Recombinant Human Retinoid isomerohydrolase (RPE65)

Function

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)

Subcellular Location

Cytoplasm; Cell membrane (Lipid-anchor); Microsome membrane

Disease Association

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. [The disease is caused by variants affecting the gene represented in this entry] | 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. [The disease is caused by variants affecting the gene represented in this entry] | 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. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Retina (at protein level). Retinal pigment epithelium specific

Subunit

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

• Nicoletti A. et al. Molecular characterization of the human gene encoding an abundant 61 kDa protein specific to the retinal pigment epithelium. — Hum. Mol. Genet. (1995)
• Morimura H. et al. Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or Leber congenital amaurosis. — Proc. Natl. Acad. Sci. U.S.A. (1998)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Gregory S.G. et al. The DNA sequence and biological annotation of human chromosome 1. — Nature (2006)
• Mural R.J. et al. PubMed: CI-5GBD0VIIJ7C63 (SEP-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Takahashi Y. et al. Identification of a novel palmitylation site essential for membrane association and isomerohydrolase activity of RPE65. — J. Biol. Chem. (2009)
• Takahashi Y. et al. Identification of conserved histidines and glutamic acid as key residues for isomerohydrolase activity of RPE65, an enzyme of the visual cycle in the retinal pigment epithelium. — FEBS Lett. (2005)