ID RPE65_HUMAN Reviewed; 533 AA. AC Q16518; A8K1L0; Q5T9U3; DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 187. DE RecName: Full=Retinoid isomerohydrolase {ECO:0000305}; DE EC=3.1.1.64 {ECO:0000269|PubMed:25112876, ECO:0000269|PubMed:29659842}; DE AltName: Full=All-trans-retinyl-palmitate hydrolase; DE AltName: Full=Lutein isomerase; DE AltName: Full=Meso-zeaxanthin isomerase {ECO:0000303|PubMed:28874556}; DE EC=5.3.3.22 {ECO:0000269|PubMed:28874556}; DE AltName: Full=Retinal pigment epithelium-specific 65 kDa protein; DE AltName: Full=Retinol isomerase; GN Name=RPE65 {ECO:0000312|HGNC:HGNC:10294}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RC TISSUE=Retinal pigment epithelium; RX PubMed=7633413; DOI=10.1093/hmg/4.4.641; RA Nicoletti A., Wong D.J., Kawase K., Gibson L.H., Yang-Feng T.L., RA Richards J.E., Thompson D.A.; RT "Molecular characterization of the human gene encoding an abundant 61 kDa RT protein specific to the retinal pigment epithelium."; RL Hum. Mol. Genet. 4:641-649(1995). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS RP20 TRP-91; LYS-102; RP THR-132; SER-341; GLY-452 AND ASP-473. RX PubMed=9501220; DOI=10.1073/pnas.95.6.3088; RA Morimura H., Fishman G.A., Grover S.A., Fulton A.B., Berson E.L., RA Dryja T.P.; RT "Mutations in the RPE65 gene in patients with autosomal recessive retinitis RT pigmentosa or Leber congenital amaurosis."; RL Proc. Natl. Acad. Sci. U.S.A. 95:3088-3093(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Hippocampus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Fetal brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PROTEIN SEQUENCE OF 98-118, PHOSPHORYLATION AT THR-101; THR-105 AND RP SER-117, PALMITOYLATION AT CYS-112, MUTAGENESIS OF CYS-106 AND CYS-112, RP ACETYLATION AT LYS-113, IDENTIFICATION BY MASS SPECTROMETRY, AND RP SUBCELLULAR LOCATION. RX PubMed=19049981; DOI=10.1074/jbc.m807248200; RA Takahashi Y., Moiseyev G., Ablonczy Z., Chen Y., Crouch R.K., Ma J.X.; RT "Identification of a novel palmitylation site essential for membrane RT association and isomerohydrolase activity of RPE65."; RL J. Biol. Chem. 284:3211-3218(2009). RN [8] RP MUTAGENESIS OF HIS-180; HIS-241; HIS-313; GLU-469 AND HIS-527. RX PubMed=16198348; DOI=10.1016/j.febslet.2005.09.002; RA Takahashi Y., Moiseyev G., Chen Y., Ma J.X.; RT "Identification of conserved histidines and glutamic acid as key residues RT for isomerohydrolase activity of RPE65, an enzyme of the visual cycle in RT the retinal pigment epithelium."; RL FEBS Lett. 579:5414-5418(2005). RN [9] RP FUNCTION. RX PubMed=16116091; DOI=10.1073/pnas.0503460102; RA Moiseyev G., Chen Y., Takahashi Y., Wu B.X., Ma J.X.; RT "RPE65 is the isomerohydrolase in the retinoid visual cycle."; RL Proc. Natl. Acad. Sci. U.S.A. 102:12413-12418(2005). RN [10] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=17848510; DOI=10.1073/pnas.0706367104; RA Jacobson S.G., Aleman T.S., Cideciyan A.V., Heon E., Golczak M., RA Beltran W.A., Sumaroka A., Schwartz S.B., Roman A.J., Windsor E.A., RA Wilson J.M., Aguirre G.D., Stone E.M., Palczewski K.; RT "Human cone photoreceptor dependence on RPE65 isomerase."; RL Proc. Natl. Acad. Sci. U.S.A. 104:15123-15128(2007). RN [11] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH MYO7A. RX PubMed=21493626; DOI=10.1093/hmg/ddr155; RA Lopes V.S., Gibbs D., Libby R.T., Aleman T.S., Welch D.L., Lillo C., RA Jacobson S.G., Radu R.A., Steel K.P., Williams D.S.; RT "The Usher 1B protein, MYO7A, is required for normal localization and RT function of the visual retinoid cycle enzyme, RPE65."; RL Hum. Mol. Genet. 20:2560-2570(2011). RN [12] RP MUTAGENESIS OF THR-39; CYS-106; ASN-170; LYS-297; CYS-330; GLN-497; LEU-510 RP AND SER-533, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=25112876; DOI=10.1074/jbc.m114.558619; RA Takahashi Y., Moiseyev G., Ma J.X.; RT "Identification of key residues determining isomerohydrolase activity of RT human RPE65."; RL J. Biol. Chem. 289:26743-26751(2014). RN [13] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=28874556; DOI=10.1073/pnas.1706332114; RA Shyam R., Gorusupudi A., Nelson K., Horvath M.P., Bernstein P.S.; RT "RPE65 has an additional function as the lutein to meso-zeaxanthin RT isomerase in the vertebrate eye."; RL Proc. Natl. Acad. Sci. U.S.A. 114:10882-10887(2017). RN [14] RP VARIANT LCA2 234-ARG--SER-533 DEL. RX PubMed=9326927; DOI=10.1038/ng1097-139; RA Marlhens F., Bareil C., Griffoin J.M., Zrenner E., Amalric P., Eliaou C., RA Liu S.Y., Harris E., Redmond T.M., Arnaud B., Claustres M., Hamel C.P.; RT "Mutations in RPE65 cause Leber's congenital amaurosis."; RL Nat. Genet. 17:139-141(1997). RN [15] RP VARIANT LCA2 THR-363. RX PubMed=9326941; DOI=10.1038/ng1097-194; RA Gu S.M., Thompson D.A., Srikumari C.R., Lorenz B., Finckh U., Nicoletti A., RA Murthy K.R., Rathmann M., Kumaramanickavel G., Denton M.J., Gal A.; RT "Mutations in RPE65 cause autosomal recessive childhood-onset severe RT retinal dystrophy."; RL Nat. Genet. 17:194-197(1997). RN [16] RP VARIANTS LCA2 PRO-22 AND TYR-68. RX PubMed=9801879; DOI=10.1038/sj.ejhg.5200205; RA Marlhens F., Griffoin J.