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Q16518

- RPE65_HUMAN

UniProt

Q16518 - RPE65_HUMAN

Protein

Retinoid isomerohydrolase

Gene

RPE65

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 123 (01 Oct 2014)
      Sequence version 3 (23 Jan 2007)
      Previous versions | rss
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    Functioni

    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.2 Publications

    Catalytic activityi

    An all-trans-retinyl ester + H2O = 11-cis-retinol + a fatty acid.

    Cofactori

    Binds 1 Fe2+ ion per subunit.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi180 – 1801Iron; catalyticBy similarity
    Metal bindingi241 – 2411Iron; catalyticBy similarity
    Metal bindingi313 – 3131Iron; catalyticBy similarity
    Metal bindingi527 – 5271Iron; catalyticBy similarity

    GO - Molecular functioni

    1. all-trans-retinyl-ester hydrolase, 11-cis retinol forming activity Source: UniProtKB-EC
    2. all-trans-retinyl-palmitate hydrolase, 11-cis retinol forming activity Source: UniProtKB-EC
    3. metal ion binding Source: UniProtKB-KW
    4. retinal isomerase activity Source: Ensembl

    GO - Biological processi

    1. cellular response to electrical stimulus Source: Ensembl
    2. detection of light stimulus involved in visual perception Source: UniProt
    3. insulin receptor signaling pathway Source: Ensembl
    4. phototransduction, visible light Source: Reactome
    5. regulation of rhodopsin gene expression Source: Ensembl
    6. retina homeostasis Source: UniProt
    7. retinal metabolic process Source: Ensembl
    8. retina morphogenesis in camera-type eye Source: Ensembl
    9. retinoid metabolic process Source: Reactome
    10. visual perception Source: ProtInc
    11. vitamin A metabolic process Source: ProtInc

    Keywords - Molecular functioni

    Hydrolase, Isomerase

    Keywords - Biological processi

    Sensory transduction, Vision

    Keywords - Ligandi

    Iron, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000116745-MONOMER.
    ReactomeiREACT_160156. The canonical retinoid cycle in rods (twilight vision).

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Retinoid isomerohydrolase (EC:3.1.1.64)
    Alternative name(s):
    All-trans-retinyl-palmitate hydrolase
    Retinal pigment epithelium-specific 65 kDa protein
    Retinol isomerase
    Gene namesi
    Name:RPE65
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:10294. RPE65.

    Subcellular locationi

    Cytoplasm By similarity. Cell membrane By similarity; Lipid-anchor By similarity. Microsome membrane By similarity
    Note: Attached to the membrane by a lipid anchor when palmitoylated (membrane form), soluble when unpalmitoylated By similarity. Undergoes light-dependent intracellular transport to become more concentrated in the central region of the retina pigment epithelium cells.By similarity1 Publication

    GO - Cellular componenti

    1. endoplasmic reticulum Source: UniProtKB-KW
    2. organelle membrane Source: UniProtKB-SubCell
    3. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Involvement in diseasei

