RDH5_HUMAN
ID RDH5_HUMAN Reviewed; 318 AA.
AC Q92781; O00179; Q8TAI2;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Retinol dehydrogenase 5;
DE EC=1.1.1.209 {ECO:0000269|PubMed:29541409, ECO:0000269|PubMed:9931293};
DE EC=1.1.1.315 {ECO:0000269|PubMed:10588954, ECO:0000269|PubMed:11675386, ECO:0000269|PubMed:9931293};
DE EC=1.1.1.53 {ECO:0000269|PubMed:9931293};
DE AltName: Full=11-cis retinol dehydrogenase {ECO:0000303|PubMed:8884265};
DE Short=11-cis RDH;
DE Short=11-cis RoDH;
DE AltName: Full=9-cis retinol dehydrogenase;
DE Short=9cRDH;
DE AltName: Full=Short chain dehydrogenase/reductase family 9C member 5 {ECO:0000303|PubMed:19027726};
GN Name=RDH5 {ECO:0000312|HGNC:HGNC:9940};
GN Synonyms=HSD17B9, RDH1 {ECO:0000312|HGNC:HGNC:9940},
GN SDR9C5 {ECO:0000303|PubMed:19027726};
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 [MRNA].
RX PubMed=8884265; DOI=10.1006/geno.1996.0487;
RA Simon A., Lagercrantz J., Bajalica-Lagercrantz S., Eriksson U.;
RT "Primary structure of human 11-cis retinol dehydrogenase and organization
RT and chromosomal localization of the corresponding gene.";
RL Genomics 36:424-430(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, AND VARIANT GLY-70.
RC TISSUE=Mammary gland;
RX PubMed=9115228; DOI=10.1074/jbc.272.18.11744;
RA Mertz J.R., Shang E., Piantedosi R., Wei S., Wolgemuth D.J., Blaner W.S.;
RT "Identification and characterization of a stereospecific human enzyme that
RT catalyzes 9-cis-retinol oxidation. A possible role in 9-cis-retinoic acid
RT formation.";
RL J. Biol. Chem. 272:11744-11749(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Blood;
RA Gu S., Jablonka S., Gal A.;
RT "Retinol dehydrogenase: complete genomic sequence and its relationship to
RT retinitis pigmentosa.";
RL Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 [5]
RP CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=9931293; DOI=10.1042/bj3380023;
RA Wang J., Chai X., Eriksson U., Napoli J.L.;
RT "Activity of human 11-cis-retinol dehydrogenase (Rdh5) with steroids and
RT retinoids and expression of its mRNA in extra-ocular human tissue.";
RL Biochem. J. 338:23-27(1999).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=10588954;
RA Gamble M.V., Shang E., Zott R.P., Mertz J.R., Wolgemuth D.J., Blaner W.S.;
RT "Biochemical properties, tissue expression, and gene structure of a short
RT chain dehydrogenase/reductase able to catalyze cis-retinol oxidation.";
RL J. Lipid Res. 40:2279-2292(1999).
RN [7]
RP SUBUNIT, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF
RP VARIANTS FALBI SER-35; PHE-73; ILE-105; ASN-128; TRP-157; TRP-238; GLY-264;
RP HIS-280; PRO-294 AND LEU-310 DELINS GLU-VAL.
RX PubMed=11675386; DOI=10.1074/jbc.m107337200;
RA Liden M., Romert A., Tryggvason K., Persson B., Eriksson U.;
RT "Biochemical defects in 11-cis-retinol dehydrogenase mutants associated
RT with fundus albipunctatus.";
RL J. Biol. Chem. 276:49251-49257(2001).
RN [8]
RP GENE FAMILY, AND NOMENCLATURE.
RX PubMed=19027726; DOI=10.1016/j.cbi.2008.10.040;
RA Persson B., Kallberg Y., Bray J.E., Bruford E., Dellaporta S.L.,
RA Favia A.D., Duarte R.G., Joernvall H., Kavanagh K.L., Kedishvili N.,
RA Kisiela M., Maser E., Mindnich R., Orchard S., Penning T.M., Thornton J.M.,
RA Adamski J., Oppermann U.;
RT "The SDR (short-chain dehydrogenase/reductase and related enzymes)
RT nomenclature initiative.";
RL Chem. Biol. Interact. 178:94-98(2009).
RN [9]
RP VARIANTS FALBI TRP-238; HIS-280 AND PRO-294.
