ID ALDH5_YEAST Reviewed; 520 AA.
AC P40047; D3DLX8;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 4.
DT 27-MAR-2024, entry version 200.
DE RecName: Full=Aldehyde dehydrogenase 5, mitochondrial {ECO:0000303|PubMed:9473035};
DE EC=1.2.1.- {ECO:0000269|PubMed:9473035};
DE EC=1.2.1.4 {ECO:0000269|PubMed:9473035};
DE Flags: Precursor;
GN Name=ALD5; Synonyms=ALD3, ALDH5; OrderedLocusNames=YER073W;
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=9059631; DOI=10.1007/978-1-4615-5871-2_32;
RA Wang X., Bai Y., Ni L., Weiner H.;
RT "Saccharomyces cerevisiae aldehyde dehydrogenases. Identification and
RT expression.";
RL Adv. Exp. Med. Biol. 414:277-280(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169868;
RA Dietrich F.S., Mulligan J.T., Hennessy K.M., Yelton M.A., Allen E.,
RA Araujo R., Aviles E., Berno A., Brennan T., Carpenter J., Chen E.,
RA Cherry J.M., Chung E., Duncan M., Guzman E., Hartzell G., Hunicke-Smith S.,
RA Hyman R.W., Kayser A., Komp C., Lashkari D., Lew H., Lin D., Mosedale D.,
RA Nakahara K., Namath A., Norgren R., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Sehl P., Schramm S., Shogren T., Smith V., Taylor P., Wei Y.,
RA Botstein D., Davis R.W.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome V.";
RL Nature 387:78-81(1997).
RN [3]
RP GENOME REANNOTATION, AND SEQUENCE REVISION TO 411.
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 CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND
RP SUBCELLULAR LOCATION.
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 [5]
RP FUNCTION.
RX PubMed=10585550; DOI=10.1111/j.1574-6968.1999.tb08856.x;
RA Kurita O., Nishida Y.;
RT "Involvement of mitochondrial aldehyde dehydrogenase ALD5 in maintenance of
RT the mitochondrial electron transport chain in Saccharomyces cerevisiae.";
RL FEMS Microbiol. Lett. 181:281-287(1999).
RN [6]
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 [7]
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 [8]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 76625 / YPH499;
RX PubMed=14576278; DOI=10.1073/pnas.2135385100;
RA Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E.,
RA Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P.,
RA Pfanner N., Meisinger C.;
RT "The proteome of Saccharomyces cerevisiae mitochondria.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(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).
CC -!- FUNCTION: Minor mitochondrial aldehyde dehydrogenase isoform. Plays a
CC role in regulation or biosynthesis of electron transport chain
CC components. Involved in the biosynthesis of acetate during anaerobic
CC growth on glucose. {ECO:0000269|PubMed:10585550,
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 -!- ACTIVITY REGULATION: The activity increases in the presence of K(+)
CC ions: 15-fold with NADP and 40-fold with NAD, respectively.
CC {ECO:0000269|PubMed:9473035}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.64 mM for NADP (with acetaldehyde as cosubstrate)
CC {ECO:0000269|PubMed:9473035};
CC KM=3.47 mM for NADP (with propionaldehyde as cosubstrate)
CC {ECO:0000269|PubMed:9473035};
CC KM=6.43 mM for NAD (with propionaldehyde as cosubstrate)
CC {ECO:0000269|PubMed:9473035};
CC KM=0.058 mM for acetaldehyde (with NADP as cosubstrate)
CC {ECO:0000269|PubMed:9473035};
CC KM=0.39 mM for propionaldehyde (with NADP as cosubstrate)
CC {ECO:0000269|PubMed:9473035};
CC KM=0.83 mM for propionaldehyde (with NAD as cosubstrate)
CC {ECO:0000269|PubMed:9473035};
CC Vmax=1.1 umol/min/mg enzyme with acetaldehyde and NADP as substrates
CC {ECO:0000269|PubMed:9473035};
CC Vmax=0.45 umol/min/mg enzyme with propionaldehyde and NADP as
CC substrates {ECO:0000269|PubMed:9473035};
CC Vmax=0.011 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:0000305}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:14562095, ECO:0000269|PubMed:14576278,
CC ECO:0000269|PubMed:9473035}.
CC -!- MISCELLANEOUS: Present with 23300 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; U56605; AAB01220.1; -; Genomic_DNA.
