RPE65

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]

RPE65, Retinoid Isomerohydrolase

Critical isomerohydrolase in the retinoid cycle involved in regeneration of 11-cis-retinal, the chromophore of rod and cone opsins. Catalyzes the cleavage and isomerization of all-trans-retinyl fatty acid esters to 11-cis-retinol which is further oxidized by 11-cis retinol dehydrogenase to 11-cis-retinal for use as visual chromophore (PubMed:16116091).
Essential for the production of 11-cis retinal for both rod and cone photoreceptors (PubMed:17848510).
Also capable of catalyzing the isomerization of lutein to meso-zeaxanthin an eye-specific carotenoid (PubMed:28874556).
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 (By similarity).

Biological Process cellular response to electrical stimulusIEA:Ensembl
Biological Process circadian rhythmIEA:Ensembl
Biological Process detection of light stimulus involved in visual perceptionManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process insulin receptor signaling pathwayIEA:Ensembl
Biological Process neural retina developmentIEA:Ensembl
Biological Process regulation of gene expressionIEA:Ensembl
Biological Process retina homeostasisManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process retina morphogenesis in camera-type eyeIEA:Ensembl
Biological Process retinal metabolic processIEA:Ensembl
Biological Process retinoid metabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process visual perceptionManual Assertion Based On ExperimentTAS:ProtInc
Biological Process vitamin A metabolic processManual Assertion Based On ExperimentTAS:ProtInc
Biological Process zeaxanthin biosynthetic processManual Assertion Based On ExperimentIDA:UniProtKB

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

Leber congenital amaurosis 2 (LCA2):
A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.
Retinitis pigmentosa 20 (RP20):
A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.
Retinitis pigmentosa 87 with choroidal involvement (RP87):
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. RP87 is an autosomal dominant form characterized by a slowly progressive visual disturbance accompanied by extensive choroid/retinal atrophy that mimics certain aspects of choroideremia. Disease severity and age of onset are variable, and some carriers are unaffected.

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) (By similarity).