RX PubMed=10617778;
RA Gonzalez-Fernandez F., Kurz D., Bao Y., Newman S., Conway B.P., Young J.E.,
RA Han D.P., Khani S.C.;
RT "11-cis retinol dehydrogenase mutations as a major cause of the congenital
RT night-blindness disorder known as fundus albipunctatus.";
RL Mol. Vis. 5:41-41(1999).
RN [10]
RP VARIANTS FALBI PHE-73 AND TRP-238, AND VARIANT VAL-33.
RX PubMed=10369264; DOI=10.1038/9707;
RA Yamamoto H., Simon A., Eriksson U., Harris E., Berson E.L., Dryja T.P.;
RT "Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed
RT dark adaptation and fundus albipunctatus.";
RL Nat. Genet. 22:188-191(1999).
RN [11]
RP VARIANTS FALBI GLY-177 AND HIS-280.
RX PubMed=11078852; DOI=10.1016/s0002-9394(00)00765-0;
RA Kuroiwa S., Kikuchi T., Yoshimura N.;
RT "A novel compound heterozygous mutation in the RDH5 gene in a patient with
RT fundus albipunctatus.";
RL Am. J. Ophthalmol. 130:672-675(2000).
RN [12]
RP VARIANTS FALBI SER-35; ARG-107; MET-132; HIS-280; HIS-281 AND
RP 309-GLU-VAL-310 DELINS.
RX PubMed=11053295;
RA Nakamura M., Hotta Y., Tanikawa A., Terasaki H., Miyake Y.;
RT "A high association with cone dystrophy in Fundus albipunctatus caused by
RT mutations of the RDH5 gene.";
RL Invest. Ophthalmol. Vis. Sci. 41:3925-3932(2000).
RN [13]
RP VARIANTS FALBI GLY-264 AND LEU-310 DELINS GLU-VAL.
RX PubMed=11053296;
RA Hirose E., Inoue Y., Morimura H., Okamoto N., Fukuda M., Yamamoto S.,
RA Fujikado T., Tano Y.;
RT "Mutations in the 11-cis retinol dehydrogenase gene in Japanese patients
RT with Fundus albipunctatus.";
RL Invest. Ophthalmol. Vis. Sci. 41:3933-3935(2000).
RN [14]
RP VARIANT FALBI TRP-267.
RX PubMed=11470705; DOI=10.1016/s0161-6420(01)00640-6;
RA Driessen C.A., Janssen B.P., Winkens H.J., Kuhlmann L.D., Van Vugt A.H.,
RA Pinckers A.J., Deutman A.F., Janssen J.J.;
RT "Null mutation in the human 11-cis retinol dehydrogenase gene associated
RT with fundus albipunctatus.";
RL Ophthalmology 108:1479-1484(2001).
RN [15]
RP VARIANT FALBI ARG-107.
RX PubMed=12788147; DOI=10.1016/s0002-9394(02)02290-0;
RA Hotta K., Nakamura M., Kondo M., Ito S., Terasaki H., Miyake Y., Hida T.;
RT "Macular dystrophy in a Japanese family with fundus albipunctatus.";
RL Am. J. Ophthalmol. 135:917-919(2003).
RN [16]
RP VARIANT FALBI PHE-164.
RX PubMed=12967826; DOI=10.1016/s0002-9394(03)00332-5;
RA Yamamoto H., Yakushijin K., Kusuhara S., Escano M.F., Nagai A., Negi A.;
RT "A novel RDH5 gene mutation in a patient with fundus albipunctatus
RT presenting with macular atrophy and fading white dots.";
RL Am. J. Ophthalmol. 136:572-574(2003).
RN [17]
RP VARIANT FALBI ARG-253.
RX PubMed=22736946;
RA Ajmal M., Khan M.I., Neveling K., Khan Y.M., Ali S.H., Ahmed W.,
RA Iqbal M.S., Azam M., den Hollander A.I., Collin R.W., Qamar R.,
RA Cremers F.P.;
RT "Novel mutations in RDH5 cause fundus albipunctatus in two consanguineous
RT Pakistani families.";
RL Mol. Vis. 18:1558-1571(2012).
RN [18]
RP VARIANT FALBI ARG-179.
RX PubMed=24603341; DOI=10.1016/j.ygeno.2014.02.006;
RA Maranhao B., Biswas P., Duncan J.L., Branham K.E., Silva G.A., Naeem M.A.,
RA Khan S.N., Riazuddin S., Hejtmancik J.F., Heckenlively J.R.,
RA Riazuddin S.A., Lee P.L., Ayyagari R.;
RT "exomeSuite: Whole exome sequence variant filtering tool for rapid
RT identification of putative disease causing SNVs/indels.";
RL Genomics 103:169-176(2014).
