ID ADHX_HUMAN Reviewed; 374 AA. AC P11766; Q6FHR2; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 4. DT 27-MAR-2024, entry version 233. DE RecName: Full=Alcohol dehydrogenase class-3 {ECO:0000305}; DE EC=1.1.1.1 {ECO:0000269|PubMed:8460164}; DE AltName: Full=Alcohol dehydrogenase 5; DE AltName: Full=Alcohol dehydrogenase class chi chain; DE AltName: Full=Alcohol dehydrogenase class-III; DE AltName: Full=Glutathione-dependent formaldehyde dehydrogenase; DE Short=FALDH; DE Short=FDH; DE Short=GSH-FDH; DE EC=1.1.1.-; DE AltName: Full=S-(hydroxymethyl)glutathione dehydrogenase; DE EC=1.1.1.284 {ECO:0000269|PubMed:8460164}; GN Name=ADH5 {ECO:0000312|HGNC:HGNC:253}; Synonyms=ADHX, FDH; 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=2818582; DOI=10.1016/0006-291x(89)91507-6; RA Sharma C.P., Fox E.A., Holmquist B., Joernvall H., Vallee B.L.; RT "cDNA sequence of human class III alcohol dehydrogenase."; RL Biochem. Biophys. Res. Commun. 164:631-637(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2679557; DOI=10.1016/0006-291x(89)91741-5; RA Giri P.R., Krug J.F., Kozak C., Moretti T., O'Brien S.J., Seuanez H.N., RA Goldman D.; RT "Cloning and comparative mapping of a human class III (chi) alcohol RT dehydrogenase cDNA."; RL Biochem. Biophys. Res. Commun. 164:453-460(1989). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1446828; DOI=10.1016/0378-1119(92)90135-c; RA Hur M.W., Edenberg H.J.; RT "Cloning and characterization of the ADH5 gene encoding human alcohol RT dehydrogenase 5, formaldehyde dehydrogenase."; RL Gene 121:305-311(1992). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., RA LaBaer J.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-163 AND ILE-309. RG NIEHS SNPs program; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=B-cell; 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 [8] RP PROTEIN SEQUENCE OF 2-374, AND COFACTOR. RC TISSUE=Liver; RX PubMed=3365377; DOI=10.1021/bi00404a009; RA Kaiser R., Holmquist B., Hempel J., Vallee B.L., Joernvall H.; RT "Class III human liver alcohol dehydrogenase: a novel structural type RT equidistantly related to the class I and class II enzymes."; RL Biochemistry 27:1132-1140(1988). RN [9] RP PARTIAL PROTEIN SEQUENCE, AND MUTAGENESIS OF ARG-115. RX PubMed=8494891; DOI=10.1021/bi00070a024; RA Holmquist B., Moulis J.-M., Engeland K., Vallee B.L.; RT "Role of arginine 115 in fatty acid activation and formaldehyde RT dehydrogenase activity of human class III alcohol dehydrogenase."; RL Biochemistry 32:5139-5144(1993). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ARG-115. RX PubMed=8460164; DOI=10.1073/pnas.90.6.2491; RA Engeland K., Hoeoeg J.-O., Holmquist B., Estonius M., Joernvall H., RA Vallee B.L.; RT "Mutation of Arg-115 of human class III alcohol dehydrogenase: a binding RT site required for formaldehyde dehydrogenase activity and fatty acid RT activation."; RL Proc. Natl. Acad. Sci. U.S.A. 90:2491-2494(1993). RN [11] RP CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES. 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 [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324 AND SER-351, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-247, AND IDENTIFICATION BY RP 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 [16] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS), AND SUBUNIT. RX PubMed=9018047; DOI=10.1006/jmbi.1996.0731; RA Yang Z.-N., Bosron W.F., Hurley T.D.; RT "Structure of human chi chi alcohol dehydrogenase: a glutathione-dependent RT formaldehyde dehydrogenase."; RL J. Mol. Biol. 265:330-343(1997). RN [17] RP VARIANT AMEDS PRO-278, INVOLVEMENT IN AMEDS, AND FUNCTION. RX PubMed=33355142; DOI=10.1126/sciadv.abd7197; RA Oka Y., Hamada M., Nakazawa Y., Muramatsu H., Okuno Y., Higasa K., RA Shimada M., Takeshima H., Hanada K., Hirano T., Kawakita T., Sakaguchi H., RA Ichimura T., Ozono S., Yuge K., Watanabe Y., Kotani Y., Yamane M., RA Kasugai Y., Tanaka M., Suganami T., Nakada S., Mitsutake N., Hara Y., RA Kato K., Mizuno S., Miyake N., Kawai Y., Tokunaga K., Nagasaki M., Kito S., RA Isoyama K., Onodera M., Kaneko H., Matsumoto N., Matsuda F., Matsuo K., RA Takahashi Y., Mashimo T., Kojima S., Ogi T.; RT "Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and RT cause a multisystem disorder, AMeD syndrome."; RL Sci. Adv. 6:0-0(2020). CC -!- FUNCTION: Catalyzes the oxidation of long-chain primary alcohols and CC the oxidation of S-(hydroxymethyl) glutathione (PubMed:8460164). Also CC oxidizes long chain omega-hydroxy fatty acids, such as 20-HETE, CC producing both the intermediate aldehyde, 20-oxoarachidonate and the CC end product, a dicarboxylic acid, (5Z,8Z,11Z,14Z)-eicosatetraenedioate CC (PubMed:16081420). Class-III ADH is remarkably ineffective in oxidizing CC ethanol (PubMed:8460164). Required for clearance of cellular CC formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA CC damage (PubMed:33355142). {ECO:0000269|PubMed:16081420, CC ECO:0000269|PubMed:33355142, ECO:0000269|PubMed:8460164}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a primary alcohol + NAD(+) = an aldehyde + H(+) + NADH; CC Xref=Rhea:RHEA:10736, ChEBI:CHEBI:15378, ChEBI:CHEBI:15734, CC ChEBI:CHEBI:17478, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1; CC Evidence={ECO:0000269|PubMed:8460164}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a secondary alcohol + NAD(+) = a ketone + H(+) + NADH; CC Xref=Rhea:RHEA:10740, ChEBI:CHEBI:15378, ChEBI:CHEBI:17087, CC ChEBI:CHEBI:35681, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1; CC Evidence={ECO:0000269|PubMed:8460164}; CC -!- CATALYTIC ACTIVITY: CC Reaction=NADP(+) + S-(hydroxymethyl)glutathione = H(+) + NADPH + S- CC formylglutathione; Xref=Rhea:RHEA:19981, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57688, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, CC ChEBI:CHEBI:58758; EC=1.1.1.284; CC Evidence={ECO:0000269|PubMed:8460164}; CC -!- CATALYTIC ACTIVITY: CC Reaction=NAD(+) + S-(hydroxymethyl)glutathione = H(+) + NADH + S- CC formylglutathione; Xref=Rhea:RHEA:19985, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57688, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:58758; EC=1.1.1.284; CC Evidence={ECO:0000269|PubMed:8460164}; 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 -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:3365377}; CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:3365377}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=21 uM for 20-HETE {ECO:0000269|PubMed:16081420}; CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:9018047}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. CC -!- DISEASE: AMED syndrome, digenic (AMEDS) [MIM:619151]: A form of bone CC marrow failure syndrome, a heterogeneous group of life-threatening CC disorders characterized by hematopoietic defects in association with a CC range of variable extra-hematopoietic manifestations. AMEDS is an CC autosomal recessive, digenic form characterized by childhood onset of CC bone marrow failure resulting in aplastic anemia, in association with CC global developmental delay, intellectual disability, and poor overall CC growth with short stature. {ECO:0000269|PubMed:33355142}. Note=The CC disease is caused by variants affecting distinct genetic loci, CC including the gene represented in this entry. AMEDS patients carry ADH5 CC biallelic variants and homozygous or heterozygous ALDH2 variant CC p.Glu504Lys, affecting protein activity. Cellular and animal studies CC demonstrate that the simultaneous loss of ALDH2 and ADH5 activities CC leads to an increase of cellular formaldehyde sensitivity and CC multisystem abnormalities including hematopoietic failure. CC {ECO:0000269|PubMed:33355142}. 