background:
The retinal pigment epithelium (RPE) is a monolayer simple epithelium in proximity to the outer surface of the retinal photoreceptor cells. Retinal pigment epithelium-specific protein (RPE65) is a 65 kDa protein belonging to the β-carotene dioxygenase family. This protein is important in 11-cis retinal production as well as in visual pigment regeneration. RPE65 is attached to the membrane by a lipid anchor when palmitoylated (membrane form) and soluble when unpalmitoylated. The soluble form of the protein binds vitamin A. Defects in RPE65 causes autosomal dominant retinitis pigmentosa and/or Leber congenital amaurosis type 2.
Function:
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.
Subunit:
Interacts with MYO7A; this mediates light-dependent intracellular transport of RPE65.
Subcellular Location:
Cytoplasm. Cell membrane. Attached to the membrane by a lipid anchor when palmitoylated (membrane form), soluble when unpalmitoylated.
Tissue Specificity:
Retinal pigment epithelium specific.
Post-translational modifications:
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).
DISEASE:
Defects in RPE65 are the cause of Leber congenital amaurosis type 2 (LCA2) [MIM:204100]. LCA designates a clinically and genetically heterogeneous group of childhood retinal degenerations, generally inherited in an autosomal recessive manner. Affected infants have little or no retinal photoreceptor function as tested by electroretinography. LCA represents the most common genetic cause of congenital visual impairment in infants and children.
Similarity:
Belongs to the carotenoid oxygenase family.
Database links:
Entrez Gene: 6121 Human
Entrez Gene: 19892 Mouse
Entrez Gene: 89826 Rat
Omim: 36069 Human
SwissProt: Q9YGX2 Chicken
SwissProt: Q28175 Cow
SwissProt: Q16518 Human
SwissProt: Q91ZQ5 Mouse
SwissProt: O70276 Rat
Unigene: 2133 Human
Unigene: 131708 Mouse
Unigene: 76724 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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