RN [19]
RP VARIANT FALBI PHE-175.
RX PubMed=25820994; DOI=10.1007/s13353-015-0281-x;
RA Skorczyk-Werner A., Pawlowski P., Michalczuk M., Warowicka A., Wawrocka A.,
RA Wicher K., Bakunowicz-Lazarczyk A., Krawczynski M.R.;
RT "Fundus albipunctatus: review of the literature and report of a novel RDH5
RT gene mutation affecting the invariant tyrosine (p.Tyr175Phe).";
RL J. Appl. Genet. 56:317-327(2015).
RN [20]
RP VARIANTS FALBI ARG-179 AND ARG-253.
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 [21]
RP MUTAGENESIS OF 175-TYR--LYS-179, AND CATALYTIC ACTIVITY.
RX PubMed=29541409; DOI=10.18632/oncotarget.24107;
RA Fiandalo M.V., Stocking J.J., Pop E.A., Wilton J.H., Mantione K.M., Li Y.,
RA Attwood K.M., Azabdaftari G., Wu Y., Watt D.S., Wilson E.M., Mohler J.L.;
RT "Inhibition of dihydrotestosterone synthesis in prostate cancer by combined
RT frontdoor and backdoor pathway blockade.";
RL Oncotarget 9:11227-11242(2018).
CC -!- FUNCTION: Catalyzes the oxidation of cis-isomers of retinol, including
CC 11-cis-, 9-cis-, and 13-cis-retinol in an NAD-dependent manner
CC (PubMed:11675386, PubMed:10588954, PubMed:9931293, PubMed:9115228). Has
CC no activity towards all-trans retinal (By similarity). Plays a
CC significant role in 11-cis retinol oxidation in the retinal pigment
CC epithelium cells (RPE). Also recognizes steroids (androsterone,
CC androstanediol) as its substrates (PubMed:9931293, PubMed:29541409).
CC {ECO:0000250|UniProtKB:Q27979, ECO:0000269|PubMed:10588954,
CC ECO:0000269|PubMed:11675386, ECO:0000269|PubMed:29541409,
CC ECO:0000269|PubMed:9115228, ECO:0000269|PubMed:9931293}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11-cis-retinol + NAD(+) = 11-cis-retinal + H(+) + NADH;
CC Xref=Rhea:RHEA:42060, ChEBI:CHEBI:15378, ChEBI:CHEBI:16066,
CC ChEBI:CHEBI:16302, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC EC=1.1.1.315; Evidence={ECO:0000269|PubMed:10588954,
CC ECO:0000269|PubMed:11675386, ECO:0000269|PubMed:9931293};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=9-cis-retinol + NAD(+) = 9-cis-retinal + H(+) + NADH;
CC Xref=Rhea:RHEA:42052, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:78272, ChEBI:CHEBI:78273;
CC Evidence={ECO:0000269|PubMed:9115228, ECO:0000269|PubMed:9931293};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=13-cis-retinol + NAD(+) = 13-cis-retinal + H(+) + NADH;
CC Xref=Rhea:RHEA:42056, ChEBI:CHEBI:15378, ChEBI:CHEBI:45479,
CC ChEBI:CHEBI:45487, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:9931293};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3alpha-hydroxy-5alpha-androstan-17-one + NAD(+) = 5alpha-
CC androstan-3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:20381,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16032,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.209;
CC Evidence={ECO:0000269|PubMed:29541409, ECO:0000269|PubMed:9931293};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-androstane-3alpha,17beta-diol + NAD(+) = 17beta-
CC hydroxy-5alpha-androstan-3-one + H(+) + NADH; Xref=Rhea:RHEA:42004,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:36713,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.53;
CC Evidence={ECO:0000269|PubMed:9931293};
CC -!- ACTIVITY REGULATION: Inhibited by 9-cis-, 13-cis- and all-trans-
CC retinoic acids, with the most potent inhibitor being 13-cis-retinoic
CC acid. Weakly inhibited by oleic acid. {ECO:0000269|PubMed:10588954}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.5-8.0 for 9-cis retinol dehydrogenase activity.
CC {ECO:0000269|PubMed:9115228};
CC -!- PATHWAY: Cofactor metabolism; retinol metabolism.
CC {ECO:0000269|PubMed:9115228}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11675386}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:11675386}; Multi-pass membrane protein
CC {ECO:0000255}; Lumenal side {ECO:0000269|PubMed:11675386}.
