ID   ALDH2_HUMAN             Reviewed;         517 AA.
AC   P05091; B4DW54; E7EUE5; Q03639; Q6IB13; Q6IV71;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1990, sequence version 2.
DT   27-MAR-2024, entry version 257.
DE   RecName: Full=Aldehyde dehydrogenase, mitochondrial;
DE            EC=1.2.1.3;
DE   AltName: Full=ALDH class 2;
DE   AltName: Full=ALDH-E2;
DE   AltName: Full=ALDHI;
DE   Flags: Precursor;
GN   Name=ALDH2; Synonyms=ALDM;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Muscle;
RX   PubMed=3582651; DOI=10.1016/0014-5793(87)80152-7;
RA   Braun T., Bober E., Singh S., Agarwal D.P., Goedde H.W.;
RT   "Evidence for a signal peptide at the amino-terminal end of human
RT   mitochondrial aldehyde dehydrogenase.";
RL   FEBS Lett. 215:233-236(1987).
RN   [2]
RP   ERRATUM OF PUBMED:3582651, AND SEQUENCE REVISION TO N-TERMINUS.
RA   Braun T., Bober E., Singh S., Agarwal D.P., Goedde H.W.;
RL   FEBS Lett. 233:440-440(1988).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Muscle;
RX   PubMed=3562250; DOI=10.1093/nar/15.7.3179;
RA   Braun T., Bober E., Singh S., Agarwal D.P., Goedde H.W.;
RT   "Isolation and sequence analysis of a full length cDNA clone coding for
RT   human mitochondrial aldehyde dehydrogenase.";
RL   Nucleic Acids Res. 15:3179-3179(1987).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2838413; DOI=10.1016/0888-7543(88)90109-7;
RA   Hsu L.C., Bendel R.E., Yoshida A.;
RT   "Genomic structure of the human mitochondrial aldehyde dehydrogenase
RT   gene.";
RL   Genomics 2:57-65(1988).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Lassen N., Estey T., Vasiliou V.;
RL   Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Synovium;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16541075; DOI=10.1038/nature04569;
RA   Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA   Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA   Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA   Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA   Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA   Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA   Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA   Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA   Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA   Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA   Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA   Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA   Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA   Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA   Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA   Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA   Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA   David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA   D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA   Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA   Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA   Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA   LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA   Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA   Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA   Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA   Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA   Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA   Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA   Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA   Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA   Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA   Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA   Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA   Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA   Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA   Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA   Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA   Gibbs R.A.;
RT   "The finished DNA sequence of human chromosome 12.";
RL   Nature 440:346-351(2006).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain, and Lymph;
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   [10]
RP   PROTEIN SEQUENCE OF 18-517 (ISOFORM 1).
RC   TISSUE=Liver;
RX   PubMed=4065146; DOI=10.1111/j.1432-1033.1985.tb09260.x;
RA   Hempel J., Kaiser R., Joernvall H.;
RT   "Mitochondrial aldehyde dehydrogenase from human liver. Primary structure,
RT   differences in relation to the cytosolic enzyme, and functional
RT   correlations.";
RL   Eur. J. Biochem. 153:13-28(1985).
RN   [11]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 119-517 (ISOFORM 1).
RC   TISSUE=Liver;
RX   PubMed=2987944; DOI=10.1073/pnas.82.11.3771;
RA   Hsu L.C., Tani K., Fujiyoshi T., Kurachi K., Yoshida A.;
RT   "Cloning of cDNAs for human aldehyde dehydrogenases 1 and 2.";
RL   Proc. Natl. Acad. Sci. U.S.A. 82:3771-3775(1985).
RN   [12]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 119-517 (ISOFORM 1).
RX   PubMed=4015823; DOI=10.1016/0741-8329(85)90024-2;
RA   Yoshida A., Ikawa M., Hsu L.C., Tani K.;
RT   "Molecular abnormality and cDNA cloning of human aldehyde dehydrogenases.";
RL   Alcohol 2:103-106(1985).
RN   [13]
RP   PROTEIN SEQUENCE OF 160-172 AND 325-338, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   TISSUE=Brain, and Cajal-Retzius cell;
RA   Lubec G., Vishwanath V.;
RL   Submitted (MAR-2007) to UniProtKB.
