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Q16518 (RPE65_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:RPE65
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length533 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.9 Ref.26

Catalytic activity

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

Cofactor

Binds 1 Fe2+ ion per subunit By similarity.

Subunit structure

Interacts with MYO7A; this mediates light-dependent intracellular transport of RPE65. Ref.10

Subcellular location

Cytoplasm By similarity. Cell membrane; 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. Ref.10

Tissue specificity

Retinal pigment epithelium specific. Ref.10

Post-translational modification

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. Ref.7

Involvement in 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12 Ref.13 Ref.14 Ref.16 Ref.18 Ref.19 Ref.20 Ref.22 Ref.23 Ref.24 Ref.25

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.15 Ref.17 Ref.21 Ref.28

Defects in RPE65 are a cause of autosomal dominant retinitis pigmentosa with choroidal involvement (Ref.26). Affected individuals show reduction of central vision, constriction of visual fields, night blindness and chorioretinal atrophy.

Sequence similarities

Belongs to the carotenoid oxygenase family.

Ontologies

Keywords
   Biological processSensory transduction
Vision
   Cellular componentCell membrane
Cytoplasm
Endoplasmic reticulum
Membrane
Microsome
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Leber congenital amaurosis
Retinitis pigmentosa
   LigandIron
Metal-binding
   Molecular functionHydrolase
Isomerase
   PTMAcetylation
Lipoprotein
Palmitate
Phosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to electrical stimulus

Inferred from electronic annotation. Source: Ensembl

detection of light stimulus involved in visual perception

Inferred from mutant phenotype Ref.21. Source: UniProt

insulin receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

phototransduction, visible light

Traceable author statement. Source: Reactome

regulation of rhodopsin gene expression

Inferred from electronic annotation. Source: Ensembl

retina homeostasis

Inferred from mutant phenotype Ref.21. Source: UniProt

retina morphogenesis in camera-type eye

Inferred from electronic annotation. Source: Ensembl

retinal metabolic process

Inferred from electronic annotation. Source: Ensembl

retinoid metabolic process

Traceable author statement. Source: Reactome

visual perception

Traceable author statement Ref.11. Source: ProtInc

vitamin A metabolic process

Traceable author statement Ref.11. Source: ProtInc

   Cellular_componentendoplasmic reticulum

Inferred from electronic annotation. Source: UniProtKB-KW

organelle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionall-trans-retinyl-ester hydrolase, 11-cis retinol forming activity

Inferred from electronic annotation. Source: UniProtKB-EC

all-trans-retinyl-palmitate hydrolase, 11-cis retinol forming activity

Inferred from electronic annotation. Source: UniProtKB-EC

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

retinal isomerase activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 533532Retinoid isomerohydrolase
PRO_0000143943

Sites

Metal binding1801Iron; catalytic By similarity
Metal binding2411Iron; catalytic By similarity
Metal binding3131Iron; catalytic By similarity
Metal binding5271Iron; catalytic By similarity

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue1011Phosphothreonine Ref.7
Modified residue1051Phosphothreonine Ref.7
Modified residue1131N6-acetyllysine Ref.7
Modified residue1171Phosphoserine Ref.7
Lipidation1121S-palmitoyl cysteine; in membrane form Ref.7
Lipidation2311S-palmitoyl cysteine; in membrane form By similarity
Lipidation3291S-palmitoyl cysteine; in membrane form By similarity
Lipidation3301S-palmitoyl cysteine; in membrane form By similarity