-M., Bareil C., Arnaud B., Claustres M., RA Hamel C.P.; RT "Autosomal recessive retinal dystrophy associated with two novel mutations RT in the RPE65 gene."; RL Eur. J. Hum. Genet. 6:527-531(1998). RN [17] RP VARIANTS LCA2 TYR-330; THR-363 AND VAL-434. RX PubMed=10090910; DOI=10.1086/302335; RA Perrault I., Rozet J.-M., Ghazi I., Leowski C., Bonnemaison M., Gerber S., RA Ducroq D., Cabot A., Souied E., Dufier J.-L., Munnich A., Kaplan J.; RT "Different functional outcome of RetGC1 and RPE65 gene mutations in Leber RT congenital amaurosis."; RL Am. J. Hum. Genet. 64:1225-1228(1999). RN [18] RP VARIANTS LCA2 PHE-287 AND GLY-393, AND VARIANT LYS-321. RX PubMed=10766140; DOI=10.1001/archopht.118.4.538; RA Lotery A.J., Namperumalsamy P., Jacobson S.G., Weleber R.G., Fishman G.A., RA Musarella M.A., Hoyt C.S., Heon E., Levin A., Jan J., Lam B., Carr R.E., RA Franklin A., Radha S., Andorf J.L., Sheffield V.C., Stone E.M.; RT "Mutation analysis of 3 genes in patients with Leber congenital RT amaurosis."; RL Arch. Ophthalmol. 118:538-543(2000). RN [19] RP VARIANTS RP20 HIS-79; HIS-85; TRP-91; GLN-95; THR-132; TYR-167; THR-294; RP VAL-436 AND VAL-528. RX PubMed=11095629; RA Thompson D.A., Gyuerues P., Fleischer L.L., Bingham E.L., McHenry C.L., RA Apfelstedt-Sylla E., Zrenner E., Lorenz B., Richards J.E., Jacobson S.G., RA Sieving P.A., Gal A.; RT "Genetics and phenotypes of RPE65 mutations in inherited retinal RT degeneration."; RL Invest. Ophthalmol. Vis. Sci. 41:4293-4299(2000). RN [20] RP VARIANTS LCA2 SER-40; GLN-44; GLN-91; ASP-144; TYR-182 AND GLN-417, AND RP VARIANT LYS-321. RX PubMed=11462243; DOI=10.1002/humu.1168; RA Simovich M.J., Miller B., Ezzeldin H., Kirkland B.T., McLeod G., Fulmer C., RA Nathans J., Jacobson S.G., Pittler S.J.; RT "Four novel mutations in the RPE65 gene in patients with Leber congenital RT amaurosis."; RL Hum. Mutat. 18:164-164(2001). RN [21] RP VARIANT RP20 HIS-368. RX PubMed=12960219; DOI=10.1136/jmg.40.9.709; RA Yzer S., van den Born L.I., Schuil J., Kroes H.Y., van Genderen M.M., RA Boonstra F.N., van den Helm B., Brunner H.G., Koenekoop R.K., Cremers F.P.; RT "A Tyr368His RPE65 founder mutation is associated with variable expression RT and progression of early onset retinal dystrophy in 10 families of a RT genetically isolated population."; RL J. Med. Genet. 40:709-713(2003). RN [22] RP VARIANTS LCA2 36-LEU--LEU-38 DEL AND CYS-435. RX PubMed=14611946; DOI=10.1016/j.visres.2003.08.008; RA Sitorus R.S., Lorenz B., Preising M.N.; RT "Analysis of three genes in Leber congenital amaurosis in Indonesian RT patients."; RL Vision Res. 43:3087-3093(2003). RN [23] RP VARIANT LCA2 CYS-431. RX PubMed=14962443; DOI=10.1016/s0002-9394(03)00913-9; RA Al-Khayer K., Hagstrom S., Pauer G., Zegarra H., Sears J., Traboulsi E.I.; RT "Thirty-year follow-up of a patient with Leber congenital amaurosis and RT novel RPE65 mutations."; RL Am. J. Ophthalmol. 137:375-377(2004). RN [24] RP VARIANTS LCA2 GLN-44; ASP-148; ASN-182; TYR-330; THR-363; VAL-434 AND RP ASP-473. RX PubMed=15024725; DOI=10.1002/humu.20010; RA Hanein S., Perrault I., Gerber S., Tanguy G., Barbet F., Ducroq D., RA Calvas P., Dollfus H., Hamel C., Lopponen T., Munier F., Santos L., RA Shalev S., Zafeiriou D., Dufier J.-L., Munnich A., Rozet J.-M., Kaplan J.; RT "Leber congenital amaurosis: comprehensive survey of the genetic RT heterogeneity, refinement of the clinical definition, and genotype- RT phenotype correlations as a strategy for molecular diagnosis."; RL Hum. Mutat. 23:306-317(2004). RN [25] RP VARIANT RP20 TRP-515. RX PubMed=15557452; DOI=10.1167/iovs.04-0544; RA Kondo H., Qin M., Mizota A., Kondo M., Hayashi H., Hayashi K., Oshima K., RA Tahira T., Hayashi K.; RT "A homozygosity-based search for mutations in patients with autosomal RT recessive retinitis pigmentosa, using microsatellite markers."; RL Invest. Ophthalmol. Vis. Sci. 45:4433-4439(2004). RN [26] RP VARIANTS LCA2 SER-40; TRP-91; TYR-182; ASP-239; GLU-393 AND ASP-473. RX PubMed=16205573; DOI=10.1097/00006982-200510000-00016; RA Galvin J.A., Fishman G.A., Stone E.M., Koenekoop R.K.; RT "Evaluation of genotype-phenotype associations in Leber congenital RT amaurosis."; RL Retina 25:919-929(2005). RN [27] RP VARIANT LCA2 LEU-470. RX PubMed=17297704; RA Gandra M., Sundaramurthy S., Kumaramanickavel G.; RT "Gene symbol: RPE65. Disease: Leber's congenital amaurosis. Accession RT #Hm0548."; RL Hum. Genet. 118:780-780(2006). RN [28] RP VARIANTS LCA2 ILE-101; SER-118; PRO-162; ASN-318; 402-TRP--SER-533 DEL; RP PRO-408; ALA-443; 460-TRP--SER-533 DEL AND THR-533. RX PubMed=17964524; DOI=10.1016/j.ajo.2007.08.022; RA Stone E.M.; RT "Leber congenital amaurosis - a model for efficient genetic testing of RT heterogeneous disorders: LXIV Edward Jackson Memorial Lecture."; RL Am. J. Ophthalmol. 144:791-811(2007). RN [29] RP VARIANTS LCA2 PRO-22; VAL-70; PRO-91; LYS-102; ASP-144; TYR-167 AND RP ARG-313. RX PubMed=17724218; DOI=10.1167/iovs.07-0068; RA Simonelli F., Ziviello C., Testa F., Rossi S., Fazzi E., Bianchi P.E., RA Fossarello M., Signorini S., Bertone C., Galantuomo S., Brancati F., RA Valente E.M., Ciccodicola A., Rinaldi E., Auricchio A., Banfi S.; RT "Clinical and molecular genetics of Leber's congenital amaurosis: a RT multicenter study of Italian patients."; RL Invest. Ophthalmol. Vis. Sci. 48:4284-4290(2007). RN [30] RP VARIANT LCA2 TRP-91. RX PubMed=18682808; RA Seong M.W., Kim S.Y., Yu Y.S., Hwang J.M., Kim J.Y., Park S.S.; RT "Molecular characterization of Leber congenital amaurosis in Koreans."; RL Mol. Vis. 14:1429-1436(2008). RN [31] RP CHARACTERIZATION OF VARIANTS LCA2 SER-40; GLN-44; GLN-91; TRP-91; ILE-101; RP ASP-239; ASN-318; PRO-408 AND VAL-434, CHARACTERIZATION OF VARIANT LYS-321, RP AND CHARACTERIZATION OF VARIANT RP20 THR-294. RX PubMed=19431183; DOI=10.1002/humu.21033; RA Philp A.R., Jin M., Li S., Schindler E.I., Iannaccone A., Lam B.L., RA Weleber R.G., Fishman G.A., Jacobson S.G., Mullins R.F., Travis G.H., RA Stone E.M.; RT "Predicting the pathogenicity of RPE65 mutations."; RL Hum. Mutat. 30:1183-1188(2009). RN [32] RP INVOLVEMENT IN RP87, AND VARIANT RP87 GLY-477. RX PubMed=21654732; DOI=10.1038/ejhg.2011.86; RA Bowne S.J., Humphries M.M., Sullivan L.S., Kenna P.F., Tam L.C., RA Kiang A.S., Campbell M., Weinstock G.M., Koboldt D.C., Ding L., RA Fulton R.S., Sodergren E.J., Allman D., Millington-Ward S., Palfi A., RA McKee A., Blanton S.H., Slifer S., Konidari I., Farrar G.J., Daiger S.P., RA Humphries P.; RT "A dominant mutation in RPE65 identified by whole-exome sequencing causes RT retinitis pigmentosa with choroidal involvement."; RL Eur. J. Hum. Genet. 19:1074-1081(2011). RN [33] RP INVOLVEMENT IN RP87, AND VARIANT RP87 GLY-477. RX PubMed=27307694; RA Hull S., Mukherjee R., Holder G.E., Moore A.T., Webster A.R.; RT "The clinical features of retinal disease due to a dominant mutation in RT RPE65."; RL Mol. Vis. 22:626-635(2016). RN [34] RP CHARACTERIZATION OF VARIANT RP87 GLY-477, SUBCELLULAR LOCATION, AND RP CATALYTIC ACTIVITY. RX PubMed=29659842; DOI=10.1093/hmg/ddy128; RA Choi E.H., Suh S., Sander C.L., Hernandez C.J.O., Bulman E.R., Khadka N., RA Dong Z., Shi W., Palczewski K., Kiser P.D.; RT "Insights into the pathogenesis of dominant retinitis pigmentosa associated RT with a D477G mutation in RPE65."; RL Hum. Mol. Genet. 27:2225-2243(2018). RN [35] RP VARIANTS LCA2 ILE-99 AND ARG-333. RX PubMed=21602930; DOI=10.1371/journal.pone.0019458; RA Li L., Xiao X., Li S., Jia X., Wang P., Guo X., Jiao X., Zhang Q., RA Hejtmancik J.F.; RT "Detection of variants in 15 genes in 87 unrelated Chinese patients with RT Leber congenital amaurosis."; RL PLoS ONE 6:E19458-E19458(2011). RN [36] RP VARIANTS RP20 VAL-70; TRP-91; ASP-239 AND HIS-368. RX PubMed=22334370; DOI=10.1002/humu.22045; RA Neveling K., Collin R.W., Gilissen C., van Huet R.A., Visser L., RA Kwint M.P., Gijsen S.J., Zonneveld M.N., Wieskamp N., de Ligt J., RA Siemiatkowska A.M., Hoefsloot L.H., Buckley M.F., Kellner U., Branham K.E., RA den Hollander A.I., Hoischen A., Hoyng C., Klevering B.J., RA van den Born L.I., Veltman J.A., Cremers F.P., Scheffer H.; RT "Next-generation genetic testing for retinitis pigmentosa."; RL Hum. Mutat. 33:963-972(2012). RN [37] RP VARIANTS LCA2 ARG-67 AND CYS-368. RX PubMed=22509104; RA Xu F., Dong Q., Liu L., Li H., Liang X., Jiang R., Sui R., Dong F.; RT "Novel RPE65 mutations associated with Leber congenital amaurosis in RT Chinese patients."; RL Mol. Vis. 18:744-750(2012). RN [38] RP VARIANT RP20 PRO-60. RX PubMed=23878505; RA Kabir F., Naz S., Riazuddin S.A., Naeem M.A., Khan S.N., Husnain T., RA Akram J., Sieving P.A., Hejtmancik J.F., Riazuddin S.; RT "Novel mutations in RPE65 identified in consanguineous Pakistani families RT with retinal dystrophy."; RL Mol. Vis. 19:1554-1564(2013). RN [39] RP VARIANT LYS-321. RX PubMed=27535533; DOI=10.1038/nature19057; RG Exome Aggregation Consortium; RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T., RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T., RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J., RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M., RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N., RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P., RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A., RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G., RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M., RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C., RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M., RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M., RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P., RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G., RA Daly M.J., MacArthur D.G.; RT "Analysis of protein-coding genetic variation in 60,706 humans."; RL Nature 536:285-291(2016). RN [40] RP VARIANT LCA2 ASP-40. RX PubMed=28418496; DOI=10.1167/iovs.17-21424; RA Li L., Chen Y., Jiao X., Jin C., Jiang D., Tanwar M., Ma Z., Huang L., RA Ma X., Sun W., Chen J., Ma Y., M'hamdi O., Govindarajan G., Cabrera P.E., RA Li J., Gupta N., Naeem M.A., Khan S.N., Riazuddin S., Akram J., RA Ayyagari R., Sieving P.A., Riazuddin S.A., Hejtmancik J.F.; RT "Homozygosity Mapping and Genetic Analysis of Autosomal Recessive Retinal RT Dystrophies in 144 Consanguineous Pakistani Families."; RL Invest. Ophthalmol. Vis. Sci. 58:2218-2238(2017). RN [41] RP CHARACTERIZATION OF VARIANT RP87 GLY-477. RX PubMed=30628748; DOI=10.1002/humu.23706; RA Li Y., Furhang R., Ray A., Duncan T., Soucy J., Mahdi R., Chaitankar V., RA Gieser L., Poliakov E., Qian H., Liu P., Dong L., Rogozin I.B., RA Redmond T.M.; RT "Aberrant RNA splicing is the major pathogenic effect in a knock-in mouse RT model of the dominantly inherited c.1430A>G human RPE65 mutation."; RL Hum. Mutat. 