RN   [14]
RP   PROTEIN SEQUENCE OF 196-226 AND 325-338.
RC   TISSUE=Adipocyte;
RX   PubMed=15242332; DOI=10.1042/bj20040647;
RA   Aboulaich N., Vainonen J.P., Stralfors P., Vener A.V.;
RT   "Vectorial proteomics reveal targeting, phosphorylation and specific
RT   fragmentation of polymerase I and transcript release factor (PTRF) at the
RT   surface of caveolae in human adipocytes.";
RL   Biochem. J. 383:237-248(2004).
RN   [15]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 214-500, AND VARIANT VAL-337.
RC   TISSUE=Liver;
RX   PubMed=3610592;
RA   Agarwal D.P., Goedde H.W.;
RT   "Human aldehyde dehydrogenase isozymes and alcohol sensitivity.";
RL   Isozymes Curr. Top. Biol. Med. Res. 16:21-48(1987).
RN   [16]
RP   DESCRIPTION OF ORIGIN OF CONFLICTS BETWEEN THE SEQUENCE DESCRIBED IN
RP   PUBMED:4065146 AND DNA SEQUENCES.
RX   PubMed=3653404; DOI=10.1016/0014-5793(87)80198-9;
RA   Hempel J., Hoeoeg J.-O., Joernvall H.;
RT   "Mitochondrial aldehyde dehydrogenase. Homology of putative targeting
RT   sequence to that of carbamyl phosphate synthetase I revealed by correlation
RT   of cDNA and protein data.";
RL   FEBS Lett. 222:95-98(1987).
RN   [17]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [18]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [19]
RP   X-RAY CRYSTALLOGRAPHY (2.58 ANGSTROMS).
RX   PubMed=10631996; DOI=10.1110/ps.8.12.2784;
RA   Ni L., Zhou J., Hurley T.D., Weiner H.;
RT   "Human liver mitochondrial aldehyde dehydrogenase: three-dimensional
RT   structure and the restoration of solubility and activity of chimeric
RT   forms.";
RL   Protein Sci. 8:2784-2790(1999).
RN   [20]
RP   VARIANT LYS-504.
RX   PubMed=6582480; DOI=10.1073/pnas.81.1.258;
RA   Yoshida A., Huang I.-Y., Ikawa M.;
RT   "Molecular abnormality of an inactive aldehyde dehydrogenase variant
RT   commonly found in Orientals.";
RL   Proc. Natl. Acad. Sci. U.S.A. 81:258-261(1984).
RN   [21]
RP   VARIANT LYS-496.
RX   PubMed=8561277; DOI=10.1111/j.1530-0277.1995.tb01587.x;
RA   Novoradovsky A., Tsai S.J., Goldfarb L., Peterson R., Long J.C.,
RA   Goldman D.;
RT   "Mitochondrial aldehyde dehydrogenase polymorphism in Asian and American
RT   Indian populations: detection of new ALDH2 alleles.";
RL   Alcohol. Clin. Exp. Res. 19:1105-1110(1995).
RN   [22]
RP   VARIANT AMEDS LYS-504, INVOLVEMENT IN AMEDS, AND FUNCTION.
RX   PubMed=33355142; DOI=10.1126/sciadv.abd7197;
RA   Oka Y., Hamada M., Nakazawa Y., Muramatsu H., Okuno Y., Higasa K.,
RA   Shimada M., Takeshima H., Hanada K., Hirano T., Kawakita T., Sakaguchi H.,
RA   Ichimura T., Ozono S., Yuge K., Watanabe Y., Kotani Y., Yamane M.,
RA   Kasugai Y., Tanaka M., Suganami T., Nakada S., Mitsutake N., Hara Y.,
RA   Kato K., Mizuno S., Miyake N., Kawai Y., Tokunaga K., Nagasaki M., Kito S.,
RA   Isoyama K., Onodera M., Kaneko H., Matsumoto N., Matsuda F., Matsuo K.,
RA   Takahashi Y., Mashimo T., Kojima S., Ogi T.;
RT   "Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and
RT   cause a multisystem disorder, AMeD syndrome.";
RL   Sci. Adv. 6:0-0(2020).
