UniProtKB - Q16518 (RPE65_HUMAN)
Protein
Retinoid isomerohydrolase
Gene
RPE65
Organism
Homo sapiens (Human)
Status
Functioni
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).By similarity3 Publications
Catalytic activityi
Cofactori
Fe2+By similarityNote: Binds 1 Fe2+ ion per subunit.By similarity
Kineticsi
- KM=0.35 µM for all-trans-retinyl palmitate1 Publication
- Vmax=21 pmol/min/mg enzyme for all-trans-retinyl palmitate as substrate1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 180 | Iron; catalyticBy similarity | 1 | |
Metal bindingi | 241 | Iron; catalyticBy similarity | 1 | |
Metal bindingi | 313 | Iron; catalyticBy similarity | 1 | |
Metal bindingi | 527 | Iron; catalyticBy similarity | 1 |
GO - Molecular functioni
- all-trans-retinyl-ester hydrolase, 11-cis retinol forming activity Source: AgBase
- all-trans-retinyl-palmitate hydrolase, 11-cis retinol forming activity Source: UniProtKB
- cardiolipin binding Source: AgBase
- isomerase activity Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
- oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Source: InterPro
- phosphatidylcholine binding Source: AgBase
- phosphatidylserine binding Source: AgBase
- retinal isomerase activity Source: UniProtKB
- retinol isomerase activity Source: GO_Central
GO - Biological processi
- cellular response to electrical stimulus Source: Ensembl
- circadian rhythm Source: Ensembl
- detection of light stimulus involved in visual perception Source: UniProtKB
- insulin receptor signaling pathway Source: Ensembl
- neural retina development Source: Ensembl
- regulation of rhodopsin gene expression Source: Ensembl
- retina homeostasis Source: UniProtKB
- retinal metabolic process Source: Ensembl
- retina morphogenesis in camera-type eye Source: Ensembl
- retinoid metabolic process Source: UniProtKB
- visual perception Source: ProtInc
- vitamin A metabolic process Source: ProtInc
- zeaxanthin biosynthetic process Source: UniProtKB
Keywordsi
Molecular function | Hydrolase, Isomerase |
Biological process | Sensory transduction, Vision |
Ligand | Iron, Metal-binding |
Enzyme and pathway databases
BioCyci | MetaCyc:ENSG00000116745-MONOMER |
PathwayCommonsi | Q16518 |
Reactomei | R-HSA-2453902, The canonical retinoid cycle in rods (twilight vision) |
Chemistry databases
SwissLipidsi | SLP:000000687 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:RPE65Imported |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:10294, RPE65 |
MIMi | 180069, gene |
neXtProti | NX_Q16518 |
VEuPathDBi | HostDB:ENSG00000116745.6 |
Subcellular locationi
Endoplasmic reticulum
- Microsome membrane By similarity
Plasma membrane
- Cell membrane 1 Publication; Lipid-anchor 1 Publication
Other locations
- Cytoplasm By similarity
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.2 Publications
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: UniProtKB
Nucleus
- nucleus Source: Ensembl
Plasma Membrane
- plasma membrane Source: Reactome
Other locations
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Endoplasmic reticulum, Membrane, MicrosomePathology & Biotechi
Involvement in diseasei
Leber congenital amaurosis 2 (LCA2)18 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_017126 | 22 | L → P in LCA2. 2 PublicationsCorresponds to variant dbSNP:rs61751277EnsemblClinVar. | 1 | |
Natural variantiVAR_060808 | 36 – 38 | Missing in LCA2. 1 Publication | 3 | |
Natural variantiVAR_081684 | 40 | G → D in LCA2. 1 Publication | 1 | |
Natural variantiVAR_017127 | 40 | G → S in LCA2; reduced protein levels; decreased function in the retinoid cycle. 3 PublicationsCorresponds to variant dbSNP:rs61751281EnsemblClinVar. | 1 | |
Natural variantiVAR_017128 | 44 | R → Q in LCA2; severely decreased retinol isomerase activity. 3 PublicationsCorresponds to variant dbSNP:rs61751282EnsemblClinVar. | 1 | |
Natural variantiVAR_070172 | 67 | L → R in LCA2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1344724754Ensembl. | 1 | |
