ALDH2_MOUSE
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 03-AUG-2022, entry version 178.
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, Pancreas,
RC 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: Is capable of converting retinaldehyde to retinoic acid.
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}.
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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; 21.
DR IntAct; P47738; 14.
DR MINT; P47738; -.
DR STRING; 10090.ENSMUSP00000031411; -.
DR iPTMnet; P47738; -.
DR PhosphoSitePlus; P47738; -.
DR SwissPalm; P47738; -.
DR REPRODUCTION-2DPAGE; P47738; -.
DR SWISS-2DPAGE; P47738; -.
DR UCD-2DPAGE; P47738; -.
DR EPD; P47738; -.
DR jPOST; P47738; -.
DR PaxDb; P47738; -.
DR PeptideAtlas; P47738; -.
DR PRIDE; P47738; -.
DR ProteomicsDB; 281966; -.
DR DNASU; 11669; -.
DR Ensembl; ENSMUST00000031411; ENSMUSP00000031411; ENSMUSG00000029455.
DR GeneID; 11669; -.
DR KEGG; mmu:11669; -.
DR UCSC; uc008zjt.1; mouse.
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; 153834at2759; -.
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-71384; Ethanol oxidation.
DR UniPathway; UPA00780; UER00768.
DR BioGRID-ORCS; 11669; 1 hit in 76 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 264 other tissues.
DR ExpressionAtlas; P47738; baseline and differential.
DR Genevisible; P47738; MM.
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:0052689; F:carboxylic ester hydrolase 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:0050727; P:regulation of inflammatory response; ISO:MGI.
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 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 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
