RPE65

Protein identityUniProt · HPA

UniProt accession

Q16518

Gene

RPE65

Ensembl

ENSG00000116745

Chromosome

1

Canonical length

533 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted intracellular proteins

OverviewNCBI Gene

The protein encoded by this gene is a component of the vitamin A visual cycle of the retina which supplies the 11-cis retinal chromophore of the photoreceptors opsin visual pigments. It is a member of the carotenoid cleavage oxygenase superfamily. All members of this superfamily are non-heme iron oxygenases with a seven-bladed propeller fold and oxidatively cleave carotenoid carbon:carbon double bonds. However, the protein encoded by this gene has acquired a divergent function that involves the concerted O-alkyl ester cleavage of its all-trans retinyl ester substrate and all-trans to 11-cis double bond isomerization of the retinyl moiety. As such, it performs the essential enzymatic isomerization step in the synthesis of 11-cis retinal. Mutations in this gene are associated with early-onset severe blinding disorders such as Leber congenital. [provided by RefSeq, Oct 2017]

Canonical amino-acid sequenceUniProt

533 residues, UniProt reviewed canonical sequence.

>Q16518|RPE65
     1  MSIQVEHPAG GYKKLFETVE ELSSPLTAHV TGRIPLWLTG SLLRCGPGLF EVGSEPFYHL
    61  FDGQALLHKF DFKEGHVTYH RRFIRTDAYV RAMTEKRIVI TEFGTCAFPD PCKNIFSRFF
   121  SYFRGVEVTD NALVNVYPVG EDYYACTETN FITKINPETL ETIKQVDLCN YVSVNGATAH
   181  PHIENDGTVY NIGNCFGKNF SIAYNIVKIP PLQADKEDPI SKSEIVVQFP CSDRFKPSYV
   241  HSFGLTPNYI VFVETPVKIN LFKFLSSWSL WGANYMDCFE SNETMGVWLH IADKKRKKYL
   301  NNKYRTSPFN LFHHINTYED NGFLIVDLCC WKGFEFVYNY LYLANLRENW EEVKKNARKA
   361  PQPEVRRYVL PLNIDKADTG KNLVTLPNTT ATAILCSDET IWLEPEVLFS GPRQAFEFPQ
   421  INYQKYCGKP YTYAYGLGLN HFVPDRLCKL NVKTKETWVW QEPDSYPSEP IFVSHPDALE
   481  EDDGVVLSVV VSPGAGQKPA YLLILNAKDL SEVARAEVEI NIPVTFHGLF KKS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RPE65 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.21

Highest tissue expression

7.8 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about RPE65.

Disease | AllUniProt

Conditions RPE65 is implicated in, by any mechanism.

• Leber congenital amaurosis 2 (LCA2) MIM:204100
• Retinitis pigmentosa 20 (RP20) MIM:613794
• Retinitis pigmentosa 87 with choroidal involvement (RP87) MIM:618697

Disease | GeneticClinVar

332 pathogenic / likely-pathogenic of 1,144 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Leber congenital amaurosis 2
• Retinitis pigmentosa 20
• RPE65-related recessive retinopathy
• Leber congenital amaurosis
• Retinitis pigmentosa 87 with choroidal involvement

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.11

gnomAD pLI

0

gnomAD missense Z

-0.24

DepMap mean gene effect

-0.25

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• circadian rhythm
• detection of light stimulus involved in visual perception
• neural retina development
• retina homeostasis
• retinal metabolic process
• retinoid metabolic process
• visual perception
• vitamin A metabolic process
• zeaxanthin biosynthetic process

Molecular functions

• beta-carotene 15,15'-dioxygenase activity
• cardiolipin binding
• isomerase activity
• metal ion binding
• phosphatidylcholine binding
• phosphatidylserine binding
• retinol isomerase activity
• all-trans-retinyl-ester hydrolase, 11-cis retinol forming activity
• all-trans-retinyl-palmitate hydrolase, 11-cis retinol forming activity

Cellular components

• cell body
• endoplasmic reticulum membrane
• membrane
• nucleus
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Carotenoid oxygenase
• Retinal pigment epithelial membrane protein

KeywordsUniProt

• Acetylation
• Cell membrane
• Cytoplasm
• Endoplasmic reticulum
• Hydrolase
• Iron
• Isomerase
• Leber congenital amaurosis
• Lipid metabolism
• Lipoprotein
• Membrane
• Metal-binding
• Microsome
• Palmitate
• Phosphoprotein
• Retinitis pigmentosa
• Sensory transduction
• Vision

InteractionsUniProt · HPA

Protein binding partners of RPE65 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MYO7A