Natural variantiVAR_017129 | 68 | H → Y in LCA2. 1 PublicationCorresponds to variant dbSNP:rs61752866EnsemblClinVar. | 1 | |
Natural variantiVAR_067160 | 70 | F → V in LCA2 and RP20. 2 Publications | 1 | |
Natural variantiVAR_067161 | 91 | R → P in LCA2. 1 PublicationCorresponds to variant dbSNP:rs61752873EnsemblClinVar. | 1 | |
Natural variantiVAR_017131 | 91 | R → Q in LCA2; severely decreased retinol isomerase activity. 2 PublicationsCorresponds to variant dbSNP:rs61752873EnsemblClinVar. | 1 | |
Natural variantiVAR_017130 | 91 | R → W in RP20 and LCA2; reduced protein levels; decreased function in the retinoid cycle. 6 PublicationsCorresponds to variant dbSNP:rs61752871EnsemblClinVar. | 1 | |
Natural variantiVAR_067162 | 99 | V → I in LCA2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs143056561EnsemblClinVar. | 1 | |
Natural variantiVAR_083292 | 101 | T → I in LCA2; severely decreased retinol isomerase activity. 2 PublicationsCorresponds to variant dbSNP:rs1444234037Ensembl. | 1 | |
Natural variantiVAR_060812 | 102 | E → K in RP20 and LCA2. 2 PublicationsCorresponds to variant dbSNP:rs62642584EnsemblClinVar. | 1 | |
Natural variantiVAR_083293 | 118 | R → S in LCA2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs61752876Ensembl. | 1 | |
Natural variantiVAR_017133 | 144 | Y → D in LCA2. 2 PublicationsCorresponds to variant dbSNP:rs61752880EnsemblClinVar. | 1 | |
Natural variantiVAR_060813 | 148 | E → D in LCA2. 1 PublicationCorresponds to variant dbSNP:rs61752882EnsemblClinVar. | 1 | |
Natural variantiVAR_083294 | 162 | T → P in LCA2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs774309607Ensembl. | 1 | |
Natural variantiVAR_060814 | 167 | D → Y in RP20 and LCA2. 2 PublicationsCorresponds to variant dbSNP:rs61752883EnsemblClinVar. | 1 | |
Natural variantiVAR_060815 | 182 | H → N in LCA2. 1 PublicationCorresponds to variant dbSNP:rs61752884EnsemblClinVar. | 1 | |
Natural variantiVAR_017134 | 182 | H → Y in LCA2. 2 PublicationsCorresponds to variant dbSNP:rs61752884EnsemblClinVar. | 1 | |
Natural variantiVAR_080043 | 234 – 533 | Missing in LCA2; unknown pathological significance. 1 PublicationAdd BLAST | 300 | |
Natural variantiVAR_060816 | 239 | Y → D in LCA2 and RP20; severely decreased retinol isomerase activity. 3 PublicationsCorresponds to variant dbSNP:rs61752896EnsemblClinVar. | 1 | |
Natural variantiVAR_017135 | 287 | V → F in LCA2. 1 PublicationCorresponds to variant dbSNP:rs281865289EnsemblClinVar. | 1 | |
Natural variantiVAR_067163 | 313 | H → R in LCA2. 1 PublicationCorresponds to variant dbSNP:rs1375943362Ensembl. | 1 | |
Natural variantiVAR_083295 | 318 | Y → N in LCA2; severely decreased retinol isomerase activity. 2 PublicationsCorresponds to variant dbSNP:rs61752905EnsemblClinVar. | 1 | |
Natural variantiVAR_060818 | 330 | C → Y in LCA2. 2 PublicationsCorresponds to variant dbSNP:rs61752908EnsemblClinVar. | 1 | |
Natural variantiVAR_067164 | 333 | G → R in LCA2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1459522532Ensembl. | 1 | |
Natural variantiVAR_017138 | 363 | P → T in LCA2. 3 PublicationsCorresponds to variant dbSNP:rs121917744EnsemblClinVar. | 1 | |
Natural variantiVAR_070173 | 368 | Y → C in LCA2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs62653012EnsemblClinVar. | 1 | |
Natural variantiVAR_060819 | 393 | A → E in LCA2. 1 Publication | 1 | |
Natural variantiVAR_017140 | 393 | A → G in LCA2. 1 PublicationCorresponds to variant dbSNP:rs62635773EnsemblClinVar. | 1 | |
Natural variantiVAR_083296 | 402 – 533 | Missing in LCA2. 1 PublicationAdd BLAST | 132 | |
Natural variantiVAR_083297 | 408 | L → P in LCA2; severely decreased retinol isomerase activity. 2 PublicationsCorresponds to variant dbSNP:rs62636298EnsemblClinVar. | 1 | |
Natural variantiVAR_017141 | 417 | E → Q in LCA2. 1 PublicationCorresponds to variant dbSNP:rs62636299EnsemblClinVar. | 1 | |