CC -!- TISSUE SPECIFICITY: Widely expressed. In the eye, abundant in the
CC retinal pigment epithelium. {ECO:0000269|PubMed:9115228,
CC ECO:0000269|PubMed:9931293}.
CC -!- DOMAIN: The last 8 amino acids of the C-terminal tail are important for
CC a proper localization as well as for the in vivo enzymatic activity.
CC {ECO:0000250|UniProtKB:O55240}.
CC -!- DISEASE: Fundus albipunctatus (FALBI) [MIM:136880]: A form of fleck
CC retina disease characterized by discrete uniform white dots over the
CC entire fundus with greatest density in the mid-periphery and no macular
CC involvement. Night blindness occurs. Inheritance can be autosomal
CC dominant or autosomal recessive. {ECO:0000269|PubMed:10369264,
CC ECO:0000269|PubMed:10617778, ECO:0000269|PubMed:11053295,
CC ECO:0000269|PubMed:11053296, ECO:0000269|PubMed:11078852,
CC ECO:0000269|PubMed:11470705, ECO:0000269|PubMed:11675386,
CC ECO:0000269|PubMed:12788147, ECO:0000269|PubMed:12967826,
CC ECO:0000269|PubMed:22736946, ECO:0000269|PubMed:24603341,
CC ECO:0000269|PubMed:25820994, ECO:0000269|PubMed:28418496}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Mutations of the RDH5 gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/rdh5mut.htm";
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DR EMBL; U43559; AAC50725.1; -; mRNA.
DR EMBL; U89717; AAB93668.1; -; mRNA.
DR EMBL; AF037062; AAC09250.1; -; Genomic_DNA.
DR EMBL; BC028298; AAH28298.1; -; mRNA.
DR CCDS; CCDS31829.1; -.
DR RefSeq; NP_001186700.1; NM_001199771.1.
DR RefSeq; NP_002896.2; NM_002905.3.
DR AlphaFoldDB; Q92781; -.
DR SMR; Q92781; -.
DR BioGRID; 111892; 16.
DR IntAct; Q92781; 4.
DR STRING; 9606.ENSP00000257895; -.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB00162; Vitamin A.
DR DrugCentral; Q92781; -.
DR SwissLipids; SLP:000000797; -.
DR GlyGen; Q92781; 1 site.
DR iPTMnet; Q92781; -.
DR PhosphoSitePlus; Q92781; -.
DR BioMuta; RDH5; -.
DR DMDM; 2492753; -.
DR MassIVE; Q92781; -.
DR PaxDb; Q92781; -.
DR PeptideAtlas; Q92781; -.
DR PRIDE; Q92781; -.
DR ProteomicsDB; 75459; -.
DR Antibodypedia; 27694; 101 antibodies from 28 providers.
DR DNASU; 5959; -.
DR Ensembl; ENST00000257895.10; ENSP00000257895.6; ENSG00000135437.10.
DR Ensembl; ENST00000548082.1; ENSP00000447128.1; ENSG00000135437.10.
DR GeneID; 5959; -.
DR KEGG; hsa:5959; -.
DR MANE-Select; ENST00000257895.10; ENSP00000257895.6; NM_002905.5; NP_002896.2.
DR UCSC; uc001shk.4; human.
DR CTD; 5959; -.
DR DisGeNET; 5959; -.
DR GeneCards; RDH5; -.
DR HGNC; HGNC:9940; RDH5.
DR HPA; ENSG00000135437; Tissue enhanced (adipose tissue, liver).
DR MalaCards; RDH5; -.
DR MIM; 136880; phenotype.
DR MIM; 601617; gene.
DR neXtProt; NX_Q92781; -.
DR OpenTargets; ENSG00000135437; -.
DR Orphanet; 227796; Fundus albipunctatus.
DR Orphanet; 52427; Retinitis punctata albescens.
DR PharmGKB; PA34308; -.
DR VEuPathDB; HostDB:ENSG00000135437; -.
DR eggNOG; KOG1610; Eukaryota.
DR GeneTree; ENSGT00940000161168; -.
DR HOGENOM; CLU_010194_2_0_1; -.
DR InParanoid; Q92781; -.
DR OMA; WLTQNDF; -.
DR OrthoDB; 1313182at2759; -.
DR PhylomeDB; Q92781; -.
DR TreeFam; TF325617; -.
DR BioCyc; MetaCyc:HS06003-MON; -.
