ID   ALDH2_MOUSE             Reviewed;         519 AA.
AC   P47738;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   27-MAR-2024, entry version 187.
DE   RecName: Full=Aldehyde dehydrogenase, mitochondrial;
DE            EC=1.2.1.3;
DE   AltName: Full=AHD-M1;
DE   AltName: Full=ALDH class 2;
DE   AltName: Full=ALDH-E2;
DE   AltName: Full=ALDHI;
DE   Flags: Precursor;
GN   Name=Aldh2; Synonyms=Ahd-1, Ahd1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=7958964; DOI=10.1016/0378-1119(94)90708-0;
RA   Chang C., Yoshida A.;
RT   "Cloning and characterization of the gene encoding mouse mitochondrial
RT   aldehyde dehydrogenase.";
RL   Gene 148:331-336(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=8058062;
RA   Chen M., Achkar C., Gudas L.J.;
RT   "Enzymatic conversion of retinaldehyde to retinoic acid by cloned murine
RT   cytosolic and mitochondrial aldehyde dehydrogenases.";
RL   Mol. Pharmacol. 46:88-96(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Mammary gland;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   PROTEIN SEQUENCE OF 54-80; 87-96; 162-174; 198-228; 260-282; 327-340;
RP   349-370; 386-409; 417-428; 431-438 AND 444-453, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   STRAIN=C57BL/6J, and OF1; TISSUE=Brain, and Hippocampus;
RA   Lubec G., Kang S.U., Klug S., Sunyer B., Chen W.-Q.;
RL   Submitted (JAN-2009) to UniProtKB.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 472-509.
RX   PubMed=7937138; DOI=10.1093/nar/22.20.4132;
RA   Caubin J., Iglesias T., Bernal J., Munoz A., Marquez G., Barbero J.L.,
RA   Zaballos A.;
RT   "Isolation of genomic DNA fragments corresponding to genes modulated in
RT   vivo by a transcription factor.";
RL   Nucleic Acids Res. 22:4132-4138(1994).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [7]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-430, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Embryonic fibroblast;
RX   PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA   Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA   Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT   "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT   pathways.";
RL   Mol. Cell 50:919-930(2013).
RN   [8]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-54; LYS-75; LYS-80; LYS-161;
RP   LYS-370; LYS-377; LYS-385; LYS-409; LYS-428; LYS-430; LYS-443 AND LYS-453,
RP   AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA   Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA   Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT   "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT   identifies substrates of SIRT3 in metabolic pathways.";
RL   Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC   -!- FUNCTION: Required for clearance of cellular formaldehyde, a cytotoxic
CC       and carcinogenic metabolite that induces DNA damage.
CC       {ECO:0000250|UniProtKB:P05091}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an aldehyde + H2O + NAD(+) = a carboxylate + 2 H(+) + NADH;
CC         Xref=Rhea:RHEA:16185, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17478, ChEBI:CHEBI:29067, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945; EC=1.2.1.3;
CC   -!- PATHWAY: Alcohol metabolism; ethanol degradation; acetate from ethanol:
CC       step 2/2.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000250}.
CC   -!- INTERACTION:
CC       P47738; Q8R104: Sirt3; NbExp=2; IntAct=EBI-2308120, EBI-6999888;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC   -!- INDUCTION: By retinoic acid; 3-5 fold increase.
CC   -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC       {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; U07235; AAA64636.1; -; mRNA.
DR   EMBL; S71509; AAC60691.1; -; mRNA.
DR   EMBL; BC005476; AAH05476.1; -; mRNA.
DR   EMBL; Z32545; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS19638.1; -.
DR   PIR; I48966; I48966.
DR   RefSeq; NP_033786.1; NM_009656.4.
DR   AlphaFoldDB; P47738; -.
DR   SMR; P47738; -.
DR   BioGRID; 198064; 22.
DR   IntAct; P47738; 14.
DR   MINT; P47738; -.
DR   STRING; 10090.ENSMUSP00000031411; -.
DR   GlyGen; P47738; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P47738; -.
DR   PhosphoSitePlus; P47738; -.
DR   SwissPalm; P47738; -.
DR   REPRODUCTION-2DPAGE; P47738; -.
DR   EPD; P47738; -.
DR   jPOST; P47738; -.
DR   PaxDb; 10090-ENSMUSP00000031411; -.
DR   PeptideAtlas; P47738; -.
DR   ProteomicsDB; 281966; -.
DR   Pumba; P47738; -.
DR   DNASU; 11669; -.
DR   Ensembl; ENSMUST00000031411.15; ENSMUSP00000031411.9; ENSMUSG00000029455.15.
DR   GeneID; 11669; -.
DR   KEGG; mmu:11669; -.
DR   UCSC; uc008zjt.1; mouse.
DR   AGR; MGI:99600; -.
DR   CTD; 217; -.
DR   MGI; MGI:99600; Aldh2.
DR   VEuPathDB; HostDB:ENSMUSG00000029455; -.
DR   eggNOG; KOG2450; Eukaryota.
DR   GeneTree; ENSGT00940000156240; -.
DR   HOGENOM; CLU_005391_0_2_1; -.
DR   InParanoid; P47738; -.
DR   OMA; HGIGYYP; -.
DR   OrthoDB; 2291791at2759; -.
DR   PhylomeDB; P47738; -.
DR   TreeFam; TF300455; -.
