RPE65_BOVIN
ID RPE65_BOVIN Reviewed; 533 AA.
AC Q28175; Q05661;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Retinoid isomerohydrolase;
DE EC=3.1.1.64 {ECO:0000269|PubMed:16096063, ECO:0000269|PubMed:19805034, ECO:0000269|PubMed:20100834};
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Retinal pigment epithelium;
RX PubMed=8340400; DOI=10.1016/s0021-9258(18)82319-5;
RA Hamel C.P., Tsilou E., Pfeffer B.A., Hooks J.J., Detrick B., Redmond T.M.;
RT "Molecular cloning and expression of a novel retinal pigment epithelium-
RT specific microsomal protein that is translationally regulated in vitro.";
RL J. Biol. Chem. 268:15751-15757(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Steinholtz; TISSUE=Eye;
RX PubMed=8397208; DOI=10.1016/s0021-9258(20)80759-5;
RA Bavik C.O., Hellman U., Wernstedt C., Eriksson U.;
RT "The retinal pigment epithelial membrane receptor for plasma retinol
RT binding protein: isolation cDNA cloning and expression of the 63 kDa
RT protein.";
RL J. Biol. Chem. 268:20540-20546(1993).
RN [3]
RP PROTEIN SEQUENCE OF 98-118, PALMITOYLATION, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=19049981; DOI=10.1074/jbc.m807248200;
RA Takahashi Y., Moiseyev G., Ablonczy Z., Chen Y., Crouch R.K., Ma J.X.;
RT "Identification of a novel palmitylation site essential for membrane
RT association and isomerohydrolase activity of RPE65.";
RL J. Biol. Chem. 284:3211-3218(2009).
RN [4]
RP ACETYLATION AT SER-2, PALMITOYLATION AT CYS-231; CYS-329 AND CYS-330,
RP IDENTIFICATION BY MASS SPECTROMETRY, AND FUNCTION.
RX PubMed=15186777; DOI=10.1016/j.cell.2004.05.016;
RA Xue L., Gollapalli D.R., Maiti P., Jahng W.J., Rando R.R.;
RT "A palmitoylation switch mechanism in the regulation of the visual cycle.";
RL Cell 117:761-771(2004).
RN [5]
RP CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=16096063; DOI=10.1016/j.cell.2005.06.042;
RA Jin M., Li S., Moghrabi W.N., Sun H., Travis G.H.;
RT "Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium.";
RL Cell 122:449-459(2005).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.14 ANGSTROMS) IN COMPLEX WITH IRON ION, CATALYTIC
RP ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-112,
RP IDENTIFICATION BY MASS SPECTROMETRY, COFACTOR, TISSUE SPECIFICITY, AND
RP METAL-BINDING.
RX PubMed=19805034; DOI=10.1073/pnas.0906600106;
RA Kiser P.D., Golczak M., Lodowski D.T., Chance M.R., Palczewski K.;
RT "Crystal structure of native RPE65, the retinoid isomerase of the visual
RT cycle.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:17325-17330(2009).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH IRON ION, CATALYTIC
RP ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, COFACTOR, AND TISSUE SPECIFICITY.
RX PubMed=20100834; DOI=10.1074/jbc.m109.063941;
RA Golczak M., Kiser P.D., Lodowski D.T., Maeda A., Palczewski K.;
RT "Importance of membrane structural integrity for RPE65 retinoid
RT isomerization activity.";
RL J. Biol. Chem. 285:9667-9682(2010).
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:16096063, PubMed:19805034, PubMed:20100834). Essential for the
CC production of 11-cis retinal for both rod and cone photoreceptors. Also
CC capable of catalyzing the isomerization of lutein to meso-zeaxanthin an
CC eye-specific carotenoid (By similarity). The soluble form binds vitamin
CC A (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 (PubMed:15186777).
CC {ECO:0000250|UniProtKB:Q16518, ECO:0000269|PubMed:15186777,
CC ECO:0000269|PubMed:16096063, ECO:0000269|PubMed:19805034,
CC ECO:0000269|PubMed:20100834}.
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:16096063, ECO:0000269|PubMed:19805034,
CC ECO:0000269|PubMed:20100834};
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:19805034, ECO:0000269|PubMed:20100834};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:19805034,
CC ECO:0000269|PubMed:20100834};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.1 uM for all-trans-retinyl palmitate
CC {ECO:0000269|PubMed:16096063};
CC Vmax=26.1 pmol/min/mg enzyme {ECO:0000269|PubMed:16096063};
CC -!- SUBUNIT: Interacts with MYO7A; this mediates light-dependent
CC intracellular transport of RPE65. {ECO:0000250|UniProtKB:Q16518}.
CC -!- INTERACTION:
CC Q28175; Q28175: RPE65; NbExp=2; IntAct=EBI-15804453, EBI-15804453;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:A9C3R9}. Cell
CC membrane {ECO:0000269|PubMed:19805034}; Lipid-anchor
CC {ECO:0000269|PubMed:19805034}. Microsome membrane
CC {ECO:0000269|PubMed:19805034, ECO:0000269|PubMed:20100834}.
