RPE65
entrez
6121
canonical
uniprot
Q16518
canonical
ensembl
ENSG00000116745
resolver
ensp
ENSP00000262340
resolver
ensp
ENSP00000519234
resolver
enst
ENST00000262340
resolver
genesymbol
RPE65
resolver
hgnc
HGNC:10294
resolver
uniprot
A8K1L0
resolver
uniprot
Q5T9U3
resolver
uniprot_entry
RPE65_HUMAN
resolver
uniprot_sec
A8K1L0
resolver
uniprot_sec
Q5T9U3
resolver
amino_acid_sequence
MSIQVEHPAGGYKKLFETVEELSSPLTAHVTGRIPLWLTGSLLRCGPGLFEVGSEPFYHLFDGQALLHKFDFKEGHVTYHRRFIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSRFFSYFRGVEVTDNALVNVYPVGEDYYACTETNFITKINPETLETIKQVDLCNYVSVNGATAHPHIENDGTVYNIGNCFGKNFSIAYNIVKIPPLQADKEDPISKSEIVVQFPCSDRFKPSYVHSFGLTPNYIVFVETPVKINLFKFLSSWSLWGANYMDCFESNETMGVWLHIADKKRKKYLNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKGFEFVYNYLYLANLRENWEEVKKNARKAPQPEVRRYVLPLNIDKADTGKNLVTLPNTTATAILCSDETIWLEPEVLFSGPRQAFEFPQINYQKYCGKPYTYAYGLGLNHFVPDRLCKLNVKTKETWVWQEPDSYPSEPIFVSHPDALEEDDGVVLSVVVSPGAGQKPAYLLILNAKDLSEVARAEVEINIPVTFHGLFKKS
uniprot
proteins
disease_involvement
DISEASE: Leber congenital amaurosis 2 (LCA2) [MIM:204100]: 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. {ECO:0000269|PubMed:10090910, ECO:0000269|PubMed:10766140, ECO:0000269|PubMed:11462243, ECO:0000269|PubMed:14611946, ECO:0000269|PubMed:14962443, ECO:0000269|PubMed:15024725, ECO:0000269|PubMed:16205573, ECO:0000269|PubMed:17297704, ECO:0000269|PubMed:17724218, ECO:0000269|PubMed:17964524, ECO:0000269|PubMed:18682808, ECO:0000269|PubMed:19431183, ECO:0000269|PubMed:21602930, ECO:0000269|PubMed:22509104, ECO:0000269|PubMed:28418496, ECO:0000269|PubMed:9326927, ECO:0000269|PubMed:9326941, ECO:0000269|PubMed:9801879}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Retinitis pigmentosa 20 (RP20) [MIM:613794]: 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. {ECO:0000269|PubMed:11095629, ECO:0000269|PubMed:12960219, ECO:0000269|PubMed:15557452, ECO:0000269|PubMed:19431183, ECO:0000269|PubMed:22334370, ECO:0000269|PubMed:23878505, ECO:0000269|PubMed:9501220}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Retinitis pigmentosa 87 with choroidal involvement (RP87) [MIM:618697]: 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. {ECO:0000269|PubMed:21654732, ECO:0000269|PubMed:27307694, ECO:0000269|PubMed:29659842, ECO:0000269|PubMed:30628748}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.1.1.64
uniprot
proteins
ec_number
5.3.3.22
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:Q28175, ECO:0000269|PubMed:16116091, ECO:0000269|PubMed:17848510, ECO:0000269|PubMed:28874556}.
