RP65A_DANRE
ID RP65A_DANRE Reviewed; 531 AA.
AC Q6PBW5;
DT 05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Retinoid isomerohydrolase;
DE EC=3.1.1.64 {ECO:0000250|UniProtKB:Q28175};
DE AltName: Full=All-trans-retinylester 11-cis isomerohydrolase A;
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 homolog A;
DE Short=RPE56a;
GN Name=rpe65a; Synonyms=rpepa;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=17868371; DOI=10.1111/j.1460-9568.2007.05801.x;
RA Schonthaler H.B., Lampert J.M., Isken A., Rinner O., Mader A., Gesemann M.,
RA Oberhauser V., Golczak M., Biehlmaier O., Palczewski K., Neuhauss S.C.,
RA von Lintig J.;
RT "Evidence for RPE65-independent vision in the cone-dominated zebrafish
RT retina.";
RL Eur. J. Neurosci. 26:1940-1949(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Plays important roles in the production of 11-cis retinal and
CC in visual pigment regeneration. Capable of catalyzing the isomerization
CC of lutein to meso-zeaxanthin an eye-specific carotenoid (By
CC similarity). {ECO:0000250|UniProtKB:Q16518,
CC ECO:0000305|PubMed:17868371}.
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:A9C3R9};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:A9C3R9};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:A9C3R9}. Cell
CC membrane {ECO:0000250|UniProtKB:A9C3R9}; Lipid-anchor
CC {ECO:0000250|UniProtKB:A9C3R9}. 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 {ECO:0000269|PubMed:17868371}.
CC -!- DEVELOPMENTAL STAGE: Expressed at 16 hours post fertilization (hpf) in
CC the pineal gland, a light-sensitive endocrine organ. Expression in the
CC retinal pigment epithelium (RPE) is initiated in the ventronasal patch
CC at 40 hpf, preceding photoreceptor differentiation by a few hours.
CC During subsequent development, expression in the RPE becomes stronger
CC and more widespread, covering the entire RPE except for the cilliary
CC margin by 56 hpf. {ECO:0000269|PubMed:17868371}.
CC -!- PTM: Palmitoylated. {ECO:0000250|UniProtKB:Q28175}.
CC -!- SIMILARITY: Belongs to the carotenoid oxygenase family. {ECO:0000305}.
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DR EMBL; AY646886; AAV65107.1; -; mRNA.
DR EMBL; FP102801; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC059559; AAH59559.1; -; mRNA.
DR RefSeq; NP_957045.1; NM_200751.1.
DR AlphaFoldDB; Q6PBW5; -.
DR SMR; Q6PBW5; -.
DR STRING; 7955.ENSDARP00000017189; -.
DR PaxDb; Q6PBW5; -.
DR Ensembl; ENSDART00000004533; ENSDARP00000017189; ENSDARG00000007480.
DR GeneID; 393724; -.
DR KEGG; dre:393724; -.
DR CTD; 393724; -.
DR ZFIN; ZDB-GENE-040426-1717; rpe65a.
DR eggNOG; KOG1285; Eukaryota.
DR GeneTree; ENSGT00950000182913; -.
DR HOGENOM; CLU_016472_1_1_1; -.
DR InParanoid; Q6PBW5; -.
DR OMA; GTWIHIA; -.
DR OrthoDB; 895046at2759; -.
DR PhylomeDB; Q6PBW5; -.
DR TreeFam; TF314019; -.
DR BRENDA; 3.1.1.64; 928.
DR Reactome; R-DRE-2453902; The canonical retinoid cycle in rods (twilight vision).
DR PRO; PR:Q6PBW5; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 2.
DR Bgee; ENSDARG00000007480; Expressed in larva and 12 other tissues.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
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; IEA:UniProtKB-EC.
DR GO; GO:0052884; F:all-trans-retinyl-palmitate hydrolase, 11-cis retinol forming activity; IEA:UniProtKB-EC.
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: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; ISS:UniProtKB.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR GO; GO:1901827; P:zeaxanthin biosynthetic process; IBA:GO_Central.
DR InterPro; IPR004294; Carotenoid_Oase.
DR PANTHER; PTHR10543; PTHR10543; 1.
DR Pfam; PF03055; RPE65; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cytoplasm; Hydrolase; Iron; Isomerase; Lipoprotein;
KW Membrane; Metal-binding; Palmitate; Reference proteome;
KW Sensory transduction; Vision.
FT CHAIN 1..531
FT /note="Retinoid isomerohydrolase"
FT /id="PRO_0000418730"
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 526
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
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 329
FT /note="S-palmitoyl cysteine; in membrane form"
FT /evidence="ECO:0000250|UniProtKB:Q28175"
SQ SEQUENCE 531 AA; 60789 MW; FD274CB929CD377D CRC64;
MVSRFEHPAG GYKKIFETAE ELNEPLPATV TGRIPSFIKG SLLRLGPGLF EAGAEPFYHL
FDGQALMHKF DFSNGQVTYF RKFVKTDAYV RAITEKRVVI TEFGTCAYPD PCKNIFSRFF
SYFKGVEVTD NCLVNVYPIG EDFYAVTETN YITKVNVDTL ETLKKVDMCN YVNINGVTAH
PHIERDGTVY NIGNCMGKGA SLAYNIVRIP PTQKDKSDPI EKSKVVVQFP SAERFKPSYV
HSFGMTENYF VFVETPVKIN LLKFLSAWSI RGSNYMDCFE SDEEKGTWIH IARKHPGEYI
DYKFRTSAMG LFHHINCYED SGFIVFDLCA WKGFEFVYNY LWLANLRANW EEVKRNAMIA
PQPEVRRYVI PLDPFREEQG KNLISLPYTT ATATMRADGT IWLEPEVLFS GPRQAFEFPQ
INYRMVNGKN YTYAYGLGLN HFVPDRICKL NVRTKETWVW QEPDSYPSEP LFVQTPDGVD
EDDGILMTIV VSPGAQRPTY CLILNAKDLS EIARAEVEIL TPVTFHGMYK P