    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.12 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti22 – 221L → P in LCA2. 2 Publications
    VAR_017126
    Natural varianti36 – 383Missing in LCA2.
    VAR_060808
    Natural varianti40 – 401G → S in LCA2. 2 Publications
    VAR_017127
    Natural varianti44 – 441R → Q in LCA2. 2 Publications
    VAR_017128
    Natural varianti67 – 671L → R Found in a patient with relatively mild LCA2; uncertain pathological significance. 1 Publication
    VAR_070172
    Natural varianti68 – 681H → Y in LCA2. 1 Publication
    VAR_017129
    Natural varianti70 – 701F → V in LCA2 and RP20. 2 Publications
    VAR_067160
    Natural varianti91 – 911R → P in LCA2. 1 Publication
    VAR_067161
    Natural varianti91 – 911R → Q in LCA2. 1 Publication
    VAR_017131
    Natural varianti99 – 991V → I Found in a patient with LCA2; uncertain pathological significance. 1 Publication
    VAR_067162
    Natural varianti102 – 1021E → K in RP20 and LCA2. 2 Publications
    VAR_060812
    Natural varianti144 – 1441Y → D in LCA2. 2 Publications
    VAR_017133
    Natural varianti148 – 1481E → D in LCA2. 1 Publication
    VAR_060813
    Natural varianti167 – 1671D → Y in RP20 and LCA2. 2 Publications
    VAR_060814
    Natural varianti182 – 1821H → N in LCA2. 1 Publication
    VAR_060815
    Natural varianti182 – 1821H → Y in LCA2. 2 Publications
    VAR_017134
    Natural varianti239 – 2391Y → D in LCA2 and RP20. 2 Publications
    VAR_060816
    Natural varianti287 – 2871V → F in LCA2. 1 Publication
    VAR_017135
    Natural varianti313 – 3131H → R in LCA2. 1 Publication
    VAR_067163
    Natural varianti321 – 3211N → K in LCA2. 2 Publications
    Corresponds to variant rs149916178 [ dbSNP | Ensembl ].
    VAR_017136
    Natural varianti330 – 3301C → Y in LCA2. 2 Publications
    VAR_060818
    Natural varianti333 – 3331G → R Found in a patient with LCA2. 1 Publication
    VAR_067164
    Natural varianti363 – 3631P → T in LCA2. 3 Publications
    VAR_017138
    Natural varianti368 – 3681Y → C Found in a patient with relatively mild LCA2; uncertain pathological significance. 1 Publication
    VAR_070173
    Natural varianti393 – 3931A → E in LCA2. 1 Publication
    VAR_060819
    Natural varianti393 – 3931A → G in LCA2. 1 Publication
    VAR_017140
    Natural varianti417 – 4171E → Q in LCA2. 1 Publication
    VAR_017141
    Natural varianti431 – 4311Y → C in LCA2. 1 Publication
    VAR_018151
    Natural varianti434 – 4341A → V in LCA2. 2 Publications
    Corresponds to variant rs34627040 [ dbSNP | Ensembl ].
    VAR_034477
    Natural varianti435 – 4351Y → C in LCA2. 1 Publication
    VAR_060820
    Natural varianti470 – 4701P → L in LCA2. 1 Publication
    VAR_060822
    Natural varianti515 – 5151R → W in RP20; this mutation has been found in compound heterozygosity in LCA2. 1 Publication
    VAR_037619
    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.5 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti70 – 701F → V in LCA2 and RP20. 2 Publications
    VAR_067160
    Natural varianti79 – 791Y → H in RP20. 1 Publication
    VAR_060809
    Natural varianti85 – 851R → H in RP20; uncertain pathological significance. 1 Publication
    VAR_060810
    Natural varianti91 – 911R → W in RP20. 5 Publications
    VAR_017130
    Natural varianti95 – 951E → Q in RP20. 1 Publication
    VAR_060811
    Natural varianti102 – 1021E → K in RP20 and LCA2. 2 Publications
    VAR_060812
    Natural varianti132 – 1321A → T in RP20. 2 Publications
    VAR_017132
    Natural varianti167 – 1671D → Y in RP20 and LCA2. 2 Publications
    VAR_060814
    Natural varianti239 – 2391Y → D in LCA2 and RP20. 2 Publications
    VAR_060816
    Natural varianti294 – 2941K → T in RP20. 1 Publication
    Corresponds to variant rs61752901 [ dbSNP | Ensembl ].
    VAR_060817
    Natural varianti341 – 3411L → S in RP20. 1 Publication
    VAR_017137
    Natural varianti368 – 3681Y → H in RP20. 2 Publications
    VAR_017139
    Natural varianti436 – 4361G → V in RP20. 1 Publication
    VAR_060821
    Natural varianti452 – 4521V → G in RP20. 1 Publication
    VAR_017142
    Natural varianti473 – 4731V → D in RP20. 3 Publications
    VAR_060823
    Natural varianti515 – 5151R → W in RP20; this mutation has been found in compound heterozygosity in LCA2. 1 Publication
    VAR_037619
    Natural varianti528 – 5281G → V in RP20. 1 Publication
    VAR_060824
    Defects in RPE65 are a cause of autosomal dominant retinitis pigmentosa with choroidal involvement (PubMed:21654732). Affected individuals show reduction of central vision, constriction of visual fields, night blindness and chorioretinal atrophy.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi106 – 1061C → A: Membrane associated. 1 Publication
    Mutagenesisi112 – 1121C → A: Loss of enzymatic activity. No palmitoylation. Loss of membrane association. 1 Publication
    Mutagenesisi180 – 1801H → A: Loss of enzymatic activity. 1 Publication
    Mutagenesisi241 – 2411H → A: Decreasing protein levels. Loss of enzymatic activity. Significantly decreased protein stability. 1 Publication
    Mutagenesisi313 – 3131H → A: Decreasing protein levels. Loss of enzymatic activity. Significantly decreased protein stability. 1 Publication
    Mutagenesisi469 – 4691E → A: Decreasing protein levels. Loss of enzymatic activity. 1 Publication
    Mutagenesisi469 – 4691E → Q: Decreasing protein levels. Loss of enzymatic activity. 1 Publication
    Mutagenesisi527 – 5271H → A: Decreasing protein levels. Loss of enzymatic activity. Significantly decreased protein stability. 1 Publication