CC   -!- FUNCTION: Required for clearance of cellular formaldehyde, a cytotoxic
CC       and carcinogenic metabolite that induces DNA damage.
CC       {ECO:0000269|PubMed:33355142}.
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.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P05091-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P05091-2; Sequence=VSP_046715;
CC   -!- POLYMORPHISM: Genetic variation in ALDH2 is responsible for individual
CC       differences in responses to drinking alcohol [MIM:610251]. Allele
CC       ALDH2*2 is associated with a very high incidence of acute alcohol
CC       intoxication in Orientals and South American Indians, as compared to
CC       Caucasians. {ECO:0000269|PubMed:8561277}.
CC   -!- DISEASE: AMED syndrome, digenic (AMEDS) [MIM:619151]: A form of bone
CC       marrow failure syndrome, a heterogeneous group of life-threatening
CC       disorders characterized by hematopoietic defects in association with a
CC       range of variable extra-hematopoietic manifestations. AMEDS is an
CC       autosomal recessive, digenic form characterized by childhood onset of
CC       bone marrow failure resulting in aplastic anemia, in association with
CC       global developmental delay, intellectual disability, and poor overall
CC       growth with short stature. {ECO:0000269|PubMed:33355142}. Note=The
CC       disease is caused by variants affecting distinct genetic loci,
CC       including the gene represented in this entry. AMEDS patients carry ADH5
CC       biallelic variants and homozygous or heterozygous ALDH2 variant
CC       p.Glu504Lys, affecting protein activity. Cellular and animal studies
CC       demonstrate that the simultaneous loss of ALDH2 and ADH5 activities
CC       leads to an increase of cellular formaldehyde sensitivity and
CC       multisystem abnormalities including hematopoietic failure.
CC       {ECO:0000269|PubMed:33355142}.
CC   -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA62825.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=CAA68290.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=CAA68290.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="https://atlasgeneticsoncology.org/gene/250/ALDH2";
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DR   EMBL; X05409; CAA28990.1; -; mRNA.
DR   EMBL; Y00109; CAA68290.1; ALT_SEQ; mRNA.
DR   EMBL; M20456; AAA51693.1; -; Genomic_DNA.
DR   EMBL; M20444; AAA51693.1; JOINED; Genomic_DNA.
DR   EMBL; M20445; AAA51693.1; JOINED; Genomic_DNA.
DR   EMBL; M20446; AAA51693.1; JOINED; Genomic_DNA.
DR   EMBL; M20447; AAA51693.1; JOINED; Genomic_DNA.
DR   EMBL; M20448; AAA51693.1; JOINED; Genomic_DNA.
DR   EMBL; M20449; AAA51693.1; JOINED; Genomic_DNA.
DR   EMBL; M20450; AAA51693.1; JOINED; Genomic_DNA.
DR   EMBL; M20451; AAA51693.1; JOINED; Genomic_DNA.
DR   EMBL; M20452; AAA51693.1; JOINED; Genomic_DNA.
DR   EMBL; M20453; AAA51693.1; JOINED; Genomic_DNA.
DR   EMBL; M20454; AAA51693.1; JOINED; Genomic_DNA.
DR   EMBL; AY621070; AAT41621.1; -; mRNA.
DR   EMBL; CR456991; CAG33272.1; -; mRNA.
DR   EMBL; AK301375; BAG62916.1; -; mRNA.
DR   EMBL; AC002996; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC003029; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC002967; AAH02967.1; -; mRNA.
DR   EMBL; BC071839; AAH71839.1; -; mRNA.
DR   EMBL; K03001; AAB59500.1; -; mRNA.
DR   EMBL; M26760; AAA51694.1; -; mRNA.
DR   EMBL; M54931; AAA62825.1; ALT_FRAME; mRNA.
DR   CCDS; CCDS55885.1; -. [P05091-2]
DR   CCDS; CCDS9155.1; -. [P05091-1]
DR   PIR; A29975; DEHUE2.
DR   RefSeq; NP_000681.2; NM_000690.3. [P05091-1]
DR   RefSeq; NP_001191818.1; NM_001204889.1. [P05091-2]
DR   PDB; 1CW3; X-ray; 2.58 A; A/B/C/D/E/F/G/H=24-517.