Natural variantiVAR_018151 | 431 | Y → C in LCA2. 1 PublicationCorresponds to variant dbSNP:rs62636300EnsemblClinVar. | 1 | |
Natural variantiVAR_034477 | 434 | A → V in LCA2; benign variant; no effect on retinol isomerase activity. 3 PublicationsCorresponds to variant dbSNP:rs34627040EnsemblClinVar. | 1 | |
Natural variantiVAR_060820 | 435 | Y → C in LCA2. 1 PublicationCorresponds to variant dbSNP:rs62636302EnsemblClinVar. | 1 | |
Natural variantiVAR_083298 | 443 | V → A in LCA2; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_083299 | 460 – 533 | Missing in LCA2. 1 PublicationAdd BLAST | 74 | |
Natural variantiVAR_060822 | 470 | P → L in LCA2. 1 PublicationCorresponds to variant dbSNP:rs774211361Ensembl. | 1 | |
Natural variantiVAR_083300 | 533 | S → T in LCA2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs577335767Ensembl. | 1 |
Retinitis pigmentosa 20 (RP20)7 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_071672 | 60 | L → P in RP20. 1 PublicationCorresponds to variant dbSNP:rs1266217912Ensembl. | 1 | |
Natural variantiVAR_067160 | 70 | F → V in LCA2 and RP20. 2 Publications | 1 | |
Natural variantiVAR_060809 | 79 | Y → H in RP20. 1 PublicationCorresponds to variant dbSNP:rs61752869EnsemblClinVar. | 1 | |
Natural variantiVAR_060810 | 85 | R → H in RP20; uncertain pathological significance. 1 PublicationCorresponds to variant dbSNP:rs61752870EnsemblClinVar. | 1 | |
Natural variantiVAR_017130 | 91 | R → W in RP20 and LCA2; reduced protein levels; decreased function in the retinoid cycle. 6 PublicationsCorresponds to variant dbSNP:rs61752871EnsemblClinVar. | 1 | |
Natural variantiVAR_060811 | 95 | E → Q in RP20. 1 PublicationCorresponds to variant dbSNP:rs61752874EnsemblClinVar. | 1 | |
Natural variantiVAR_060812 | 102 | E → K in RP20 and LCA2. 2 PublicationsCorresponds to variant dbSNP:rs62642584EnsemblClinVar. | 1 | |
Natural variantiVAR_017132 | 132 | A → T in RP20; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs61752878EnsemblClinVar. | 1 | |
Natural variantiVAR_060814 | 167 | D → Y in RP20 and LCA2. 2 PublicationsCorresponds to variant dbSNP:rs61752883EnsemblClinVar. | 1 | |
Natural variantiVAR_060816 | 239 | Y → D in LCA2 and RP20; severely decreased retinol isomerase activity. 3 PublicationsCorresponds to variant dbSNP:rs61752896EnsemblClinVar. | 1 | |
Natural variantiVAR_060817 | 294 | K → T in RP20; likely benign variant; very mild decrease of retinol isomerase activity. 2 PublicationsCorresponds to variant dbSNP:rs61752901EnsemblClinVar. | 1 | |
Natural variantiVAR_017137 | 341 | L → S in RP20. 1 PublicationCorresponds to variant dbSNP:rs61752909EnsemblClinVar. | 1 | |
Natural variantiVAR_017139 | 368 | Y → H in RP20. 2 PublicationsCorresponds to variant dbSNP:rs62653011EnsemblClinVar. | 1 | |
Natural variantiVAR_060821 | 436 | G → V in RP20. 1 PublicationCorresponds to variant dbSNP:rs62637002EnsemblClinVar. | 1 | |
Natural variantiVAR_017142 | 452 | V → G in RP20. 1 PublicationCorresponds to variant dbSNP:rs62637004EnsemblClinVar. | 1 | |
Natural variantiVAR_060823 | 473 | V → D in RP20. 3 PublicationsCorresponds to variant dbSNP:rs62637007EnsemblClinVar. | 1 | |
Natural variantiVAR_037619 | 515 | R → W in RP20; this mutation has been found in compound heterozygosity in LCA2. 1 PublicationCorresponds to variant dbSNP:rs121917745EnsemblClinVar. | 1 | |
Natural variantiVAR_060824 | 528 | G → V in RP20. 1 PublicationCorresponds to variant dbSNP:rs1193631220EnsemblClinVar. | 1 |
Retinitis pigmentosa 87 with choroidal involvement (RP87)4 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_067757 | 477 | D → G in RP87; unknown pathological significance; does not affect protein abundance; does not affect subcellular localization; does not affect isomerization activity; may cause abnormal splicing mRNAs thereby decreasing protein levels. 4 Publications | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 39 | T → R: Does not affect isomerohydrolase activity. 1 Publication | 1 | |