    Keywords - Diseasei

    Disease mutation, Leber congenital amaurosis, Retinitis pigmentosa

    Organism-specific databases

    MIMi204100. phenotype.
    613794. phenotype.
    Orphaneti180. Choroideremia.
    65. Leber congenital amaurosis.
    791. Retinitis pigmentosa.
    364055. Severe early-childhood-onset retinal dystrophy.
    PharmGKBiPA34655.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 533532Retinoid isomerohydrolasePRO_0000143943Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserineBy similarity
    Modified residuei101 – 1011Phosphothreonine1 Publication
    Modified residuei105 – 1051Phosphothreonine1 Publication
    Lipidationi112 – 1121S-palmitoyl cysteine; in membrane form1 Publication
    Modified residuei113 – 1131N6-acetyllysine1 Publication
    Modified residuei117 – 1171Phosphoserine1 Publication
    Lipidationi231 – 2311S-palmitoyl cysteine; in membrane formBy similarity
    Lipidationi329 – 3291S-palmitoyl cysteine; in membrane formBy similarity
    Lipidationi330 – 3301S-palmitoyl cysteine; in membrane formBy similarity

    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

    Keywords - PTMi

    Acetylation, Lipoprotein, Palmitate, Phosphoprotein

    Proteomic databases

    PaxDbiQ16518.
    PRIDEiQ16518.

    PTM databases

    PhosphoSiteiQ16518.

    Expressioni

    Tissue specificityi

    Retinal pigment epithelium specific.1 Publication

    Gene expression databases

    BgeeiQ16518.
    CleanExiHS_RPE65.
    GenevestigatoriQ16518.

    Interactioni

    Subunit structurei

    Interacts with MYO7A; this mediates light-dependent intracellular transport of RPE65.1 Publication

    Protein-protein interaction databases

    BioGridi112041. 4 interactions.
    STRINGi9606.ENSP00000262340.

    Structurei

    3D structure databases

    ProteinModelPortaliQ16518.
    SMRiQ16518. Positions 4-533.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the carotenoid oxygenase family.Curated

    Phylogenomic databases

    eggNOGiCOG3670.
    HOGENOMiHOG000232156.
    HOVERGENiHBG050679.
    InParanoidiQ16518.
    KOiK11158.
    OMAiTIREPSV.
    OrthoDBiEOG7353WB.
    PhylomeDBiQ16518.
    TreeFamiTF314019.

