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Protein

Retinoid isomerohydrolase

Gene

RPE65

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays important roles in the production of 11-cis retinal and in visual pigment regeneration. The soluble form binds vitamin A (all-trans-retinol), making it available for LRAT processing to all-trans-retinyl ester. The membrane form, palmitoylated by LRAT, binds all-trans-retinyl esters, making them available for IMH (isomerohydrolase) processing to all-cis-retinol. The soluble form is regenerated by transferring its palmitoyl groups onto 11-cis-retinol, a reaction catalyzed by LRAT. The enzymatic activity is linearly dependent of the expression levels and membrane association.3 Publications

Catalytic activityi

An all-trans-retinyl ester + H2O = 11-cis-retinol + a fatty acid.3 Publications

Cofactori

Fe2+2 PublicationsNote: Binds 1 Fe2+ ion per subunit.2 Publications

Kineticsi

  1. KM=7.1 µM for all-trans-retinyl palmitate1 Publication
  1. Vmax=26.1 pmol/min/mg enzyme1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi180 – 1801Iron; catalytic
Metal bindingi241 – 2411Iron; catalytic
Metal bindingi313 – 3131Iron; catalytic
Metal bindingi527 – 5271Iron; catalytic

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Isomerase

Keywords - Biological processi

Sensory transduction, Vision

Keywords - Ligandi

Iron, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.1.64. 908.
SABIO-RKQ28175.

Names & Taxonomyi

Protein namesi
Recommended name:
Retinoid isomerohydrolase (EC:3.1.1.64)
Alternative name(s):
All-trans-retinyl-palmitate hydrolase
Retinal pigment epithelium-specific 65 kDa protein
Retinol isomerase
Gene namesi
Name:RPE65
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

  • Cytoplasm
  • Cell membrane; Lipid-anchor
  • Microsome membrane

  • Note: Undergoes light-dependent intracellular transport to become more concentrated in the central region of the retina pigment epithelium cells (By similarity). Attached to the membrane by a lipid anchor when palmitoylated (membrane form), soluble when unpalmitoylated.By similarity

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB-KW
  • membrane Source: AgBase
  • organelle membrane Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endoplasmic reticulum, Membrane, Microsome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved1 Publication
Chaini2 – 533532Retinoid isomerohydrolasePRO_0000143940Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserine1 Publication
Modified residuei101 – 1011PhosphothreonineBy similarity
Modified residuei105 – 1051PhosphothreonineBy similarity
Lipidationi112 – 1121S-palmitoyl cysteine; in membrane form1 Publication
Modified residuei113 – 1131N6-acetyllysineBy similarity
Modified residuei117 – 1171PhosphoserineBy similarity
Lipidationi231 – 2311S-palmitoyl cysteine; in membrane form1 Publication
Lipidationi329 – 3291S-palmitoyl cysteine; in membrane form1 Publication
Lipidationi330 – 3301S-palmitoyl cysteine; in membrane form1 Publication

Post-translational modificationi

Palmitoylation by LRAT regulates ligand binding specificity; the palmitoylated form (membrane form) specifically binds all-trans-retinyl-palmitate, while the soluble unpalmitoylated form binds all-trans-retinol (vitamin A).3 Publications

Keywords - PTMi

Acetylation, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiQ28175.
PRIDEiQ28175.

PTM databases

SwissPalmiQ28175.

Expressioni

Tissue specificityi

Retinal pigment epithelium specific.2 Publications

Interactioni

Subunit structurei

Interacts with MYO7A; this mediates light-dependent intracellular transport of RPE65.By similarity

Protein-protein interaction databases

DIPiDIP-48993N.
STRINGi9913.ENSBTAP00000041254.