Natural variations

Natural variant221L → P in LCA2. Ref.12 Ref.24
VAR_017126
Natural variant36 – 383Missing in LCA2.
VAR_060808
Natural variant401G → S in LCA2. Ref.16 Ref.22
VAR_017127
Natural variant441R → Q in LCA2. Ref.16 Ref.20
VAR_017128
Natural variant671L → R Found in a patient with relatively mild LCA2; uncertain pathological significance. Ref.29
VAR_070172
Natural variant681H → Y in LCA2. Ref.12
VAR_017129
Natural variant701F → V in LCA2 and RP20. Ref.24 Ref.28
VAR_067160
Natural variant791Y → H in RP20. Ref.15
VAR_060809
Natural variant851R → H in RP20; uncertain pathological significance. Ref.15
VAR_060810
Natural variant911R → P in LCA2. Ref.24
VAR_067161
Natural variant911R → Q in LCA2. Ref.16
VAR_017131
Natural variant911R → W in RP20. Ref.2 Ref.15 Ref.22 Ref.25 Ref.28
VAR_017130
Natural variant951E → Q in RP20. Ref.15
VAR_060811
Natural variant991V → I Found in a patient with LCA2; uncertain pathological significance. Ref.27
VAR_067162
Natural variant1021E → K in RP20 and LCA2. Ref.2 Ref.24
VAR_060812
Natural variant1321A → T in RP20. Ref.2 Ref.15
VAR_017132
Natural variant1441Y → D in LCA2. Ref.16 Ref.24
VAR_017133
Natural variant1481E → D in LCA2. Ref.20
VAR_060813
Natural variant1671D → Y in RP20 and LCA2. Ref.15 Ref.24
VAR_060814
Natural variant1821H → N in LCA2. Ref.20
VAR_060815
Natural variant1821H → Y in LCA2. Ref.16 Ref.22
VAR_017134
Natural variant2391Y → D in LCA2 and RP20. Ref.22 Ref.28
VAR_060816
Natural variant2871V → F in LCA2. Ref.14
VAR_017135
Natural variant2941K → T in RP20. Ref.15
Corresponds to variant rs61752901 [ dbSNP | Ensembl ].
VAR_060817
Natural variant3131H → R in LCA2. Ref.24
VAR_067163
Natural variant3211N → K in LCA2. Ref.14 Ref.16
Corresponds to variant rs149916178 [ dbSNP | Ensembl ].
VAR_017136
Natural variant3301C → Y in LCA2. Ref.13 Ref.20
VAR_060818
Natural variant3331G → R Found in a patient with LCA2. Ref.27
VAR_067164
Natural variant3411L → S in RP20. Ref.2
VAR_017137
Natural variant3631P → T in LCA2. Ref.11 Ref.13 Ref.20
VAR_017138
Natural variant3681Y → C Found in a patient with relatively mild LCA2; uncertain pathological significance. Ref.29
VAR_070173
Natural variant3681Y → H in RP20. Ref.17 Ref.28
VAR_017139
Natural variant3931A → E in LCA2. Ref.22
VAR_060819
Natural variant3931A → G in LCA2. Ref.14
VAR_017140
Natural variant4171E → Q in LCA2. Ref.16
VAR_017141
Natural variant4311Y → C in LCA2. Ref.19
VAR_018151
Natural variant4341A → V in LCA2. Ref.13 Ref.20
Corresponds to variant rs34627040 [ dbSNP | Ensembl ].
VAR_034477
Natural variant4351Y → C in LCA2. Ref.18
VAR_060820
Natural variant4361G → V in RP20. Ref.15
VAR_060821
Natural variant4521V → G in RP20. Ref.2
VAR_017142
Natural variant4701P → L in LCA2. Ref.23
VAR_060822
Natural variant4731V → D in RP20. Ref.2 Ref.20 Ref.22
VAR_060823
Natural variant4771D → G Probable disease-associated mutation found in autosomal dominant retinitis pigmentosa with choroidal involvement. Ref.26
VAR_067757
Natural variant5151R → W in RP20; this mutation has been found in compound heterozygosity in LCA2. Ref.21
VAR_037619
Natural variant5281G → V in RP20. Ref.15
VAR_060824

Experimental info

Mutagenesis1061C → A: Membrane associated. Ref.7
Mutagenesis1121C → A: Loss of enzymatic activity. No palmitoylation. Loss of membrane association. Ref.7
Mutagenesis1801H → A: Loss of enzymatic activity. Ref.8
Mutagenesis2411H → A: Decreasing protein levels. Loss of enzymatic activity. Significantly decreased protein stability. Ref.8
Mutagenesis3131H → A: Decreasing protein levels. Loss of enzymatic activity. Significantly decreased protein stability. Ref.8
Mutagenesis4691E → A: Decreasing protein levels. Loss of enzymatic activity. Ref.8
Mutagenesis4691E → Q: Decreasing protein levels. Loss of enzymatic activity. Ref.8
Mutagenesis5271H → A: Decreasing protein levels. Loss of enzymatic activity. Significantly decreased protein stability. Ref.8
Sequence conflict2541E → G in BAF82614. Ref.3
Sequence conflict2741N → D in BAF82614. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q16518 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 7193C93F3325798D

FASTA53360,948
        10         20         30         40         50         60 
MSIQVEHPAG GYKKLFETVE ELSSPLTAHV TGRIPLWLTG SLLRCGPGLF EVGSEPFYHL 

        70         80         90        100        110        120 
FDGQALLHKF DFKEGHVTYH RRFIRTDAYV RAMTEKRIVI TEFGTCAFPD PCKNIFSRFF 

       130        140        150        160        170        180 
SYFRGVEVTD NALVNVYPVG EDYYACTETN FITKINPETL ETIKQVDLCN YVSVNGATAH 

       190        200        210        220        230        240 
PHIENDGTVY NIGNCFGKNF SIAYNIVKIP PLQADKEDPI SKSEIVVQFP CSDRFKPSYV 

       250        260        270        280        290        300 
HSFGLTPNYI VFVETPVKIN LFKFLSSWSL WGANYMDCFE SNETMGVWLH IADKKRKKYL 

       310        320        330        340        350        360 
NNKYRTSPFN LFHHINTYED NGFLIVDLCC WKGFEFVYNY LYLANLRENW EEVKKNARKA 

       370        380        390        400        410        420 
PQPEVRRYVL PLNIDKADTG KNLVTLPNTT ATAILCSDET IWLEPEVLFS GPRQAFEFPQ 

       430        440        450        460        470        480 
INYQKYCGKP YTYAYGLGLN HFVPDRLCKL NVKTKETWVW QEPDSYPSEP IFVSHPDALE 