Mutagenesisi | 106 | C → A: No loss of enzymatic activity. No effect on palmitoylation. No loss of membrane association. 1 Publication | 1 | |
Mutagenesisi | 106 | C → Y: Does not affect isomerohydrolase activity. 1 Publication | 1 | |
Mutagenesisi | 112 | C → A: Loss of enzymatic activity. No palmitoylation. Loss of membrane association. 1 Publication | 1 | |
Mutagenesisi | 170 | N → K: Increased isomerohydrolase activity. 1 Publication | 1 | |
Mutagenesisi | 180 | H → A: Loss of enzymatic activity. 1 Publication | 1 | |
Mutagenesisi | 241 | H → A: Decreasing protein levels. Loss of enzymatic activity. Significantly decreased protein stability. 1 Publication | 1 | |
Mutagenesisi | 297 | K → G: Increased isomerohydrolase activity. 1 Publication | 1 | |
Mutagenesisi | 313 | H → A: Decreasing protein levels. Loss of enzymatic activity. Significantly decreased protein stability. 1 Publication | 1 | |
Mutagenesisi | 330 | C → T: Does not affect isomerohydrolase activity. 1 Publication | 1 | |
Mutagenesisi | 469 | E → A: Decreasing protein levels. Loss of enzymatic activity. 1 Publication | 1 | |
Mutagenesisi | 469 | E → Q: Decreasing protein levels. Loss of enzymatic activity. 1 Publication | 1 | |
Mutagenesisi | 497 | Q → P: Does not affect isomerohydrolase activity. 1 Publication | 1 | |
Mutagenesisi | 510 | L → M: Does not affect isomerohydrolase activity. 1 Publication | 1 | |
Mutagenesisi | 527 | H → A: Decreasing protein levels. Loss of enzymatic activity. Significantly decreased protein stability. 1 Publication | 1 | |
Mutagenesisi | 533 | S → A: Does not affect isomerohydrolase activity. 1 Publication | 1 |
Keywords - Diseasei
Disease variant, Leber congenital amaurosis, Retinitis pigmentosaOrganism-specific databases
DisGeNETi | 6121 |
GeneReviewsi | RPE65 |
MalaCardsi | RPE65 |
MIMi | 204100, phenotype 613794, phenotype 618697, phenotype |
OpenTargetsi | ENSG00000116745 |
Orphaneti | 65, Leber congenital amaurosis 791, Retinitis pigmentosa 364055, Severe early-childhood-onset retinal dystrophy |
PharmGKBi | PA34655 |
Miscellaneous databases
Pharosi | Q16518, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3831182 |
DrugBanki | DB13932, Voretigene neparvovec |
Genetic variation databases
BioMutai | RPE65 |
DMDMi | 44888872 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedBy similarity | |||
ChainiPRO_0000143943 | 2 – 533 | Retinoid isomerohydrolaseAdd BLAST | 532 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylserineBy similarity | 1 | |
Modified residuei | 101 | Phosphothreonine1 Publication | 1 | |
Modified residuei | 105 | Phosphothreonine1 Publication | 1 | |
Lipidationi | 112 | S-palmitoyl cysteine; in membrane form1 Publication | 1 | |
Modified residuei | 113 | N6-acetyllysine1 Publication | 1 | |
Modified residuei | 117 | Phosphoserine1 Publication | 1 | |
Lipidationi | 231 | S-palmitoyl cysteine; in membrane formBy similarity | 1 | |
Lipidationi | 329 | S-palmitoyl cysteine; in membrane formBy similarity | 1 | |
Lipidationi | 330 | S-palmitoyl cysteine; in membrane formBy similarity | 1 |
Post-translational modificationi
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).By similarity
Keywords - PTMi
Acetylation, Lipoprotein, Palmitate, PhosphoproteinProteomic databases
MassIVEi | Q16518 |
PaxDbi | Q16518 |
PeptideAtlasi | Q16518 |
PRIDEi | Q16518 |
ProteomicsDBi | 60891 |
PTM databases
iPTMneti | Q16518 |
PhosphoSitePlusi | Q16518 |
SwissPalmi | Q16518 |
Expressioni
Tissue specificityi
Retina (at protein level). Retinal pigment epithelium specific.2 Publications
Gene expression databases
Bgeei | ENSG00000116745, Expressed in pigmented layer of retina and 77 other tissues |
Genevisiblei | Q16518, HS |
Organism-specific databases
HPAi | ENSG00000116745, Tissue enriched (retina) |
Interactioni
Subunit structurei
Interacts with MYO7A; this mediates light-dependent intracellular transport of RPE65.
