RDHE2_HUMAN
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 03-AUG-2022, entry version 153.
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};
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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.ENSP00000307607; -.
DR MoonProt; Q8N3Y7; -.
DR CarbonylDB; Q8N3Y7; -.
DR GlyGen; Q8N3Y7; 1 site, 1 O-linked glycan (1 site).
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; Q8N3Y7; -.
DR PeptideAtlas; Q8N3Y7; -.
DR PRIDE; Q8N3Y7; -.
DR ProteomicsDB; 71850; -. [Q8N3Y7-1]
DR ProteomicsDB; 71851; -. [Q8N3Y7-2]
DR Antibodypedia; 11761; 118 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 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; VNVMAHV; -.
DR OrthoDB; 1373099at2759; -.
DR PhylomeDB; Q8N3Y7; -.
DR TreeFam; TF312837; -.
DR BioCyc; MetaCyc:ENSG00000170786-MON; -.
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 1067 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 128 other tissues.
DR ExpressionAtlas; Q8N3Y7; baseline and differential.
DR Genevisible; Q8N3Y7; HS.
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: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:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central.
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:0035067; P:negative regulation of histone acetylation; IDA:CAFA.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:CAFA.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; IDA:CAFA.
DR GO; GO:0042574; P:retinal metabolic process; IDA:UniProtKB.
DR GO; GO:0042572; P:retinol metabolic process; IDA:UniProtKB.
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 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