Structurei

Secondary structure

1
533
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi11 – 166Combined sources
Beta strandi29 – 324Combined sources
Beta strandi40 – 4910Combined sources
Turni60 – 623Combined sources
Beta strandi63 – 7311Combined sources
Beta strandi76 – 838Combined sources
Helixi87 – 959Combined sources
Beta strandi134 – 1396Combined sources
Beta strandi142 – 1465Combined sources
Beta strandi148 – 1558Combined sources
Turni157 – 1593Combined sources
Beta strandi162 – 1676Combined sources
Helixi168 – 1703Combined sources
Beta strandi189 – 1957Combined sources
Helixi198 – 2003Combined sources
Beta strandi203 – 2097Combined sources
Helixi219 – 2224Combined sources
Beta strandi224 – 2307Combined sources
Beta strandi232 – 2354Combined sources
Beta strandi247 – 2548Combined sources
Beta strandi256 – 2594Combined sources
Helixi261 – 2644Combined sources
Helixi268 – 2714Combined sources
Helixi276 – 2783Combined sources
Beta strandi279 – 2813Combined sources
Beta strandi283 – 2853Combined sources
Beta strandi287 – 2937Combined sources
Turni294 – 2974Combined sources
Beta strandi298 – 3069Combined sources
Beta strandi309 – 32012Combined sources
Beta strandi323 – 33513Combined sources
Helixi337 – 3404Combined sources
Helixi343 – 3464Combined sources
Helixi350 – 3567Combined sources
Turni357 – 3593Combined sources
Beta strandi362 – 37211Combined sources
Helixi376 – 3783Combined sources
Beta strandi392 – 3954Combined sources
Beta strandi399 – 4046Combined sources
Beta strandi406 – 4094Combined sources
Beta strandi414 – 4207Combined sources
Helixi423 – 4264Combined sources
Beta strandi433 – 4408Combined sources
Beta strandi443 – 4519Combined sources
Turni452 – 4543Combined sources
Beta strandi457 – 4604Combined sources
Beta strandi471 – 4744Combined sources
Beta strandi480 – 4823Combined sources
Beta strandi484 – 4918Combined sources
Beta strandi494 – 4974Combined sources
Beta strandi499 – 5068Combined sources
Turni507 – 5093Combined sources
Beta strandi512 – 5209Combined sources
Beta strandi527 – 5326Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3FSNX-ray2.14A/B1-533[»]
3KVCX-ray1.90A/B1-533[»]
4F2ZX-ray3.00A/E1-533[»]
4F30X-ray3.15A1-533[»]
4F3AX-ray2.60A1-533[»]
4F3DX-ray2.50A/B1-533[»]
4RSCX-ray1.80A/B1-533[»]
4RSEX-ray2.39A/B2-533[»]
4RYXX-ray2.00A1-533[»]
4RYYX-ray2.30A/B2-533[»]
4RYZX-ray2.50A/B2-533[»]
4ZHKX-ray2.09A/B2-533[»]
ProteinModelPortaliQ28175.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ28175.

Family & Domainsi

Sequence similaritiesi

Belongs to the carotenoid oxygenase family.Curated

Phylogenomic databases

eggNOGiKOG1285. Eukaryota.
COG3670. LUCA.
HOGENOMiHOG000232156.
HOVERGENiHBG050679.
InParanoidiQ28175.
KOiK11158.
OrthoDBiEOG7353WB.
TreeFamiTF314019.

Family and domain databases

InterProiIPR004294. Carotenoid_Oase.
[Graphical view]
PANTHERiPTHR10543. PTHR10543. 2 hits.
PfamiPF03055. RPE65. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q28175-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSQVEHPAG GYKKLFETVE ELSSPLTAHV TGRIPLWLTG SLLRCGPGLF
60 70 80 90 100
EVGSEPFYHL FDGQALLHKF DFKEGHVTYH RRFIRTDAYV RAMTEKRIVI
110 120 130 140 150
TEFGTCAFPD PCKNIFSRFF SYFRGVEVTD NALVNIYPVG EDYYACTETN
160 170 180 190 200
FITKVNPETL ETIKQVDLCN YVSVNGATAH PHIENDGTVY NIGNCFGKNF
210 220 230 240 250
SIAYNIVKIP PLQADKEDPI SKSEIVVQFP CSDRFKPSYV HSFGLTPNYI
260 270 280 290 300
VFVETPVKIN LFKFLSSWSL WGANYMDCFE SNETMGVWLH IADKKRKKYI
310 320 330 340 350
NNKYRTSPFN LFHHINTYED HEFLIVDLCC WKGFEFVYNY SYLANLRENW
360 370 380 390 400
EEVKKNARKA PQPEVRRYVL PLNIDKADTG KNLVTLPNTT ATAILCSDET
410 420 430 440 450
IWLEPEVLFS GPRQAFEFPQ INYQKYGGKP YTYAYGLGLN HFVPDRLCKL
460 470 480 490 500
NVKTKETWVW QEPDSYPSEP IFVSHPDALE EDDGVVLSVV VSPGAGQKPA
510 520 530
YLLILNAKDL SEVARAEVEI NIPVTFHGLF KKS
Length:533
Mass (Da):60,944
Last modified:January 23, 2007 - v3
Checksum:i28B5E4B15ACD8087
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti341 – 3411S → L in CAA46988 (PubMed:8397208).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L11356 mRNA. Translation: AAC37306.1.
X66277 mRNA. Translation: CAA46988.1.
PIRiA47143.
RefSeqiNP_776878.1. NM_174453.2.
UniGeneiBt.108.

