -!- SUBUNIT: Interacts with MYO7A; this mediates light-dependent
CC intracellular transport of RPE65. {ECO:0000250|UniProtKB:Q16518}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:A9C3R9}. Cell
CC membrane {ECO:0000250|UniProtKB:Q28175}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q28175}. Microsome membrane
CC {ECO:0000250|UniProtKB:Q28175}. Note=Attached to the membrane by a
CC lipid anchor when palmitoylated (membrane form), soluble when
CC unpalmitoylated. Undergoes light-dependent intracellular transport to
CC become more concentrated in the central region of the retina pigment
CC epithelium cells (By similarity). {ECO:0000250|UniProtKB:Q16518,
CC ECO:0000250|UniProtKB:Q28175}.
CC -!- TISSUE SPECIFICITY: Retinal pigment epithelium specific.
CC -!- PTM: Palmitoylation by LRAT regulates ligand binding specificity; the
CC palmitoylated form (membrane form) specifically binds all-trans-
CC retinyl-palmitate, while the soluble unpalmitoylated form binds all-
CC trans-retinol (vitamin A). {ECO:0000250|UniProtKB:Q28175}.
CC -!- SIMILARITY: Belongs to the carotenoid oxygenase family. {ECO:0000305}.
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DR EMBL; AF035673; AAC40059.1; -; mRNA.
DR EMBL; AABR06021792; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06021793; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473952; EDL82582.1; -; Genomic_DNA.
DR RefSeq; NP_446014.2; NM_053562.3.
DR AlphaFoldDB; O70276; -.
DR SMR; O70276; -.
DR STRING; 10116.ENSRNOP00000040609; -.
DR ChEMBL; CHEMBL4523147; -.
DR PaxDb; O70276; -.
DR PRIDE; O70276; -.
DR Ensembl; ENSRNOT00000078187; ENSRNOP00000069757; ENSRNOG00000009582.
DR GeneID; 89826; -.
DR KEGG; rno:89826; -.
DR CTD; 6121; -.
DR RGD; 621396; Rpe65.
DR eggNOG; KOG1285; Eukaryota.
DR GeneTree; ENSGT00950000182913; -.
DR InParanoid; O70276; -.
DR OMA; HHIPYGL; -.
DR OrthoDB; 895046at2759; -.
DR TreeFam; TF314019; -.
DR Reactome; R-RNO-2453902; The canonical retinoid cycle in rods (twilight vision).
DR PRO; PR:O70276; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Proteomes; UP000234681; Chromosome 2.
DR Bgee; ENSRNOG00000009582; Expressed in cerebellum and 3 other tissues.
DR Genevisible; O70276; RN.
DR GO; GO:0044297; C:cell body; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:AgBase.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0052885; F:all-trans-retinyl-ester hydrolase, 11-cis retinol forming activity; IMP:RGD.
DR GO; GO:0052884; F:all-trans-retinyl-palmitate hydrolase, 11-cis retinol forming activity; ISS:UniProtKB.
DR GO; GO:1901612; F:cardiolipin binding; ISS:AgBase.
DR GO; GO:0016853; F:isomerase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016702; F:oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; IEA:InterPro.
DR GO; GO:0031210; F:phosphatidylcholine binding; ISS:AgBase.
DR GO; GO:0001786; F:phosphatidylserine binding; ISS:AgBase.
DR GO; GO:0004744; F:retinal isomerase activity; ISO:RGD.
DR GO; GO:0050251; F:retinol isomerase activity; IBA:GO_Central.
DR GO; GO:0043010; P:camera-type eye development; IEP:RGD.
DR GO; GO:0071257; P:cellular response to electrical stimulus; ISO:RGD.
DR GO; GO:0007623; P:circadian rhythm; IEP:RGD.
DR GO; GO:0050908; P:detection of light stimulus involved in visual perception; ISO:RGD.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISO:RGD.
DR GO; GO:0003407; P:neural retina development; IDA:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0009416; P:response to light stimulus; IEP:RGD.
DR GO; GO:0060041; P:retina development in camera-type eye; ISO:RGD.
DR GO; GO:0001895; P:retina homeostasis; ISO:RGD.
DR GO; GO:0060042; P:retina morphogenesis in camera-type eye; ISO:RGD.
DR GO; GO:0042574; P:retinal metabolic process; IMP:RGD.
DR GO; GO:0001523; P:retinoid metabolic process; ISO:RGD.
DR GO; GO:0042572; P:retinol metabolic process; IDA:RGD.
DR GO; GO:0007601; P:visual perception; ISO:RGD.
DR GO; GO:1901827; P:zeaxanthin biosynthetic process; ISS:UniProtKB.
DR InterPro; IPR004294; Carotenoid_Oase.
DR PANTHER; PTHR10543; PTHR10543; 1.
DR Pfam; PF03055; RPE65; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cell membrane; Cytoplasm; Endoplasmic reticulum; Hydrolase;
KW Iron; Isomerase; Lipid metabolism; Lipoprotein; Membrane; Metal-binding;
KW Microsome; Palmitate; Phosphoprotein; Reference proteome;
KW Sensory transduction; Vision.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q28175"
FT CHAIN 2..533
FT /note="Retinoid isomerohydrolase"
FT /id="PRO_0000143945"
FT BINDING 180
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q28175"
FT BINDING 241
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q28175"
FT BINDING 313
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q28175"
FT BINDING 527
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q28175"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q28175"
FT MOD_RES 101
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q16518"
FT MOD_RES 105
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q16518"
FT MOD_RES 113
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q16518"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16518"
FT LIPID 112
FT /note="S-palmitoyl cysteine; in membrane form"
FT /evidence="ECO:0000250|UniProtKB:Q28175"
FT LIPID 231
FT /note="S-palmitoyl cysteine; in membrane form"
FT /evidence="ECO:0000250|UniProtKB:Q28175"
FT LIPID 329
FT /note="S-palmitoyl cysteine; in membrane form"
FT /evidence="ECO:0000250|UniProtKB:Q28175"
FT LIPID 330
FT /note="S-palmitoyl cysteine; in membrane form"
FT /evidence="ECO:0000250|UniProtKB:Q28175"
FT CONFLICT 128
FT /note="I -> V (in Ref. 1; AAC40059)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 533 AA; 61004 MW; 13045E236F6E723D CRC64;
MSIQIEHPAG GYKKLFETVE ELSTPLTAHV TGRIPLWLTG SLLRCGPGLF EVGSEPFYHL
FDGQALLHKF DFKEGHVTYY RRFIRTDAYV RAMTEKRIVI TEFGTCAFPD PCKNIFSRFF
SYFRGVEITD NALVNIYPVG EDYYACTETN FITKINPETL ETIKQVDLCN YVSVNGATAH
PHIESDGTVY NIGNCFGKNF TVAYNIIKIP PLKADKEDPI NKSEVVVQFP CSDRFKPSYV
HSFGLTPNYI VFVETPVKIN LFKFLSSWSL WGANYMDCFE SNESMGVWLH VADKKRRKYF
NNKYRTSPFN LFHHINTYED NGFLIVDLCC WKGFEFVYNY LYLANLRENW EEVKRNAMKA
PQPEVRRYVL PLTIDKADTG RNLVTLPHTT ATAILCSDET IWLEPEVLFS GPRQAFEFPQ
INYQKCGGKP YTYAYGLGLN HFVPDKLCKL NVKTKEIWMW QEPDSYPSEP IFVSQPDALE
EDDGVVLSVV VSPGAGQKPA YLLVLNAKDL SEIARAEVET NIPVTFHGLF KKP