DR   BRENDA; 1.2.1.3; 3474.
DR   Reactome; R-MMU-380612; Metabolism of serotonin.
DR   Reactome; R-MMU-445355; Smooth Muscle Contraction.
DR   Reactome; R-MMU-71384; Ethanol oxidation.
DR   UniPathway; UPA00780; UER00768.
DR   BioGRID-ORCS; 11669; 1 hit in 81 CRISPR screens.
DR   ChiTaRS; Aldh2; mouse.
DR   PRO; PR:P47738; -.
DR   Proteomes; UP000000589; Chromosome 5.
DR   RNAct; P47738; Protein.
DR   Bgee; ENSMUSG00000029455; Expressed in granulocyte and 268 other cell types or tissues.
DR   ExpressionAtlas; P47738; baseline and differential.
DR   GO; GO:0005759; C:mitochondrial matrix; ISO:MGI.
DR   GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR   GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; ISS:UniProtKB.
DR   GO; GO:0106435; F:carboxylesterase activity; ISS:UniProtKB.
DR   GO; GO:0043878; F:glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity; IEA:UniProtKB-EC.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0051287; F:NAD binding; ISS:CAFA.
DR   GO; GO:0070404; F:NADH binding; ISO:MGI.
DR   GO; GO:0018547; F:nitroglycerin reductase activity; ISS:UniProtKB.
DR   GO; GO:0008957; F:phenylacetaldehyde dehydrogenase activity; ISS:UniProtKB.
DR   GO; GO:0006117; P:acetaldehyde metabolic process; ISO:MGI.
DR   GO; GO:0046185; P:aldehyde catabolic process; ISS:UniProtKB.
DR   GO; GO:0048149; P:behavioral response to ethanol; ISO:MGI.
DR   GO; GO:0110095; P:cellular detoxification of aldehyde; ISO:MGI.
DR   GO; GO:0006068; P:ethanol catabolic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; ISO:MGI.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR   GO; GO:1903179; P:regulation of dopamine biosynthetic process; IMP:UniProtKB.
DR   GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; ISO:MGI.
DR   GO; GO:1905627; P:regulation of serotonin biosynthetic process; IMP:UniProtKB.
DR   GO; GO:0014070; P:response to organic cyclic compound; ISO:MGI.
DR   CDD; cd07141; ALDH_F1AB_F2_RALDH1; 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:SF233; ALDEHYDE DEHYDROGENASE, MITOCHONDRIAL; 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.
DR   SWISS-2DPAGE; P47738; -.
DR   UCD-2DPAGE; P47738; -.
DR   Genevisible; P47738; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Direct protein sequencing; Mitochondrion; NAD; Oxidoreductase;
KW   Reference proteome; Transit peptide.
FT   TRANSIT         1..19
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250"
FT   CHAIN           20..519
FT                   /note="Aldehyde dehydrogenase, mitochondrial"
FT                   /id="PRO_0000007169"
FT   ACT_SITE        287
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT                   ECO:0000255|PROSITE-ProRule:PRU10008"
FT   ACT_SITE        321
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT                   ECO:0000255|PROSITE-ProRule:PRU10008"
FT   BINDING         264..269
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   SITE            188
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250|UniProtKB:P20000"
FT   MOD_RES         54
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         75
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         80
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         161
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         370
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         377
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         385
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         409
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         428
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         430
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753,
FT                   ECO:0007744|PubMed:23806337"
FT   MOD_RES         443
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         453
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   CONFLICT        88..89
FT                   /note="AF -> C (in Ref. 2; AAC60691)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        181
FT                   /note="Missing (in Ref. 2; AAC60691)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        227
FT                   /note="I -> S (in Ref. 2; AAC60691)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        344
FT                   /note="R -> G (in Ref. 2; AAC60691)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        370
FT                   /note="K -> N (in Ref. 2; AAC60691)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        378
FT                   /note="S -> M (in Ref. 2; AAC60691)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        476
FT                   /note="D -> V (in Ref. 2; AAC60691)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   519 AA;  56538 MW;  200806F63D48F4DA CRC64;
     MLRAALTTVR RGPRLSRLLS AAATSAVPAP NHQPEVFCNQ IFINNEWHDA VSRKTFPTVN
     PSTGEVICQV AEGNKEDVDK AVKAARAAFQ LGSPWRRMDA SDRGRLLYRL ADLIERDRTY
     LAALETLDNG KPYVISYLVD LDMVLKCLRY YAGWADKYHG KTIPIDGDFF SYTRHEPVGV
     CGQIIPWNFP LLMQAWKLGP ALATGNVVVM KVAEQTPLTA LYVANLIKEA GFPPGVVNIV
     PGFGPTAGAA IASHEGVDKV AFTGSTEVGH LIQVAAGSSN LKRVTLELGG KSPNIIMSDA
     DMDWAVEQAH FALFFNQGQC CCAGSRTFVQ ENVYDEFVER SVARAKSRVV GNPFDSRTEQ
     GPQVDETQFK KILGYIKSGQ QEGAKLLCGG GAAADRGYFI QPTVFGDVKD GMTIAKEEIF
     GPVMQILKFK TIEEVVGRAN DSKYGLAAAV FTKDLDKANY LSQALQAGTV WINCYDVFGA
     QSPFGGYKMS GSGRELGEYG LQAYTEVKTV TVKVPQKNS
//