40:426-443(2019). CC -!- FUNCTION: Critical isomerohydrolase in the retinoid cycle involved in CC regeneration of 11-cis-retinal, the chromophore of rod and cone opsins. CC Catalyzes the cleavage and isomerization of all-trans-retinyl fatty CC acid esters to 11-cis-retinol which is further oxidized by 11-cis CC retinol dehydrogenase to 11-cis-retinal for use as visual chromophore CC (PubMed:16116091). Essential for the production of 11-cis retinal for CC both rod and cone photoreceptors (PubMed:17848510). Also capable of CC catalyzing the isomerization of lutein to meso-zeaxanthin an eye- CC specific carotenoid (PubMed:28874556). The soluble form binds vitamin A CC (all-trans-retinol), making it available for LRAT processing to all- CC trans-retinyl ester. The membrane form, palmitoylated by LRAT, binds CC all-trans-retinyl esters, making them available for IMH CC (isomerohydrolase) processing to all-cis-retinol. The soluble form is CC regenerated by transferring its palmitoyl groups onto 11-cis-retinol, a CC reaction catalyzed by LRAT (By similarity). CC {ECO:0000250|UniProtKB:Q28175, ECO:0000269|PubMed:16116091, CC ECO:0000269|PubMed:17848510, ECO:0000269|PubMed:28874556}. CC -!- CATALYTIC ACTIVITY: CC Reaction=an all-trans-retinyl ester + H2O = 11-cis-retinol + a fatty CC acid + H(+); Xref=Rhea:RHEA:31771, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16302, ChEBI:CHEBI:28868, CC ChEBI:CHEBI:63410; EC=3.1.1.64; CC Evidence={ECO:0000269|PubMed:29659842}; CC -!- CATALYTIC ACTIVITY: CC Reaction=lutein = (3R,3'S)-zeaxanthin; Xref=Rhea:RHEA:12729, CC ChEBI:CHEBI:28838, ChEBI:CHEBI:138919; EC=5.3.3.22; CC Evidence={ECO:0000269|PubMed:28874556}; CC -!- CATALYTIC ACTIVITY: CC Reaction=all-trans-retinyl hexadecanoate + H2O = 11-cis-retinol + H(+) CC + hexadecanoate; Xref=Rhea:RHEA:31775, ChEBI:CHEBI:7896, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16302, CC ChEBI:CHEBI:17616; EC=3.1.1.64; CC Evidence={ECO:0000269|PubMed:25112876}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; CC Evidence={ECO:0000250|UniProtKB:Q28175}; CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:Q28175}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.35 uM for all-trans-retinyl palmitate CC {ECO:0000269|PubMed:25112876}; CC Vmax=21 pmol/min/mg enzyme for all-trans-retinyl palmitate as CC substrate {ECO:0000269|PubMed:25112876}; CC -!- SUBUNIT: Interacts with MYO7A; this mediates light-dependent CC intracellular transport of RPE65. {ECO:0000269|PubMed:21493626}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:A9C3R9}. Cell CC membrane {ECO:0000269|PubMed:19049981}; Lipid-anchor CC {ECO:0000269|PubMed:19049981}. Microsome membrane CC {ECO:0000250|UniProtKB:Q28175}. Note=Attached to the membrane by a CC lipid anchor when palmitoylated (membrane form), soluble when CC unpalmitoylated. Undergoes light-dependent intracellular transport to CC become more concentrated in the central region of the retina pigment CC epithelium cells. {ECO:0000269|PubMed:19049981, CC ECO:0000269|PubMed:21493626}. CC -!- TISSUE SPECIFICITY: Retina (at protein level). Retinal pigment CC epithelium specific. {ECO:0000269|PubMed:17848510, CC ECO:0000269|PubMed:21493626}. CC -!- PTM: Palmitoylation by LRAT regulates ligand binding specificity; the CC palmitoylated form (membrane form) specifically binds all-trans- CC retinyl-palmitate, while the soluble unpalmitoylated form binds all- CC trans-retinol (vitamin A) (By similarity). CC {ECO:0000250|UniProtKB:Q28175}. CC -!- DISEASE: Leber congenital amaurosis 2 (LCA2) [MIM:204100]: A severe CC dystrophy of the retina, typically becoming evident in the first years CC of life. Visual function is usually poor and often accompanied by CC nystagmus, sluggish or near-absent pupillary responses, photophobia, CC high hyperopia and keratoconus. {ECO:0000269|PubMed:10090910, CC ECO:0000269|PubMed:10766140, ECO:0000269|PubMed:11462243, CC ECO:0000269|PubMed:14611946, ECO:0000269|PubMed:14962443, CC ECO:0000269|PubMed:15024725, ECO:0000269|PubMed:16205573, CC ECO:0000269|PubMed:17297704, ECO:0000269|PubMed:17724218, CC ECO:0000269|PubMed:17964524, ECO:0000269|PubMed:18682808, CC ECO:0000269|PubMed:19431183, ECO:0000269|PubMed:21602930, CC ECO:0000269|PubMed:22509104, ECO:0000269|PubMed:28418496, CC ECO:0000269|PubMed:9326927, ECO:0000269|PubMed:9326941, CC ECO:0000269|PubMed:9801879}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Retinitis pigmentosa 20 (RP20) [MIM:613794]: A retinal CC dystrophy belonging to the group of pigmentary retinopathies. Retinitis CC pigmentosa is characterized by retinal pigment deposits visible on CC fundus examination and primary loss of rod photoreceptor cells followed CC by secondary loss of cone photoreceptors. Patients typically have night CC vision blindness and loss of midperipheral visual field. As their CC