DR   PDB; 1NZW; X-ray; 2.65 A; A/B/C/D/E/F/G/H=18-517.
DR   PDB; 1NZX; X-ray; 2.45 A; A/B/C/D/E/F/G/H=18-517.
DR   PDB; 1NZZ; X-ray; 2.45 A; A/B/C/D/E/F/G/H=18-517.
DR   PDB; 1O00; X-ray; 2.60 A; A/B/C/D/E/F/G/H=18-517.
DR   PDB; 1O01; X-ray; 2.15 A; A/B/C/D/E/F/G/H=18-517.
DR   PDB; 1O02; X-ray; 1.90 A; A/B/C/D/E/F/G/H=18-517.
DR   PDB; 1O04; X-ray; 1.42 A; A/B/C/D/E/F/G/H=18-517.
DR   PDB; 1O05; X-ray; 2.25 A; A/B/C/D/E/F/G/H=18-517.
DR   PDB; 1ZUM; X-ray; 2.10 A; A/B/C/D/E/F/G/H/I/J/K/L=18-517.
DR   PDB; 2ONM; X-ray; 2.50 A; A/B/C/D/E/F/G/H/I/J/K/L=18-517.
DR   PDB; 2ONN; X-ray; 2.75 A; A/B/C/D/E/F/G/H=18-517.
DR   PDB; 2ONO; X-ray; 2.15 A; A/B/C/D/E/F/G/H=18-517.
DR   PDB; 2ONP; X-ray; 2.00 A; A/B/C/D/E/F/G/H=18-517.
DR   PDB; 2VLE; X-ray; 2.40 A; A/B/C/D/E/F/G/H=24-517.
DR   PDB; 3INJ; X-ray; 1.69 A; A/B/C/D/E/F/G/H=18-517.
DR   PDB; 3INL; X-ray; 1.86 A; A/B/C/D/E/F/G/H=18-517.
DR   PDB; 3N80; X-ray; 1.50 A; A/B/C/D/E/F/G/H=18-517.
DR   PDB; 3N81; X-ray; 1.70 A; A/B/C/D/E/F/G/H=18-517.
DR   PDB; 3N82; X-ray; 2.25 A; A/B/C/D/E/F/G/H=18-517.
DR   PDB; 3N83; X-ray; 1.90 A; A/B/C/D/E/F/G/H=18-517.
DR   PDB; 3SZ9; X-ray; 2.10 A; A/B/C/D/E/F/G/H=18-517.
DR   PDB; 4FQF; X-ray; 2.28 A; A/B/C/D=18-517.
DR   PDB; 4FR8; X-ray; 2.20 A; A/B/C/D/E/F/G/H=18-517.
DR   PDB; 4KWF; X-ray; 2.31 A; A/B/C/D/E/F/G/H=24-517.
DR   PDB; 4KWG; X-ray; 2.10 A; A/B/C/D/E/F/G/H=24-517.
DR   PDB; 5L13; X-ray; 2.40 A; A/B/C/D/E/F/G/H=1-517.
DR   PDB; 8DR9; X-ray; 1.50 A; A/B=18-517.
DR   PDBsum; 1CW3; -.
DR   PDBsum; 1NZW; -.
DR   PDBsum; 1NZX; -.
DR   PDBsum; 1NZZ; -.
DR   PDBsum; 1O00; -.
DR   PDBsum; 1O01; -.
DR   PDBsum; 1O02; -.
DR   PDBsum; 1O04; -.
DR   PDBsum; 1O05; -.
DR   PDBsum; 1ZUM; -.
DR   PDBsum; 2ONM; -.
DR   PDBsum; 2ONN; -.
DR   PDBsum; 2ONO; -.
DR   PDBsum; 2ONP; -.
DR   PDBsum; 2VLE; -.
DR   PDBsum; 3INJ; -.
DR   PDBsum; 3INL; -.
DR   PDBsum; 3N80; -.
DR   PDBsum; 3N81; -.
DR   PDBsum; 3N82; -.
DR   PDBsum; 3N83; -.
DR   PDBsum; 3SZ9; -.