    Family and domain databases

    InterProiIPR004294. Carotenoid_Oase.
    [Graphical view]
    PANTHERiPTHR10543. PTHR10543. 1 hit.
    PfamiPF03055. RPE65. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q16518-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSIQVEHPAG GYKKLFETVE ELSSPLTAHV TGRIPLWLTG SLLRCGPGLF    50
    EVGSEPFYHL FDGQALLHKF DFKEGHVTYH RRFIRTDAYV RAMTEKRIVI 100
    TEFGTCAFPD PCKNIFSRFF SYFRGVEVTD NALVNVYPVG EDYYACTETN 150
    FITKINPETL ETIKQVDLCN YVSVNGATAH PHIENDGTVY NIGNCFGKNF 200
    SIAYNIVKIP PLQADKEDPI SKSEIVVQFP CSDRFKPSYV HSFGLTPNYI 250
    VFVETPVKIN LFKFLSSWSL WGANYMDCFE SNETMGVWLH IADKKRKKYL 300
    NNKYRTSPFN LFHHINTYED NGFLIVDLCC WKGFEFVYNY LYLANLRENW 350
    EEVKKNARKA PQPEVRRYVL PLNIDKADTG KNLVTLPNTT ATAILCSDET 400
    IWLEPEVLFS GPRQAFEFPQ INYQKYCGKP YTYAYGLGLN HFVPDRLCKL 450
    NVKTKETWVW QEPDSYPSEP IFVSHPDALE EDDGVVLSVV VSPGAGQKPA 500
    YLLILNAKDL SEVARAEVEI NIPVTFHGLF KKS 533
    Length:533
    Mass (Da):60,948
    Last modified:January 23, 2007 - v3
    Checksum:i7193C93F3325798D
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti254 – 2541E → G in BAF82614. (PubMed:14702039)Curated
    Sequence conflicti274 – 2741N → D in BAF82614. (PubMed:14702039)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti22 – 221L → P in LCA2. 2 Publications
    VAR_017126
    Natural varianti36 – 383Missing in LCA2.
    VAR_060808
    Natural varianti40 – 401G → S in LCA2. 2 Publications
    VAR_017127
    Natural varianti44 – 441R → Q in LCA2. 2 Publications
    VAR_017128
    Natural varianti67 – 671L → R Found in a patient with relatively mild LCA2; uncertain pathological significance. 1 Publication
    VAR_070172
    Natural varianti68 – 681H → Y in LCA2. 1 Publication
    VAR_017129
    Natural varianti70 – 701F → V in LCA2 and RP20. 2 Publications
    VAR_067160
    Natural varianti79 – 791Y → H in RP20. 1 Publication
    VAR_060809
    Natural varianti85 – 851R → H in RP20; uncertain pathological significance. 1 Publication
    VAR_060810
    Natural varianti91 – 911R → P in LCA2. 1 Publication
    VAR_067161
    Natural varianti91 – 911R → Q in LCA2. 1 Publication
    VAR_017131
    Natural varianti91 – 911R → W in RP20. 5 Publications
    VAR_017130
    Natural varianti95 – 951E → Q in RP20. 1 Publication
    VAR_060811
    Natural varianti99 – 991V → I Found in a patient with LCA2; uncertain pathological significance. 1 Publication
    VAR_067162
    Natural varianti102 – 1021E → K in RP20 and LCA2. 2 Publications
    VAR_060812
    Natural varianti132 – 1321A → T in RP20. 2 Publications
    VAR_017132
    Natural varianti144 – 1441Y → D in LCA2. 2 Publications
    VAR_017133
    Natural varianti148 – 1481E → D in LCA2. 1 Publication
    VAR_060813
    Natural varianti167 – 1671D → Y in RP20 and LCA2. 2 Publications
    VAR_060814
    Natural varianti182 – 1821H → N in LCA2. 1 Publication
    VAR_060815
    Natural varianti182 – 1821H → Y in LCA2. 2 Publications
    VAR_017134
    Natural varianti239 – 2391Y → D in LCA2 and RP20. 2 Publications
    VAR_060816
    Natural varianti287 – 2871V → F in LCA2. 1 Publication
    VAR_017135
    Natural varianti294 – 2941K → T in RP20. 1 Publication
    Corresponds to variant rs61752901 [ dbSNP | Ensembl ].
    VAR_060817
    Natural varianti313 – 3131H → R in LCA2. 1 Publication
    VAR_067163
    Natural varianti321 – 3211N → K in LCA2. 2 Publications
    Corresponds to variant rs149916178 [ dbSNP | Ensembl ].
    VAR_017136
    Natural varianti330 – 3301C → Y in LCA2. 2 Publications
    VAR_060818
    Natural varianti333 – 3331G → R Found in a patient with LCA2. 1 Publication
    VAR_067164
    Natural varianti341 – 3411L → S in RP20. 1 Publication
    VAR_017137
    Natural varianti363 – 3631P → T in LCA2. 3 Publications
    VAR_017138
    Natural varianti368 – 3681Y → C Found in a patient with relatively mild LCA2; uncertain pathological significance. 1 Publication
    VAR_070173
    Natural varianti368 – 3681Y → H in RP20. 2 Publications
    VAR_017139
    Natural varianti393 – 3931A → E in LCA2. 1 Publication
    VAR_060819
    Natural varianti393 – 3931A → G in LCA2. 1 Publication
    VAR_017140
    Natural varianti417 – 4171E → Q in LCA2. 1 Publication
    VAR_017141
    Natural varianti431 – 4311Y → C in LCA2. 1 Publication
    VAR_018151
    Natural varianti434 – 4341A → V in LCA2. 2 Publications
    Corresponds to variant rs34627040 [ dbSNP | Ensembl ].
    VAR_034477
    Natural varianti435 – 4351Y → C in LCA2. 1 Publication
    VAR_060820
    Natural varianti436 – 4361G → V in RP20. 1 Publication
    VAR_060821
    Natural varianti452 – 4521V → G in RP20. 1 Publication
    VAR_017142
    Natural varianti470 – 4701P → L in LCA2. 1 Publication
    VAR_060822
    Natural varianti473 – 4731V → D in RP20. 3 Publications
    VAR_060823
    Natural varianti477 – 4771D → G Probable disease-associated mutation found in autosomal dominant retinitis pigmentosa with choroidal involvement. 1 Publication
    VAR_067757
    Natural varianti515 – 5151R → W in RP20; this mutation has been found in compound heterozygosity in LCA2. 1 Publication
    VAR_037619
    Natural varianti528 – 5281G → V in RP20. 1 Publication
    VAR_060824