condition progresses, they lose their far peripheral visual field and CC eventually central vision as well. {ECO:0000269|PubMed:11095629, CC ECO:0000269|PubMed:12960219, ECO:0000269|PubMed:15557452, CC ECO:0000269|PubMed:19431183, ECO:0000269|PubMed:22334370, CC ECO:0000269|PubMed:23878505, ECO:0000269|PubMed:9501220}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Retinitis pigmentosa 87 with choroidal involvement (RP87) CC [MIM:618697]: A form of retinitis pigmentosa, a retinal dystrophy CC belonging to the group of pigmentary retinopathies. Retinitis CC pigmentosa is characterized by retinal pigment deposits visible on CC fundus examination and primary loss of rod photoreceptor cells followed CC by secondary loss of cone photoreceptors. Patients typically have night CC vision blindness and loss of midperipheral visual field. RP87 is an CC autosomal dominant form characterized by a slowly progressive visual CC disturbance accompanied by extensive choroid/retinal atrophy that CC mimics certain aspects of choroideremia. Disease severity and age of CC onset are variable, and some carriers are unaffected. CC {ECO:0000269|PubMed:21654732, ECO:0000269|PubMed:27307694, CC ECO:0000269|PubMed:29659842, ECO:0000269|PubMed:30628748}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the carotenoid oxygenase family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Mutations of the RPE65 gene; Note=Retina CC International's Scientific Newsletter; CC URL="https://www.retina-international.org/files/sci-news/rpe65mut.htm"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U18991; AAA99012.1; -; mRNA. DR EMBL; U20510; AAC14586.1; -; Genomic_DNA. DR EMBL; U20476; AAC14586.1; JOINED; Genomic_DNA. DR EMBL; U20477; AAC14586.1; JOINED; Genomic_DNA. DR EMBL; U20478; AAC14586.1; JOINED; Genomic_DNA. DR EMBL; U20479; AAC14586.1; JOINED; Genomic_DNA. DR EMBL; U20481; AAC14586.1; JOINED; Genomic_DNA. DR EMBL; U20482; AAC14586.1; JOINED; Genomic_DNA. DR EMBL; U20484; AAC14586.1; JOINED; Genomic_DNA. DR EMBL; U20485; AAC14586.1; JOINED; Genomic_DNA. DR EMBL; U20486; AAC14586.1; JOINED; Genomic_DNA. DR EMBL; AF039868; AAC39660.1; -; Genomic_DNA. DR EMBL; AF039855; AAC39660.1; JOINED; Genomic_DNA. DR EMBL; AF039856; AAC39660.1; JOINED; Genomic_DNA. DR EMBL; AF039857; AAC39660.1; JOINED; Genomic_DNA. DR EMBL; AF039858; AAC39660.1; JOINED; Genomic_DNA. DR EMBL; AF039859; AAC39660.1; JOINED; Genomic_DNA. DR EMBL; AF039860; AAC39660.1; JOINED; Genomic_DNA. DR EMBL; AF039861; AAC39660.1; JOINED; Genomic_DNA. DR EMBL; AF039862; AAC39660.1; JOINED; Genomic_DNA. DR EMBL; AF039863; AAC39660.1; JOINED; Genomic_DNA. DR EMBL; AF039864; AAC39660.1; JOINED; Genomic_DNA. DR EMBL; AF039865; AAC39660.1; JOINED; Genomic_DNA. DR EMBL; AF039866; AAC39660.1; JOINED; Genomic_DNA. DR EMBL; AF039867; AAC39660.1; JOINED; Genomic_DNA. DR EMBL; AK289925; BAF82614.1; -; mRNA. DR EMBL; AL139413; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX06478.1; -; Genomic_DNA. DR EMBL; BC075035; AAH75035.1; -; mRNA. DR EMBL; BC075036; AAH75036.1; -; mRNA. DR CCDS; CCDS643.1; -. DR RefSeq; NP_000320.1; NM_000329.2. DR AlphaFoldDB; Q16518; -. DR SMR; Q16518; -. DR BioGRID; 112041; 10. DR IntAct; Q16518; 4. DR STRING; 9606.ENSP00000262340; -. DR BindingDB; Q16518; -. DR ChEMBL; CHEMBL3831182; -. DR DrugBank; DB13932; Voretigene neparvovec. DR SwissLipids; SLP:000000687; -. DR iPTMnet; Q16518; -. DR PhosphoSitePlus; Q16518; -. DR SwissPalm; Q16518; -. DR BioMuta; RPE65; -. DR DMDM; 44888872; -. DR MassIVE; Q16518; -. DR PaxDb; 9606-ENSP00000262340; -. DR PeptideAtlas; Q16518; -. DR ProteomicsDB; 60891; -. DR Antibodypedia; 33418; 289 antibodies from 33 providers. DR DNASU; 6121; -. DR Ensembl; ENST00000262340.6; ENSP00000262340.5; ENSG00000116745.7. DR GeneID; 6121; -. DR KEGG; hsa:6121; -. DR MANE-Select; ENST00000262340.6; ENSP00000262340.5; NM_000329.3; NP_000320.1. DR UCSC; uc001dei.2; human. DR AGR; HGNC:10294; -. DR CTD; 6121; -. DR DisGeNET; 6121; -. DR GeneCards; RPE65; -. DR GeneReviews; RPE65; -. DR HGNC; HGNC:10294; RPE65. DR HPA; ENSG00000116745; Tissue enhanced (brain, choroid plexus, retina, seminal vesicle). DR MalaCards; RPE65; -. DR MIM; 180069; gene. DR MIM; 204100; phenotype. DR MIM; 613794; phenotype. DR MIM; 618697; phenotype. DR neXtProt; NX_Q16518; -. DR OpenTargets; ENSG00000116745; -. DR Orphanet; 65; Leber congenital amaurosis. DR Orphanet; 791; Retinitis pigmentosa. DR Orphanet; 364055; Severe early-childhood-onset retinal dystrophy. DR PharmGKB; PA34655; -. DR VEuPathDB; HostDB:ENSG00000116745; -. DR eggNOG; KOG1285; Eukaryota. DR GeneTree; ENSGT00950000182913; -. DR HOGENOM; CLU_016472_1_1_1; -. DR InParanoid; Q16518; -. DR OMA; VHHPFDG; -. DR OrthoDB; 294919at2759; -. DR PhylomeDB; Q16518; -. DR TreeFam; TF314019; -. DR BioCyc; MetaCyc:ENSG00000116745-MONOMER; -. DR BRENDA; 3.1.1.64; 2681. DR BRENDA; 5.3.3.22; 2681. DR PathwayCommons; Q16518; -. DR Reactome; R-HSA-2453902; The canonical retinoid cycle in rods (twilight vision). DR SignaLink; Q16518; -. DR BioGRID-ORCS; 6121; 25 hits in 1138 CRISPR screens. DR ChiTaRS; RPE65; human. DR GeneWiki; RPE65; -. DR GenomeRNAi; 6121; -. DR Pharos; Q16518; Tbio. DR PRO; PR:Q16518; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q16518; Protein. DR Bgee; ENSG00000116745; Expressed in pigmented layer of retina and 66 other cell types or tissues. DR GO; GO:0044297; C:cell body; IEA:Ensembl. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; ISS:AgBase. DR GO; GO:0005634; C:nucleus; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0052885; F:all-trans-retinyl-ester hydrolase, 11-cis retinol forming activity; ISS:AgBase. DR GO; GO:0052884; F:all-trans-retinyl-palmitate hydrolase, 11-cis retinol forming activity; IDA:UniProtKB. DR GO; GO:0003834; F:beta-carotene 15,15'-dioxygenase activity; IBA:GO_Central. DR GO; GO:1901612; F:cardiolipin binding; ISS:AgBase. DR GO; GO:0016853; F:isomerase activity; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0031210; F:phosphatidylcholine binding; ISS:AgBase. DR GO; GO:0001786; F:phosphatidylserine binding; ISS:AgBase. DR GO; GO:0050251; F:retinol isomerase activity; IBA:GO_Central. DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl. DR GO; GO:0050908; P:detection of light stimulus involved in visual perception; IMP:UniProtKB. DR GO; GO:0003407; P:neural retina development; IEA:Ensembl. DR GO; GO:0001895; P:retina homeostasis; IMP:UniProtKB. DR GO; GO:0042574; P:retinal metabolic process; IBA:GO_Central. DR GO; GO:0001523; P:retinoid metabolic process; IDA:UniProtKB. DR GO; GO:0007601; P:visual perception; TAS:ProtInc. DR GO; GO:0006776; P:vitamin A metabolic process; TAS:ProtInc. DR GO; GO:1901827; P:zeaxanthin biosynthetic process; IDA:UniProtKB. DR InterPro; IPR004294; Carotenoid_Oase. DR PANTHER; PTHR10543; BETA-CAROTENE DIOXYGENASE; 1. DR PANTHER; PTHR10543:SF57; RETINOID ISOMEROHYDROLASE; 1. DR Pfam; PF03055; RPE65; 1. DR Genevisible; Q16518; HS. PE 1: Evidence at protein level; KW Acetylation; Cell membrane; Cytoplasm; Direct protein sequencing; KW Disease variant; Endoplasmic reticulum; Hydrolase; Iron; Isomerase; KW Leber congenital amaurosis; Lipid metabolism; Lipoprotein; Membrane; KW Metal-binding; Microsome; Palmitate; Phosphoprotein; Reference proteome; KW Retinitis pigmentosa; Sensory transduction; Vision. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:Q28175" FT CHAIN 2..533 FT /note="Retinoid isomerohydrolase" FT /id="PRO_0000143943" FT BINDING 180 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:Q28175" FT BINDING 241 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:Q28175" FT BINDING 313 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:Q28175" FT BINDING 527 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:Q28175" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000250|UniProtKB:Q28175" FT MOD_RES 101 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:19049981" FT MOD_RES 105 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:19049981" FT MOD_RES 113 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:19049981" FT MOD_RES 117 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19049981" FT LIPID 112 FT /note="S-palmitoyl cysteine; in membrane form" FT /evidence="ECO:0000269|PubMed:19049981" FT LIPID 231 FT /note="S-palmitoyl cysteine; in membrane form" FT /evidence="ECO:0000250|UniProtKB:Q28175" FT LIPID 329 FT /note="S-palmitoyl cysteine; in membrane form" FT /evidence="ECO:0000250|UniProtKB:Q28175" FT LIPID 330 FT /note="S-palmitoyl cysteine; in membrane form" FT /evidence="ECO:0000250" FT VARIANT 22 FT /note="L -> P (in LCA2; dbSNP:rs61751277)" FT /evidence="ECO:0000269|PubMed:17724218, FT ECO:0000269|PubMed:9801879" FT /id="VAR_017126" FT VARIANT 36..38 FT /note="Missing (in LCA2)" FT /evidence="ECO:0000269|PubMed:14611946" FT /id="VAR_060808" FT VARIANT 40 FT /note="G -> D (in LCA2)" FT /evidence="ECO:0000269|PubMed:28418496" FT /id="VAR_081684" FT VARIANT 40 FT /note="G -> S (in LCA2; reduced protein levels; decreased FT function in the retinoid cycle; dbSNP:rs61751281)" FT /evidence="ECO:0000269|PubMed:11462243, FT ECO:0000269|PubMed:16205573, ECO:0000269|PubMed:19431183" FT /id="VAR_017127" FT VARIANT 44 FT /note="R -> Q (in LCA2; severely decreased retinol FT isomerase activity; dbSNP:rs61751282)" FT /evidence="ECO:0000269|PubMed:11462243, FT ECO:0000269|PubMed:15024725, ECO:0000269|PubMed:19431183" FT /id="VAR_017128" FT VARIANT 60 FT /note="L -> P (in RP20; dbSNP:rs1266217912)" FT /evidence="ECO:0000269|PubMed:23878505" FT /id="VAR_071672" FT VARIANT 67 FT /note="L -> R (in LCA2; uncertain significance; FT dbSNP:rs1344724754)" FT /evidence="ECO:0000269|PubMed:22509104" FT /id="VAR_070172" FT VARIANT 68 FT /note="H -> Y (in LCA2; dbSNP:rs61752866)" FT /evidence="ECO:0000269|PubMed:9801879" FT /id="VAR_017129" FT VARIANT 70 FT /note="F -> V (in LCA2 and RP20)" FT /evidence="ECO:0000269|PubMed:17724218, FT ECO:0000269|PubMed:22334370" FT /id="VAR_067160" FT VARIANT 79 FT /note="Y -> H (in RP20; dbSNP:rs61752869)" FT /evidence="ECO:0000269|PubMed:11095629" FT /id="VAR_060809" FT VARIANT 85 FT /note="R -> H (in RP20; uncertain significance; FT dbSNP:rs61752870)" FT /evidence="ECO:0000269|PubMed:11095629" FT /id="VAR_060810" FT VARIANT 91 FT /note="R -> P (in LCA2; dbSNP:rs61752873)" FT /evidence="ECO:0000269|PubMed:17724218" FT /id="VAR_067161" FT VARIANT 91 FT /note="R -> Q (in