       490        500        510        520        530 
EDDGVVLSVV VSPGAGQKPA YLLILNAKDL SEVARAEVEI NIPVTFHGLF KKS 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"RPE65 is the isomerohydrolase in the retinoid visual cycle."
Moiseyev G., Chen Y., Takahashi Y., Wu B.X., Ma J.X.
Proc. Natl. Acad. Sci. U.S.A. 102:12413-12418(2005) [PubMed] [Europe PMC] [Abstract]
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]"Mutation analysis of 3 genes in patients with Leber congenital amaurosis."
Lotery A.J., Namperumalsamy P., Jacobson S.G., Weleber R.G., Fishman G.A., Musarella M.A., Hoyt C.S., Heon E., Levin A., Jan J., Lam B., Carr R.E., Franklin A., Radha S., Andorf J.L., Sheffield V.C., Stone E.M.
Arch. Ophthalmol. 118:538-543(2000) [PubMed] [Europe PMC] [Abstract]
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]"Clinical and molecular genetics of Leber's congenital amaurosis: a multicenter study of Italian patients."
Simonelli F., Ziviello C., Testa F., Rossi S., Fazzi E., Bianchi P.E., Fossarello M., Signorini S., Bertone C., Galantuomo S., Brancati F., Valente E.M., Ciccodicola A., Rinaldi E., Auricchio A., Banfi S.
Invest. Ophthalmol. Vis. Sci. 48:4284-4290(2007) [PubMed] [Europe PMC] [Abstract]
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]"A dominant mutation in RPE65 identified by whole-exome sequencing causes retinitis pigmentosa with choroidal involvement."
Bowne S.J., Humphries M.M., Sullivan L.S., Kenna P.F., Tam L.C., Kiang A.S., Campbell M., Weinstock G.M., Koboldt D.C., Ding L., Fulton R.S., Sodergren E.J., Allman D., Millington-Ward S., Palfi A., McKee A., Blanton S.H., Slifer S. expand/collapse author list , Konidari I., Farrar G.J., Daiger S.P., Humphries P.
Eur. J. Hum. Genet. 19:1074-1081(2011) [PubMed] [Europe PMC] [Abstract]
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]"Next-generation genetic testing for retinitis pigmentosa."
Neveling K., Collin R.W., Gilissen C., van Huet R.A., Visser L., Kwint M.P., Gijsen S.J., Zonneveld M.N., Wieskamp N., de Ligt J., Siemiatkowska A.M., Hoefsloot L.H., Buckley M.F., Kellner U., Branham K.E., den Hollander A.I., Hoischen A., Hoyng C. expand/collapse author list , Klevering B.J., van den Born L.I., Veltman J.A., Cremers F.P., Scheffer H.
Hum. Mutat. 33:963-972(2012) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Web resources

Mutations of the RPE65 gene

Retina International's Scientific Newsletter

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U18991 mRNA. Translation: AAA99012.1.
U20510 expand/collapse EMBL AC list , U20476, U20477, U20478, U20479, U20481, U20482, U20484, U20485, U20486 Genomic DNA. Translation: AAC14586.1.
AF039868 expand/collapse EMBL AC list , 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.
CCDSCCDS643.1.
RefSeqNP_000320.1. NM_000329.2.
UniGeneHs.2133.

3D structure databases

ProteinModelPortalQ16518.
SMRQ16518. Positions 4-533.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112041. 2 interactions.
STRING9606.ENSP00000262340.

PTM databases

PhosphoSiteQ16518.

Polymorphism databases

DMDM44888872.

Proteomic databases

PaxDbQ16518.
PRIDEQ16518.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262340; ENSP00000262340; ENSG00000116745.
GeneID6121.
KEGGhsa:6121.
UCSCuc001dei.1. human.

Organism-specific databases

CTD6121.
GeneCardsGC01M068894.
GeneReviewsRPE65.
HGNCHGNC:10294. RPE65.
MIM180069. gene.
204100. phenotype.
613794. phenotype.
neXtProtNX_Q16518.
Orphanet180. Choroideremia.
65. Leber congenital amaurosis.
791. Retinitis pigmentosa.
364055. Severe early-childhood-onset retinal dystrophy.
PharmGKBPA34655.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3670.
HOGENOMHOG000232156.
HOVERGENHBG050679.
InParanoidQ16518.
KOK11158.
OMATIREPSV.
OrthoDBEOG7353WB.
PhylomeDBQ16518.
TreeFamTF314019.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000116745-MONOMER.
ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.

Gene expression databases

BgeeQ16518.
CleanExHS_RPE65.
GenevestigatorQ16518.

Family and domain databases

InterProIPR004294. Carotenoid_Oase.
[Graphical view]
PANTHERPTHR10543. PTHR10543. 1 hit.
PfamPF03055. RPE65. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRPE65. human.
GeneWikiRPE65.
GenomeRNAi6121.
NextBio23773.
PROQ16518.
SOURCESearch...

Entry information

Entry nameRPE65_HUMAN
AccessionPrimary (citable) accession number: Q16518
Secondary accession number(s): A8K1L0, Q5T9U3
Entry history
Integrated into UniProtKB/Swiss-Prot: October 10, 2003
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 121 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM