ID   ADH4_HUMAN              Reviewed;         380 AA.
AC   P08319; A8K470; B4DIE7; C9J4A9; Q8TCD7;
DT   01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT   05-OCT-2010, sequence version 5.
DT   27-MAR-2024, entry version 220.
DE   RecName: Full=All-trans-retinol dehydrogenase [NAD(+)] ADH4 {ECO:0000305};
DE            EC=1.1.1.105 {ECO:0000269|PubMed:17279314};
DE   AltName: Full=Alcohol dehydrogenase 2 {ECO:0000303|PubMed:17279314};
DE   AltName: Full=Alcohol dehydrogenase 4;
DE   AltName: Full=Alcohol dehydrogenase class II pi chain;
GN   Name=ADH4 {ECO:0000312|HGNC:HGNC:252};
GN   Synonyms=ADH2 {ECO:0000303|PubMed:17279314};
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 PARTIAL PROTEIN SEQUENCE.
RX   PubMed=3036213; DOI=10.1021/bi00381a021;
RA   Hoeoeg J.-O., von Bahr-Lindstroem H., Heden L.-O., Holmquist B.,
RA   Larsson K., Hempel J., Vallee B.L., Joernvall H.;
RT   "Structure of the class II enzyme of human liver alcohol dehydrogenase:
RT   combined cDNA and protein sequence determination of the pi subunit.";
RL   Biochemistry 26:1926-1932(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RC   TISSUE=Fetal liver;
RX   PubMed=1889753; DOI=10.1016/0378-1119(91)90285-j;
RA   von Bahr-Lindstroem H., Joernvall H., Hoeoeg J.-O.;
RT   "Cloning and characterization of the human ADH4 gene.";
RL   Gene 103:269-274(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP   VAL-309 AND ILE-374.
RC   TISSUE=Hippocampus, and Liver;
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 [GENOMIC DNA], AND VARIANT HIS-318.
RG   NIEHS SNPs program;
RL   Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS VAL-309
RP   AND ILE-374.
RC   TISSUE=Liver;
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   CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC   TISSUE=Liver;
RX   PubMed=10514444; DOI=10.1074/jbc.274.42.29712;
RA   Svensson S., Stroemberg P., Hoeoeg J.-O.;
RT   "A novel subtype of class II alcohol dehydrogenase in rodents. Unique
RT   Pro(47) and Ser(182) modulates hydride transfer in the mouse enzyme.";
RL   J. Biol. Chem. 274:29712-29719(1999).
RN   [8]
RP   CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP   REGULATION.
RX   PubMed=16081420; DOI=10.1074/jbc.m504055200;
RA   Collins X.H., Harmon S.D., Kaduce T.L., Berst K.B., Fang X., Moore S.A.,
RA   Raju T.V., Falck J.R., Weintraub N.L., Duester G., Plapp B.V.,
RA   Spector A.A.;
RT   "Omega-oxidation of 20-hydroxyeicosatetraenoic acid (20-HETE) in cerebral
RT   microvascular smooth muscle and endothelium by alcohol dehydrogenase 4.";
RL   J. Biol. Chem. 280:33157-33164(2005).
RN   [9]
RP   CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=17279314; DOI=10.1007/s00018-007-6449-8;
RA   Hellgren M., Stroemberg P., Gallego O., Martras S., Farres J., Persson B.,
RA   Pares X., Hoeoeg J.O.;
RT   "Alcohol dehydrogenase 2 is a major hepatic enzyme for human retinol
RT   metabolism.";
RL   Cell. Mol. Life Sci. 64:498-505(2007).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-121 AND SER-278, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH NAD AND ZINC IONS.
RG   Structural genomics consortium (SGC);
RT   "Crystal structure of human class II alcohol dehydrogenase (ADH4) in
RT   complex with NAD and Zn.";
RL   Submitted (APR-2008) to the PDB data bank.
