ID RDHE2_HUMAN Reviewed; 309 AA. AC Q8N3Y7; B4DGK2; Q330K3; Q8TDV9; Q96LX1; DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2004, sequence version 2. DT 27-MAR-2024, entry version 161. DE RecName: Full=Epidermal retinol dehydrogenase 2 {ECO:0000303|PubMed:18926804}; DE Short=EPHD-2; DE Short=RDH-E2 {ECO:0000303|PubMed:12372410}; DE EC=1.1.1.105 {ECO:0000269|PubMed:18926804}; DE AltName: Full=Retinal short-chain dehydrogenase reductase 2; DE Short=retSDR2; DE AltName: Full=Short-chain dehydrogenase/reductase family 16C member 5; GN Name=SDR16C5 {ECO:0000312|HGNC:HGNC:30311}; GN Synonyms=RDHE2 {ECO:0000303|PubMed:12372410}; 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] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Keratinocyte; RX PubMed=12372410; DOI=10.1016/s0006-291x(02)02344-6; RA Matsuzaka Y., Okamoto K., Tsuji H., Mabuchi T., Ozawa A., Tamiya G., RA Inoko H.; RT "Identification of the hRDH-E2 gene, a novel member of the SDR family, and RT its increased expression in psoriatic lesion."; RL Biochem. Biophys. Res. Commun. 297:1171-1180(2002). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Zheng H., Xie Y., Mao Y.; RT "Cloning of a novel splice variant of RDH-E2."; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain, and Trachea; 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]. 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [6] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND SUBCELLULAR LOCATION. RX PubMed=18926804; DOI=10.1016/j.cbi.2008.09.019; RA Lee S.-A., Belyaeva O.V., Kedishvili N.Y.; RT "Biochemical characterization of human epidermal retinol dehydrogenase 2."; RL Chem. Biol. Interact. 178:182-187(2009). RN [7] RP VARIANT TRP-62. RX PubMed=15457346; DOI=10.1007/s00335-004-2349-5; RA Matsuzaka Y., Okamoto K., Yoshikawa Y., Takaki A., Oka A., Mabuchi T., RA Iizuka M., Ozawa A., Tamiya G., Kulski J.K., Inoko H.; RT "hRDH-E2 gene polymorphisms, variable transcriptional start sites, and RT psoriasis."; RL Mamm. Genome 15:668-675(2004). CC -!- FUNCTION: Oxidoreductase with strong preference for NAD CC (PubMed:18926804). Active in both the oxidative and reductive CC directions (PubMed:18926804). Oxidizes all-trans-retinol in all-trans- CC retinaldehyde (PubMed:18926804). No activity was detected with 11-cis- CC retinol or 11-cis-retinaldehyde as substrates with either NAD(+)/NADH CC or NADP(+)/NADPH (PubMed:18926804). {ECO:0000269|PubMed:18926804}. CC -!- CATALYTIC ACTIVITY: CC Reaction=all-trans-retinol--[retinol-binding protein] + NAD(+) = all- CC trans-retinal--[retinol-binding protein] + H(+) + NADH; CC Xref=Rhea:RHEA:48488, Rhea:RHEA-COMP:14428, Rhea:RHEA-COMP:14430, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17336, ChEBI:CHEBI:17898, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:83228; CC EC=1.1.1.105; Evidence={ECO:0000269|PubMed:18926804}; CC -!- PATHWAY: Cofactor metabolism; retinol metabolism. CC {ECO:0000269|PubMed:18926804}. CC -!