ID   ALDH4_YEAST             Reviewed;         519 AA.
AC   P46367; D6W367; Q08898;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 2.
DT   27-MAR-2024, entry version 197.
DE   RecName: Full=Potassium-activated aldehyde dehydrogenase, mitochondrial {ECO:0000303|PubMed:9169874};
DE            EC=1.2.1.- {ECO:0000269|PubMed:9473035};
DE            EC=1.2.1.4 {ECO:0000269|PubMed:9473035};
DE   AltName: Full=K(+)-activated acetaldehyde dehydrogenase;
DE            Short=K(+)-ACDH;
DE   Flags: Precursor;
GN   Name=ALD4; Synonyms=ALD7, ALDH2; OrderedLocusNames=YOR374W;
GN   ORFNames=O6730;
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 [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169874;
RA   Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J.,
RA   Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A.,
RA   Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B.,
RA   Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H.,
RA   Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E.,
RA   Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U.,
RA   Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B.,
RA   Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A.,
RA   Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C.,
RA   Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G.,
RA   Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B.,
RA   Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B.,
RA   Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F.,
RA   Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E.,
RA   Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I.,
RA   Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H.,
RA   Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.";
RL   Nature 387:98-102(1997).
RN   [2]
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   [3]
RP   PROTEIN SEQUENCE OF 25-65.
RX   PubMed=1989592; DOI=10.1042/bj2730099;
RA   Chalmers R.M., Keen J.N., Fewson C.A.;
RT   "Comparison of benzyl alcohol dehydrogenases and benzaldehyde
RT   dehydrogenases from the benzyl alcohol and mandelate pathways in
RT   Acinetobacter calcoaceticus and from the TOL-plasmid-encoded toluene
RT   pathway in Pseudomonas putida. N-terminal amino acid sequences, amino acid
RT   compositions and immunological cross-reactions.";
RL   Biochem. J. 273:99-107(1991).
RN   [4]
RP   PROTEIN SEQUENCE OF 25-34 AND 378-386.
RX   PubMed=9150920; DOI=10.1002/elps.1150180316;
RA   Larsson T., Norbeck J., Karlsson H., Karlsson K.-A., Blomberg A.;
RT   "Identification of two-dimensional gel electrophoresis resolved yeast
RT   proteins by matrix-assisted laser desorption ionization mass
RT   spectrometry.";
RL   Electrophoresis 18:418-423(1997).
RN   [5]
RP   PARTIAL PROTEIN SEQUENCE, AND CHARACTERIZATION.
RX   PubMed=9675847; DOI=10.1111/j.1574-6968.1998.tb13063.x;
RA   Tessier W.D., Meaden P.G., Dickinson F.M., Midgley M.;
RT   "Identification and disruption of the gene encoding the K(+)-activated
RT   acetaldehyde dehydrogenase of Saccharomyces cerevisiae.";
RL   FEMS Microbiol. Lett. 164:29-34(1998).
RN   [6]
RP   FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=9473035; DOI=10.1128/jb.180.4.822-830.1998;
RA   Wang X., Mann C.J., Bai Y., Ni L., Weiner H.;
RT   "Molecular cloning, characterization, and potential roles of cytosolic and
RT   mitochondrial aldehyde dehydrogenases in ethanol metabolism in
RT   Saccharomyces cerevisiae.";
RL   J. Bacteriol. 180:822-830(1998).
RN   [7]
RP   SUBCELLULAR LOCATION.
RX   PubMed=11502169; DOI=10.1021/bi010277r;
RA   Grandier-Vazeille X., Bathany K., Chaignepain S., Camougrand N., Manon S.,
RA   Schmitter J.-M.;
RT   "Yeast mitochondrial dehydrogenases are associated in a supramolecular
RT   complex.";
RL   Biochemistry 40:9758-9769(2001).
RN   [8]
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   [9]
RP   FUNCTION.
RX   PubMed=15256563; DOI=10.1099/mic.0.26999-0;
RA   Saint-Prix F., Boenquist L., Dequin S.;
RT   "Functional analysis of the ALD gene family of Saccharomyces cerevisiae
RT   during anaerobic growth on glucose: the NADP+-dependent Ald6p and Ald5p
RT   isoforms play a major role in acetate formation.";
RL   Microbiology 150:2209-2220(2004).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-216 AND SER-500, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   STRAIN=ATCC 76625 / YPH499;
RX   PubMed=17761666; DOI=10.1074/mcp.m700098-mcp200;
RA   Reinders J., Wagner K., Zahedi R.P., Stojanovski D., Eyrich B.,
RA   van der Laan M., Rehling P., Sickmann A., Pfanner N., Meisinger C.;
RT   "Profiling phosphoproteins of yeast mitochondria reveals a role of
RT   phosphorylation in assembly of the ATP synthase.";
RL   Mol. Cell. Proteomics 6:1896-1906(2007).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96 AND SER-500, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19779198; DOI=10.1126/science.1172867;
RA   Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT   "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT   into evolution.";
RL   Science 325:1682-1686(2009).
