Q16518 (RPE65_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

RPE65

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	533 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.8 Ref.25
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.9
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.9
Tissue specificity	Retinal pigment epithelium specific. Ref.9
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.6
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.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.17 Ref.18 Ref.19 Ref.21 Ref.22 Ref.23 Ref.24 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.14 Ref.16 Ref.20 Ref.27 Defects in RPE65 are a cause of autosomal dominant retinitis pigmentosa with choroidal involvement (Ref.25). 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 process	Sensory transduction Vision
Cellular component	Cell membrane Cytoplasm Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Polymorphism
Disease	Disease mutation Leber congenital amaurosis Retinitis pigmentosa
Ligand	Iron Metal-binding
Molecular function	Hydrolase Isomerase
PTM	Acetylation Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to electrical stimulus Inferred from electronic annotation. Source: Compara insulin receptor signaling pathway Inferred from electronic annotation. Source: Compara regulation of rhodopsin gene expression Inferred from electronic annotation. Source: Compara retina morphogenesis in camera-type eye Inferred from electronic annotation. Source: Compara retinal metabolic process Inferred from electronic annotation. Source: Compara visual perception Traceable author statement Ref.10. Source: ProtInc vitamin A metabolic process Traceable author statement Ref.10. Source: ProtInc
Cellular_component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-KW organelle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	all-trans-retinyl-ester hydrolase, 11-cis retinol forming activity Inferred from electronic annotation. Source: EC all-trans-retinyl-palmitate hydrolase, 11-cis retinol forming activity Inferred from electronic annotation. Source: EC metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW retinal isomerase activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 533	532	Retinoid isomerohydrolase		PRO_0000143943
Sites
	Metal binding	180	1	Iron; catalytic By similarity
	Metal binding	241	1	Iron; catalytic By similarity
	Metal binding	313	1	Iron; catalytic By similarity
	Metal binding	527	1	Iron; catalytic By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylserine By similarity
	Modified residue	101	1	Phosphothreonine Ref.6
	Modified residue	105	1	Phosphothreonine Ref.6
	Modified residue	113	1	N6-acetyllysine Ref.6
	Modified residue	117	1	Phosphoserine Ref.6
	Lipidation	112	1	S-palmitoyl cysteine; in membrane form Ref.6
	Lipidation	231	1	S-palmitoyl cysteine; in membrane form By similarity
	Lipidation	329	1	S-palmitoyl cysteine; in membrane form By similarity
	Lipidation	330	1	S-palmitoyl cysteine; in membrane form By similarity
Natural variations
	Natural variant	22	1	L → P in LCA2. Ref.11 Ref.23		VAR_017126
	Natural variant	36 – 38	3	Missing in LCA2.		VAR_060808
	Natural variant	40	1	G → S in LCA2. Ref.15 Ref.21		VAR_017127
	Natural variant	44	1	R → Q in LCA2. Ref.15 Ref.19		VAR_017128
	Natural variant	68	1	H → Y in LCA2. Ref.11		VAR_017129
	Natural variant	70	1	F → V in LCA2 and RP20. Ref.23 Ref.27		VAR_067160
	Natural variant	79	1	Y → H in RP20. Ref.14		VAR_060809
	Natural variant	85	1	R → H in RP20; uncertain pathological significance. Ref.14		VAR_060810
	Natural variant	91	1	R → P in LCA2. Ref.23		VAR_067161
	Natural variant	91	1	R → Q in LCA2. Ref.15		VAR_017131
	Natural variant	91	1	R → W in RP20. Ref.2 Ref.14 Ref.21 Ref.24 Ref.27		VAR_017130
	Natural variant	95	1	E → Q in RP20. Ref.14		VAR_060811
	Natural variant	99	1	V → I Found in a patient with LCA2; uncertain pathological significance. Ref.26		VAR_067162
	Natural variant	102	1	E → K in RP20 and LCA2. Ref.2 Ref.23		VAR_060812
	Natural variant	132	1	A → T in RP20. Ref.2 Ref.14		VAR_017132
	Natural variant	144	1	Y → D in LCA2. Ref.15 Ref.23		VAR_017133
	Natural variant	148	1	E → D in LCA2. Ref.19		VAR_060813
	Natural variant	167	1	D → Y in RP20 and LCA2. Ref.14 Ref.23		VAR_060814
	Natural variant	182	1	H → N in LCA2. Ref.19		VAR_060815
	Natural variant	182	1	H → Y in LCA2. Ref.15 Ref.21		VAR_017134
	Natural variant	239	1	Y → D in LCA2 and RP20. Ref.21 Ref.27		VAR_060816
	Natural variant	287	1	V → F in LCA2. Ref.13		VAR_017135
	Natural variant	294	1	K → T in RP20. Ref.14		VAR_060817
	Natural variant	313	1	H → R in LCA2. Ref.23		VAR_067163
	Natural variant	321	1	N → K in LCA2. Ref.13 Ref.15		VAR_017136
	Natural variant	330	1	C → Y in LCA2. Ref.12 Ref.19		VAR_060818
	Natural variant	333	1	G → R Found in a patient with LCA2. Ref.26		VAR_067164
	Natural variant	341	1	L → S in RP20. Ref.2		VAR_017137
	Natural variant	363	1	P → T in LCA2. Ref.10 Ref.12 Ref.19		VAR_017138
	Natural variant	368	1	Y → H in RP20. Ref.16 Ref.27		VAR_017139
	Natural variant	393	1	A → E in LCA2. Ref.21		VAR_060819
	Natural variant	393	1	A → G in LCA2. Ref.13		VAR_017140
	Natural variant	417	1	E → Q in LCA2. Ref.15		VAR_017141
	Natural variant	431	1	Y → C in LCA2. Ref.18		VAR_018151
	Natural variant	434	1	A → V in LCA2. Ref.12 Ref.19 Corresponds to variant rs34627040 [ dbSNP | Ensembl ].		VAR_034477
	Natural variant	435	1	Y → C in LCA2. Ref.17		VAR_060820
	Natural variant	436	1	G → V in RP20. Ref.14		VAR_060821
	Natural variant	452	1	V → G in RP20. Ref.2		VAR_017142
	Natural variant	470	1	P → L in LCA2. Ref.22		VAR_060822
	Natural variant	473	1	V → D in RP20. Ref.2 Ref.19 Ref.21		VAR_060823
	Natural variant	477	1	D → G Probable disease-associated mutation found in autosomal dominant retinitis pigmentosa with choroidal involvement. Ref.25		VAR_067757
	Natural variant	515	1	R → W in RP20; this mutation has been found in compound heterozygosity in LCA2. Ref.20		VAR_037619
	Natural variant	528	1	G → V in RP20. Ref.14		VAR_060824
Experimental info
	Mutagenesis	106	1	C → A: Membrane associated. Ref.6
	Mutagenesis	112	1	C → A: Loss of enzymatic activity. No palmitoylation. Loss of membrane association. Ref.6
	Mutagenesis	180	1	H → A: Loss of enzymatic activity. Ref.7
	Mutagenesis	241	1	H → A: Decreasing protein levels. Loss of enzymatic activity. Significantly decreased protein stability. Ref.7
	Mutagenesis	313	1	H → A: Decreasing protein levels. Loss of enzymatic activity. Significantly decreased protein stability. Ref.7
	Mutagenesis	469	1	E → A: Decreasing protein levels. Loss of enzymatic activity. Ref.7
	Mutagenesis	469	1	E → Q: Decreasing protein levels. Loss of enzymatic activity. Ref.7
	Mutagenesis	527	1	H → A: Decreasing protein levels. Loss of enzymatic activity. Significantly decreased protein stability. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Q16518 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 7193C93F3325798D	FASTA	533	60,948
	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

