RPE65_CANLF
ID RPE65_CANLF Reviewed; 533 AA.
AC Q9TVB8; O97623; Q8MJY9;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Retinoid isomerohydrolase;
DE EC=3.1.1.64 {ECO:0000269|PubMed:16150724, ECO:0000269|PubMed:30628748};
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9808841;
RA Aguirre G.D., Baldwin V., Pearce-Kelling S., Narfstrom K., Ray K.,
RA Acland G.M.;
RT "Congenital stationary night blindness in the dog: common mutation in the
RT RPE65 gene indicates founder effect.";
RL Mol. Vis. 4:23-23(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Druttne N0606; TISSUE=Retinal pigment epithelium;
RX PubMed=10191083; DOI=10.1006/geno.1999.5754;
RA Veske A., Nilsson S.E.G., Narfstrom K., Gal A.;
RT "Retinal dystrophy of Swedish briard/briard-beagle dogs is due to a 4-bp
RT deletion in RPE65.";
RL Genomics 57:57-61(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 83-533.
RA Dekomien G., Epplen J.T.;
RT "Evaluation of the RPE65 gene as a candidate gene for generalised
RT progressive retinal atrophy.";
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP COFACTOR, MUTAGENESIS OF HIS-180; CYS-231; HIS-241; HIS-313; CYS-329;
RP 329-CYS-CYS-330; CYS-330; GLU-417 AND HIS-527, METAL-BINDING, AND CATALYTIC
RP ACTIVITY.
RX PubMed=16150724; DOI=10.1073/pnas.0504167102;
RA Redmond T.M., Poliakov E., Yu S., Tsai J.Y., Lu Z., Gentleman S.;
RT "Mutation of key residues of RPE65 abolishes its enzymatic role as
RT isomerohydrolase in the visual cycle.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:13658-13663(2005).
RN [5]
RP MUTAGENESIS OF ASP-477.
RX PubMed=30628748; DOI=10.1002/humu.23706;
RA Li Y., Furhang R., Ray A., Duncan T., Soucy J., Mahdi R., Chaitankar V.,
RA Gieser L., Poliakov E., Qian H., Liu P., Dong L., Rogozin I.B.,
RA Redmond T.M.;
RT "Aberrant RNA splicing is the major pathogenic effect in a knock-in mouse
RT model of the dominantly inherited c.1430A>G human RPE65 mutation.";
RL Hum. Mutat. 40:426-443(2019).
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:0000269|PubMed:16150724, ECO:0000269|PubMed:30628748};
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:0000269|PubMed:16150724};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:16150724};
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; AF084537; AAC72356.1; -; mRNA.
DR EMBL; Y16567; CAA76290.1; -; mRNA.
DR EMBL; AJ506754; CAD45010.1; -; Genomic_DNA.
DR EMBL; AJ506755; CAD45010.1; JOINED; Genomic_DNA.
DR EMBL; AJ506756; CAD45010.1; JOINED; Genomic_DNA.
DR EMBL; AJ506757; CAD45010.1; JOINED; Genomic_DNA.
DR EMBL; AJ251207; CAD45010.1; JOINED; Genomic_DNA.
DR EMBL; AJ506759; CAD45010.1; JOINED; Genomic_DNA.
DR RefSeq; NP_001003176.1; NM_001003176.1.
DR AlphaFoldDB; Q9TVB8; -.
DR SMR; Q9TVB8; -.
DR STRING; 9612.ENSCAFP00000030301; -.
DR PaxDb; Q9TVB8; -.
DR GeneID; 403803; -.
DR KEGG; cfa:403803; -.
DR CTD; 6121; -.
DR eggNOG; KOG1285; Eukaryota.
DR InParanoid; Q9TVB8; -.
DR OrthoDB; 895046at2759; -.
DR Proteomes; UP000002254; 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; 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; IDA: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 1: Evidence at protein 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_0000143941"
FT BINDING 180
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:16150724"
FT BINDING 241
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:16150724"
FT BINDING 313
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:16150724"
FT BINDING 527
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:16150724"
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 MUTAGEN 180
FT /note="H->A: Loss of enzymatic activity."
FT /evidence="ECO:0000269|PubMed:16150724"
FT MUTAGEN 231
FT /note="C->S: Does not affect isomerization activity."
FT /evidence="ECO:0000269|PubMed:16150724"
FT MUTAGEN 241
FT /note="H->A: Loss of isomerohydrolase activity."
FT /evidence="ECO:0000269|PubMed:16150724"
FT MUTAGEN 313
FT /note="H->A: Loss of isomerohydrolase activity."
FT /evidence="ECO:0000269|PubMed:16150724"
FT MUTAGEN 329..330
FT /note="CC->SS: Decreasing protein levels. Loss of
FT isomerohydrolase activity."
FT /evidence="ECO:0000269|PubMed:16150724"
FT MUTAGEN 329
FT /note="C->S: Decreasing protein levels. isomerohydrolase
FT activity."
FT /evidence="ECO:0000269|PubMed:16150724"
FT MUTAGEN 330
FT /note="C->T: Does not affect isomerohydrolase activity."
FT /evidence="ECO:0000269|PubMed:16150724"
FT MUTAGEN 417
FT /note="E->A: Loss of enzymatic isomerohydrolase."
FT /evidence="ECO:0000269|PubMed:16150724"
FT MUTAGEN 477
FT /note="D->G,E,N: Does not affect isomerohydrolase
FT activity."
FT /evidence="ECO:0000269|PubMed:30628748"
FT MUTAGEN 527
FT /note="H->A: Loss of isomerohydrolase activity."
FT /evidence="ECO:0000269|PubMed:16150724"
FT CONFLICT 368
FT /note="Y -> S (in Ref. 1; AAC72356)"
FT /evidence="ECO:0000305"
FT CONFLICT 426
FT /note="S -> Y (in Ref. 1; AAC72356)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 533 AA; 60880 MW; EBEC87458BA4C91B CRC64;
MSIQVEHPAG GYKKLFETVE ELSSPLTAHV TGRIPLWLTG SLLRCGPGLF EVGSEPFYHL
FDGQALLHKF DFKEGHVTYH RRFIRTDAYV RAMTEKRIVI TEFGTCAFPD PCKNIFSRFF
SYFRGVEVTD NALVNVYPVG EDYYACTETN FITKINPETL ETIKQVDLCN YVSVNGATAH
PHIENDGTVY NIGNCFGKNF SIAYNIVKIP PLQADKEDPI SKSEVVVQFP CSDRFKPSYV
HSFGLTPNYI VFVETPVKIN LLKFLSSWSL WGANYMDCFE SNETMGVWLH IADKKRKKYL
NNKYRTSSFN LFHHINTYED NEFLIVDLCC WKGFEFVYNY LYLANLRENW EEVKKNARKA
PQPEVRRYVL PLNIDKADTG KNLVTLPNTT ATATLRSDET IWLEPEVLFS GPRQAFEFPQ
INYQKSGGKP YTYAYGLGLN HFVPDRLCKL NVKTKETWVW QEPDSYPSEP IFVSHPDALE
EDDGVVLSVV VSPGAGQKPA YLLILNAKDL SEVARAEVEI NIPVTFHGLF KKS