CC   -!- FUNCTION: Potassium-activated aldehyde dehydrogenase involved in
CC       acetate formation during anaerobic growth on glucose.
CC       {ECO:0000269|PubMed:15256563}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=acetaldehyde + H2O + NADP(+) = acetate + 2 H(+) + NADPH;
CC         Xref=Rhea:RHEA:25298, ChEBI:CHEBI:15343, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58349; EC=1.2.1.4; Evidence={ECO:0000269|PubMed:9473035};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25299;
CC         Evidence={ECO:0000269|PubMed:9473035};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + NADP(+) + propanal = 2 H(+) + NADPH + propanoate;
CC         Xref=Rhea:RHEA:27918, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17153, ChEBI:CHEBI:17272, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:9473035};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27919;
CC         Evidence={ECO:0000269|PubMed:9473035};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + NAD(+) + propanal = 2 H(+) + NADH + propanoate;
CC         Xref=Rhea:RHEA:67256, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17153, ChEBI:CHEBI:17272, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:9473035};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67257;
CC         Evidence={ECO:0000269|PubMed:9473035};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=1.4 mM for NADP (with acetaldehyde as cosubstrate)
CC         {ECO:0000269|PubMed:9473035};
CC         KM=447 uM for NADP (with propionaldehyde as cosubstrate)
CC         {ECO:0000269|PubMed:9473035};
CC         KM=1.1 mM for NAD (with propionaldehyde as cosubstrate)
CC         {ECO:0000269|PubMed:9473035};
CC         KM=10 uM for acetaldehyde (with NADP as cosubstrate)
CC         {ECO:0000269|PubMed:9473035};
CC         KM=17 uM for propionaldehyde (with NADP as cosubstrate)
CC         {ECO:0000269|PubMed:9473035};
CC         KM=13 uM for propionaldehyde (with NAD as cosubstrate)
CC         {ECO:0000269|PubMed:9473035};
CC         Vmax=5.2 umol/min/mg enzyme with acetaldehyde and NADP as substrates
CC         {ECO:0000269|PubMed:9473035};
CC         Vmax=2.1 umol/min/mg enzyme with propionaldehyde and NADP as
CC         substrates {ECO:0000269|PubMed:9473035};
CC         Vmax=4.2 umol/min/mg enzyme with propionaldehyde and NAD as
CC         substrates {ECO:0000269|PubMed:9473035};
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC       {ECO:0000269|PubMed:11502169}.
CC   -!- MISCELLANEOUS: Present with 22200 molecules/cell in log phase SD
CC       medium. {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC       {ECO:0000305}.
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DR   EMBL; Z75282; CAA99705.1; -; Genomic_DNA.
DR   EMBL; BK006948; DAA11133.1; -; Genomic_DNA.
DR   PIR; S67286; S67286.
DR   RefSeq; NP_015019.1; NM_001183794.1.
DR   AlphaFoldDB; P46367; -.
DR   SMR; P46367; -.
DR   BioGRID; 34757; 116.
DR   DIP; DIP-4053N; -.
DR   IntAct; P46367; 43.
DR   MINT; P46367; -.
DR   STRING; 4932.YOR374W; -.
DR   iPTMnet; P46367; -.
DR   MaxQB; P46367; -.
DR   PaxDb; 4932-YOR374W; -.
DR   PeptideAtlas; P46367; -.
DR   TopDownProteomics; P46367; -.
DR   EnsemblFungi; YOR374W_mRNA; YOR374W; YOR374W.
DR   GeneID; 854556; -.
DR   KEGG; sce:YOR374W; -.
DR   AGR; SGD:S000005901; -.
DR   SGD; S000005901; ALD4.
DR   VEuPathDB; FungiDB:YOR374W; -.
DR   eggNOG; KOG2450; Eukaryota.
DR   GeneTree; ENSGT00940000176713; -.
DR   HOGENOM; CLU_005391_0_2_1; -.
DR   InParanoid; P46367; -.
DR   OMA; HGIGYYP; -.
DR   OrthoDB; 216092at2759; -.
DR   BioCyc; MetaCyc:MONOMER-13666; -.
DR   BioCyc; YEAST:MONOMER-13666; -.
DR   Reactome; R-SCE-380612; Metabolism of serotonin.
