RPE65_CHICK
ID RPE65_CHICK Reviewed; 533 AA.
AC Q9YGX2;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Retinoid isomerohydrolase;
DE EC=3.1.1.64 {ECO:0000269|PubMed:19490105, ECO:0000269|PubMed:25112876};
DE AltName: Full=All-trans-retinyl-palmitate hydrolase;
DE AltName: Full=Lutein isomerase;
DE AltName: Full=Meso-zeaxanthin isomerase {ECO:0000303|PubMed:28874556};
DE EC=5.3.3.22 {ECO:0000269|PubMed:28874556};
DE AltName: Full=Retinal pigment epithelium-specific 65 kDa protein;
DE AltName: Full=Retinol isomerase;
GN Name=RPE65;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Eye;
RA Hirosawa K., Sagara H.;
RT "Investigation of an endoplasmic reticulum related protein in the
RT vertebrate retinal pigment epithelium.";
RL Thesis (1998), University of Tokyo, Japan.
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=19490105; DOI=10.1111/j.1742-4658.2009.07021.x;
RA Nikolaeva O., Takahashi Y., Moiseyev G., Ma J.X.;
RT "Purified RPE65 shows isomerohydrolase activity after reassociation with a
RT phospholipid membrane.";
RL FEBS J. 276:3020-3030(2009).
RN [3]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=25112876; DOI=10.1074/jbc.m114.558619;
RA Takahashi Y., Moiseyev G., Ma J.X.;
RT "Identification of key residues determining isomerohydrolase activity of
RT human RPE65.";
RL J. Biol. Chem. 289:26743-26751(2014).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND DEVELOPMENTAL STAGE.
RX PubMed=28874556; DOI=10.1073/pnas.1706332114;
RA Shyam R., Gorusupudi A., Nelson K., Horvath M.P., Bernstein P.S.;
RT "RPE65 has an additional function as the lutein to meso-zeaxanthin
RT isomerase in the vertebrate eye.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:10882-10887(2017).
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 (PubMed:19490105). Essential for the production of 11-cis retinal for
CC both rod and cone photoreceptors (By similarity). Also capable of
CC catalyzing the isomerization of lutein to meso-zeaxanthin an eye-
CC specific carotenoid (PubMed:28874556). The soluble form binds vitamin A
CC (all-trans-retinol), making it available for LRAT processing to all-
CC trans-retinyl ester. The membrane form, palmitoylated by LRAT, binds
CC 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 (By similarity).
CC {ECO:0000250|UniProtKB:Q16518, ECO:0000250|UniProtKB:Q28175,
CC ECO:0000269|PubMed:19490105, ECO:0000269|PubMed:28874556}.
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:0000269|PubMed:19490105};
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:0000269|PubMed:28874556};
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:0000269|PubMed:25112876};
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.7 uM for all-trans-retinyl palmitate
CC {ECO:0000269|PubMed:19490105};
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. {ECO:0000250|UniProtKB:Q28175}.
CC -!- TISSUE SPECIFICITY: Retinal pigment epithelium specific.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in the retinal pigment epithelium
CC (RPE)/ choroid of the E21 embryos (at protein level).
CC {ECO:0000269|PubMed:28874556}.
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; AB017594; BAA75667.1; -; mRNA.
DR RefSeq; NP_990215.1; NM_204884.1.
DR AlphaFoldDB; Q9YGX2; -.
DR SMR; Q9YGX2; -.
DR STRING; 9031.ENSGALP00000018351; -.
DR ChEMBL; CHEMBL4523514; -.
DR PaxDb; Q9YGX2; -.
DR GeneID; 395700; -.
DR KEGG; gga:395700; -.
DR CTD; 6121; -.
DR VEuPathDB; HostDB:geneid_395700; -.
DR eggNOG; KOG1285; Eukaryota.
DR HOGENOM; CLU_016472_1_1_1; -.
DR InParanoid; Q9YGX2; -.
DR OrthoDB; 895046at2759; -.
DR PhylomeDB; Q9YGX2; -.
DR BRENDA; 5.3.3.22; 1306.
DR PRO; PR:Q9YGX2; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:AgBase.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0052885; F:all-trans-retinyl-ester hydrolase, 11-cis retinol forming activity; IDA:UniProtKB.
DR GO; GO:0052884; F:all-trans-retinyl-palmitate hydrolase, 11-cis retinol forming activity; IEA:UniProtKB-EC.
DR GO; GO:1901612; F:cardiolipin binding; ISS:AgBase.
DR GO; GO:0016853; F:isomerase activity; IDA: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:0050251; F:retinol isomerase activity; IBA:GO_Central.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0001523; P:retinoid metabolic process; IDA:UniProtKB.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR GO; GO:1901827; P:zeaxanthin biosynthetic process; IDA:UniProtKB.
DR InterPro; IPR004294; Carotenoid_Oase.
DR PANTHER; PTHR10543; PTHR10543; 1.
DR Pfam; PF03055; RPE65; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; Endoplasmic reticulum; Hydrolase; Iron;
KW Isomerase; Lipid metabolism; Lipoprotein; Membrane; Metal-binding;
KW Microsome; Palmitate; Phosphoprotein; Reference proteome;
KW Sensory transduction; Vision.
FT CHAIN 1..533
FT /note="Retinoid isomerohydrolase"
FT /id="PRO_0000143946"
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 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"
SQ SEQUENCE 533 AA; 60930 MW; 67ECA3B5993084A0 CRC64;
MYSQVEHPAG GYKKLFETVE ELSSPVTAHV TGRIPTWLRG SLLRCGPGLF EVGAEPFYHL
FDGQALLHKF DFKEGHVTYH RRFVRTDAYV RAMTEKRIVI TEFGTYAYPD PCKNIFSRFF
SYFKGVEVTD NALVNVYPVG EDYYACTETN FITKINPDTL ETIKQVDLCK YVSVNGATAH
PHVENDGTVY NIGNCFGKNF SLAYNIIRIP PLQADKEDPM NKSEVVVQFP CSDRFKPSYV
HSFGLTPNYI VFVETPVKIN LLKFLSSWSL WGANYMDCFE SNETMGVWLH VAEKKKGRLL
NIKYRTSAFN LFHHINTFED NGFLIVDLCT WKGFEFVYNY LYLANLRANW DEVKKQAEKA
PQPEARRYVL PLRIDKADTG KNLVTLPYTT ATATLRSDET VWLEPEVIFS GPRHAFEFPQ
INYKKYGGKP YTYTYGLGLN HFVPDRLCKL NVKTKETWVW QEPDSYPSEP IFVSHPDALE
EDDGVVLSIV ISPGSGPKPA YLLILNAKDM SEVARAEVEV NIPVTFHGLF KRA
