ADH4_YEAST
ID ADH4_YEAST Reviewed; 382 AA.
AC P10127; D6VV79;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 3.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Alcohol dehydrogenase 4;
DE EC=1.1.1.1 {ECO:0000269|PubMed:3282541};
DE AltName: Full=Alcohol dehydrogenase IV;
DE Short=ADHIV;
GN Name=ADH4; Synonyms=ZRG5; OrderedLocusNames=YGL256W; ORFNames=NRC465;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2823079; DOI=10.1007/bf00329668;
RA Williamson V.M., Paquin C.E.;
RT "Homology of Saccharomyces cerevisiae ADH4 to an iron-activated alcohol
RT dehydrogenase from Zymomonas mobilis.";
RL Mol. Gen. Genet. 209:374-381(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 96604 / S288c / FY1679;
RX PubMed=8972578;
RX DOI=10.1002/(sici)1097-0061(199612)12:15<1555::aid-yea43>3.0.co;2-q;
RA Coissac E., Maillier E., Robineau S., Netter P.;
RT "Sequence of a 39,411 bp DNA fragment covering the left end of chromosome
RT VII of Saccharomyces cerevisiae.";
RL Yeast 12:1555-1562(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169869;
RA Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J.,
RA Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M.,
RA Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L.,
RA Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H.,
RA Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P.,
RA Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M.,
RA Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A.,
RA Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K.,
RA Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P.,
RA Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E.,
RA Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K.,
RA Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A.,
RA Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S.,
RA Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M.,
RA Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C.,
RA Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M.,
RA Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M.,
RA Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y.,
RA Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L.,
RA Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D.,
RA Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F.,
RA Zaccaria P., Zimmermann M., Zollner A., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.";
RL Nature 387:81-84(1997).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [5]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, COFACTOR,
RP ACTIVITY REGULATION, AND SUBSTRATE SPECIFICITY.
RX PubMed=3282541; DOI=10.1016/0167-4781(88)90072-3;
RA Drewke C., Ciriacy M.;
RT "Overexpression, purification and properties of alcohol dehydrogenase IV
RT from Saccharomyces cerevisiae.";
RL Biochim. Biophys. Acta 950:54-60(1988).
RN [6]
RP INDUCTION.
RX PubMed=10978274; DOI=10.1093/genetics/156.1.45;
RA Yuan D.S.;
RT "Zinc-regulated genes in Saccharomyces cerevisiae revealed by transposon
RT tagging.";
RL Genetics 156:45-58(2000).
RN [7]
RP INDUCTION, AND IDENTIFICATION OF PROBABLE INITIATION SITE.
RX PubMed=10884426; DOI=10.1073/pnas.97.14.7957;
RA Lyons T.J., Gasch A.P., Gaither L.A., Botstein D., Brown P.O., Eide D.J.;
RT "Genome-wide characterization of the Zap1p zinc-responsive regulon in
RT yeast.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:7957-7962(2000).
RN [8]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [9]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [10]
RP INDUCTION.
RX PubMed=17139254; DOI=10.1038/sj.emboj.7601453;
RA Bird A.J., Gordon M., Eide D.J., Winge D.R.;
RT "Repression of ADH1 and ADH3 during zinc deficiency by Zap1-induced
RT intergenic RNA transcripts.";
RL EMBO J. 25:5726-5734(2006).
RN [11]
RP EXPRESSION LEVEL IN BREWING STRAINS.
RX PubMed=16503288; DOI=10.1263/jbb.101.31;
RA Mizuno A., Tabei H., Iwahuti M.;
RT "Characterization of low-acetic-acid-producing yeast isolated from 2-
RT deoxyglucose-resistant mutants and its application to high-gravity
RT brewing.";
RL J. Biosci. Bioeng. 101:31-37(2006).
RN [12]
RP INDUCTION.
RX PubMed=17933919; DOI=10.1128/aem.01445-07;
RA De Nicola R., Hazelwood L.A., De Hulster E.A.F., Walsh M.C.,
RA Knijnenburg T.A., Reinders M.J.T., Walker G.M., Pronk J.T., Daran J.-M.,
RA Daran-Lapujade P.;
RT "Physiological and transcriptional responses of Saccharomyces cerevisiae to
RT zinc limitation in chemostat cultures.";
RL Appl. Environ. Microbiol. 73:7680-7692(2007).
RN [13]
RP FUNCTION, AND INDUCTION.
RX PubMed=17938904; DOI=10.1007/s00253-007-1234-z;
RA Cheraiti N., Sauvage F.-X., Salmon J.-M.;
RT "Acetaldehyde addition throughout the growth phase alleviates the
RT phenotypic effect of zinc deficiency in Saccharomyces cerevisiae.";
RL Appl. Microbiol. Biotechnol. 77:1093-1109(2008).
CC -!- FUNCTION: Reduces acetaldehyde to ethanol during glucose fermentation.
CC Specific for ethanol. Shows drastically reduced activity towards
CC primary alcohols from 4 carbon atoms upward. Isomers of aliphatic
CC alcohol, as well as secondary alcohols and glycerol are not used at
CC all. {ECO:0000269|PubMed:17938904, ECO:0000269|PubMed:3282541}.
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:3282541};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ethanol + NAD(+) = acetaldehyde + H(+) + NADH;
CC Xref=Rhea:RHEA:25290, ChEBI:CHEBI:15343, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16236, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1;
CC Evidence={ECO:0000269|PubMed:3282541};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:25292;
CC Evidence={ECO:0000269|PubMed:3282541};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:3282541};
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:3282541};
CC Note=Zinc. May bind iron when zinc levels are limiting.
