ID ALDH2_BOVIN Reviewed; 520 AA.
AC P20000; Q1LZC6;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 2.
DT 27-MAR-2024, entry version 166.
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;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=1689984; DOI=10.1016/0003-9861(90)90590-u;
RA Guan K., Weiner H.;
RT "Sequence of the precursor of bovine liver mitochondrial aldehyde
RT dehydrogenase as determined from its cDNA, its gene, and its
RT functionality.";
RL Arch. Biochem. Biophys. 277:351-360(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Ascending colon;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 92-520.
RX PubMed=2540003; DOI=10.1111/j.1432-1033.1989.tb14616.x;
RA Farres J., Guan K.-L., Weiner H.;
RT "Primary structures of rat and bovine liver mitochondrial aldehyde
RT dehydrogenases deduced from cDNA sequences.";
RL Eur. J. Biochem. 180:67-74(1989).
RN [4]
RP PROTEIN SEQUENCE OF 22-34.
RC TISSUE=Brain;
RX PubMed=1449496; DOI=10.1016/0006-291x(92)91530-4;
RA Lee J.E., Cho Y.D.;
RT "Purification and characterization of bovine brain gamma-aminobutyraldehyde
RT dehydrogenase.";
RL Biochem. Biophys. Res. Commun. 189:450-454(1992).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 22-520 IN COMPLEX WITH NAD, AND
RP SITE.
RX PubMed=9195888; DOI=10.1016/s0969-2126(97)00224-4;
RA Steinmetz C.G., Xie P., Weiner H., Hurley T.D.;
RT "Structure of mitochondrial aldehyde dehydrogenase: the genetic component
RT of ethanol aversion.";
RL Structure 5:701-711(1997).
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.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
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; BC116084; AAI16085.1; -; mRNA.
DR PIR; S09030; S09030.
DR RefSeq; NP_001068835.1; NM_001075367.1.
DR PDB; 1A4Z; X-ray; 2.75 A; A/B/C/D=22-520.
DR PDB; 1AG8; X-ray; 2.65 A; A/B/C/D=22-520.
DR PDBsum; 1A4Z; -.
DR PDBsum; 1AG8; -.
DR AlphaFoldDB; P20000; -.
DR SMR; P20000; -.
DR STRING; 9913.ENSBTAP00000011521; -.
DR PaxDb; 9913-ENSBTAP00000011521; -.
DR PeptideAtlas; P20000; -.
DR Ensembl; ENSBTAT00000011521.5; ENSBTAP00000011521.4; ENSBTAG00000008743.5.
DR GeneID; 508629; -.
DR KEGG; bta:508629; -.
DR CTD; 217; -.
DR VEuPathDB; HostDB:ENSBTAG00000008743; -.
DR VGNC; VGNC:106425; ALDH2.
DR eggNOG; KOG2450; Eukaryota.
DR GeneTree; ENSGT00940000156240; -.
DR HOGENOM; CLU_005391_0_1_1; -.
DR InParanoid; P20000; -.
DR OMA; HGIGYYP; -.
DR OrthoDB; 2291791at2759; -.
DR TreeFam; TF300455; -.
DR Reactome; R-BTA-380612; Metabolism of serotonin.
DR Reactome; R-BTA-445355; Smooth Muscle Contraction.
DR Reactome; R-BTA-71384; Ethanol oxidation.
DR SABIO-RK; P20000; -.
DR UniPathway; UPA00780; UER00768.
DR EvolutionaryTrace; P20000; -.
DR Proteomes; UP000009136; Chromosome 17.
DR Bgee; ENSBTAG00000008743; Expressed in cortex of kidney and 106 other cell types or tissues.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
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:0051287; F:NAD binding; ISS:CAFA.
DR GO; GO:0018547; F:nitroglycerin reductase activity; ISS:UniProtKB.
DR GO; GO:0008957; F:phenylacetaldehyde dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0046185; P:aldehyde catabolic process; ISS:UniProtKB.
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.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing; Mitochondrion; NAD;
KW Oxidoreductase; Reference proteome; Transit peptide.