CC   -!- FUNCTION: Catalyzes the NAD-dependent oxidation of either all-trans-
CC       retinol or 9-cis-retinol (PubMed:17279314). Also oxidizes long chain
CC       omega-hydroxy fatty acids, such as 20-HETE, producing both the
CC       intermediate aldehyde, 20-oxoarachidonate and the end product, a
CC       dicarboxylic acid, (5Z,8Z,11Z,14Z)-eicosatetraenedioate
CC       (PubMed:16081420). Also catalyzes the reduction of benzoquinones
CC       (PubMed:10514444). {ECO:0000269|PubMed:10514444,
CC       ECO:0000269|PubMed:16081420, ECO:0000269|PubMed:17279314}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=all-trans-retinol + NAD(+) = all-trans-retinal + H(+) + NADH;
CC         Xref=Rhea:RHEA:21284, ChEBI:CHEBI:15378, ChEBI:CHEBI:17336,
CC         ChEBI:CHEBI:17898, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC         EC=1.1.1.105; Evidence={ECO:0000269|PubMed:17279314};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21285;
CC         Evidence={ECO:0000305|PubMed:17279314};
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:17279314};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42053;
CC         Evidence={ECO:0000305|PubMed:17279314};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=20-oxo-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H2O + NAD(+) =
CC         (5Z,8Z,11Z,14Z)-eicosatetraenedioate + 2 H(+) + NADH;
CC         Xref=Rhea:RHEA:39803, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:76645,
CC         ChEBI:CHEBI:76647; Evidence={ECO:0000269|PubMed:16081420};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39804;
CC         Evidence={ECO:0000305|PubMed:16081420};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + NAD(+) = 20-
CC         oxo-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) + NADH;
CC         Xref=Rhea:RHEA:39799, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945, ChEBI:CHEBI:76624, ChEBI:CHEBI:76645;
CC         Evidence={ECO:0000269|PubMed:16081420};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39800;
CC         Evidence={ECO:0000305|PubMed:16081420};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1,4-benzoquinone + H(+) + NADH = hydroquinone + NAD(+);
CC         Xref=Rhea:RHEA:60660, ChEBI:CHEBI:15378, ChEBI:CHEBI:16509,
CC         ChEBI:CHEBI:17594, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC         Evidence={ECO:0000269|PubMed:10514444};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60661;
CC         Evidence={ECO:0000305|PubMed:10514444};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC       Note=Binds 2 Zn(2+) ions per subunit.;
CC   -!- ACTIVITY REGULATION: Oxydation of 20-HETE is inhibited by low
CC       concentrations of N-heptylformamide (PubMed:16081420). Oxydation of 20-
CC       HETE is a decreased by 55-65% by either all-trans-retinol or all-trans-
CC       retinoic acid. Strongly inhibited by omega-hydroxy fatty acids (By
CC       similarity). {ECO:0000250|UniProtKB:Q9QYY9,
CC       ECO:0000269|PubMed:16081420}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.14 uM for all-trans-retinol {ECO:0000269|PubMed:17279314};
CC         KM=0.29 uM for all-trans-retinal {ECO:0000269|PubMed:17279314};
CC         KM=0.054 uM for 9-cis-retinol {ECO:0000269|PubMed:17279314};
CC         KM=0.21 uM for 9-cis-retinal {ECO:0000269|PubMed:17279314};
CC         KM=9.5 uM for 20-HETE {ECO:0000269|PubMed:16081420};
CC         KM=0.088 mM for 1,4-benzoquinone {ECO:0000269|PubMed:10514444};
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|Ref.11}.
CC   -!- INTERACTION:
CC       P08319; Q86WT6-2: TRIM69; NbExp=3; IntAct=EBI-3927856, EBI-11525489;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P08319-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P08319-2; Sequence=VSP_036788;
CC   -!- MISCELLANEOUS: There are 7 different ADH's isozymes in human: three
CC       belongs to class-I: alpha, beta, and gamma, one to class-II: pi, one to
CC       class-III: chi, one to class-IV: ADH7 and one to class-V: ADH6.
CC   -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC       family. Class-II subfamily. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/adh4/";
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DR   EMBL; M15943; AAA51595.1; -; mRNA.
DR   EMBL; X56411; CAA39813.1; -; Genomic_DNA.
DR   EMBL; X56412; CAA39813.1; JOINED; Genomic_DNA.