CC {ECO:0000269|PubMed:3282541};
CC -!- ACTIVITY REGULATION: Inhibited by EDTA. {ECO:0000269|PubMed:3282541}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=59 mM for NAD {ECO:0000269|PubMed:3282541};
CC KM=122 uM for NADH {ECO:0000269|PubMed:3282541};
CC KM=2.83 mM for acetaldehyde {ECO:0000269|PubMed:3282541};
CC KM=16.7 mM for ethanol {ECO:0000269|PubMed:3282541};
CC pH dependence:
CC Optimum pH is 8.3. {ECO:0000269|PubMed:3282541};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:3282541}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14562095}.
CC -!- INDUCTION: Induced by transcription factor ZAP1 in response to zinc
CC deficiency. {ECO:0000269|PubMed:10884426, ECO:0000269|PubMed:10978274,
CC ECO:0000269|PubMed:17139254, ECO:0000269|PubMed:17933919,
CC ECO:0000269|PubMed:17938904}.
CC -!- MISCELLANEOUS: While ADH4 is expressed at only low levels in laboratory
CC strains, it is often highly expressed in brewing strains.
CC {ECO:0000269|PubMed:16503288}.
CC -!- MISCELLANEOUS: Present with 125 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the iron-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA64131.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA96976.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; X05992; CAA29410.1; -; Genomic_DNA.
DR EMBL; X94357; CAA64131.1; ALT_INIT; Genomic_DNA.
DR EMBL; Z72778; CAA96976.1; ALT_INIT; Genomic_DNA.
DR EMBL; BK006941; DAA07863.1; -; Genomic_DNA.
DR PIR; S61605; DEBY4.
DR RefSeq; NP_011258.2; NM_001181122.1.
DR AlphaFoldDB; P10127; -.
DR SMR; P10127; -.
DR BioGRID; 33023; 210.
DR DIP; DIP-4812N; -.
DR IntAct; P10127; 10.
DR MINT; P10127; -.
DR STRING; 4932.YGL256W; -.
DR MaxQB; P10127; -.
DR PaxDb; P10127; -.
DR PRIDE; P10127; -.
DR EnsemblFungi; YGL256W_mRNA; YGL256W; YGL256W.
DR GeneID; 852636; -.
DR KEGG; sce:YGL256W; -.
DR SGD; S000003225; ADH4.
DR VEuPathDB; FungiDB:YGL256W; -.
DR eggNOG; KOG3857; Eukaryota.
DR GeneTree; ENSGT00390000003849; -.
DR HOGENOM; CLU_007207_0_0_1; -.
DR InParanoid; P10127; -.
DR OMA; HAMSHQV; -.
DR BioCyc; MetaCyc:YGL256W-MON; -.
DR BioCyc; YEAST:YGL256W-MON; -.
DR SABIO-RK; P10127; -.
DR PRO; PR:P10127; -.
DR Proteomes; UP000002311; Chromosome VII.
DR RNAct; P10127; protein.
DR GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR GO; GO:0004022; F:alcohol dehydrogenase (NAD+) activity; IDA:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000947; P:amino acid catabolic process to alcohol via Ehrlich pathway; IGI:SGD.
DR GO; GO:0006113; P:fermentation; IMP:SGD.
DR InterPro; IPR001670; ADH_Fe/GldA.
DR InterPro; IPR018211; ADH_Fe_CS.
DR InterPro; IPR039697; Alcohol_dehydrogenase_Fe.
DR PANTHER; PTHR11496; PTHR11496; 1.
DR Pfam; PF00465; Fe-ADH; 1.
DR PROSITE; PS00913; ADH_IRON_1; 1.
DR PROSITE; PS00060; ADH_IRON_2; 1.
PE 1: Evidence at protein level;
KW Metal-binding; Mitochondrion; NAD; Oxidoreductase; Reference proteome;
KW Zinc.
FT CHAIN 1..382
FT /note="Alcohol dehydrogenase 4"
FT /id="PRO_0000087817"
FT CONFLICT 60
FT /note="D -> G (in Ref. 1; CAA29410)"
FT /evidence="ECO:0000305"
FT CONFLICT 88
FT /note="Q -> E (in Ref. 1; CAA29410)"
FT /evidence="ECO:0000305"
FT CONFLICT 310
FT /note="F -> C (in Ref. 1; CAA29410)"
FT /evidence="ECO:0000305"
FT CONFLICT 339
FT /note="E -> D (in Ref. 1; CAA29410)"
FT /evidence="ECO:0000305"
FT CONFLICT 348
FT /note="E -> D (in Ref. 1; CAA29410)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 382 AA; 41142 MW; 7DFFD43830FB269B CRC64;
MSSVTGFYIP PISFFGEGAL EETADYIKNK DYKKALIVTD PGIAAIGLSG RVQKMLEERD
LNVAIYDKTQ PNPNIANVTA GLKVLKEQNS EIVVSIGGGS AHDNAKAIAL LATNGGEIGD
YEGVNQSKKA ALPLFAINTT AGTASEMTRF TIISNEEKKI KMAIIDNNVT PAVAVNDPST
MFGLPPALTA ATGLDALTHC IEAYVSTASN PITDACALKG IDLINESLVA AYKDGKDKKA
RTDMCYAEYL AGMAFNNASL GYVHALAHQL GGFYHLPHGV CNAVLLPHVQ EANMQCPKAK
KRLGEIALHF GASQEDPEET IKALHVLNRT MNIPRNLKEL GVKTEDFEIL AEHAMHDACH
LTNPVQFTKE QVVAIIKKAY EY