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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. Translation: CAI18957.1.
    CH471059 Genomic DNA. Translation: EAX06478.1.
    BC075035 mRNA. Translation: AAH75035.1.
    BC075036 mRNA. Translation: AAH75036.1.
    CCDSiCCDS643.1.
    RefSeqiNP_000320.1. NM_000329.2.
    UniGeneiHs.2133.

    Genome annotation databases

    EnsembliENST00000262340; ENSP00000262340; ENSG00000116745.
    GeneIDi6121.
    KEGGihsa:6121.
    UCSCiuc001dei.1. human.

    Polymorphism databases

    DMDMi44888872.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Mutations of the RPE65 gene

    Retina International's Scientific Newsletter

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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. Translation: CAI18957.1 .
    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.
    UniGenei Hs.2133.

    3D structure databases

    ProteinModelPortali Q16518.
    SMRi Q16518. Positions 4-533.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112041. 4 interactions.
    STRINGi 9606.ENSP00000262340.

    PTM databases

    PhosphoSitei Q16518.

    Polymorphism databases

    DMDMi 44888872.

    Proteomic databases

    PaxDbi Q16518.
    PRIDEi Q16518.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000262340 ; ENSP00000262340 ; ENSG00000116745 .
    GeneIDi 6121.
    KEGGi hsa:6121.
    UCSCi uc001dei.1. human.

    Organism-specific databases

    CTDi 6121.
    GeneCardsi GC01M068894.
    GeneReviewsi RPE65.
    HGNCi HGNC:10294. RPE65.
    MIMi 180069. gene.
    204100. phenotype.
    613794. phenotype.
    neXtProti NX_Q16518.
    Orphaneti 180. Choroideremia.
    65. Leber congenital amaurosis.
    791. Retinitis pigmentosa.
    364055. Severe early-childhood-onset retinal dystrophy.
    PharmGKBi PA34655.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG3670.
    HOGENOMi HOG000232156.
    HOVERGENi HBG050679.
    InParanoidi Q16518.
    KOi K11158.
    OMAi TIREPSV.
    OrthoDBi EOG7353WB.
    PhylomeDBi Q16518.
    TreeFami TF314019.

    Enzyme and pathway databases

    BioCyci MetaCyc:ENSG00000116745-MONOMER.
    Reactomei REACT_160156. The canonical retinoid cycle in rods (twilight vision).

    Miscellaneous databases

    ChiTaRSi RPE65. human.
    GeneWikii RPE65.
    GenomeRNAii 6121.
    NextBioi 23773.
    PROi Q16518.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q16518.
    CleanExi HS_RPE65.
    Genevestigatori Q16518.