- INTERACTION: CC Q8N3Y7; Q08426: EHHADH; NbExp=3; IntAct=EBI-3923480, EBI-2339219; CC Q8N3Y7; Q9BWH2: FUNDC2; NbExp=3; IntAct=EBI-3923480, EBI-714482; CC Q8N3Y7; Q05329: GAD2; NbExp=3; IntAct=EBI-3923480, EBI-9304251; CC Q8N3Y7; Q9UBD0: HSFX2; NbExp=3; IntAct=EBI-3923480, EBI-947253; CC Q8N3Y7; Q9ULP0-2: NDRG4; NbExp=3; IntAct=EBI-3923480, EBI-11978907; CC Q8N3Y7; Q9HC62: SENP2; NbExp=3; IntAct=EBI-3923480, EBI-714881; CC Q8N3Y7; Q13596: SNX1; NbExp=3; IntAct=EBI-3923480, EBI-2822329; CC Q8N3Y7; Q17RD7: SYT16; NbExp=3; IntAct=EBI-3923480, EBI-10238936; CC Q8N3Y7; P49638: TTPA; NbExp=3; IntAct=EBI-3923480, EBI-10210710; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:18926804}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8N3Y7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8N3Y7-2; Sequence=VSP_028389; CC -!- TISSUE SPECIFICITY: Detected in adult lung. Detected at low levels in CC adult brain, heart, testis, placenta, cervix, pancreas, uterus, CC stomach, rectum, small intestine, colon, esophagus, thymus, skin, and CC skin keratinocyte. Expression is higher in psoriasis lesions relative CC to unaffected skin from psoriasis patients. Detected in fetal kidney, CC skin and lung. {ECO:0000269|PubMed:12372410}. CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR) CC family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB71545.1; Type=Frameshift; Evidence={ECO:0000305}; 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; AB083038; BAB91014.1; -; mRNA. DR EMBL; AY444559; AAS68535.1; -; mRNA. DR EMBL; AK057667; BAB71545.1; ALT_FRAME; mRNA. DR EMBL; AK294634; BAG57813.1; -; mRNA. DR EMBL; CH471068; EAW86780.1; -; Genomic_DNA. DR EMBL; BC037219; AAH37219.2; -; mRNA. DR EMBL; BC064525; AAH64525.1; -; mRNA. DR CCDS; CCDS6167.1; -. [Q8N3Y7-1] DR CCDS; CCDS83295.1; -. [Q8N3Y7-2] DR PIR; JC7895; JC7895. DR RefSeq; NP_001304978.1; NM_001318049.1. DR RefSeq; NP_001304979.1; NM_001318050.1. [Q8N3Y7-2] DR RefSeq; NP_620419.2; NM_138969.3. [Q8N3Y7-1] DR AlphaFoldDB; Q8N3Y7; -. DR SMR; Q8N3Y7; -. DR BioGRID; 128184; 50. DR IntAct; Q8N3Y7; 15. DR STRING; 9606.ENSP00000431010; -. DR MoonProt; Q8N3Y7; -. DR CarbonylDB; Q8N3Y7; -. DR GlyGen; Q8N3Y7; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q8N3Y7; -. DR PhosphoSitePlus; Q8N3Y7; -. DR BioMuta; SDR16C5; -. DR DMDM; 74750974; -. DR EPD; Q8N3Y7; -. DR jPOST; Q8N3Y7; -. DR MassIVE; Q8N3Y7; -. DR MaxQB; Q8N3Y7; -. DR PaxDb; 9606-ENSP00000307607; -. DR PeptideAtlas; Q8N3Y7; -. DR PRIDE; Q8N3Y7; -. DR ProteomicsDB; 71850; -. [Q8N3Y7-1] DR ProteomicsDB; 71851; -. [Q8N3Y7-2] DR Antibodypedia; 11761; 122 antibodies from 22 providers. DR DNASU; 195814; -. DR Ensembl; ENST00000303749.8; ENSP00000307607.3; ENSG00000170786.13. [Q8N3Y7-1] DR Ensembl; ENST00000396721.6; ENSP00000379947.2; ENSG00000170786.13. [Q8N3Y7-2] DR GeneID; 195814; -. DR KEGG; hsa:195814; -. DR MANE-Select; ENST00000303749.8; ENSP00000307607.3; NM_138969.4; NP_620419.2. DR UCSC; uc003xsy.2; human. [Q8N3Y7-1] DR AGR; HGNC:30311; -. DR CTD; 195814; -. DR GeneCards; SDR16C5; -. DR HGNC; HGNC:30311; SDR16C5. DR HPA; ENSG00000170786; Tissue enhanced (esophagus, lung, skin). DR MIM; 608989; gene. DR neXtProt; NX_Q8N3Y7; -. DR OpenTargets; ENSG00000170786; -. DR PharmGKB; PA164725585; -. DR VEuPathDB; HostDB:ENSG00000170786; -. DR eggNOG; KOG1201; Eukaryota. DR GeneTree; ENSGT00940000156731; -. DR HOGENOM; CLU_010194_2_5_1; -. DR InParanoid; Q8N3Y7; -. DR OMA; VHAICPQ; -. DR OrthoDB; 6845at2759; -. DR