uniprot
proteins
mass_dalton
60948
uniprot
proteins
mutagenesis
MUTAGEN 39; /note="T->R: Does not affect isomerohydrolase activity."; /evidence="ECO:0000269|PubMed:25112876"; MUTAGEN 106; /note="C->A: No loss of enzymatic activity. No effect on palmitoylation. No loss of membrane association."; /evidence="ECO:0000269|PubMed:19049981"; MUTAGEN 106; /note="C->Y: Does not affect isomerohydrolase activity."; /evidence="ECO:0000269|PubMed:25112876"; MUTAGEN 112; /note="C->A: Loss of enzymatic activity. No palmitoylation. Loss of membrane association."; /evidence="ECO:0000269|PubMed:19049981"; MUTAGEN 170; /note="N->K: Increased isomerohydrolase activity."; /evidence="ECO:0000269|PubMed:25112876"; MUTAGEN 180; /note="H->A: Loss of enzymatic activity."; /evidence="ECO:0000269|PubMed:16198348"; MUTAGEN 241; /note="H->A: Decreasing protein levels. Loss of enzymatic activity. Significantly decreased protein stability."; /evidence="ECO:0000269|PubMed:16198348"; MUTAGEN 297; /note="K->G: Increased isomerohydrolase activity."; /evidence="ECO:0000269|PubMed:25112876"; MUTAGEN 313; /note="H->A: Decreasing protein levels. Loss of enzymatic activity. Significantly decreased protein stability."; /evidence="ECO:0000269|PubMed:16198348"; MUTAGEN 330; /note="C->T: Does not affect isomerohydrolase activity."; /evidence="ECO:0000269|PubMed:25112876"; MUTAGEN 469; /note="E->A: Decreasing protein levels. Loss of enzymatic activity."; /evidence="ECO:0000269|PubMed:16198348"; MUTAGEN 469; /note="E->Q: Decreasing protein levels. Loss of enzymatic activity."; /evidence="ECO:0000269|PubMed:16198348"; MUTAGEN 497; /note="Q->P: Does not affect isomerohydrolase activity."; /evidence="ECO:0000269|PubMed:25112876"; MUTAGEN 510; /note="L->M: Does not affect isomerohydrolase activity."; /evidence="ECO:0000269|PubMed:25112876"; MUTAGEN 527; /note="H->A: Decreasing protein levels. Loss of enzymatic activity. Significantly decreased protein stability."; /evidence="ECO:0000269|PubMed:16198348"; MUTAGEN 533; /note="S->A: Does not affect isomerohydrolase activity."; /evidence="ECO:0000269|PubMed:25112876
uniprot
proteins
post_translational_modification
PTM: 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). {ECO:0000250|UniProtKB:Q28175}.
uniprot
proteins
protein_family
Carotenoid oxygenase family
uniprot
proteins
pubmed
10090910
uniprot
proteins
pubmed
10766140
uniprot
proteins
pubmed
11095629
uniprot
proteins
pubmed
11462243
uniprot
proteins
pubmed
12960219
uniprot
proteins
pubmed
14611946
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14962443
uniprot
proteins
pubmed
15024725
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15557452
uniprot
proteins
pubmed
16116091
uniprot
proteins
pubmed
16198348
uniprot
proteins
pubmed
16205573
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17297704
uniprot
proteins
pubmed
17724218
uniprot
proteins
pubmed
17848510
uniprot
proteins
pubmed
17964524
uniprot
proteins
pubmed
18682808
uniprot
proteins
pubmed
19049981
uniprot
proteins
pubmed
19431183
uniprot
proteins
pubmed
21493626
uniprot
proteins
pubmed
21602930
uniprot
proteins
pubmed
21654732
uniprot
proteins
pubmed
22334370
uniprot
proteins
pubmed
22509104
uniprot
proteins
pubmed
23878505
uniprot
proteins
pubmed
25112876
uniprot
proteins
pubmed
27307694
uniprot
proteins
pubmed
27535533
uniprot
proteins
pubmed
28418496
uniprot
proteins
pubmed
28874556
uniprot
proteins
pubmed
29659842
uniprot
proteins
pubmed
30628748
uniprot
proteins
pubmed
7633413
uniprot
proteins
pubmed
9326927
uniprot
proteins
pubmed
9326941
uniprot
proteins
pubmed
9501220
uniprot
proteins
pubmed
9801879
uniprot
proteins
sequence_length
533
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:A9C3R9}. Cell membrane {ECO:0000269|PubMed:19049981}; Lipid-anchor {ECO:0000269|PubMed:19049981}. Microsome membrane {ECO:0000250|UniProtKB:Q28175}. Note=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. {ECO:0000269|PubMed:19049981, ECO:0000269|PubMed:21493626}.
uniprot
proteins