1 PublicationProtein-protein interaction databases
BioGRIDi | 112041, 10 interactors |
IntActi | Q16518, 4 interactors |
STRINGi | 9606.ENSP00000262340 |
Chemistry databases
BindingDBi | Q16518 |
Miscellaneous databases
RNActi | Q16518, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the carotenoid oxygenase family.Curated
Phylogenomic databases
eggNOGi | KOG1285, Eukaryota |
GeneTreei | ENSGT00950000182913 |
HOGENOMi | CLU_016472_1_1_1 |
InParanoidi | Q16518 |
OMAi | GPGLWNL |
OrthoDBi | 895046at2759 |
PhylomeDBi | Q16518 |
TreeFami | TF314019 |
Family and domain databases
InterProi | View protein in InterPro IPR004294, Carotenoid_Oase |
PANTHERi | PTHR10543, PTHR10543, 1 hit |
Pfami | View protein in Pfam PF03055, RPE65, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
Q16518-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MSIQVEHPAG GYKKLFETVE ELSSPLTAHV TGRIPLWLTG SLLRCGPGLF
60 70 80 90 100
EVGSEPFYHL FDGQALLHKF DFKEGHVTYH RRFIRTDAYV RAMTEKRIVI
110 120 130 140 150
TEFGTCAFPD PCKNIFSRFF SYFRGVEVTD NALVNVYPVG EDYYACTETN
160 170 180 190 200
FITKINPETL ETIKQVDLCN YVSVNGATAH PHIENDGTVY NIGNCFGKNF
210 220 230 240 250
SIAYNIVKIP PLQADKEDPI SKSEIVVQFP CSDRFKPSYV HSFGLTPNYI
260 270 280 290 300
VFVETPVKIN LFKFLSSWSL WGANYMDCFE SNETMGVWLH IADKKRKKYL
310 320 330 340 350
NNKYRTSPFN LFHHINTYED NGFLIVDLCC WKGFEFVYNY LYLANLRENW
360 370 380 390 400
EEVKKNARKA PQPEVRRYVL PLNIDKADTG KNLVTLPNTT ATAILCSDET
410 420 430 440 450
IWLEPEVLFS GPRQAFEFPQ INYQKYCGKP YTYAYGLGLN HFVPDRLCKL
460 470 480 490 500
NVKTKETWVW QEPDSYPSEP IFVSHPDALE EDDGVVLSVV VSPGAGQKPA
510 520 530
YLLILNAKDL SEVARAEVEI NIPVTFHGLF KKS
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 254 | E → G in BAF82614 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 274 | N → D in BAF82614 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_017126 | 22 | L → P in LCA2. 2 PublicationsCorresponds to variant dbSNP:rs61751277EnsemblClinVar. | 1 | |
Natural variantiVAR_060808 | 36 – 38 | Missing in LCA2. 1 Publication | 3 | |
Natural variantiVAR_081684 | 40 | G → D in LCA2. 1 Publication | 1 | |
Natural variantiVAR_017127 | 40 | G → S in LCA2; reduced protein levels; decreased function in the retinoid cycle. 3 PublicationsCorresponds to variant dbSNP:rs61751281EnsemblClinVar. | 1 | |
Natural variantiVAR_017128 | 44 | R → Q in LCA2; severely decreased retinol isomerase activity. 3 PublicationsCorresponds to variant dbSNP:rs61751282EnsemblClinVar. | 1 | |
Natural variantiVAR_071672 | 60 | L → P in RP20. 1 PublicationCorresponds to variant dbSNP:rs1266217912Ensembl. | 1 | |
Natural variantiVAR_070172 | 67 | L → R in LCA2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1344724754Ensembl. | 1 | |
Natural variantiVAR_017129 | 68 | H → Y in LCA2. 1 PublicationCorresponds to variant dbSNP:rs61752866EnsemblClinVar. | 1 | |
Natural variantiVAR_067160 | 70 | F → V in LCA2 and RP20. 2 Publications | 1 | |
Natural variantiVAR_060809 | 79 | Y → H in RP20. 1 PublicationCorresponds to variant dbSNP:rs61752869EnsemblClinVar. | 1 | |
Natural variantiVAR_060810 | 85 | R → H in RP20; uncertain pathological significance. 1 PublicationCorresponds to variant dbSNP:rs61752870EnsemblClinVar. | 1 | |
Natural variantiVAR_067161 | 91 | R → P in LCA2. 1 PublicationCorresponds to variant dbSNP:rs61752873EnsemblClinVar. | 1 | |
Natural variantiVAR_017131 | 91 | R → Q in LCA2; severely decreased retinol isomerase activity. 2 PublicationsCorresponds to variant dbSNP:rs61752873EnsemblClinVar. | 1 | |