    Family and domain databases

    InterProi IPR004294. Carotenoid_Oase.
    [Graphical view ]
    PANTHERi PTHR10543. PTHR10543. 1 hit.
    Pfami PF03055. RPE65. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular characterization of the human gene encoding an abundant 61 kDa protein specific to the retinal pigment epithelium."
      Nicoletti A., Wong D.J., Kawase K., Gibson L.H., Yang-Feng T.L., Richards J.E., Thompson D.A.
      Hum. Mol. Genet. 4:641-649(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
      Tissue: Retinal pigment epithelium.
    2. "Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or Leber congenital amaurosis."
      Morimura H., Fishman G.A., Grover S.A., Fulton A.B., Berson E.L., Dryja T.P.
      Proc. Natl. Acad. Sci. U.S.A. 95:3088-3093(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS RP20 TRP-91; LYS-102; THR-132; SER-341; GLY-452 AND ASP-473.
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Hippocampus.
    4. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Fetal brain.
    7. "Identification of a novel palmitylation site essential for membrane association and isomerohydrolase activity of RPE65."
      Takahashi Y., Moiseyev G., Ablonczy Z., Chen Y., Crouch R.K., Ma J.X.
      J. Biol. Chem. 284:3211-3218(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 98-118, PHOSPHORYLATION AT THR-101; THR-105 AND SER-117, PALMITOYLATION AT CYS-112, MUTAGENESIS OF CYS-106 AND CYS-112, ACETYLATION AT LYS-113, IDENTIFICATION BY MASS SPECTROMETRY.
    8. "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."
      Takahashi Y., Moiseyev G., Chen Y., Ma J.X.
      FEBS Lett. 579:5414-5418(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF HIS-180; HIS-241; HIS-313; GLU-469 AND HIS-527.
    9. Cited for: FUNCTION.
    10. "The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65."
      Lopes V.S., Gibbs D., Libby R.T., Aleman T.S., Welch D.L., Lillo C., Jacobson S.G., Radu R.A., Steel K.P., Williams D.S.
      Hum. Mol. Genet. 20:2560-2570(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH MYO7A.
    11. "Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy."
      Gu S.M., Thompson D.A., Srikumari C.R., Lorenz B., Finckh U., Nicoletti A., Murthy K.R., Rathmann M., Kumaramanickavel G., Denton M.J., Gal A.
      Nat. Genet. 17:194-197(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT LCA2 THR-363.
    12. "Autosomal recessive retinal dystrophy associated with two novel mutations in the RPE65 gene."
      Marlhens F., Griffoin J.-M., Bareil C., Arnaud B., Claustres M., Hamel C.P.
      Eur. J. Hum. Genet. 6:527-531(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS LCA2 PRO-22 AND TYR-68.
    13. "Different functional outcome of RetGC1 and RPE65 gene mutations in Leber congenital amaurosis."
      Perrault I., Rozet J.-M., Ghazi I., Leowski C., Bonnemaison M., Gerber S., Ducroq D., Cabot A., Souied E., Dufier J.-L., Munnich A., Kaplan J.
      Am. J. Hum. Genet. 64:1225-1228(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS LCA2 TYR-330; THR-363 AND VAL-434.
    14. Cited for: VARIANTS LCA2 PHE-287; LYS-321 AND GLY-393.
    15. "Genetics and phenotypes of RPE65 mutations in inherited retinal degeneration."
      Thompson D.A., Gyuerues P., Fleischer L.L., Bingham E.L., McHenry C.L., Apfelstedt-Sylla E., Zrenner E., Lorenz B., Richards J.E., Jacobson S.G., Sieving P.A., Gal A.
      Invest. Ophthalmol. Vis. Sci. 41:4293-4299(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS RP20 HIS-79; HIS-85; TRP-91; GLN-95; THR-132; TYR-167; THR-294; VAL-436 AND VAL-528.
    16. "Four novel mutations in the RPE65 gene in patients with Leber congenital amaurosis."
      Simovich M.J., Miller B., Ezzeldin H., Kirkland B.T., McLeod G., Fulmer C., Nathans J., Jacobson S.G., Pittler S.J.
