ALDH4_YEAST
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 03-AUG-2022, entry version 189.
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; 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; 79.
DR DIP; DIP-4053N; -.
DR IntAct; P46367; 43.
DR MINT; P46367; -.
DR STRING; 4932.YOR374W; -.
DR iPTMnet; P46367; -.
DR MaxQB; P46367; -.
DR PaxDb; P46367; -.
DR PRIDE; P46367; -.
DR TopDownProteomics; P46367; -.
DR EnsemblFungi; YOR374W_mRNA; YOR374W; YOR374W.
DR GeneID; 854556; -.
DR KEGG; sce:YOR374W; -.
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 BioCyc; MetaCyc:MON-13666; -.
DR BioCyc; YEAST:MON-13666; -.
DR Reactome; R-SCE-196757; Metabolism of folate and pterines.
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 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 Gene3D; 3.40.309.10; -; 1.
DR Gene3D; 3.40.605.10; -; 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 Pfam; PF00171; Aldedh; 1.
DR SUPFAM; SSF53720; SSF53720; 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