References

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[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 [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]	"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].
[4]	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. , 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].
[5]	"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.
[6]	"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, MASS SPECTROMETRY.
[7]	"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.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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.
[16]	"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.
[17]	"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.
[18]	"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.
[19]	"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.
[20]	"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.
[21]	"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.
[22]	"Disease: Leber's congenital amaurosis." Gandra M., Sundaramurthy S., Kumaramanickavel G. Hum. Genet. 118:780-780(2006) Cited for: VARIANT LCA2 LEU-470.
[23]	"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.
[24]	"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.
[25]	"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. , 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.
[26]	"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.
[27]	"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. , 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.
+	Additional computationally mapped references.

Web resources

Mutations of the RPE65 gene

Retina International's Scientific Newsletter

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. AL139413 Genomic DNA. Translation: CAI18957.1. CH471059 Genomic DNA. Translation: EAX06478.1. BC075035 mRNA. Translation: AAH75035.1. BC075036 mRNA. Translation: AAH75036.1.
IPI	IPI00029250.
RefSeq	NP_000320.1. NM_000329.2.
UniGene	Hs.2133.
3D structure databases
ProteinModelPortal	Q16518.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000262340.
PTM databases
PhosphoSite	Q16518.
Polymorphism databases
DMDM	44888872.
Proteomic databases
PaxDb	Q16518.
PRIDE	Q16518.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262340; ENSP00000262340; ENSG00000116745.
GeneID	6121.
KEGG	hsa:6121.
UCSC	uc001dei.1. human.
Organism-specific databases
CTD	6121.
GeneCards	GC01M068894.
HGNC	HGNC:10294. RPE65.
MIM	180069. gene. 204100. phenotype. 613794. phenotype.
neXtProt	NX_Q16518.
Orphanet	180. Choroideremia. 65. Leber congenital amaurosis. 791. Retinitis pigmentosa.
PharmGKB	PA34655.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG3670.
HOGENOM	HOG000232156.
HOVERGEN	HBG050679.
InParanoid	Q16518.
KO	K11158.
OMA	WLHVADK.
OrthoDB	EOG47M1XK.
PhylomeDB	Q16518.
Enzyme and pathway databases
BioCyc	MetaCyc:ENSG00000116745-MONOMER.
Gene expression databases
ArrayExpress	Q16518.
Bgee	Q16518.
CleanEx	HS_RPE65.
Genevestigator	Q16518.
GermOnline	ENSG00000116745. Homo sapiens.
Family and domain databases
InterPro	IPR004294. Carotenoid_Oase. [Graphical view]
PANTHER	PTHR10543. PTHR10543. 1 hit.
Pfam	PF03055. RPE65. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	RPE65. human.
GenomeRNAi	6121.
NextBio	23773.
SOURCE	Search...

Entry information

Entry name

RPE65_HUMAN

Accession

Primary (citable) accession number: Q16518
Secondary accession number(s): Q5T9U3

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 10, 2003
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 107 of the entry and version 3 of the sequence. [Complete history]

Entry status

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.