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-III subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/adh5/"; 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; M30471; AAA79018.1; -; mRNA. DR EMBL; M29872; AAA51597.1; -; mRNA. DR EMBL; M81118; AAA51596.1; -; Genomic_DNA. DR EMBL; M81112; AAA51596.1; JOINED; Genomic_DNA. DR EMBL; M81113; AAA51596.1; JOINED; Genomic_DNA. DR EMBL; M81114; AAA51596.1; JOINED; Genomic_DNA. DR EMBL; M81115; AAA51596.1; JOINED; Genomic_DNA. DR EMBL; M81116; AAA51596.1; JOINED; Genomic_DNA. DR EMBL; M81117; AAA51596.1; JOINED; Genomic_DNA. DR EMBL; CR541689; CAG46490.1; -; mRNA. DR EMBL; BT019832; AAV38635.1; -; mRNA. DR EMBL; AY987960; AAX81412.1; -; Genomic_DNA. DR EMBL; BC014665; AAH14665.1; -; mRNA. DR CCDS; CCDS47111.1; -. DR PIR; JH0789; DEHUC2. DR RefSeq; NP_000662.3; NM_000671.4. DR PDB; 1M6H; X-ray; 2.00 A; A/B=2-374. DR PDB; 1M6W; X-ray; 2.30 A; A/B=2-374. DR PDB; 1MA0; X-ray; 2.30 A; A/B=2-374. DR PDB; 1MC5; X-ray; 2.60 A; A/B=1-374. DR PDB; 1MP0; X-ray; 2.20 A; A/B=2-374. DR PDB; 1TEH; X-ray; 2.70 A; A/B=2-374. DR PDB; 2FZE; X-ray; 1.90 A; A/B=2-374. DR PDB; 2FZW; X-ray; 1.84 A; A/B=2-374. DR PDB; 3QJ5; X-ray; 1.90 A; A/B=2-374. DR PDB; 8GV3; EM; 3.05 A; A/B=1-374. DR PDBsum; 1M6H; -. DR PDBsum; 1M6W; -. DR PDBsum; 1MA0; -. DR PDBsum; 1MC5; -. DR PDBsum; 1MP0; -. DR PDBsum; 1TEH; -. DR PDBsum; 2FZE; -. DR PDBsum; 2FZW; -. DR PDBsum; 3QJ5; -. DR PDBsum; 8GV3; -. DR AlphaFoldDB; P11766; -. DR EMDB; EMD-34282; -. DR SMR; P11766; -. DR BioGRID; 106640; 53. DR IntAct; P11766; 12. DR MINT; P11766; -. DR STRING; 9606.ENSP00000296412; -. DR BindingDB; P11766; -. DR ChEMBL; CHEMBL4116; -. DR DrugBank; DB03704; 12-Hydroxydodecanoic Acid. DR DrugBank; DB00898; Ethanol. DR DrugBank; DB01020; Isosorbide mononitrate. DR DrugBank; DB03017; Lauric acid. DR DrugBank; DB00157; NADH. DR DrugBank; DB12612; Ozanimod. DR DrugBank; DB11077; Polyethylene glycol 400. DR DrugBank; DB04153; S-Hydroxymethyl Glutathione. DR SwissLipids; SLP:000000500; -. DR CarbonylDB; P11766; -. DR GlyGen; P11766; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P11766; -. DR MetOSite; P11766; -. DR PhosphoSitePlus; P11766; -. DR SwissPalm; P11766; -. DR BioMuta; ADH5; -. DR DMDM; 113408; -. DR REPRODUCTION-2DPAGE; IPI00746777; -. DR EPD; P11766; -. DR jPOST; P11766; -. DR MassIVE; P11766; -. DR PaxDb; 9606-ENSP00000296412; -. DR PeptideAtlas; P11766; -. DR ProteomicsDB; 52803; -. DR Pumba; P11766; -. DR Antibodypedia; 25845; 502 antibodies from 37 providers. DR DNASU; 128; -. DR Ensembl; ENST00000296412.14; ENSP00000296412.8; ENSG00000197894.12. DR GeneID; 128; -. DR KEGG; hsa:128; -. DR MANE-Select; ENST00000296412.14; ENSP00000296412.8; NM_000671.4; NP_000662.3. DR AGR; HGNC:253; -. DR CTD; 128; -. DR DisGeNET; 128; -. DR GeneCards; ADH5; -. DR HGNC; HGNC:253; ADH5. DR HPA; ENSG00000197894; Low tissue specificity. DR MalaCards; ADH5; -. DR MIM; 103710; gene. DR MIM; 619151; phenotype. DR neXtProt; NX_P11766; -. DR OpenTargets; ENSG00000197894; -. DR PharmGKB; PA24574; -. DR VEuPathDB; HostDB:ENSG00000197894; -. DR eggNOG; KOG0022; Eukaryota. DR GeneTree; ENSGT00940000155196; -. DR HOGENOM; CLU_026673_14_0_1; -. DR InParanoid; P11766; -. DR OMA; IKGRSEM; -. DR OrthoDB; 1077476at2759; -. DR PhylomeDB; P11766; -. DR TreeFam; TF300429; -. DR BioCyc; MetaCyc:HS10601-MONOMER; -. DR PathwayCommons; P11766; -. DR Reactome; R-HSA-71384; Ethanol oxidation. DR SABIO-RK; P11766; -. DR SignaLink; P11766; -. DR BioGRID-ORCS; 128; 121 hits in 1159 CRISPR screens. DR ChiTaRS; ADH5; human. DR EvolutionaryTrace; P11766; -. DR GeneWiki; ADH5; -. DR GenomeRNAi; 128; -. DR Pharos; P11766; Tchem. DR PRO; PR:P11766; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; P11766; Protein. DR Bgee; ENSG00000197894; Expressed in mucosa of stomach and 211 other cell types or tissues. DR ExpressionAtlas; P11766; baseline and differential. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl. DR GO; GO:0004024; F:alcohol dehydrogenase activity, zinc-dependent; IBA:GO_Central. DR GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB. DR GO; GO:0005504; F:fatty acid binding; IDA:UniProtKB. DR GO; GO:0018467; F:formaldehyde dehydrogenase activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0051903; F:S-(hydroxymethyl)glutathione dehydrogenase activity; IBA:GO_Central. DR GO; GO:0106322; F:S-(hydroxymethyl)glutathione dehydrogenase NAD activity; IEA:UniProtKB-EC. DR GO; GO:0106321; F:S-(hydroxymethyl)glutathione dehydrogenase NADP activity; IEA:UniProtKB-EC. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0006069; P:ethanol oxidation; IEA:InterPro. 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:0045777; P:positive regulation of blood pressure; IEA:Ensembl. DR GO; GO:0003016; P:respiratory system process; IEA:Ensembl. DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0051409; P:response to nitrosative stress; IEA:Ensembl. DR GO; GO:0051775; P:response to redox state; IDA:UniProtKB. DR GO; GO:0001523; P:retinoid metabolic process; IEA:Ensembl. DR CDD; cd08300; alcohol_DH_class_III; 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; IPR014183; ADH_3. DR InterPro; IPR002328; ADH_Zn_CS. DR InterPro; IPR011032; GroES-like_sf. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR NCBIfam; TIGR02818; adh_III_F_hyde; 1. DR PANTHER; PTHR43880; ALCOHOL DEHYDROGENASE; 1. DR PANTHER; PTHR43880:SF4; ALCOHOL DEHYDROGENASE CLASS-3; 1. DR Pfam; PF08240; ADH_N; 1. DR Pfam; PF00107; ADH_zinc_N; 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; P11766; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; KW Disease variant; Dwarfism; Intellectual disability; Lipid metabolism; KW Metal-binding; NAD; Oxidoreductase; Phosphoprotein; Reference proteome; KW Zinc. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:3365377, FT ECO:0007744|PubMed:19413330" FT CHAIN 2..374 FT /note="Alcohol dehydrogenase class-3" FT /id="PRO_0000160759" FT BINDING 45 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:3365377" FT BINDING 67 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:3365377" FT BINDING 97 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:3365377" FT BINDING 100 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:3365377" FT BINDING 103 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:3365377" FT BINDING 111 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:3365377" FT BINDING 174 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:3365377" FT SITE 115 FT /note="Important for FDH activity and activation by fatty FT acids" FT /evidence="ECO:0000269|PubMed:8460164, FT ECO:0000269|PubMed:8494891" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330" FT MOD_RES 233 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P28474" FT MOD_RES 247 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 315 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P28474" FT