LCA2; severely decreased retinol FT isomerase activity; dbSNP:rs61752873)" FT /evidence="ECO:0000269|PubMed:11462243, FT ECO:0000269|PubMed:19431183" FT /id="VAR_017131" FT VARIANT 91 FT /note="R -> W (in RP20 and LCA2; reduced protein levels; FT decreased function in the retinoid cycle; FT dbSNP:rs61752871)" FT /evidence="ECO:0000269|PubMed:11095629, FT ECO:0000269|PubMed:16205573, ECO:0000269|PubMed:18682808, FT ECO:0000269|PubMed:19431183, ECO:0000269|PubMed:22334370, FT ECO:0000269|PubMed:9501220" FT /id="VAR_017130" FT VARIANT 95 FT /note="E -> Q (in RP20; dbSNP:rs61752874)" FT /evidence="ECO:0000269|PubMed:11095629" FT /id="VAR_060811" FT VARIANT 99 FT /note="V -> I (in LCA2; uncertain significance; FT dbSNP:rs143056561)" FT /evidence="ECO:0000269|PubMed:21602930" FT /id="VAR_067162" FT VARIANT 101 FT /note="T -> I (in LCA2; severely decreased retinol FT isomerase activity; dbSNP:rs1444234037)" FT /evidence="ECO:0000269|PubMed:17964524, FT ECO:0000269|PubMed:19431183" FT /id="VAR_083292" FT VARIANT 102 FT /note="E -> K (in RP20 and LCA2; dbSNP:rs62642584)" FT /evidence="ECO:0000269|PubMed:17724218, FT ECO:0000269|PubMed:9501220" FT /id="VAR_060812" FT VARIANT 118 FT /note="R -> S (in LCA2; uncertain significance; FT dbSNP:rs61752876)" FT /evidence="ECO:0000269|PubMed:17964524" FT /id="VAR_083293" FT VARIANT 132 FT /note="A -> T (in RP20; uncertain significance; FT dbSNP:rs61752878)" FT /evidence="ECO:0000269|PubMed:11095629, FT ECO:0000269|PubMed:9501220" FT /id="VAR_017132" FT VARIANT 144 FT /note="Y -> D (in LCA2; dbSNP:rs61752880)" FT /evidence="ECO:0000269|PubMed:11462243, FT ECO:0000269|PubMed:17724218" FT /id="VAR_017133" FT VARIANT 148 FT /note="E -> D (in LCA2; dbSNP:rs61752882)" FT /evidence="ECO:0000269|PubMed:15024725" FT /id="VAR_060813" FT VARIANT 162 FT /note="T -> P (in LCA2; uncertain significance; FT dbSNP:rs774309607)" FT /evidence="ECO:0000269|PubMed:17964524" FT /id="VAR_083294" FT VARIANT 167 FT /note="D -> Y (in RP20 and LCA2; dbSNP:rs61752883)" FT /evidence="ECO:0000269|PubMed:11095629, FT ECO:0000269|PubMed:17724218" FT /id="VAR_060814" FT VARIANT 182 FT /note="H -> N (in LCA2; dbSNP:rs61752884)" FT /evidence="ECO:0000269|PubMed:15024725" FT /id="VAR_060815" FT VARIANT 182 FT /note="H -> Y (in LCA2; dbSNP:rs61752884)" FT /evidence="ECO:0000269|PubMed:11462243, FT ECO:0000269|PubMed:16205573" FT /id="VAR_017134" FT VARIANT 234..533 FT /note="Missing (in LCA2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:9326927" FT /id="VAR_080043" FT VARIANT 239 FT /note="Y -> D (in LCA2 and RP20; severely decreased retinol FT isomerase activity; dbSNP:rs61752896)" FT /evidence="ECO:0000269|PubMed:16205573, FT ECO:0000269|PubMed:19431183, ECO:0000269|PubMed:22334370" FT /id="VAR_060816" FT VARIANT 287 FT /note="V -> F (in LCA2; dbSNP:rs281865289)" FT /evidence="ECO:0000269|PubMed:10766140" FT /id="VAR_017135" FT VARIANT 294 FT /note="K -> T (in RP20; likely benign; very mild decrease FT of retinol isomerase activity; dbSNP:rs61752901)" FT /evidence="ECO:0000269|PubMed:11095629, FT ECO:0000269|PubMed:19431183" FT /id="VAR_060817" FT VARIANT 313 FT /note="H -> R (in LCA2; dbSNP:rs1375943362)" FT /evidence="ECO:0000269|PubMed:17724218" FT /id="VAR_067163" FT VARIANT 318 FT /note="Y -> N (in LCA2; severely decreased retinol FT isomerase activity; dbSNP:rs61752905)" FT /evidence="ECO:0000269|PubMed:17964524, FT ECO:0000269|PubMed:19431183" FT /id="VAR_083295" FT VARIANT 321 FT /note="N -> K (no effect on retinol isomerase activity; FT dbSNP:rs149916178)" FT /evidence="ECO:0000269|PubMed:10766140, FT ECO:0000269|PubMed:11462243, ECO:0000269|PubMed:19431183, FT ECO:0000269|PubMed:27535533" FT /id="VAR_017136" FT VARIANT 330 FT /note="C -> Y (in LCA2; dbSNP:rs61752908)" FT /evidence="ECO:0000269|PubMed:10090910, FT ECO:0000269|PubMed:15024725" FT /id="VAR_060818" FT VARIANT 333 FT /note="G -> R (in LCA2; uncertain significance; FT dbSNP:rs1459522532)" FT /evidence="ECO:0000269|PubMed:21602930" FT /id="VAR_067164" FT VARIANT 341 FT /note="L -> S (in RP20; dbSNP:rs61752909)" FT /evidence="ECO:0000269|PubMed:9501220" FT /id="VAR_017137" FT VARIANT 363 FT /note="P -> T (in LCA2; dbSNP:rs121917744)" FT /evidence="ECO:0000269|PubMed:10090910, FT ECO:0000269|PubMed:15024725, ECO:0000269|PubMed:9326941" FT /id="VAR_017138" FT VARIANT 368 FT /note="Y -> C (in LCA2; uncertain significance; FT dbSNP:rs62653012)" FT /evidence="ECO:0000269|PubMed:22509104" FT /id="VAR_070173" FT VARIANT 368 FT /note="Y -> H (in RP20; dbSNP:rs62653011)" FT /evidence="ECO:0000269|PubMed:12960219, FT ECO:0000269|PubMed:22334370" FT /id="VAR_017139" FT VARIANT 393 FT /note="A -> E (in LCA2)" FT /evidence="ECO:0000269|PubMed:16205573" FT /id="VAR_060819" FT VARIANT 393 FT /note="A -> G (in LCA2; dbSNP:rs62635773)" FT /evidence="ECO:0000269|PubMed:10766140" FT /id="VAR_017140" FT VARIANT 402..533 FT /note="Missing (in LCA2)" FT /evidence="ECO:0000269|PubMed:17964524" FT /id="VAR_083296" FT VARIANT 408 FT /note="L -> P (in LCA2; severely decreased retinol FT isomerase activity; dbSNP:rs62636298)" FT /evidence="ECO:0000269|PubMed:17964524, FT ECO:0000269|PubMed:19431183" FT /id="VAR_083297" FT VARIANT 417 FT /note="E -> Q (in