DR   EMBL; X56413; CAA39813.1; JOINED; Genomic_DNA.
DR   EMBL; X56414; CAA39813.1; JOINED; Genomic_DNA.
DR   EMBL; X56415; CAA39813.1; JOINED; Genomic_DNA.
DR   EMBL; X56416; CAA39813.1; JOINED; Genomic_DNA.
DR   EMBL; X56417; CAA39813.1; JOINED; Genomic_DNA.
DR   EMBL; X56418; CAA39813.1; JOINED; Genomic_DNA.
DR   EMBL; X56419; CAA39813.1; JOINED; Genomic_DNA.
DR   EMBL; AK290835; BAF83524.1; -; mRNA.
DR   EMBL; AK295556; BAG58459.1; -; mRNA.
DR   EMBL; AY974245; AAX59034.1; -; Genomic_DNA.
DR   EMBL; AC019131; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AP002026; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC022319; AAH22319.1; -; mRNA.
DR   CCDS; CCDS34032.1; -. [P08319-1]
DR   CCDS; CCDS77942.1; -. [P08319-2]
DR   PIR; A27109; DEHUAP.
DR   RefSeq; NP_000661.2; NM_000670.4. [P08319-1]
DR   RefSeq; NP_001293100.1; NM_001306171.1. [P08319-2]
DR   RefSeq; NP_001293101.1; NM_001306172.1. [P08319-2]
DR   PDB; 3COS; X-ray; 2.10 A; A/B/C/D=1-380.
DR   PDBsum; 3COS; -.
DR   AlphaFoldDB; P08319; -.
DR   SMR; P08319; -.
DR   BioGRID; 106639; 7.
DR   IntAct; P08319; 2.
DR   STRING; 9606.ENSP00000424630; -.
DR   BindingDB; P08319; -.
DR   ChEMBL; CHEMBL2990; -.
DR   DrugBank; DB03559; Cyclohexylformamide.
DR   DrugBank; DB00898; Ethanol.
DR   DrugBank; DB00157; NADH.
DR   DrugCentral; P08319; -.
DR   SwissLipids; SLP:000000499; -.
DR   GlyGen; P08319; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P08319; -.
DR   PhosphoSitePlus; P08319; -.
DR   BioMuta; ADH4; -.
DR   DMDM; 308153684; -.
DR   MassIVE; P08319; -.
DR   MaxQB; P08319; -.
DR   PaxDb; 9606-ENSP00000265512; -.
DR   PeptideAtlas; P08319; -.
DR   ProteomicsDB; 52106; -. [P08319-1]
DR   ProteomicsDB; 52107; -. [P08319-2]
DR   Antibodypedia; 14813; 314 antibodies from 30 providers.
DR   DNASU; 127; -.
DR   Ensembl; ENST00000265512.12; ENSP00000265512.7; ENSG00000198099.10. [P08319-1]
DR   Ensembl; ENST00000505590.5; ENSP00000425416.1; ENSG00000198099.10. [P08319-2]
DR   Ensembl; ENST00000508393.5; ENSP00000424630.1; ENSG00000198099.10. [P08319-2]
DR   GeneID; 127; -.
DR   KEGG; hsa:127; -.
DR   MANE-Select; ENST00000265512.12; ENSP00000265512.7; NM_000670.5; NP_000661.2.
DR   UCSC; uc003hun.4; human. [P08319-1]
DR   AGR; HGNC:252; -.
DR   CTD; 127; -.
DR   DisGeNET; 127; -.
DR   GeneCards; ADH4; -.
DR   HGNC; HGNC:252; ADH4.
DR   HPA; ENSG00000198099; Tissue enriched (liver).
DR   MIM; 103740; gene.
DR   neXtProt; NX_P08319; -.
DR   OpenTargets; ENSG00000198099; -.
DR   PharmGKB; PA24573; -.
DR   VEuPathDB; HostDB:ENSG00000198099; -.
DR   eggNOG; KOG0022; Eukaryota.
DR   GeneTree; ENSGT00940000162645; -.
DR   HOGENOM; CLU_026673_14_0_1; -.
DR   InParanoid; P08319; -.
DR   OMA; LNWAPSC; -.