Natural variantiVAR_017130 | 91 | R → W in RP20 and LCA2; reduced protein levels; decreased function in the retinoid cycle. 6 PublicationsCorresponds to variant dbSNP:rs61752871EnsemblClinVar. | 1 | |
Natural variantiVAR_060811 | 95 | E → Q in RP20. 1 PublicationCorresponds to variant dbSNP:rs61752874EnsemblClinVar. | 1 | |
Natural variantiVAR_067162 | 99 | V → I in LCA2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs143056561EnsemblClinVar. | 1 | |
Natural variantiVAR_083292 | 101 | T → I in LCA2; severely decreased retinol isomerase activity. 2 PublicationsCorresponds to variant dbSNP:rs1444234037Ensembl. | 1 | |
Natural variantiVAR_060812 | 102 | E → K in RP20 and LCA2. 2 PublicationsCorresponds to variant dbSNP:rs62642584EnsemblClinVar. | 1 | |
Natural variantiVAR_083293 | 118 | R → S in LCA2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs61752876Ensembl. | 1 | |
Natural variantiVAR_017132 | 132 | A → T in RP20; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs61752878EnsemblClinVar. | 1 | |
Natural variantiVAR_017133 | 144 | Y → D in LCA2. 2 PublicationsCorresponds to variant dbSNP:rs61752880EnsemblClinVar. | 1 | |
Natural variantiVAR_060813 | 148 | E → D in LCA2. 1 PublicationCorresponds to variant dbSNP:rs61752882EnsemblClinVar. | 1 | |
Natural variantiVAR_083294 | 162 | T → P in LCA2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs774309607Ensembl. | 1 | |
Natural variantiVAR_060814 | 167 | D → Y in RP20 and LCA2. 2 PublicationsCorresponds to variant dbSNP:rs61752883EnsemblClinVar. | 1 | |
Natural variantiVAR_060815 | 182 | H → N in LCA2. 1 PublicationCorresponds to variant dbSNP:rs61752884EnsemblClinVar. | 1 | |
Natural variantiVAR_017134 | 182 | H → Y in LCA2. 2 PublicationsCorresponds to variant dbSNP:rs61752884EnsemblClinVar. | 1 | |
Natural variantiVAR_080043 | 234 – 533 | Missing in LCA2; unknown pathological significance. 1 PublicationAdd BLAST | 300 | |
Natural variantiVAR_060816 | 239 | Y → D in LCA2 and RP20; severely decreased retinol isomerase activity. 3 PublicationsCorresponds to variant dbSNP:rs61752896EnsemblClinVar. | 1 | |
Natural variantiVAR_017135 | 287 | V → F in LCA2. 1 PublicationCorresponds to variant dbSNP:rs281865289EnsemblClinVar. | 1 | |
Natural variantiVAR_060817 | 294 | K → T in RP20; likely benign variant; very mild decrease of retinol isomerase activity. 2 PublicationsCorresponds to variant dbSNP:rs61752901EnsemblClinVar. | 1 | |
Natural variantiVAR_067163 | 313 | H → R in LCA2. 1 PublicationCorresponds to variant dbSNP:rs1375943362Ensembl. | 1 | |
Natural variantiVAR_083295 | 318 | Y → N in LCA2; severely decreased retinol isomerase activity. 2 PublicationsCorresponds to variant dbSNP:rs61752905EnsemblClinVar. | 1 | |
Natural variantiVAR_017136 | 321 | N → K No effect on retinol isomerase activity. 4 PublicationsCorresponds to variant dbSNP:rs149916178EnsemblClinVar. | 1 | |
Natural variantiVAR_060818 | 330 | C → Y in LCA2. 2 PublicationsCorresponds to variant dbSNP:rs61752908EnsemblClinVar. | 1 | |
Natural variantiVAR_067164 | 333 | G → R in LCA2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1459522532Ensembl. | 1 | |
Natural variantiVAR_017137 | 341 | L → S in RP20. 1 PublicationCorresponds to variant dbSNP:rs61752909EnsemblClinVar. | 1 | |
Natural variantiVAR_017138 | 363 | P → T in LCA2. 3 PublicationsCorresponds to variant dbSNP:rs121917744EnsemblClinVar. | 1 | |
Natural variantiVAR_070173 | 368 | Y → C in LCA2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs62653012EnsemblClinVar. | 1 | |
Natural variantiVAR_017139 | 368 | Y → H in RP20. 2 PublicationsCorresponds to variant dbSNP:rs62653011EnsemblClinVar. | 1 | |
Natural variantiVAR_060819 | 393 | A → E in LCA2. 1 Publication | 1 | |
Natural variantiVAR_017140 | 393 | A → G in LCA2. 1 PublicationCorresponds to variant dbSNP:rs62635773EnsemblClinVar. | 1 | |
Natural variantiVAR_083296 | 402 – 533 | Missing in LCA2. 1 PublicationAdd BLAST | 132 | |
Natural variantiVAR_083297 | 408 | L → P in LCA2; severely decreased retinol isomerase activity. 2 PublicationsCorresponds to variant dbSNP:rs62636298EnsemblClinVar. | 1 | |
Natural variantiVAR_017141 | 417 | E → Q in LCA2. 1 PublicationCorresponds to variant dbSNP:rs62636299EnsemblClinVar. | 1 | |
Natural variantiVAR_018151 | 431 | Y → C in LCA2. 1 PublicationCorresponds to variant dbSNP:rs62636300EnsemblClinVar. | 1 | |
Natural variantiVAR_034477 | 434 | A → V in LCA2; benign variant; no effect on retinol isomerase activity. 3 PublicationsCorresponds to variant dbSNP:rs34627040EnsemblClinVar. | 1 | |
Natural variantiVAR_060820 | 435 | Y → C in LCA2. 1 PublicationCorresponds to variant dbSNP:rs62636302EnsemblClinVar. | 1 | |
Natural variantiVAR_060821 | 436 | G → V in RP20. 1 PublicationCorresponds to variant dbSNP:rs62637002EnsemblClinVar. | 1 | |
Natural variantiVAR_083298 | 443 | V → A in LCA2; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_017142 | 452 | V → G in RP20. 1 PublicationCorresponds to variant dbSNP:rs62637004EnsemblClinVar. | 1 | |
Natural variantiVAR_083299 | 460 – 533 | Missing in LCA2. 1 PublicationAdd BLAST | 74 | |
Natural variantiVAR_060822 | 470 | P → L in LCA2. 1 PublicationCorresponds to variant dbSNP:rs774211361Ensembl. | 1 | |
Natural variantiVAR_060823 | 473 | V → D in RP20. 3 PublicationsCorresponds to variant dbSNP:rs62637007EnsemblClinVar. | 1 | |
Natural variantiVAR_067757 | 477 | D → G in RP87; unknown pathological significance; does not affect protein abundance; does not affect subcellular localization; does not affect isomerization activity; may cause abnormal splicing mRNAs thereby decreasing protein levels. 4 Publications | 1 | |
Natural variantiVAR_037619 | 515 | R → W in RP20; this mutation has been found in compound heterozygosity in LCA2. 1 PublicationCorresponds to variant dbSNP:rs121917745EnsemblClinVar. | 1 | |
Natural variantiVAR_060824 | 528 | G → V in RP20. 1 PublicationCorresponds to variant dbSNP:rs1193631220EnsemblClinVar. | 1 | |
Natural variantiVAR_083300 | 533 | S → T in LCA2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs577335767Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U18991 mRNA Translation: AAA99012.1 U20510 , U20476, U20477, U20478, U20479, U20481, U20482, U20484, U20485, U20486 Genomic DNA Translation: AAC14586.1 AF039868 , AF039855, AF039856, AF039857, AF039858, AF039859, AF039860, AF039861, AF039862, AF039863, AF039864, AF039865, AF039866, AF039867 Genomic DNA Translation: AAC39660.1 AK289925 mRNA Translation: BAF82614.1 AL139413 Genomic DNA No translation available. CH471059 Genomic DNA Translation: EAX06478.1 BC075035 mRNA Translation: AAH75035.1 BC075036 mRNA Translation: AAH75036.1 |
CCDSi | CCDS643.1 |
RefSeqi | NP_000320.1, NM_000329.2 |
Genome annotation databases
Ensembli | ENST00000262340; ENSP00000262340; ENSG00000116745 |
GeneIDi | 6121 |
KEGGi | hsa:6121 |
UCSCi | uc001dei.2, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
