RP65C_DANRE
ID RP65C_DANRE Reviewed; 532 AA.
AC A9C3R8; E7FBT0;
DT 05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 1.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=Retinal Mueller cells isomerohydrolase;
DE EC=3.1.1.64 {ECO:0000269|PubMed:21676174};
DE AltName: Full=All-trans-retinyl ester 13-cis isomerohydrolase C;
DE EC=3.1.1.90 {ECO:0000269|PubMed:21676174};
DE AltName: Full=All-trans-retinylester 11-cis isomerohydrolase C;
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 C;
DE Short=RPE56c;
GN Name=rpe65c; ORFNames=si:ch211-198n5.12;
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 [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 [2]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=21676174; DOI=10.1111/j.1742-4658.2011.08216.x;
RA Takahashi Y., Moiseyev G., Chen Y., Nikolaeva O., Ma J.X.;
RT "An alternative isomerohydrolase in the retinal Muller cells of a cone-
RT dominant species.";
RL FEBS J. 278:2913-2926(2011).
CC -!- FUNCTION: Catalyzes both 11-cis retinol and 13-cis retinol, 2
CC stereoisomeric forms of retinoic acid from all-trans-retinyl ester.
CC Acts as an alternative isomerohydrolase in retinal Mueller cells by
CC catalyzing formation of 11-cis retinol, to meet the high demand for the
CC chromophore by cones (PubMed:21676174). Capable of catalyzing the
CC isomerization of lutein to meso-zeaxanthin an eye-specific carotenoid
CC (By similarity). {ECO:0000250|UniProtKB:Q16518,
CC ECO:0000269|PubMed:21676174}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an all-trans-retinyl ester + H2O = 13-cis-retinol + a fatty
CC acid + H(+); Xref=Rhea:RHEA:31779, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28868, ChEBI:CHEBI:45479,
CC ChEBI:CHEBI:63410; EC=3.1.1.90;
CC Evidence={ECO:0000269|PubMed:21676174};
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=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:21676174};
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:0000305|PubMed:21676174};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000305|PubMed:21676174};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.91 uM for 11-cis retinol {ECO:0000269|PubMed:21676174};
CC KM=2.95 uM for 13-cis retinol {ECO:0000269|PubMed:21676174};
CC Vmax=1.82 nmol/h/mg enzyme for 11-cis retinol
CC {ECO:0000269|PubMed:21676174};
CC Vmax=0.91 nmol/h/mg enzyme for 13-cis retinol
CC {ECO:0000269|PubMed:21676174};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21676174}. Cell
CC membrane {ECO:0000269|PubMed:21676174}; Lipid-anchor
CC {ECO:0000269|PubMed:21676174}. Note=Attached to the membrane by a lipid
CC anchor when palmitoylated (membrane form), soluble when
CC unpalmitoylated. {ECO:0000250|UniProtKB:Q28175}.
CC -!- TISSUE SPECIFICITY: Retinal Mueller cells. Detected in the inner retina
CC near the ganglion cell layer, in a region where the Mueller end feet
CC are located, and a weak signal is observed between the outer nuclear
CC and ganglion cell layers (at protein level).
CC {ECO:0000269|PubMed:21676174}.
CC -!- PTM: Palmitoylated. {ECO:0000250|UniProtKB:Q28175}.
CC -!- SIMILARITY: Belongs to the carotenoid oxygenase family. {ECO:0000305}.
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DR EMBL; CR759968; CAP19511.1; -; Genomic_DNA.
DR RefSeq; NP_001107125.1; NM_001113653.1.
DR AlphaFoldDB; A9C3R8; -.
DR SMR; A9C3R8; -.
DR IntAct; A9C3R8; 1.
DR MINT; A9C3R8; -.
DR STRING; 7955.ENSDARP00000071071; -.
DR PaxDb; A9C3R8; -.
DR PeptideAtlas; A9C3R8; -.
DR Ensembl; ENSDART00000076600; ENSDARP00000071071; ENSDARG00000054420.
DR GeneID; 100004076; -.
DR KEGG; dre:100004076; -.
DR CTD; 100004076; -.
DR ZFIN; ZDB-GENE-081104-505; rpe65c.
DR eggNOG; KOG1285; Eukaryota.
DR GeneTree; ENSGT00950000182913; -.
DR HOGENOM; CLU_016472_1_1_1; -.
DR InParanoid; A9C3R8; -.
DR OMA; NLRQEWE; -.
DR OrthoDB; 895046at2759; -.
DR PhylomeDB; A9C3R8; -.
DR TreeFam; TF314019; -.
DR BRENDA; 3.1.1.64; 928.
DR SignaLink; A9C3R8; -.
DR PRO; PR:A9C3R8; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 8.
DR Bgee; ENSDARG00000054420; Expressed in zone of skin and 8 other tissues.
DR ExpressionAtlas; A9C3R8; baseline.
DR GO; GO:0005829; C:cytosol; IDA:ZFIN.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:ZFIN.
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; IDA:ZFIN.
DR GO; GO:0001523; P:retinoid metabolic process; ISS:UniProtKB.
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 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; Hydrolase; Iron; Isomerase; Lipoprotein;
KW Membrane; Metal-binding; Palmitate; Reference proteome.
FT CHAIN 1..532
FT /note="Retinal Mueller cells isomerohydrolase"
FT /id="PRO_0000418732"
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 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 532 AA; 60879 MW; C890C678BAB2B92B CRC64;
MVSRLEHPAG GYKKVFESCE ELAEPIPAHV SGEIPAWLSG SLLRMGPGLF EVGDEPFYHL
FDGQALLHKF DLKDGRVTYH RRFIRTDAYV RAMTEKRVVI TEFGTTAYPD PCKNIFSRFF
TYFQGIEVTD NCLVNIYPIG EDFYACTETN FITKVDPDTL ETVKKVDLCN YLSVNGLTAH
PHIEADGTVY NIGNCFGKNM SLAYNIVKIP PLQEDKSDQF EKSKILVQFP SSERFKPSYV
HSFGITENHF VFVETPVKIN LLKFLTSWSI RGSNYMDCFE SNDKMGTWFH LAAKNPGKYI
DHKFRTSAFN IFHHINCFED QGFIVVDLCT WKGHEFVYNY LYLANLRQNW EEVKKAALRA
PQPEVRRYVL PLDIHREEQG KNLVSLPYTT ATAVMRSDGT VWLEPEVLFS GPRQAFEFPQ
INYSKFNGKD YTFAYGLGLN HFVPDRICKL NVKSKETWIW QEPDAYPSEP LFVQSPDAED
EDDGVLLSIV VKPGVSQRPA FLLILKATDL TEIARAEVDV LIPVTLHGIY KP