      Hum. Mutat. 18:164-164(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS LCA2 SER-40; GLN-44; GLN-91; ASP-144; TYR-182; LYS-321 AND GLN-417.
    17. "A Tyr368His RPE65 founder mutation is associated with variable expression and progression of early onset retinal dystrophy in 10 families of a genetically isolated population."
      Yzer S., van den Born L.I., Schuil J., Kroes H.Y., van Genderen M.M., Boonstra F.N., van den Helm B., Brunner H.G., Koenekoop R.K., Cremers F.P.
      J. Med. Genet. 40:709-713(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT RP20 HIS-368.
    18. "Analysis of three genes in Leber congenital amaurosis in Indonesian patients."
      Sitorus R.S., Lorenz B., Preising M.N.
      Vision Res. 43:3087-3093(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS LCA2 36-LEU--LEU-38 DEL AND CYS-435.
    19. "Thirty-year follow-up of a patient with Leber congenital amaurosis and novel RPE65 mutations."
      Al-Khayer K., Hagstrom S., Pauer G., Zegarra H., Sears J., Traboulsi E.I.
      Am. J. Ophthalmol. 137:375-377(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT LCA2 CYS-431.
    20. "Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis."
      Hanein S., Perrault I., Gerber S., Tanguy G., Barbet F., Ducroq D., Calvas P., Dollfus H., Hamel C., Lopponen T., Munier F., Santos L., Shalev S., Zafeiriou D., Dufier J.-L., Munnich A., Rozet J.-M., Kaplan J.
      Hum. Mutat. 23:306-317(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS LCA2 GLN-44; ASP-148; ASN-182; TYR-330; THR-363; VAL-434 AND ASP-473.
    21. "A homozygosity-based search for mutations in patients with autosomal recessive retinitis pigmentosa, using microsatellite markers."
      Kondo H., Qin M., Mizota A., Kondo M., Hayashi H., Hayashi K., Oshima K., Tahira T., Hayashi K.
      Invest. Ophthalmol. Vis. Sci. 45:4433-4439(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT RP20 TRP-515.
    22. "Evaluation of genotype-phenotype associations in Leber congenital amaurosis."
      Galvin J.A., Fishman G.A., Stone E.M., Koenekoop R.K.
      Retina 25:919-929(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS LCA2 SER-40; TRP-91; TYR-182; ASP-239; GLU-393 AND ASP-473.
    23. "Gene symbol: RPE65. Disease: Leber's congenital amaurosis. Accession #Hm0548."
      Gandra M., Sundaramurthy S., Kumaramanickavel G.
      Hum. Genet. 118:780-780(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT LCA2 LEU-470.
    24. Cited for: VARIANTS LCA2 PRO-22; VAL-70; PRO-91; LYS-102; ASP-144; TYR-167 AND ARG-313.
    25. "Molecular characterization of Leber congenital amaurosis in Koreans."
      Seong M.W., Kim S.Y., Yu Y.S., Hwang J.M., Kim J.Y., Park S.S.
      Mol. Vis. 14:1429-1436(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT LCA2 TRP-91.
    26. Cited for: VARIANT GLY-477, ROLE IN AUTOSOMAL DOMINANT RETINITIS PIGMENTOSA WITH CHOROIDAL INVOLVEMENT.
    27. "Detection of variants in 15 genes in 87 unrelated Chinese patients with Leber congenital amaurosis."
      Li L., Xiao X., Li S., Jia X., Wang P., Guo X., Jiao X., Zhang Q., Hejtmancik J.F.
      PLoS ONE 6:E19458-E19458(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS ILE-99 AND ARG-333.
    28. Cited for: VARIANTS RP20 VAL-70; TRP-91; ASP-239 AND HIS-368.
    29. "Novel RPE65 mutations associated with Leber congenital amaurosis in Chinese patients."
      Xu F., Dong Q., Liu L., Li H., Liang X., Jiang R., Sui R., Dong F.
      Mol. Vis. 18:744-750(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS ARG-67 AND CYS-368.

    Entry informationi

    Entry nameiRPE65_HUMAN
    AccessioniPrimary (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: October 1, 2014
    This is version 123 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny 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

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3