Mutations of the RPE65 gene Retina International's Scientific Newsletter |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U18991 mRNA Translation: AAA99012.1 U20510 , U20476, U20477, U20478, U20479, U20481, U20482, U20484, U20485, U20486 Genomic DNA Translation: AAC14586.1 AF039868 , AF039855, AF039856, AF039857, AF039858, AF039859, AF039860, AF039861, AF039862, AF039863, AF039864, AF039865, AF039866, AF039867 Genomic DNA Translation: AAC39660.1 AK289925 mRNA Translation: BAF82614.1 AL139413 Genomic DNA No translation available. CH471059 Genomic DNA Translation: EAX06478.1 BC075035 mRNA Translation: AAH75035.1 BC075036 mRNA Translation: AAH75036.1 |
CCDSi | CCDS643.1 |
RefSeqi | NP_000320.1, NM_000329.2 |
3D structure databases
SMRi | Q16518 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 112041, 10 interactors |
IntActi | Q16518, 4 interactors |
STRINGi | 9606.ENSP00000262340 |
Chemistry databases
BindingDBi | Q16518 |
ChEMBLi | CHEMBL3831182 |
DrugBanki | DB13932, Voretigene neparvovec |
SwissLipidsi | SLP:000000687 |
PTM databases
iPTMneti | Q16518 |
PhosphoSitePlusi | Q16518 |
SwissPalmi | Q16518 |
Genetic variation databases
BioMutai | RPE65 |
DMDMi | 44888872 |
Proteomic databases
MassIVEi | Q16518 |
PaxDbi | Q16518 |
PeptideAtlasi | Q16518 |
PRIDEi | Q16518 |
ProteomicsDBi | 60891 |
Protocols and materials databases
Antibodypediai | 33418, 229 antibodies |
Genome annotation databases
Ensembli | ENST00000262340; ENSP00000262340; ENSG00000116745 |
GeneIDi | 6121 |
KEGGi | hsa:6121 |
UCSCi | uc001dei.2, human |
Organism-specific databases
CTDi | 6121 |
DisGeNETi | 6121 |
GeneCardsi | RPE65 |
GeneReviewsi | RPE65 |
HGNCi | HGNC:10294, RPE65 |
HPAi | ENSG00000116745, Tissue enriched (retina) |
MalaCardsi | RPE65 |
MIMi | 180069, gene 204100, phenotype 613794, phenotype 618697, phenotype |
neXtProti | NX_Q16518 |
OpenTargetsi | ENSG00000116745 |
Orphaneti | 65, Leber congenital amaurosis 791, Retinitis pigmentosa 364055, Severe early-childhood-onset retinal dystrophy |
PharmGKBi | PA34655 |
VEuPathDBi | HostDB:ENSG00000116745.6 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1285, Eukaryota |
GeneTreei | ENSGT00950000182913 |
HOGENOMi | CLU_016472_1_1_1 |
InParanoidi | Q16518 |
OMAi | GPGLWNL |
OrthoDBi | 895046at2759 |
PhylomeDBi | Q16518 |
TreeFami | TF314019 |
Enzyme and pathway databases
BioCyci | MetaCyc:ENSG00000116745-MONOMER |
PathwayCommonsi | Q16518 |
Reactomei | R-HSA-2453902, The canonical retinoid cycle in rods (twilight vision) |
Miscellaneous databases
BioGRID-ORCSi | 6121, 20 hits in 866 CRISPR screens |
ChiTaRSi | RPE65, human |
GeneWikii | RPE65 |
GenomeRNAii | 6121 |
Pharosi | Q16518, Tbio |
PROi | PR:Q16518 |
RNActi | Q16518, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000116745, Expressed in pigmented layer of retina and 77 other tissues |
Genevisiblei | Q16518, HS |
Family and domain databases
InterProi | View protein in InterPro IPR004294, Carotenoid_Oase |
PANTHERi | PTHR10543, PTHR10543, 1 hit |
Pfami | View protein in Pfam PF03055, RPE65, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | RPE65_HUMAN | |
Accessioni | Q16518Primary (citable) accession number: Q16518 Secondary accession number(s): A8K1L0, Q5T9U3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 10, 2003 |
Last sequence update: | January 23, 2007 | |
Last modified: | February 10, 2021 | |
This is version 172 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families