ALDH6_YEAST
ID ALDH6_YEAST Reviewed; 500 AA.
AC P54115; D6W3V3; Q02782;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Magnesium-activated aldehyde dehydrogenase, cytosolic {ECO:0000303|PubMed:9473035};
DE EC=1.2.1.- {ECO:0000269|PubMed:9473035};
DE EC=1.2.1.4 {ECO:0000269|PubMed:9473035};
DE AltName: Full=Mg(2+)-activated acetaldehyde dehydrogenase {ECO:0000303|PubMed:9473035};
DE Short=Mg(2+)-ACDH {ECO:0000303|PubMed:9473035};
GN Name=ALD6; Synonyms=ALDH1 {ECO:0000303|PubMed:9473035};
GN OrderedLocusNames=YPL061W; ORFNames=LPE9;
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], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND PATHWAY.
RC STRAIN=DBY939;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169875;
RA Bussey H., Storms R.K., Ahmed A., Albermann K., Allen E., Ansorge W.,
RA Araujo R., Aparicio A., Barrell B.G., Badcock K., Benes V., Botstein D.,
RA Bowman S., Brueckner M., Carpenter J., Cherry J.M., Chung E.,
RA Churcher C.M., Coster F., Davis K., Davis R.W., Dietrich F.S., Delius H.,
RA DiPaolo T., Dubois E., Duesterhoeft A., Duncan M., Floeth M., Fortin N.,
RA Friesen J.D., Fritz C., Goffeau A., Hall J., Hebling U., Heumann K.,
RA Hilbert H., Hillier L.W., Hunicke-Smith S., Hyman R.W., Johnston M.,
RA Kalman S., Kleine K., Komp C., Kurdi O., Lashkari D., Lew H., Lin A.,
RA Lin D., Louis E.J., Marathe R., Messenguy F., Mewes H.-W., Mirtipati S.,
RA Moestl D., Mueller-Auer S., Namath A., Nentwich U., Oefner P., Pearson D.,
RA Petel F.X., Pohl T.M., Purnelle B., Rajandream M.A., Rechmann S.,
RA Rieger M., Riles L., Roberts D., Schaefer M., Scharfe M., Scherens B.,
RA Schramm S., Schroeder M., Sdicu A.-M., Tettelin H., Urrestarazu L.A.,
RA Ushinsky S., Vierendeels F., Vissers S., Voss H., Walsh S.V., Wambutt R.,
RA Wang Y., Wedler E., Wedler H., Winnett E., Zhong W.-W., Zollner A.,
RA Vo D.H., Hani J.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI.";
RL Nature 387:103-105(1997).
RN [3]
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 [4]
RP PROTEIN SEQUENCE OF 76-79 AND 482-488.
RC STRAIN=ATCC 44827 / SKQ2N;
RX PubMed=9038161; DOI=10.1074/jbc.272.9.5544;
RA Norbeck J., Blomberg A.;
RT "Metabolic and regulatory changes associated with growth of Saccharomyces
RT cerevisiae in 1.4 M NaCl. Evidence for osmotic induction of glycerol
RT dissimilation via the dihydroxyacetone pathway.";
RL J. Biol. Chem. 272:5544-5554(1997).
RN [5]
RP PROTEIN SEQUENCE OF 2-16, AND CHARACTERIZATION.
RX PubMed=9392076;
RX DOI=10.1002/(sici)1097-0061(199711)13:14<1319::aid-yea183>3.0.co;2-t;
RA Meaden P.G., Dickinson F.M., Mifsud A., Tessier W., Westwater J.,
RA Bussey H., Midgley M.;
RT "The ALD6 gene of Saccharomyces cerevisiae encodes a cytosolic, Mg(2+)-
RT activated acetaldehyde dehydrogenase.";
RL Yeast 13:1319-1327(1997).
RN [6]
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 [7]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-3, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=SUB592;
RX PubMed=12872131; DOI=10.1038/nbt849;
RA Peng J., Schwartz D., Elias J.E., Thoreen C.C., Cheng D., Marsischky G.,
RA Roelofs J., Finley D., Gygi S.P.;
RT "A proteomics approach to understanding protein ubiquitination.";
RL Nat. Biotechnol. 21:921-926(2003).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=17287358; DOI=10.1073/pnas.0607084104;
RA Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L.,
RA Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.;
RT "Analysis of phosphorylation sites on proteins from Saccharomyces
RT cerevisiae by electron transfer dissociation (ETD) mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [11]
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).
RN [12]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-142 AND LYS-196, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22106047; DOI=10.1002/pmic.201100166;
RA Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.;
RT "Sites of ubiquitin attachment in Saccharomyces cerevisiae.";
RL Proteomics 12:236-240(2012).
CC -!- FUNCTION: Cytosolic aldehyde dehydrogenase which utilizes NADP(+) as
CC the preferred coenzyme. Performs the conversion of acetaldehyde to
CC acetate. {ECO:0000269|PubMed:9473035}.
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 -!- ACTIVITY REGULATION: The activity is stimulated two- to fourfold by
CC divalent cations but is unaffected by K(+) ions.