DR   Reactome; R-SCE-445355; Smooth Muscle Contraction.
DR   Reactome; R-SCE-5365859; RA biosynthesis pathway.
DR   Reactome; R-SCE-70350; Fructose catabolism.
DR   Reactome; R-SCE-71384; Ethanol oxidation.
DR   SABIO-RK; P46367; -.
DR   BioGRID-ORCS; 854556; 0 hits in 10 CRISPR screens.
DR   PRO; PR:P46367; -.
DR   Proteomes; UP000002311; Chromosome XV.
DR   RNAct; P46367; Protein.
DR   GO; GO:0042645; C:mitochondrial nucleoid; IDA:SGD.
DR   GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR   GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; IDA:SGD.
DR   GO; GO:0004030; F:aldehyde dehydrogenase [NAD(P)+] activity; IDA:SGD.
DR   GO; GO:0019413; P:acetate biosynthetic process; IGI:SGD.
DR   GO; GO:0006067; P:ethanol metabolic process; IMP:SGD.
DR   GO; GO:0006740; P:NADPH regeneration; IGI:SGD.
DR   GO; GO:0006090; P:pyruvate metabolic process; IMP:SGD.
DR   CDD; cd07091; ALDH_F1-2_Ald2-like; 1.
DR   InterPro; IPR016161; Ald_DH/histidinol_DH.
DR   InterPro; IPR016163; Ald_DH_C.
DR   InterPro; IPR016160; Ald_DH_CS_CYS.
DR   InterPro; IPR029510; Ald_DH_CS_GLU.
DR   InterPro; IPR016162; Ald_DH_N.
DR   InterPro; IPR015590; Aldehyde_DH_dom.
DR   PANTHER; PTHR11699; ALDEHYDE DEHYDROGENASE-RELATED; 1.
DR   PANTHER; PTHR11699:SF268; MAGNESIUM-ACTIVATED ALDEHYDE DEHYDROGENASE, CYTOSOLIC-RELATED; 1.
DR   Pfam; PF00171; Aldedh; 1.
DR   SUPFAM; SSF53720; ALDH-like; 1.
DR   PROSITE; PS00070; ALDEHYDE_DEHYDR_CYS; 1.
DR   PROSITE; PS00687; ALDEHYDE_DEHYDR_GLU; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Mitochondrion; NAD; Oxidoreductase;
KW   Phosphoprotein; Reference proteome; Transit peptide.
FT   TRANSIT         1..24
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000269|PubMed:1989592,
FT                   ECO:0000269|PubMed:9150920"
FT   CHAIN           25..519
FT                   /note="Potassium-activated aldehyde dehydrogenase,
FT                   mitochondrial"
FT                   /id="PRO_0000007165"
FT   ACT_SITE        290
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT                   ECO:0000255|PROSITE-ProRule:PRU10008"
FT   ACT_SITE        324
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT                   ECO:0000255|PROSITE-ProRule:PRU10008"
FT   BINDING         268..273
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   SITE            192
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         96
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19779198"
FT   MOD_RES         216
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:17761666"
FT   MOD_RES         500
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17761666,
FT                   ECO:0007744|PubMed:19779198"
FT   CONFLICT        51
FT                   /note="N -> NN (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        63
FT                   /note="E -> V (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   519 AA;  56724 MW;  E7D9944EA25F948E CRC64;
     MFSRSTLCLK TSASSIGRLQ LRYFSHLPMT VPIKLPNGLE YEQPTGLFIN NKFVPSKQNK
     TFEVINPSTE EEICHIYEGR EDDVEEAVQA ADRAFSNGSW NGIDPIDRGK ALYRLAELIE
     QDKDVIASIE TLDNGKAISS SRGDVDLVIN YLKSSAGFAD KIDGRMIDTG RTHFSYTKRQ
     PLGVCGQIIP WNFPLLMWAW KIAPALVTGN TVVLKTAEST PLSALYVSKY IPQAGIPPGV
     INIVSGFGKI VGEAITNHPK IKKVAFTGST ATGRHIYQSA AAGLKKVTLE LGGKSPNIVF
     ADAELKKAVQ NIILGIYYNS GEVCCAGSRV YVEESIYDKF IEEFKAASES IKVGDPFDES
     TFQGAQTSQM QLNKILKYVD IGKNEGATLI TGGERLGSKG YFIKPTVFGD VKEDMRIVKE
     EIFGPVVTVT KFKSADEVIN MANDSEYGLA AGIHTSNINT ALKVADRVNA GTVWINTYND
     FHHAVPFGGF NASGLGREMS VDALQNYLQV KAVRAKLDE
//