RPE65_AMBTI
ID RPE65_AMBTI Reviewed; 533 AA.
AC Q9YI25;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 73.
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 Ambystoma tigrinum (Eastern tiger salamander).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Caudata; Salamandroidea; Ambystomatidae; Ambystoma.
OX NCBI_TaxID=8305;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RX PubMed=9838153; DOI=10.1016/s0167-4781(98)00221-8;
RA Ma J.-X., Xu L., Othersen D.K., Redmond T.M., Crouch R.K.;
RT "Cloning and localization of RPE65 mRNA in salamander cone photoreceptor
RT cells1.";
RL Biochim. Biophys. Acta 1443:255-261(1998).
CC -!- FUNCTION: Critical isomerohydrolase in the retinoid cycle involved in
CC regeneration of 11-cis-retinal, the chromophore of rod and cone
CC opsins.Catalyzes the cleavage and isomerization of all-trans-retinyl
CC fatty 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 -!- 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 and single cone cells
CC but not in isolated rods.
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; AF047465; AAD12758.1; -; mRNA.
DR AlphaFoldDB; Q9YI25; -.
DR SMR; Q9YI25; -.
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; ISS:AgBase.
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:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0001523; P:retinoid metabolic process; ISS:UniProtKB.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
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; 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_0000143947"
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-acetylthreonine"
FT /evidence="ECO:0000250|UniProtKB:Q28175"
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"
SQ SEQUENCE 533 AA; 61110 MW; 27D98315144AC971 CRC64;
MTNRVDHPAG GYKKLFESTE ELVAPVTAQV TGRIPVWLSG SLLRCGPGLF EVGSEQFYHL
FDGQALLHKF EFKGGHVIYH RRFIRTDTYV RAMTEKRIVI TEFGTFAFPD PCKNIFSRFL
SYFQGLEVTD NALVNVYPVG EDYYACTETN YITKINPETL ETVKKVDLCN YVSINGVTAH
PHIEHDGTVY NIGNCFGKHF AFAYNIVKIP PLQADKEDPI NKAKVVVQFP CSERFKPSYV
HSFGLTPNYI VFVEQPVKIN LFKFLSSWSI WGANYMDCFE SHETMGVWMH VAEKHTGEYL
NIKYRTSAFN LFHHINTYED HGFLIVDLCC WKGFEFVYNY LYLANLRENW EEVKRSAEKP
PQPEVRRYVL PLDIHKVDTG KNLVNLPYTT ATAVLRSDET IWLEPEVLFS GPRQAFEFPQ
INYKKHGGKD YTYAYGVGLN HFVPDRLSKL NVKTKETWVW QEPDTYPSEP IFVSQPDAIE
EDDGVVLSVV ISPGEGQKPA FLLILNAKDM SEIARAEVDS NIPVTFHGMF KKA