PhylomeDB; Q8N3Y7; -. DR TreeFam; TF312837; -. DR BioCyc; MetaCyc:ENSG00000170786-MONOMER; -. DR BRENDA; 1.1.1.105; 2681. DR PathwayCommons; Q8N3Y7; -. DR Reactome; R-HSA-5365859; RA biosynthesis pathway. DR SignaLink; Q8N3Y7; -. DR UniPathway; UPA00912; -. DR BioGRID-ORCS; 195814; 6 hits in 1147 CRISPR screens. DR ChiTaRS; SDR16C5; human. DR GenomeRNAi; 195814; -. DR Pharos; Q8N3Y7; Tbio. DR PRO; PR:Q8N3Y7; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q8N3Y7; Protein. DR Bgee; ENSG00000170786; Expressed in upper arm skin and 129 other cell types or tissues. DR ExpressionAtlas; Q8N3Y7; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:CAFA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0005811; C:lipid droplet; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IDA:CAFA. DR GO; GO:0017053; C:transcription repressor complex; IDA:CAFA. DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:CAFA. DR GO; GO:0004745; F:NAD-retinol dehydrogenase activity; IDA:UniProtKB. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:CAFA. DR GO; GO:0003714; F:transcription corepressor activity; IDA:CAFA. DR GO; GO:0043616; P:keratinocyte proliferation; IMP:UniProtKB. DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; IDA:CAFA. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:CAFA. DR GO; GO:0042574; P:retinal metabolic process; IDA:UniProtKB. DR GO; GO:0042572; P:retinol metabolic process; IDA:UniProtKB. DR CDD; cd05339; 17beta-HSDXI-like_SDR_c; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR InterPro; IPR002347; SDR_fam. DR PANTHER; PTHR24322:SF728; EPIDERMAL RETINOL DEHYDROGENASE 2; 1. DR PANTHER; PTHR24322; PKSB; 1. DR Pfam; PF00106; adh_short; 1. DR PRINTS; PR00081; GDHRDH. DR PRINTS; PR00080; SDRFAMILY. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR Genevisible; Q8N3Y7; HS. PE 1: Evidence at protein level; KW Alternative splicing; Endoplasmic reticulum; Membrane; NAD; NADP; KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix. FT CHAIN 1..309 FT /note="Epidermal retinol dehydrogenase 2" FT /id="PRO_0000305973" FT TRANSMEM 11..31 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 270..290 FT /note="Helical" FT /evidence="ECO:0000255" FT ACT_SITE 190 FT /note="Proton acceptor" FT /evidence="ECO:0000250|UniProtKB:Q99714" FT BINDING 44..68 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:Q8WNV7" FT BINDING 177 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q99714" FT VAR_SEQ 112..155 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.2" FT /id="VSP_028389" FT VARIANT 62 FT /note="R -> W (in dbSNP:rs4151643)" FT /evidence="ECO:0000269|PubMed:15457346" FT /id="VAR_035234" FT CONFLICT 93 FT /note="H -> R (in Ref. 1; BAB91014)" FT /evidence="ECO:0000305" FT CONFLICT 116 FT /note="V -> I (in Ref. 1; BAB91014)" FT /evidence="ECO:0000305" SQ SEQUENCE 309 AA; 34095 MW; BEA108508E903DC1 CRC64; MSFNLQSSKK LFIFLGKSLF SLLEAMIFAL LPKPRKNVAG EIVLITGAGS GLGRLLALQF ARLGSVLVLW DINKEGNEET CKMAREAGAT RVHAYTCDCS QKEGVYRVAD QVKKEVGDVS ILINNAGIVT GKKFLDCPDE LMEKSFDVNF KAHLWTYKAF LPAMIANDHG HLVCISSSAG LSGVNGLADY CASKFAAFGF AESVFVETFV QKQKGIKTTI VCPFFIKTGM FEGCTTGCPS LLPILEPKYA VEKIVEAILQ EKMYLYMPKL LYFMMFLKSF LPLKTGLLIA DYLGILHAMD GFVDQKKKL //