Genome annotation databases

GeneIDi282043.
KEGGibta:282043.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L11356 mRNA. Translation: AAC37306.1.
X66277 mRNA. Translation: CAA46988.1.
PIRiA47143.
RefSeqiNP_776878.1. NM_174453.2.
UniGeneiBt.108.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3FSNX-ray2.14A/B1-533[»]
3KVCX-ray1.90A/B1-533[»]
4F2ZX-ray3.00A/E1-533[»]
4F30X-ray3.15A1-533[»]
4F3AX-ray2.60A1-533[»]
4F3DX-ray2.50A/B1-533[»]
4RSCX-ray1.80A/B1-533[»]
4RSEX-ray2.39A/B2-533[»]
4RYXX-ray2.00A1-533[»]
4RYYX-ray2.30A/B2-533[»]
4RYZX-ray2.50A/B2-533[»]
4ZHKX-ray2.09A/B2-533[»]
ProteinModelPortaliQ28175.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-48993N.
STRINGi9913.ENSBTAP00000041254.

PTM databases

SwissPalmiQ28175.

Proteomic databases

PaxDbiQ28175.
PRIDEiQ28175.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi282043.
KEGGibta:282043.

Organism-specific databases

CTDi6121.

Phylogenomic databases

eggNOGiKOG1285. Eukaryota.
COG3670. LUCA.
HOGENOMiHOG000232156.
HOVERGENiHBG050679.
InParanoidiQ28175.
KOiK11158.
OrthoDBiEOG7353WB.
TreeFamiTF314019.

Enzyme and pathway databases

BRENDAi3.1.1.64. 908.
SABIO-RKQ28175.

Miscellaneous databases

EvolutionaryTraceiQ28175.

Family and domain databases

InterProiIPR004294. Carotenoid_Oase.
[Graphical view]
PANTHERiPTHR10543. PTHR10543. 2 hits.
PfamiPF03055. RPE65. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Molecular cloning and expression of a novel retinal pigment epithelium-specific microsomal protein that is translationally regulated in vitro."
    Hamel C.P., Tsilou E., Pfeffer B.A., Hooks J.J., Detrick B., Redmond T.M.
    J. Biol. Chem. 268:15751-15757(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
    Tissue: Retinal pigment epithelium.
  2. "The retinal pigment epithelial membrane receptor for plasma retinol binding protein: isolation cDNA cloning and expression of the 63 kDa protein."
    Bavik C.O., Hellman U., Wernstedt C., Eriksson U.
    J. Biol. Chem. 268:20540-20546(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Steinholtz.
    Tissue: Eye.
  3. "Identification of a novel palmitylation site essential for membrane association and isomerohydrolase activity of RPE65."
    Takahashi Y., Moiseyev G., Ablonczy Z., Chen Y., Crouch R.K., Ma J.X.
    J. Biol. Chem. 284:3211-3218(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 98-118, PALMITOYLATION, IDENTIFICATION BY MASS SPECTROMETRY.
  4. "A palmitoylation switch mechanism in the regulation of the visual cycle."
    Xue L., Gollapalli D.R., Maiti P., Jahng W.J., Rando R.R.
    Cell 117:761-771(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION AT SER-2, PALMITOYLATION AT CYS-231; CYS-329 AND CYS-330, IDENTIFICATION BY MASS SPECTROMETRY.
  5. "Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium."
    Jin M., Li S., Moghrabi W.N., Sun H., Travis G.H.
    Cell 122:449-459(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
  6. "Crystal structure of native RPE65, the retinoid isomerase of the visual cycle."
    Kiser P.D., Golczak M., Lodowski D.T., Chance M.R., Palczewski K.
    Proc. Natl. Acad. Sci. U.S.A. 106:17325-17330(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.14 ANGSTROMS) IN COMPLEX WITH IRON ION, CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-112, IDENTIFICATION BY MASS SPECTROMETRY, COFACTOR, TISSUE SPECIFICITY.
  7. "Importance of membrane structural integrity for RPE65 retinoid isomerization activity."
    Golczak M., Kiser P.D., Lodowski D.T., Maeda A., Palczewski K.
    J. Biol. Chem. 285:9667-9682(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH IRON ION, CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, COFACTOR, TISSUE SPECIFICITY.

Entry informationi

Entry nameiRPE65_BOVIN
AccessioniPrimary (citable) accession number: Q28175
Secondary accession number(s): Q05661
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 10, 2003
Last sequence update: January 23, 2007
Last modified: July 6, 2016
This is version 110 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.