DR BRENDA; 1.1.1.300; 2681.
DR BRENDA; 1.1.1.315; 2681.
DR PathwayCommons; Q92781; -.
DR Reactome; R-HSA-2453864; Retinoid cycle disease events.
DR Reactome; R-HSA-2453902; The canonical retinoid cycle in rods (twilight vision).
DR Reactome; R-HSA-5365859; RA biosynthesis pathway.
DR SignaLink; Q92781; -.
DR SIGNOR; Q92781; -.
DR UniPathway; UPA00912; -.
DR BioGRID-ORCS; 5959; 13 hits in 1064 CRISPR screens.
DR GeneWiki; RDH5; -.
DR GenomeRNAi; 5959; -.
DR Pharos; Q92781; Tbio.
DR PRO; PR:Q92781; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q92781; protein.
DR Bgee; ENSG00000135437; Expressed in subcutaneous adipose tissue and 98 other tissues.
DR ExpressionAtlas; Q92781; baseline and differential.
DR Genevisible; Q92781; HS.
DR GO; GO:0044297; C:cell body; IEA:Ensembl.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0047044; F:androstan-3-alpha,17-beta-diol dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0047023; F:androsterone dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0004745; F:NAD-retinol dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0016229; F:steroid dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0001523; P:retinoid metabolic process; IDA:UniProtKB.
DR GO; GO:0042572; P:retinol metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0008202; P:steroid metabolic process; IDA:UniProtKB.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Disease variant; Endoplasmic reticulum; Glycoprotein; Lipid metabolism;
KW Membrane; NAD; Oxidoreductase; Reference proteome; Sensory transduction;
KW Steroid metabolism; Transmembrane; Transmembrane helix; Vision.
FT CHAIN 1..318
FT /note="Retinol dehydrogenase 5"
FT /id="PRO_0000054758"
FT TRANSMEM 1..21
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 22..288
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:O55240"
FT TRANSMEM 289..309
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 310..318
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT ACT_SITE 175
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:29541409"
FT BINDING 32..56
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 163
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CARBOHYD 160
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 21
FT /note="R -> Q (in dbSNP:rs3138143)"
FT /id="VAR_052321"
FT VARIANT 33
FT /note="I -> V (in dbSNP:rs62638195)"
FT /evidence="ECO:0000269|PubMed:10369264"
FT /id="VAR_009272"
FT VARIANT 35
FT /note="G -> S (in FALBI; decreased stability;
FT dbSNP:rs759359491)"
FT /evidence="ECO:0000269|PubMed:11053295,
FT ECO:0000269|PubMed:11675386"
FT /id="VAR_016814"
FT VARIANT 70
FT /note="R -> G (in dbSNP:rs1058635)"
FT /evidence="ECO:0000269|PubMed:9115228"
FT /id="VAR_052322"
FT VARIANT 73
FT /note="S -> F (in FALBI; decreased stability; loss of 11-
FT cis retinol dehydrogenase activity; accumulates in the
FT perinuclear region; dbSNP:rs62638185)"
FT /evidence="ECO:0000269|PubMed:10369264,
FT ECO:0000269|PubMed:11675386"
FT /id="VAR_009273"
FT VARIANT 105
FT /note="L -> I (in FALBI; decreased stability;
FT dbSNP:rs765993603)"
FT /evidence="ECO:0000269|PubMed:11675386"
FT /id="VAR_068716"
FT VARIANT 107
FT /note="G -> R (in FALBI; associated with macular
FT dystrophy)"
FT /evidence="ECO:0000269|PubMed:11053295,
FT ECO:0000269|PubMed:12788147"
FT /id="VAR_016815"
FT VARIANT 128
FT /note="D -> N (in FALBI; decreased stability;
FT dbSNP:rs377029071)"
FT /evidence="ECO:0000269|PubMed:11675386"