DR   PDBsum; 4FQF; -.
DR   PDBsum; 4FR8; -.
DR   PDBsum; 4KWF; -.
DR   PDBsum; 4KWG; -.
DR   PDBsum; 5L13; -.
DR   PDBsum; 8DR9; -.
DR   AlphaFoldDB; P05091; -.
DR   SMR; P05091; -.
DR   BioGRID; 106719; 139.
DR   DIP; DIP-40262N; -.
DR   IntAct; P05091; 58.
DR   MINT; P05091; -.
DR   STRING; 9606.ENSP00000261733; -.
DR   BindingDB; P05091; -.
DR   ChEMBL; CHEMBL1935; -.
DR   DrugBank; DB01612; Amyl Nitrite.
DR   DrugBank; DB06770; Benzyl alcohol.
DR   DrugBank; DB04381; Crotonaldehyde.
DR   DrugBank; DB02115; Daidzin.
DR   DrugBank; DB00822; Disulfiram.
DR   DrugBank; DB00536; Guanidine.
DR   DrugBank; DB00157; NADH.
DR   DrugBank; DB00435; Nitric Oxide.
DR   DrugBank; DB00727; Nitroglycerin.
DR   DrugBank; DB09117; Paraldehyde.
DR   DrugBank; DB06154; Pentaerythritol tetranitrate.
DR   DrugBank; DB06207; Silodosin.
DR   DrugCentral; P05091; -.
DR   GuidetoPHARMACOLOGY; 2595; -.
DR   GlyGen; P05091; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P05091; -.
DR   MetOSite; P05091; -.
DR   PhosphoSitePlus; P05091; -.
DR   SwissPalm; P05091; -.
DR   BioMuta; ALDH2; -.
DR   DMDM; 118504; -.
DR   REPRODUCTION-2DPAGE; IPI00006663; -.
DR   REPRODUCTION-2DPAGE; P05091; -.
DR   CPTAC; CPTAC-12; -.
DR   CPTAC; CPTAC-13; -.
DR   CPTAC; CPTAC-14; -.
DR   CPTAC; CPTAC-1594; -.
DR   EPD; P05091; -.
DR   jPOST; P05091; -.
DR   MassIVE; P05091; -.
DR   MaxQB; P05091; -.
DR   PaxDb; 9606-ENSP00000261733; -.
DR   PeptideAtlas; P05091; -.
DR   PRIDE; P05091; -.
DR   ProteomicsDB; 18413; -.
DR   ProteomicsDB; 51788; -. [P05091-1]
DR   Pumba; P05091; -.
DR   Antibodypedia; 31130; 778 antibodies from 41 providers.
DR   DNASU; 217; -.
DR   Ensembl; ENST00000261733.7; ENSP00000261733.2; ENSG00000111275.13. [P05091-1]
DR   Ensembl; ENST00000416293.7; ENSP00000403349.3; ENSG00000111275.13. [P05091-2]
DR   GeneID; 217; -.
DR   KEGG; hsa:217; -.
DR   MANE-Select; ENST00000261733.7; ENSP00000261733.2; NM_000690.4; NP_000681.2.
DR   UCSC; uc001tst.4; human. [P05091-1]
DR   AGR; HGNC:404; -.
DR   CTD; 217; -.
DR   DisGeNET; 217; -.
DR   GeneCards; ALDH2; -.
DR   HGNC; HGNC:404; ALDH2.
DR   HPA; ENSG00000111275; Tissue enhanced (liver).
DR   MalaCards; ALDH2; -.
DR   MIM; 100650; gene+phenotype.
DR   MIM; 610251; phenotype.
DR   MIM; 619151; phenotype.
DR   neXtProt; NX_P05091; -.
DR   OpenTargets; ENSG00000111275; -.
DR   PharmGKB; PA24696; -.
DR   VEuPathDB; HostDB:ENSG00000111275; -.
DR   eggNOG; KOG2450; Eukaryota.
DR   GeneTree; ENSGT00940000156240; -.
DR   HOGENOM; CLU_005391_0_1_1; -.
DR   InParanoid; P05091; -.
DR   OMA; HGIGYYP; -.
DR   OrthoDB; 2291791at2759; -.
