RPE65_HUMAN
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 03-AUG-2022, entry version 178.
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 ---------------------------------------------------------------------------
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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; Q16518; -.
DR PeptideAtlas; Q16518; -.
DR PRIDE; Q16518; -.
DR ProteomicsDB; 60891; -.
DR Antibodypedia; 33418; 249 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 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; HHIPYGL; -.
DR OrthoDB; 895046at2759; -.
DR PhylomeDB; Q16518; -.
DR TreeFam; TF314019; -.
DR BioCyc; MetaCyc:ENSG00000116745-MON; -.
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; 24 hits in 1058 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 65 other tissues.
DR Genevisible; Q16518; HS.
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: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:0016702; F:oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; IEA:InterPro.
DR GO; GO:0031210; F:phosphatidylcholine binding; ISS:AgBase.
DR GO; GO:0001786; F:phosphatidylserine binding; ISS:AgBase.
DR GO; GO:0004744; F:retinal isomerase activity; IEA:Ensembl.
DR GO; GO:0050251; F:retinol isomerase activity; IBA:GO_Central.
DR GO; GO:0071257; P:cellular response to electrical stimulus; IEA:Ensembl.
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:0008286; P:insulin receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0003407; P:neural retina development; IEA:Ensembl.
DR GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl.
DR GO; GO:0001895; P:retina homeostasis; IMP:UniProtKB.
DR GO; GO:0060042; P:retina morphogenesis in camera-type eye; IEA:Ensembl.
DR GO; GO:0042574; P:retinal metabolic process; IEA:Ensembl.
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; PTHR10543; 1.
DR Pfam; PF03055; RPE65; 1.
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; unknown pathological 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 pathological
FT significance; 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; unknown pathological 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; unknown pathological significance;
FT dbSNP:rs61752876)"
FT /evidence="ECO:0000269|PubMed:17964524"
FT /id="VAR_083293"
FT VARIANT 132
FT /note="A -> T (in RP20; unknown pathological 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; unknown pathological 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; unknown pathological
FT 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 variant; very mild
FT decrease 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; unknown pathological 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; unknown pathological 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 variant; no effect on
FT retinol 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; unknown pathological significance)"
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; unknown pathological significance;
FT does not affect protein abundance; does not affect
FT subcellular localization; does not affect isomerization
FT activity; may cause abnormal splicing mRNAs thereby
FT decreasing protein 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; unknown pathological 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