FT /id="VAR_068717"
FT VARIANT 132
FT /note="V -> M (in FALBI; dbSNP:rs62638187)"
FT /evidence="ECO:0000269|PubMed:11053295"
FT /id="VAR_016816"
FT VARIANT 157
FT /note="R -> W (in FALBI; decreased stability;
FT dbSNP:rs104894374)"
FT /evidence="ECO:0000269|PubMed:11675386"
FT /id="VAR_068718"
FT VARIANT 164
FT /note="V -> F (in FALBI; dbSNP:rs755168439)"
FT /evidence="ECO:0000269|PubMed:12967826"
FT /id="VAR_016817"
FT VARIANT 175
FT /note="Y -> F (in FALBI; dbSNP:rs758411232)"
FT /evidence="ECO:0000269|PubMed:25820994"
FT /id="VAR_075309"
FT VARIANT 177
FT /note="V -> G (in FALBI; dbSNP:rs104894373)"
FT /evidence="ECO:0000269|PubMed:11078852"
FT /id="VAR_016818"
FT VARIANT 179
FT /note="K -> R (in FALBI; dbSNP:rs781112960)"
FT /evidence="ECO:0000269|PubMed:24603341,
FT ECO:0000269|PubMed:28418496"
FT /id="VAR_081472"
FT VARIANT 238
FT /note="G -> W (in FALBI; decreased stability; loss of 11-
FT cis retinol dehydrogenase activity; accumulates in the
FT perinuclear region; dbSNP:rs62638191)"
FT /evidence="ECO:0000269|PubMed:10369264,
FT ECO:0000269|PubMed:10617778, ECO:0000269|PubMed:11675386"
FT /id="VAR_009274"
FT VARIANT 253
FT /note="M -> R (in FALBI; dbSNP:rs780377973)"
FT /evidence="ECO:0000269|PubMed:22736946,
FT ECO:0000269|PubMed:28418496"
FT /id="VAR_081462"
FT VARIANT 264
FT /note="V -> G (in FALBI; decreased stability)"
FT /evidence="ECO:0000269|PubMed:11053296,
FT ECO:0000269|PubMed:11675386"
FT /id="VAR_068719"
FT VARIANT 267
FT /note="C -> W (in FALBI)"
FT /evidence="ECO:0000269|PubMed:11470705"
FT /id="VAR_016819"
FT VARIANT 280
FT /note="R -> H (in FALBI; decreased stability; loss of 11-
FT cis retinol dehydrogenase activity; dbSNP:rs62638193)"
FT /evidence="ECO:0000269|PubMed:10617778,
FT ECO:0000269|PubMed:11053295, ECO:0000269|PubMed:11078852,
FT ECO:0000269|PubMed:11675386"
FT /id="VAR_016820"
FT VARIANT 281
FT /note="Y -> H (in FALBI; dbSNP:rs62638194)"
FT /evidence="ECO:0000269|PubMed:11053295"
FT /id="VAR_016821"
FT VARIANT 294
FT /note="A -> P (in FALBI; no effect on 11-cis retinol
FT dehydrogenase activity; accumulates in the perinuclear
FT region; dbSNP:rs111033593)"
FT /evidence="ECO:0000269|PubMed:10617778,
FT ECO:0000269|PubMed:11675386"
FT /id="VAR_016822"
FT VARIANT 310
FT /note="L -> EV (in FALBI; loss of 11-cis retinol
FT dehydrogenase activity; accumulates in the perinuclear
FT region)"
FT /evidence="ECO:0000269|PubMed:11053296,
FT ECO:0000269|PubMed:11675386"
FT /id="VAR_016823"
FT MUTAGEN 175..179
FT /note="YCVSK->FCVSR: Decreases androsterone dehydrogenase
FT activity."
FT /evidence="ECO:0000269|PubMed:29541409"
FT CONFLICT 30
FT /note="F -> L (in Ref. 4; AAH28298)"
FT /evidence="ECO:0000305"
FT CONFLICT 51..52
FT /note="RG -> KS (in Ref. 2; AAB93668)"
FT /evidence="ECO:0000305"
FT CONFLICT 75..77
FT /note="RLH -> GFN (in Ref. 2; AAB93668)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="V -> F (in Ref. 2; AAB93668)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="V -> E (in Ref. 2; AAB93668)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 318 AA; 34979 MW; 2CE24343F2EEA4B7 CRC64;
MWLPLLLGAL LWAVLWLLRD RQSLPASNAF VFITGCDSGF GRLLALQLDQ RGFRVLASCL
TPSGAEDLQR VASSRLHTTL LDITDPQSVQ QAAKWVEMHV KEAGLFGLVN NAGVAGIIGP
TPWLTRDDFQ RVLNVNTMGP IGVTLALLPL LQQARGRVIN ITSVLGRLAA NGGGYCVSKF
GLEAFSDSLR RDVAHFGIRV SIVEPGFFRT PVTNLESLEK TLQACWARLP PATQAHYGGA
FLTKYLKMQQ RIMNLICDPD LTKVSRCLEH ALTARHPRTR YSPGWDAKLL WLPASYLPAS
LVDAVLTWVL PKPAQAVY