CC Note=Undergoes light-dependent intracellular transport to become more
CC concentrated in the central region of the retina pigment epithelium
CC cells (By similarity). Attached to the membrane by a lipid anchor when
CC palmitoylated (membrane form), soluble when unpalmitoylated.
CC {ECO:0000250|UniProtKB:Q16518, ECO:0000269|PubMed:19805034}.
CC -!- TISSUE SPECIFICITY: Retinal pigment epithelium specific.
CC {ECO:0000269|PubMed:19805034, ECO:0000269|PubMed:20100834}.
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:0000269|PubMed:15186777,
CC ECO:0000269|PubMed:19049981, ECO:0000269|PubMed:19805034}.
CC -!- SIMILARITY: Belongs to the carotenoid oxygenase family. {ECO:0000305}.
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DR EMBL; L11356; AAC37306.1; -; mRNA.
DR EMBL; X66277; CAA46988.1; -; mRNA.
DR PIR; A47143; A47143.
DR RefSeq; NP_776878.1; NM_174453.2.
DR PDB; 3FSN; X-ray; 2.14 A; A/B=1-533.
DR PDB; 3KVC; X-ray; 1.90 A; A/B=1-533.
DR PDB; 4F2Z; X-ray; 3.00 A; A/E=1-533.
DR PDB; 4F30; X-ray; 3.15 A; A=1-533.
DR PDB; 4F3A; X-ray; 2.60 A; A=1-533.
DR PDB; 4F3D; X-ray; 2.50 A; A/B=1-533.
DR PDB; 4RSC; X-ray; 1.80 A; A/B=1-533.
DR PDB; 4RSE; X-ray; 2.39 A; A/B=2-533.
DR PDB; 4RYX; X-ray; 2.00 A; A=1-533.
DR PDB; 4RYY; X-ray; 2.30 A; A/B=2-533.
DR PDB; 4RYZ; X-ray; 2.50 A; A/B=2-533.
DR PDB; 4ZHK; X-ray; 2.09 A; A/B=2-533.
DR PDB; 5UL5; X-ray; 2.20 A; A/B=1-533.
DR PDB; 5ULG; X-ray; 2.10 A; A/B=1-533.
DR PDB; 7K88; X-ray; 2.10 A; A/B=2-533.
DR PDB; 7K89; X-ray; 2.15 A; A/B=2-533.
DR PDB; 7K8G; X-ray; 1.95 A; A/B=2-533.
DR PDB; 7L0E; X-ray; 1.90 A; A/B=1-533.
DR PDBsum; 3FSN; -.
DR PDBsum; 3KVC; -.
DR PDBsum; 4F2Z; -.
DR PDBsum; 4F30; -.
DR PDBsum; 4F3A; -.
DR PDBsum; 4F3D; -.
DR PDBsum; 4RSC; -.
DR PDBsum; 4RSE; -.
DR PDBsum; 4RYX; -.
DR PDBsum; 4RYY; -.
DR PDBsum; 4RYZ; -.
DR PDBsum; 4ZHK; -.
DR PDBsum; 5UL5; -.
DR PDBsum; 5ULG; -.
DR PDBsum; 7K88; -.
DR PDBsum; 7K89; -.
DR PDBsum; 7K8G; -.
DR PDBsum; 7L0E; -.
DR AlphaFoldDB; Q28175; -.
DR SMR; Q28175; -.
DR DIP; DIP-48993N; -.
DR STRING; 9913.ENSBTAP00000041254; -.
DR BindingDB; Q28175; -.
DR ChEMBL; CHEMBL4523306; -.
DR iPTMnet; Q28175; -.
DR SwissPalm; Q28175; -.
DR PaxDb; Q28175; -.
DR GeneID; 282043; -.
DR KEGG; bta:282043; -.
DR CTD; 6121; -.
DR eggNOG; KOG1285; Eukaryota.
DR HOGENOM; CLU_016472_1_1_1; -.
DR InParanoid; Q28175; -.
DR OrthoDB; 895046at2759; -.
DR TreeFam; TF314019; -.
DR BRENDA; 3.1.1.64; 908.
DR SABIO-RK; Q28175; -.
DR EvolutionaryTrace; Q28175; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA: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: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; IDA:AgBase.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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; IDA:AgBase.
DR GO; GO:0001786; F:phosphatidylserine binding; IDA:AgBase.