DR   OrthoDB; 1077476at2759; -.
DR   PhylomeDB; P08319; -.
DR   TreeFam; TF300429; -.
DR   BioCyc; MetaCyc:HS06569-MONOMER; -.
DR   BRENDA; 1.1.1.1; 2681.
DR   PathwayCommons; P08319; -.
DR   Reactome; R-HSA-5365859; RA biosynthesis pathway.
DR   Reactome; R-HSA-71384; Ethanol oxidation.
DR   SABIO-RK; P08319; -.
DR   SignaLink; P08319; -.
DR   BioGRID-ORCS; 127; 8 hits in 1148 CRISPR screens.
DR   ChiTaRS; ADH4; human.
DR   EvolutionaryTrace; P08319; -.
DR   GeneWiki; ADH4; -.
DR   GenomeRNAi; 127; -.
DR   Pharos; P08319; Tbio.
DR   PRO; PR:P08319; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; P08319; Protein.
DR   Bgee; ENSG00000198099; Expressed in jejunal mucosa and 167 other cell types or tissues.
DR   ExpressionAtlas; P08319; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0004022; F:alcohol dehydrogenase (NAD+) activity; IDA:UniProtKB.
DR   GO; GO:0004024; F:alcohol dehydrogenase activity, zinc-dependent; IDA:UniProtKB.
DR   GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; IEA:Ensembl.
DR   GO; GO:0005503; F:all-trans retinal binding; IDA:UniProtKB.
DR   GO; GO:0019115; F:benzaldehyde dehydrogenase [NAD(P)+] activity; IDA:UniProtKB.
DR   GO; GO:0051287; F:NAD binding; IDA:UniProtKB.
DR   GO; GO:0004745; F:NAD-retinol dehydrogenase activity; IDA:UniProtKB.
DR   GO; GO:0003960; F:NADPH:quinone reductase activity; ISS:UniProtKB.
DR   GO; GO:0016620; F:oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor; IDA:UniProtKB.
DR   GO; GO:0019841; F:retinol binding; IDA:UniProtKB.
DR   GO; GO:0051903; F:S-(hydroxymethyl)glutathione dehydrogenase activity; IBA:GO_Central.
DR   GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR   GO; GO:0046164; P:alcohol catabolic process; ISS:UniProtKB.
DR   GO; GO:0006066; P:alcohol metabolic process; IDA:UniProtKB.
DR   GO; GO:0006081; P:cellular aldehyde metabolic process; IDA:UniProtKB.
DR   GO; GO:0006069; P:ethanol oxidation; IDA:UniProtKB.
DR   GO; GO:0010430; P:fatty acid omega-oxidation; IDA:UniProtKB.
DR   GO; GO:0046294; P:formaldehyde catabolic process; IBA:GO_Central.
DR   GO; GO:1901661; P:quinone metabolic process; ISS:UniProtKB.
DR   GO; GO:0001523; P:retinoid metabolic process; IDA:UniProtKB.
DR   GO; GO:0042572; P:retinol metabolic process; IDA:UniProtKB.
DR   CDD; cd08299; alcohol_DH_class_I_II_IV; 1.
DR   Gene3D; 3.90.180.10; Medium-chain alcohol dehydrogenases, catalytic domain; 1.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR   InterPro; IPR013149; ADH-like_C.
DR   InterPro; IPR013154; ADH-like_N.
DR   InterPro; IPR002328; ADH_Zn_CS.
DR   InterPro; IPR011032; GroES-like_sf.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR020843; PKS_ER.
DR   PANTHER; PTHR43880; ALCOHOL DEHYDROGENASE; 1.
DR   PANTHER; PTHR43880:SF14; ALL-TRANS-RETINOL DEHYDROGENASE [NAD(+)] ADH4; 1.
DR   Pfam; PF08240; ADH_N; 1.
DR   Pfam; PF00107; ADH_zinc_N; 1.
DR   SMART; SM00829; PKS_ER; 1.
DR   SUPFAM; SSF50129; GroES-like; 2.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR   PROSITE; PS00059; ADH_ZINC; 1.