LCA2; dbSNP:rs62636299)" FT /evidence="ECO:0000269|PubMed:11462243" FT /id="VAR_017141" FT VARIANT 431 FT /note="Y -> C (in LCA2; dbSNP:rs62636300)" FT /evidence="ECO:0000269|PubMed:14962443" FT /id="VAR_018151" FT VARIANT 434 FT /note="A -> V (in LCA2; benign; no effect on retinol FT isomerase activity; dbSNP:rs34627040)" FT /evidence="ECO:0000269|PubMed:10090910, FT ECO:0000269|PubMed:15024725, ECO:0000269|PubMed:19431183" FT /id="VAR_034477" FT VARIANT 435 FT /note="Y -> C (in LCA2; dbSNP:rs62636302)" FT /evidence="ECO:0000269|PubMed:14611946" FT /id="VAR_060820" FT VARIANT 436 FT /note="G -> V (in RP20; dbSNP:rs62637002)" FT /evidence="ECO:0000269|PubMed:11095629" FT /id="VAR_060821" FT VARIANT 443 FT /note="V -> A (in LCA2; uncertain significance; FT dbSNP:rs1645824187)" FT /evidence="ECO:0000269|PubMed:17964524" FT /id="VAR_083298" FT VARIANT 452 FT /note="V -> G (in RP20; dbSNP:rs62637004)" FT /evidence="ECO:0000269|PubMed:9501220" FT /id="VAR_017142" FT VARIANT 460..533 FT /note="Missing (in LCA2)" FT /evidence="ECO:0000269|PubMed:17964524" FT /id="VAR_083299" FT VARIANT 470 FT /note="P -> L (in LCA2; dbSNP:rs774211361)" FT /evidence="ECO:0000269|PubMed:17297704" FT /id="VAR_060822" FT VARIANT 473 FT /note="V -> D (in RP20; dbSNP:rs62637007)" FT /evidence="ECO:0000269|PubMed:15024725, FT ECO:0000269|PubMed:16205573, ECO:0000269|PubMed:9501220" FT /id="VAR_060823" FT VARIANT 477 FT /note="D -> G (in RP87; uncertain significance; does not FT affect protein abundance; does not affect subcellular FT localization; does not affect isomerization activity; may FT cause abnormal splicing mRNAs thereby decreasing protein FT levels; dbSNP:rs1571158279)" FT /evidence="ECO:0000269|PubMed:21654732, FT ECO:0000269|PubMed:27307694, ECO:0000269|PubMed:29659842, FT ECO:0000269|PubMed:30628748" FT /id="VAR_067757" FT VARIANT 515 FT /note="R -> W (in RP20; dbSNP:rs121917745)" FT /evidence="ECO:0000269|PubMed:15557452" FT /id="VAR_037619" FT VARIANT 528 FT /note="G -> V (in RP20; dbSNP:rs1193631220)" FT /evidence="ECO:0000269|PubMed:11095629" FT /id="VAR_060824" FT VARIANT 533 FT /note="S -> T (in LCA2; uncertain significance; FT dbSNP:rs577335767)" FT /evidence="ECO:0000269|PubMed:17964524" FT /id="VAR_083300" FT MUTAGEN 39 FT /note="T->R: Does not affect isomerohydrolase activity." FT /evidence="ECO:0000269|PubMed:25112876" FT MUTAGEN 106 FT /note="C->A: No loss of enzymatic activity. No effect on FT palmitoylation. No loss of membrane association." FT /evidence="ECO:0000269|PubMed:19049981" FT MUTAGEN 106 FT /note="C->Y: Does not affect isomerohydrolase activity." FT /evidence="ECO:0000269|PubMed:25112876" FT MUTAGEN 112 FT /note="C->A: Loss of enzymatic activity. No palmitoylation. FT Loss of membrane association." FT /evidence="ECO:0000269|PubMed:19049981" FT MUTAGEN 170 FT /note="N->K: Increased isomerohydrolase activity." FT /evidence="ECO:0000269|PubMed:25112876" FT MUTAGEN 180 FT /note="H->A: Loss of enzymatic activity." FT /evidence="ECO:0000269|PubMed:16198348" FT MUTAGEN 241 FT /note="H->A: Decreasing protein levels. Loss of enzymatic FT activity. Significantly decreased protein stability." FT /evidence="ECO:0000269|PubMed:16198348" FT MUTAGEN 297 FT /note="K->G: Increased isomerohydrolase activity." FT /evidence="ECO:0000269|PubMed:25112876" FT MUTAGEN 313 FT /note="H->A: Decreasing protein levels. Loss of enzymatic FT activity. Significantly decreased protein stability." FT /evidence="ECO:0000269|PubMed:16198348" FT MUTAGEN 330 FT /note="C->T: Does not affect isomerohydrolase activity." FT /evidence="ECO:0000269|PubMed:25112876" FT MUTAGEN 469 FT /note="E->A: Decreasing protein levels. Loss of enzymatic FT activity." FT /evidence="ECO:0000269|PubMed:16198348" FT MUTAGEN 469 FT /note="E->Q: Decreasing protein levels. Loss of enzymatic FT activity." FT /evidence="ECO:0000269|PubMed:16198348" FT MUTAGEN 497 FT /note="Q->P: Does not affect isomerohydrolase activity." FT /evidence="ECO:0000269|PubMed:25112876" FT MUTAGEN 510 FT /note="L->M: Does not affect isomerohydrolase activity." FT /evidence="ECO:0000269|PubMed:25112876" FT MUTAGEN 527 FT /note="H->A: Decreasing protein levels. Loss of enzymatic FT activity. Significantly decreased protein stability." FT /evidence="ECO:0000269|PubMed:16198348" FT MUTAGEN 533 FT /note="S->A: Does not affect isomerohydrolase activity." FT /evidence="ECO:0000269|PubMed:25112876" FT CONFLICT 254 FT /note="E -> G (in Ref. 3; BAF82614)" FT /evidence="ECO:0000305" FT CONFLICT 274 FT /note="N -> D (in Ref. 3; BAF82614)" FT /evidence="ECO:0000305" SQ SEQUENCE 533 AA; 60948 MW; 7193C93F3325798D CRC64; MSIQVEHPAG GYKKLFETVE ELSSPLTAHV TGRIPLWLTG SLLRCGPGLF EVGSEPFYHL FDGQALLHKF DFKEGHVTYH RRFIRTDAYV RAMTEKRIVI TEFGTCAFPD PCKNIFSRFF SYFRGVEVTD NALVNVYPVG EDYYACTETN FITKINPETL ETIKQVDLCN YVSVNGATAH PHIENDGTVY NIGNCFGKNF SIAYNIVKIP PLQADKEDPI SKSEIVVQFP CSDRFKPSYV HSFGLTPNYI VFVETPVKIN LFKFLSSWSL WGANYMDCFE SNETMGVWLH IADKKRKKYL NNKYRTSPFN LFHHINTYED NGFLIVDLCC WKGFEFVYNY LYLANLRENW EEVKKNARKA PQPEVRRYVL PLNIDKADTG KNLVTLPNTT ATAILCSDET IWLEPEVLFS GPRQAFEFPQ INYQKYCGKP YTYAYGLGLN HFVPDRLCKL NVKTKETWVW QEPDSYPSEP IFVSHPDALE EDDGVVLSVV VSPGAGQKPA YLLILNAKDL SEVARAEVEI NIPVTFHGLF KKS //