Retinoid isomerohydrolase

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. Essential for the production of 11-cis retinal for both rod and cone photoreceptors. Also capable of catalyzing the isomerization of lutein to meso-zeaxanthin an eye-specific carotenoid. 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).

Classification

Family (Pfam)

PF03055 RPE65

InterPro

Carotenoid_Oase

Functional cluster

Mixed Regulatory & Membrane Proteins

Gene Ontology · 23

• GO:0044297 cell body
• GO:0005789 endoplasmic reticulum membrane
• GO:0016020 membrane
• GO:0005634 nucleus
• GO:0005886 plasma membrane
• GO:0052885 all-trans-retinyl-ester hydrolase, 11-cis retinol forming activity
• GO:0052884 all-trans-retinyl-palmitate hydrolase, 11-cis retinol forming activity
• GO:0003834 beta-carotene 15,15'-dioxygenase activity
• GO:1901612 cardiolipin binding
• GO:0016853 isomerase activity
• GO:0046872 metal ion binding
• GO:0031210 phosphatidylcholine binding
• GO:0001786 phosphatidylserine binding
• GO:0050251 retinol isomerase activity
• GO:0007623 circadian rhythm
• GO:0050908 detection of light stimulus involved in visual perception
• GO:0003407 neural retina development
• GO:0001895 retina homeostasis
• GO:0042574 retinal metabolic process
• GO:0001523 retinoid metabolic process
• GO:0007601 visual perception
• GO:0006776 vitamin A metabolic process
• GO:1901827 zeaxanthin biosynthetic process

Disease associations

• Leber congenital amaurosis 2 MONDO:0008765
• retinitis pigmentosa 20 MONDO:0013425
• retinitis pigmentosa 87 with choroidal involvement MONDO:0032873

Drugs targeting this protein · 2

• EMIXUSTAT inhibitor
• EMIXUSTAT HYDROCHLORIDE inhibitor

Related proteins · sequence + function similarity

• Retinoid isomerohydrolase 1.00
• Retinoid isomerohydrolase 1.00
• Retinoid isomerohydrolase 1.00
• Retinoid isomerohydrolase 1.00
• Retinoid isomerohydrolase 0.99
• Retinoid isomerohydrolase 0.98
• Retinoid isomerohydrolase 0.96
• Retinal Mueller cells isomerohydrolase 0.96
• All-trans-retinyl ester 13-cis isomerohydrolase 0.95
• Retinoid isomerohydrolase 0.95
• Retinoid isomerohydrolase 0.93
• Beta,beta-carotene 15,15'-dioxygenase 0.77

Co-cited proteins · studied together in the literature

• Retinoid isomerohydrolase 2 shared papers
• Retinoid isomerohydrolase 1 shared papers
• Tubby-related protein 1 2 shared papers
• Retinoid isomerohydrolase 2 shared papers
• Protein crumbs homolog 1 6 shared papers
• Retinoid isomerohydrolase 1 shared papers
• Bestrophin-1 1 shared papers
• Retinol dehydrogenase 5 1 shared papers
• Aryl-hydrocarbon-interacting protein-like 1 2 shared papers
• Lebercilin 1 shared papers
• Retinal guanylyl cyclase 1 2 shared papers
• Cone-rod homeobox protein 3 shared papers

Literature · 40 cited papers

• Aberrant RNA splicing is the major pathogenic effect in a knock-in mouse model of the dominantly inherited c.1430A>G human RPE65 mutation. Hum. Mutat. · 2019
• Insights into the pathogenesis of dominant retinitis pigmentosa associated with a D477G mutation in RPE65. Hum. Mol. Genet. · 2018
• RPE65 has an additional function as the lutein to meso-zeaxanthin isomerase in the vertebrate eye. Proc. Natl. Acad. Sci. U.S.A. · 2017
• Homozygosity Mapping and Genetic Analysis of Autosomal Recessive Retinal Dystrophies in 144 Consanguineous Pakistani Families. Invest. Ophthalmol. Vis. Sci. · 2017
• Analysis of protein-coding genetic variation in 60,706 humans. Nature · 2016
• The clinical features of retinal disease due to a dominant mutation in RPE65. Mol. Vis. · 2016
• Identification of key residues determining isomerohydrolase activity of human RPE65. J. Biol. Chem. · 2014
• Novel mutations in RPE65 identified in consanguineous Pakistani families with retinal dystrophy. Mol. Vis. · 2013
• Novel RPE65 mutations associated with Leber congenital amaurosis in Chinese patients. Mol. Vis. · 2012
• Next-generation genetic testing for retinitis pigmentosa. Hum. Mutat. · 2012
• A dominant mutation in RPE65 identified by whole-exome sequencing causes retinitis pigmentosa with choroidal involvement. Eur. J. Hum. Genet. · 2011
• Detection of variants in 15 genes in 87 unrelated Chinese patients with Leber congenital amaurosis. PLoS ONE · 2011
• … and 28 more in the literature graph