DR EMBL; U18814; AAB64612.1; -; Genomic_DNA.
DR EMBL; BK006939; DAA07732.2; -; Genomic_DNA.
DR PIR; S50576; S50576.
DR RefSeq; NP_010996.2; NM_001178964.2.
DR AlphaFoldDB; P40047; -.
DR SMR; P40047; -.
DR BioGRID; 36816; 134.
DR DIP; DIP-3872N; -.
DR IntAct; P40047; 11.
DR STRING; 4932.YER073W; -.
DR iPTMnet; P40047; -.
DR MaxQB; P40047; -.
DR PaxDb; 4932-YER073W; -.
DR PeptideAtlas; P40047; -.
DR EnsemblFungi; YER073W_mRNA; YER073W; YER073W.
DR GeneID; 856804; -.
DR KEGG; sce:YER073W; -.
DR AGR; SGD:S000000875; -.
DR SGD; S000000875; ALD5.
DR VEuPathDB; FungiDB:YER073W; -.
DR eggNOG; KOG2450; Eukaryota.
DR GeneTree; ENSGT00940000168475; -.
DR HOGENOM; CLU_005391_0_1_1; -.
DR InParanoid; P40047; -.
DR OMA; WSNTFNK; -.
DR OrthoDB; 216092at2759; -.
DR BioCyc; MetaCyc:MONOMER-13665; -.
DR BioCyc; YEAST:MONOMER-13665; -.
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; P40047; -.
DR UniPathway; UPA00780; UER00768.
DR BioGRID-ORCS; 856804; 2 hits in 10 CRISPR screens.
DR PRO; PR:P40047; -.
DR Proteomes; UP000002311; Chromosome V.
DR RNAct; P40047; Protein.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
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; IMP:SGD.
DR GO; GO:0006068; P:ethanol catabolic process; IEA:UniProtKB-UniPathway.
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:SF211; ALDEHYDE DEHYDROGENASE FAMILY 16 MEMBER A1; 1.
DR PANTHER; PTHR11699; ALDEHYDE DEHYDROGENASE-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 Mitochondrion; NAD; NADP; Oxidoreductase; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..23
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 24..520
FT /note="Aldehyde dehydrogenase 5, mitochondrial"
FT /id="PRO_0000007166"
FT ACT_SITE 288
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT ECO:0000255|PROSITE-ProRule:PRU10008"
FT ACT_SITE 322
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT ECO:0000255|PROSITE-ProRule:PRU10008"
FT BINDING 266..271
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT SITE 190
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT CONFLICT 48
FT /note="I -> T (in Ref. 1; AAB01220)"
FT /evidence="ECO:0000305"
FT CONFLICT 90
FT /note="A -> L (in Ref. 1; AAB01220)"
FT /evidence="ECO:0000305"
FT CONFLICT 93..104
FT /note="AFETKWSIVEPE -> LLKRSVYCRAG (in Ref. 1; AAB01220)"
FT /evidence="ECO:0000305"
FT CONFLICT 411
FT /note="E -> G (in Ref. 2; AAB64612)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 520 AA; 56693 MW; DCD382A1157F800A CRC64;
MLSRTRAAAP NSRIFTRSLL RLYSQAPLRV PITLPNGFTY EQPTGLFING EFVASKQKKT
FDVINPSNEE KITTVYKAME DDVDEAVAAA KKAFETKWSI VEPEVRAKAL FNLADLVEKH
QETLAAIESM DNGKSLFCAR GDVALVSKYL RSCGGWADKI YGNVIDTGKN HFTYSIKEPL
GVCGQIIPWN FPLLMWSWKI GPALATGNTV VLKPAETTPL SALFASQLCQ EAGIPAGVVN
ILPGSGRVVG ERLSAHPDVK KIAFTGSTAT GRHIMKVAAD TVKKVTLELG GKSPNIVFAD
ADLDKAVKNI AFGIFYNSGE VCCAGSRIYI QDTVYEEVLQ KLKDYTESLK VGDPFDEEVF
QGAQTSDKQL HKILDYVDVA KSEGARLVTG GARHGSKGYF VKPTVFADVK EDMRIVKEEV
FGPIVTVSKF STVDEVIAMA NDSQYGLAAG IHTNDINKAV DVSKRVKAGT VWINTYNNFH
QNVPFGGFGQ SGIGREMGEA ALSNYTQTKS VRIAIDKPIR
//