CC {ECO:0000269|PubMed:9473035}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=40 uM for NADP (with acetaldehyde as cosubstrate)
CC {ECO:0000269|PubMed:9473035};
CC KM=99 uM for NADP (with propionaldehyde as cosubstrate)
CC {ECO:0000269|PubMed:9473035};
CC KM=17.4 mM for NAD (with propionaldehyde as cosubstrate)
CC {ECO:0000269|PubMed:9473035};
CC KM=24 uM for acetaldehyde (with NADP as cosubstrate)
CC {ECO:0000269|PubMed:9473035};
CC KM=30 uM for propionaldehyde (with NADP as cosubstrate)
CC {ECO:0000269|PubMed:9473035};
CC KM=0.7 mM for propionaldehyde (with NAD as cosubstrate)
CC {ECO:0000269|PubMed:9473035};
CC Vmax=24 umol/min/mg enzyme with acetaldehyde and NADP as substrates
CC {ECO:0000269|PubMed:9473035};
CC Vmax=14 umol/min/mg enzyme with propionaldehyde and NADP as
CC substrates {ECO:0000269|PubMed:9473035};
CC Vmax=8.3 umol/min/mg enzyme with propionaldehyde and NAD as
CC substrates {ECO:0000269|PubMed:9473035};
CC -!- PATHWAY: Alcohol metabolism; ethanol degradation; acetate from ethanol:
CC step 2/2. {ECO:0000269|PubMed:9473035}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- MISCELLANEOUS: Present with 135000 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; U56604; AAB01219.1; -; Genomic_DNA.
DR EMBL; U39205; AAB68304.1; -; Genomic_DNA.
DR EMBL; BK006949; DAA11369.1; -; Genomic_DNA.
DR PIR; S60929; S60929.
DR RefSeq; NP_015264.1; NM_001183875.1.
DR AlphaFoldDB; P54115; -.
DR SMR; P54115; -.
DR BioGRID; 36117; 253.
DR DIP; DIP-8324N; -.
DR IntAct; P54115; 74.
DR MINT; P54115; -.
DR STRING; 4932.YPL061W; -.
DR iPTMnet; P54115; -.
DR MaxQB; P54115; -.
DR PaxDb; P54115; -.
DR PRIDE; P54115; -.
DR TopDownProteomics; P54115; -.
DR EnsemblFungi; YPL061W_mRNA; YPL061W; YPL061W.
DR GeneID; 856044; -.
DR KEGG; sce:YPL061W; -.
DR SGD; S000005982; ALD6.
DR VEuPathDB; FungiDB:YPL061W; -.
DR eggNOG; KOG2450; Eukaryota.
DR GeneTree; ENSGT00940000176713; -.
DR HOGENOM; CLU_005391_0_1_1; -.
DR InParanoid; P54115; -.
DR OMA; VTGPGHT; -.
DR BioCyc; MetaCyc:MON-13664; -.
DR BioCyc; YEAST:MON-13664; -.
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; P54115; -.
DR UniPathway; UPA00780; UER00768.
DR PRO; PR:P54115; -.
DR Proteomes; UP000002311; Chromosome XVI.
DR RNAct; P54115; protein.
DR GO; GO:0005829; C:cytosol; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; IBA:GO_Central.
DR GO; GO:0033721; F:aldehyde dehydrogenase (NADP+) activity; IEA:UniProtKB-EC.
DR GO; GO:0004030; F:aldehyde dehydrogenase [NAD(P)+] activity; IDA:SGD.
DR GO; GO:0019413; P:acetate biosynthetic process; IMP:SGD.
DR GO; GO:0006068; P:ethanol catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006740; P:NADPH regeneration; IGI:SGD.
DR GO; GO:0009651; P:response to salt stress; 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; 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; PS00687; ALDEHYDE_DEHYDR_GLU; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Direct protein sequencing; Isopeptide bond; Magnesium; NADP;
KW Oxidoreductase; Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:9392076"
FT CHAIN 2..500
FT /note="Magnesium-activated aldehyde dehydrogenase,
FT cytosolic"
FT /id="PRO_0000056441"
FT ACT_SITE 272
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007"
FT ACT_SITE 306
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007"
FT BINDING 249..254
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT SITE 173
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT CROSSLNK 3
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:12872131"
FT CROSSLNK 142
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT CROSSLNK 196
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT CONFLICT 121
FT /note="L -> FK (in Ref. 1; AAB01219)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 500 AA; 54414 MW; 542AA956EFA0E676 CRC64;
MTKLHFDTAE PVKITLPNGL TYEQPTGLFI NNKFMKAQDG KTYPVEDPST ENTVCEVSSA
TTEDVEYAIE CADRAFHDTE WATQDPRERG RLLSKLADEL ESQIDLVSSI EALDNGKTLA
LARGDVTIAI NCLRDAAAYA DKVNGRTINT GDGYMNFTTL EPIGVCGQII PWNFPIMMLA
WKIAPALAMG NVCILKPAAV TPLNALYFAS LCKKVGIPAG VVNIVPGPGR TVGAALTNDP
RIRKLAFTGS TEVGKSVAVD SSESNLKKIT LELGGKSAHL VFDDANIKKT LPNLVNGIFK
NAGQICSSGS RIYVQEGIYD ELLAAFKAYL ETEIKVGNPF DKANFQGAIT NRQQFDTIMN
YIDIGKKEGA KILTGGEKVG DKGYFIRPTV FYDVNEDMRI VKEEIFGPVV TVAKFKTLEE
GVEMANSSEF GLGSGIETES LSTGLKVAKM LKAGTVWINT YNDFDSRVPF GGVKQSGYGR
EMGEEVYHAY TEVKAVRIKL