DR   PhylomeDB; P05091; -.
DR   TreeFam; TF300455; -.
DR   BioCyc; MetaCyc:MONOMER66-302; -.
DR   BRENDA; 1.2.1.3; 2681.
DR   PathwayCommons; P05091; -.
DR   Reactome; R-HSA-380612; Metabolism of serotonin.
DR   Reactome; R-HSA-445355; Smooth Muscle Contraction.
DR   Reactome; R-HSA-71384; Ethanol oxidation.
DR   SABIO-RK; P05091; -.
DR   SignaLink; P05091; -.
DR   SIGNOR; P05091; -.
DR   UniPathway; UPA00780; UER00768.
DR   BioGRID-ORCS; 217; 11 hits in 1162 CRISPR screens.
DR   ChiTaRS; ALDH2; human.
DR   EvolutionaryTrace; P05091; -.
DR   GeneWiki; ALDH2; -.
DR   GenomeRNAi; 217; -.
DR   Pharos; P05091; Tclin.
DR   PRO; PR:P05091; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; P05091; Protein.
DR   Bgee; ENSG00000111275; Expressed in right lobe of liver and 208 other cell types or tissues.
DR   ExpressionAtlas; P05091; baseline and differential.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR   GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR   GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; IDA:UniProtKB.
DR   GO; GO:0004030; F:aldehyde dehydrogenase [NAD(P)+] activity; TAS:ProtInc.
DR   GO; GO:0106435; F:carboxylesterase activity; IDA:UniProtKB.
DR   GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB.
DR   GO; GO:0043878; F:glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity; IEA:UniProtKB-EC.
DR   GO; GO:0051287; F:NAD binding; ISS:CAFA.
DR   GO; GO:0018547; F:nitroglycerin reductase activity; IDA:UniProtKB.
DR   GO; GO:0008957; F:phenylacetaldehyde dehydrogenase activity; ISS:UniProtKB.
DR   GO; GO:0006066; P:alcohol metabolic process; TAS:ProtInc.
DR   GO; GO:0046185; P:aldehyde catabolic process; IDA:UniProtKB.
DR   GO; GO:0005975; P:carbohydrate metabolic process; TAS:ProtInc.
DR   GO; GO:0006068; P:ethanol catabolic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:1903179; P:regulation of dopamine biosynthetic process; ISS:UniProtKB.
DR   GO; GO:1905627; P:regulation of serotonin biosynthetic process; ISS:UniProtKB.
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   UCD-2DPAGE; P05091; -.
DR   Genevisible; P05091; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Alternative splicing; Direct protein sequencing;
KW   Disease variant; Dwarfism; Intellectual disability; Mitochondrion; NAD;
KW   Oxidoreductase; Reference proteome; Transit peptide.
FT   TRANSIT         1..17
FT                   /note="Mitochondrion"
FT   CHAIN           18..517
FT                   /note="Aldehyde dehydrogenase, mitochondrial"
FT                   /id="PRO_0000007168"
FT   ACT_SITE        285
FT                   /note="Proton acceptor"
FT   ACT_SITE        319
FT                   /note="Nucleophile"
FT   BINDING         262..267
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   SITE            186
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250|UniProtKB:P20000"
FT   MOD_RES         52
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P47738"
FT   MOD_RES         73
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P47738"
FT   MOD_RES         78
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P47738"
FT   MOD_RES         159
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P47738"
FT   MOD_RES         368
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P47738"
FT   MOD_RES         383
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P47738"
FT   MOD_RES         426
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P47738"
FT   MOD_RES         428
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P47738"
FT   MOD_RES         451
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P47738"
FT   VAR_SEQ         74..120
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_046715"
FT   VARIANT         337
FT                   /note="E -> V (in dbSNP:rs1062136)"
FT                   /evidence="ECO:0000269|PubMed:3610592"
FT                   /id="VAR_011869"
FT   VARIANT         496
FT                   /note="E -> K (in allele ALDH2*3; dbSNP:rs769724893)"
FT                   /evidence="ECO:0000269|PubMed:8561277"
FT                   /id="VAR_011302"
FT   VARIANT         504
FT                   /note="E -> K (in AMEDS; allele ALDH2*2; drastic reduction
FT                   of enzyme activity; dbSNP:rs671)"
FT                   /evidence="ECO:0000269|PubMed:33355142,
FT                   ECO:0000269|PubMed:6582480"
FT                   /id="VAR_002248"
FT   CONFLICT        7..12
FT                   /note="RFGPRL -> ARAPP (in Ref. 1; CAA28990)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        18
FT                   /note="S -> A (in Ref. 10; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        60
FT                   /note="S -> F (in Ref. 6; CAG33272)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        80..85
FT                   /note="VKAARA -> REGRPG (in Ref. 1; CAA28990)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        101
FT                   /note="R -> S (in Ref. 1; CAA28990)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        116
FT                   /note="R -> Q (in Ref. 5; AAT41621)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        216
