ADH4_HUMAN
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 03-AUG-2022, entry version 211.
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 4;
DE AltName: Full=Alcohol dehydrogenase class II pi chain;
GN Name=ADH4 {ECO:0000312|HGNC:HGNC:252};
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-retinaldehyde {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-retinaldehyde {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; 6.
DR IntAct; P08319; 2.
DR STRING; 9606.ENSP00000265512; -.
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 iPTMnet; P08319; -.
DR PhosphoSitePlus; P08319; -.
DR BioMuta; ADH4; -.
DR DMDM; 308153684; -.
DR MassIVE; P08319; -.
DR MaxQB; P08319; -.
DR PaxDb; P08319; -.
DR PeptideAtlas; P08319; -.
DR PRIDE; P08319; -.
DR ProteomicsDB; 52106; -. [P08319-1]
DR ProteomicsDB; 52107; -. [P08319-2]
DR Antibodypedia; 14813; 281 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 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; NGTCFGG; -.
DR PhylomeDB; P08319; -.
DR TreeFam; TF300429; -.
DR BioCyc; MetaCyc:HS06569-MON; -.
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 1070 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 165 other tissues.
DR ExpressionAtlas; P08319; baseline and differential.
DR Genevisible; P08319; HS.
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:0035276; F:ethanol binding; IEA:InterPro.
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 InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR013154; ADH_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 InterPro; IPR028632; Zinc_ADH_II.
DR PANTHER; PTHR43880:SF14; PTHR43880:SF14; 1.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 2.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00059; ADH_ZINC; 1.
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