DR   Genevisible; P08319; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW   Lipid metabolism; Metal-binding; NAD; Oxidoreductase; Phosphoprotein;
KW   Reference proteome; Zinc.
FT   CHAIN           1..380
FT                   /note="All-trans-retinol dehydrogenase [NAD(+)] ADH4"
FT                   /id="PRO_0000160681"
FT   BINDING         47
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT   BINDING         48..49
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000269|Ref.11"
FT   BINDING         69
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT   BINDING         99
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT   BINDING         102
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT   BINDING         105
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT   BINDING         113
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT   BINDING         180
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT   BINDING         205..210
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000269|Ref.11"
FT   BINDING         229
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000269|Ref.11"
FT   BINDING         234
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000269|Ref.11"
FT   BINDING         298..300
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000269|Ref.11"
FT   BINDING         323..325
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000269|Ref.11"
FT   BINDING         375
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000269|Ref.11"
FT   MOD_RES         121
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         278
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   VAR_SEQ         1..6
FT                   /note="MGTKGK -> MLVRGPHFELQRCKTHLFSSNYLTQ (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_036788"
FT   VARIANT         309
FT                   /note="I -> V (in dbSNP:rs1126671)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:15489334"
FT                   /id="VAR_023461"
FT   VARIANT         318
FT                   /note="R -> H (in dbSNP:rs29001219)"
FT                   /evidence="ECO:0000269|Ref.4"
FT                   /id="VAR_023462"
FT   VARIANT         374
FT                   /note="V -> I (in dbSNP:rs1126673)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:15489334"
FT                   /id="VAR_023463"
FT   CONFLICT        52
FT                   /note="T -> S (in Ref. 1; AAA51595 and 2; CAA39813)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        380
FT                   /note="F -> FGRCQEQFRILSD (in Ref. 1; AAA51595)"
FT                   /evidence="ECO:0000305"
FT   STRAND          8..15
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   STRAND          23..29
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   STRAND          36..45
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   HELIX           48..52
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   STRAND          63..65
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   STRAND          70..78
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   STRAND          90..93
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   STRAND          100..102
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   TURN            103..106
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   HELIX           122..124
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   STRAND          135..138
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   STRAND          141..144
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   TURN            147..149
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   STRAND          152..159
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   STRAND          162..165
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   HELIX           172..175
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   HELIX           176..179
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   HELIX           181..190
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   TURN            191..193
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   STRAND          200..204
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   HELIX           208..219
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   STRAND          223..228
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   HELIX           232..234
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   HELIX           235..240
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   STRAND          244..247
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   HELIX           249..251
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   HELIX           256..263
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   STRAND          268..273
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   HELIX           278..286
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   TURN            290..292
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   STRAND          293..297
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   STRAND          307..309
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   HELIX           311..315
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   STRAND          318..322
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   HELIX           325..327
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   HELIX           330..342
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   HELIX           349..351
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   STRAND          352..357
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   HELIX           358..360
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   HELIX           361..369
FT                   /evidence="ECO:0007829|PDB:3COS"
FT   STRAND          374..379
FT                   /evidence="ECO:0007829|PDB:3COS"
SQ   SEQUENCE   380 AA;  40222 MW;  45721A08197629F1 CRC64;
     MGTKGKVIKC KAAIAWEAGK PLCIEEVEVA PPKAHEVRIQ IIATSLCHTD ATVIDSKFEG
     LAFPVIVGHE AAGIVESIGP GVTNVKPGDK VIPLYAPLCR KCKFCLSPLT NLCGKISNLK
     SPASDQQLME DKTSRFTCKG KPVYHFFGTS TFSQYTVVSD INLAKIDDDA NLERVCLLGC
     GFSTGYGAAI NNAKVTPGST CAVFGLGGVG LSAVMGCKAA GASRIIGIDI NSEKFVKAKA
     LGATDCLNPR DLHKPIQEVI IELTKGGVDF ALDCAGGSET MKAALDCTTA GWGSCTFIGV
     AAGSKGLTIF PEELIIGRTI NGTFFGGWKS VDSIPKLVTD YKNKKFNLDA LVTHTLPFDK
     ISEAFDLMNQ GKSVRTILIF
//