FT                   /note="L -> S (in Ref. 15; AAA62825)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        218
FT                   /note="A -> R (in Ref. 15; AAA62825)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        247
FT                   /note="A -> P (in Ref. 15; AAA62825)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        332
FT                   /note="Y -> C (in Ref. 7; BAG62916)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        362
FT                   /note="V -> L (in Ref. 6; CAG33272)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        380
FT                   /note="E -> Q (in Ref. 4; AAA51693)"
FT                   /evidence="ECO:0000305"
FT   STRAND          38..41
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          44..46
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          53..57
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   TURN            59..61
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          64..69
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   HELIX           73..86
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   HELIX           92..95
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   HELIX           98..114
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   HELIX           116..127
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   HELIX           131..136
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   HELIX           138..152
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   TURN            153..155
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          158..161
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          164..175
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          178..182
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          185..187
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   HELIX           188..201
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          205..209
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          212..214
FT                   /evidence="ECO:0007829|PDB:4KWF"
FT   HELIX           216..228
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          234..237
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   TURN            242..244
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   HELIX           245..250
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          257..262
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   HELIX           264..276
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          281..285
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          290..294
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   HELIX           300..312
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   HELIX           313..316
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          322..328
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   HELIX           329..345
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   HELIX           364..379
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          383..386
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          389..391
FT                   /evidence="ECO:0007829|PDB:3INL"
FT   STRAND          393..396
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          401..405
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   HELIX           411..414
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          419..427
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   HELIX           430..438
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          439..441
FT                   /evidence="ECO:0007829|PDB:3INL"
FT   STRAND          444..449
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   HELIX           453..462
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          465..471
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          478..480
FT                   /evidence="ECO:0007829|PDB:2ONO"
FT   HELIX           486..488
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          489..491
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   HELIX           496..502
FT                   /evidence="ECO:0007829|PDB:1O04"
FT   STRAND          503..511
FT                   /evidence="ECO:0007829|PDB:1O04"
SQ   SEQUENCE   517 AA;  56381 MW;  E8F74D44D285A00E CRC64;
     MLRAAARFGP RLGRRLLSAA ATQAVPAPNQ QPEVFCNQIF INNEWHDAVS RKTFPTVNPS
     TGEVICQVAE GDKEDVDKAV KAARAAFQLG SPWRRMDASH RGRLLNRLAD LIERDRTYLA
     ALETLDNGKP YVISYLVDLD MVLKCLRYYA GWADKYHGKT IPIDGDFFSY TRHEPVGVCG
     QIIPWNFPLL MQAWKLGPAL ATGNVVVMKV AEQTPLTALY VANLIKEAGF PPGVVNIVPG
     FGPTAGAAIA SHEDVDKVAF TGSTEIGRVI QVAAGSSNLK RVTLELGGKS PNIIMSDADM
     DWAVEQAHFA LFFNQGQCCC AGSRTFVQED IYDEFVERSV ARAKSRVVGN PFDSKTEQGP
     QVDETQFKKI LGYINTGKQE GAKLLCGGGI AADRGYFIQP TVFGDVQDGM TIAKEEIFGP
     VMQILKFKTI EEVVGRANNS TYGLAAAVFT KDLDKANYLS QALQAGTVWV NCYDVFGAQS
     PFGGYKMSGS GRELGEYGLQ AYTEVKTVTV KVPQKNS
//