DR GO; GO:0004744; F:retinal isomerase activity; IDA:CACAO.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
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 3D-structure; Acetylation; Cell membrane; Cytoplasm;
KW Direct protein sequencing; Endoplasmic reticulum; Hydrolase; Iron;
KW 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:0000269|PubMed:15186777"
FT CHAIN 2..533
FT /note="Retinoid isomerohydrolase"
FT /id="PRO_0000143940"
FT BINDING 180
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:19805034"
FT BINDING 241
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:19805034"
FT BINDING 313
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:19805034"
FT BINDING 527
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:19805034"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|PubMed:15186777"
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:0000269|PubMed:19805034"
FT LIPID 231
FT /note="S-palmitoyl cysteine; in membrane form"
FT /evidence="ECO:0000269|PubMed:15186777"
FT LIPID 329
FT /note="S-palmitoyl cysteine; in membrane form"
FT /evidence="ECO:0000269|PubMed:15186777"
FT LIPID 330
FT /note="S-palmitoyl cysteine; in membrane form"
FT /evidence="ECO:0000269|PubMed:15186777"
FT CONFLICT 341
FT /note="S -> L (in Ref. 2; CAA46988)"
FT /evidence="ECO:0000305"
FT HELIX 11..16
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 29..32
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 40..49
FT /evidence="ECO:0007829|PDB:4RSC"
FT TURN 60..62
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 63..73
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 76..83
FT /evidence="ECO:0007829|PDB:4RSC"
FT HELIX 87..95
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 134..139
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 142..146
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 148..155
FT /evidence="ECO:0007829|PDB:4RSC"
FT TURN 157..159
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 162..167
FT /evidence="ECO:0007829|PDB:4RSC"
FT HELIX 168..170
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 189..195
FT /evidence="ECO:0007829|PDB:4RSC"
FT HELIX 198..200
FT /evidence="ECO:0007829|PDB:4F2Z"
FT STRAND 203..209
FT /evidence="ECO:0007829|PDB:4RSC"
FT HELIX 219..222
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 224..230
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 232..235
FT /evidence="ECO:0007829|PDB:7K88"
FT STRAND 247..254
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 256..259
FT /evidence="ECO:0007829|PDB:4RSC"
FT HELIX 261..264
FT /evidence="ECO:0007829|PDB:4RSC"
FT HELIX 268..271
FT /evidence="ECO:0007829|PDB:4ZHK"
FT HELIX 276..278
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 283..285
FT /evidence="ECO:0007829|PDB:7L0E"
FT STRAND 287..293
FT /evidence="ECO:0007829|PDB:4RSC"
FT TURN 294..297
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 298..306
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 309..320
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 323..335
FT /evidence="ECO:0007829|PDB:4RSC"
FT HELIX 337..340
FT /evidence="ECO:0007829|PDB:4RSC"
FT HELIX 343..346
FT /evidence="ECO:0007829|PDB:4RSC"
FT HELIX 350..356
FT /evidence="ECO:0007829|PDB:4RSC"
FT TURN 357..359
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 362..372
FT /evidence="ECO:0007829|PDB:4RSC"
FT HELIX 376..378
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 392..395
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 399..404
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 406..409
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 414..420
FT /evidence="ECO:0007829|PDB:4RSC"
FT HELIX 423..426
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 433..440
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 443..451
FT /evidence="ECO:0007829|PDB:4RSC"
FT TURN 452..454
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 457..460
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 471..474
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 480..482
FT /evidence="ECO:0007829|PDB:3FSN"
FT STRAND 484..491
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 494..497
FT /evidence="ECO:0007829|PDB:4ZHK"
FT STRAND 499..506
FT /evidence="ECO:0007829|PDB:4RSC"
FT TURN 507..509
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 512..520
FT /evidence="ECO:0007829|PDB:4RSC"
FT STRAND 527..532
FT /evidence="ECO:0007829|PDB:4RSC"
SQ SEQUENCE 533 AA; 60944 MW; 28B5E4B15ACD8087 CRC64;
MSSQVEHPAG GYKKLFETVE ELSSPLTAHV TGRIPLWLTG SLLRCGPGLF EVGSEPFYHL
FDGQALLHKF DFKEGHVTYH RRFIRTDAYV RAMTEKRIVI TEFGTCAFPD PCKNIFSRFF
SYFRGVEVTD NALVNIYPVG EDYYACTETN FITKVNPETL ETIKQVDLCN YVSVNGATAH
PHIENDGTVY NIGNCFGKNF SIAYNIVKIP PLQADKEDPI SKSEIVVQFP CSDRFKPSYV
HSFGLTPNYI VFVETPVKIN LFKFLSSWSL WGANYMDCFE SNETMGVWLH IADKKRKKYI
NNKYRTSPFN LFHHINTYED HEFLIVDLCC WKGFEFVYNY SYLANLRENW EEVKKNARKA
PQPEVRRYVL PLNIDKADTG KNLVTLPNTT ATAILCSDET IWLEPEVLFS GPRQAFEFPQ
INYQKYGGKP YTYAYGLGLN HFVPDRLCKL NVKTKETWVW QEPDSYPSEP IFVSHPDALE
EDDGVVLSVV VSPGAGQKPA YLLILNAKDL SEVARAEVEI NIPVTFHGLF KKS