MOD_RES 324 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 351 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VARIANT 163 FT /note="L -> S (in dbSNP:rs28730623)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_025823" FT VARIANT 278 FT /note="A -> P (in AMEDS; dbSNP:rs754853545)" FT /evidence="ECO:0000269|PubMed:33355142" FT /id="VAR_086835" FT VARIANT 309 FT /note="V -> I (in dbSNP:rs28730628)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_025824" FT VARIANT 353 FT /note="D -> E (in dbSNP:rs16996593)" FT /id="VAR_048199" FT MUTAGEN 115 FT /note="R->A,D: Loss of FDH activity and loss of activation FT by fatty acids." FT /evidence="ECO:0000269|PubMed:8460164, FT ECO:0000269|PubMed:8494891" FT CONFLICT 167 FT /note="D -> Y (in Ref. 2; AAA51597)" FT /evidence="ECO:0000305" FT CONFLICT 246 FT /note="F -> L (in Ref. 2; AAA51597)" FT /evidence="ECO:0000305" FT STRAND 6..13 FT /evidence="ECO:0007829|PDB:2FZW" FT STRAND 21..27 FT /evidence="ECO:0007829|PDB:2FZW" FT STRAND 34..43 FT /evidence="ECO:0007829|PDB:2FZW" FT HELIX 46..52 FT /evidence="ECO:0007829|PDB:2FZW" FT STRAND 61..63 FT /evidence="ECO:0007829|PDB:2FZW" FT STRAND 68..76 FT /evidence="ECO:0007829|PDB:2FZW" FT STRAND 88..91 FT /evidence="ECO:0007829|PDB:2FZW" FT STRAND 98..100 FT /evidence="ECO:0007829|PDB:3QJ5" FT HELIX 101..104 FT /evidence="ECO:0007829|PDB:2FZW" FT HELIX 115..119 FT /evidence="ECO:0007829|PDB:2FZW" FT STRAND 129..132 FT /evidence="ECO:0007829|PDB:2FZW" FT STRAND 135..138 FT /evidence="ECO:0007829|PDB:2FZW" FT TURN 141..143 FT /evidence="ECO:0007829|PDB:2FZW" FT STRAND 146..153 FT /evidence="ECO:0007829|PDB:2FZW" FT HELIX 154..156 FT /evidence="ECO:0007829|PDB:2FZW" FT STRAND 157..159 FT /evidence="ECO:0007829|PDB:2FZW" FT HELIX 166..169 FT /evidence="ECO:0007829|PDB:2FZW" FT HELIX 170..173 FT /evidence="ECO:0007829|PDB:2FZW" FT HELIX 175..184 FT /evidence="ECO:0007829|PDB:2FZW" FT TURN 185..187 FT /evidence="ECO:0007829|PDB:2FZW" FT STRAND 194..198 FT /evidence="ECO:0007829|PDB:2FZW" FT HELIX 202..214 FT /evidence="ECO:0007829|PDB:2FZW" FT STRAND 217..222 FT /evidence="ECO:0007829|PDB:2FZW" FT HELIX 226..228 FT /evidence="ECO:0007829|PDB:2FZW" FT HELIX 229..235 FT /evidence="ECO:0007829|PDB:2FZW" FT STRAND 238..241 FT /evidence="ECO:0007829|PDB:2FZW" FT HELIX 243..245 FT /evidence="ECO:0007829|PDB:2FZW" FT HELIX 250..257 FT /evidence="ECO:0007829|PDB:2FZW" FT STRAND 262..267 FT /evidence="ECO:0007829|PDB:2FZW" FT HELIX 272..280 FT /evidence="ECO:0007829|PDB:2FZW" FT TURN 284..286 FT /evidence="ECO:0007829|PDB:2FZW" FT STRAND 288..291 FT /evidence="ECO:0007829|PDB:2FZW" FT STRAND 301..303 FT /evidence="ECO:0007829|PDB:2FZW" FT HELIX 306..309 FT /evidence="ECO:0007829|PDB:2FZW" FT STRAND 313..316 FT /evidence="ECO:0007829|PDB:2FZW" FT HELIX 319..321 FT /evidence="ECO:0007829|PDB:2FZW" FT HELIX 324..336 FT /evidence="ECO:0007829|PDB:2FZW" FT HELIX 343..345 FT /evidence="ECO:0007829|PDB:2FZW" FT STRAND 346..351 FT /evidence="ECO:0007829|PDB:2FZW" FT HELIX 352..354 FT /evidence="ECO:0007829|PDB:2FZW" FT HELIX 355..363 FT /evidence="ECO:0007829|PDB:2FZW" FT STRAND 368..373 FT /evidence="ECO:0007829|PDB:2FZW" SQ SEQUENCE 374 AA; 39724 MW; F4F823B4A609C952 CRC64; MANEVIKCKA AVAWEAGKPL SIEEIEVAPP KAHEVRIKII ATAVCHTDAY TLSGADPEGC FPVILGHEGA GIVESVGEGV TKLKAGDTVI PLYIPQCGEC KFCLNPKTNL CQKIRVTQGK GLMPDGTSRF TCKGKTILHY MGTSTFSEYT VVADISVAKI DPLAPLDKVC LLGCGISTGY GAAVNTAKLE PGSVCAVFGL GGVGLAVIMG CKVAGASRII GVDINKDKFA RAKEFGATEC INPQDFSKPI QEVLIEMTDG GVDYSFECIG NVKVMRAALE ACHKGWGVSV VVGVAASGEE IATRPFQLVT GRTWKGTAFG GWKSVESVPK LVSEYMSKKI KVDEFVTHNL SFDEINKAFE LMHSGKSIRT VVKI //