FT TRANSIT 1..21
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:1449496"
FT CHAIN 22..520
FT /note="Aldehyde dehydrogenase, mitochondrial"
FT /id="PRO_0000007167"
FT ACT_SITE 288
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:9195888"
FT ACT_SITE 322
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:9195888"
FT BINDING 186..188
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:9195888,
FT ECO:0007744|PDB:1A4Z"
FT BINDING 212..215
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:9195888,
FT ECO:0007744|PDB:1A4Z"
FT BINDING 245
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:9195888,
FT ECO:0007744|PDB:1A4Z"
FT BINDING 265..270
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:9195888,
FT ECO:0007744|PDB:1A4Z"
FT BINDING 288
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:9195888,
FT ECO:0007744|PDB:1A4Z"
FT BINDING 419..421
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:9195888,
FT ECO:0007744|PDB:1A4Z"
FT SITE 189
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000269|PubMed:9195888"
FT MOD_RES 55
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47738"
FT MOD_RES 76
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47738"
FT MOD_RES 162
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47738"
FT MOD_RES 371
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47738"
FT MOD_RES 378
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47738"
FT MOD_RES 386
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47738"
FT MOD_RES 429
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47738"
FT MOD_RES 431
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47738"
FT MOD_RES 444
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47738"
FT MOD_RES 454
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47738"
FT CONFLICT 289
FT /note="L -> I (in Ref. 1; no nucleotide entry and 3; no
FT nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 385
FT /note="A -> L (in Ref. 1; no nucleotide entry and 3; no
FT nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 409
FT /note="V -> L (in Ref. 1; no nucleotide entry and 3; no
FT nucleotide entry)"
FT /evidence="ECO:0000305"
FT STRAND 41..46
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:1A4Z"
FT STRAND 56..60
FT /evidence="ECO:0007829|PDB:1AG8"
FT TURN 62..64
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 67..72
FT /evidence="ECO:0007829|PDB:1AG8"
FT HELIX 76..89
FT /evidence="ECO:0007829|PDB:1AG8"
FT HELIX 95..98
FT /evidence="ECO:0007829|PDB:1AG8"
FT HELIX 101..117
FT /evidence="ECO:0007829|PDB:1AG8"
FT HELIX 119..130
FT /evidence="ECO:0007829|PDB:1AG8"
FT HELIX 134..139
FT /evidence="ECO:0007829|PDB:1AG8"
FT HELIX 141..153
FT /evidence="ECO:0007829|PDB:1AG8"
FT TURN 154..158
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 161..164
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 167..178
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 181..185
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:1AG8"
FT HELIX 191..205
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 208..213
FT /evidence="ECO:0007829|PDB:1AG8"
FT HELIX 219..231
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 237..243
FT /evidence="ECO:0007829|PDB:1AG8"
FT HELIX 245..253
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 260..265
FT /evidence="ECO:0007829|PDB:1AG8"
FT HELIX 267..279
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 284..288
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 294..297
FT /evidence="ECO:0007829|PDB:1AG8"
FT HELIX 303..315
FT /evidence="ECO:0007829|PDB:1AG8"
FT HELIX 316..319
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 327..331
FT /evidence="ECO:0007829|PDB:1AG8"
FT HELIX 332..348
FT /evidence="ECO:0007829|PDB:1AG8"
FT HELIX 367..383
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 386..389
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 392..394
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 396..398
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 404..408
FT /evidence="ECO:0007829|PDB:1AG8"
FT HELIX 414..417
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 422..430
FT /evidence="ECO:0007829|PDB:1AG8"
FT HELIX 433..441
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 447..452
FT /evidence="ECO:0007829|PDB:1AG8"
FT HELIX 456..465
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 469..474
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 492..494
FT /evidence="ECO:0007829|PDB:1AG8"
FT HELIX 500..503
FT /evidence="ECO:0007829|PDB:1AG8"
FT STRAND 506..514
FT /evidence="ECO:0007829|PDB:1AG8"
SQ SEQUENCE 520 AA; 56653 MW; 713FC1EE8F82B2C4 CRC64;
MLRAVALAAA RLGPRQGRRL LSAATQAVPT PNQQPEVLYN QIFINNEWHD AVSKKTFPTV
NPSTGDVICH VAEGDKADVD RAVKAARAAF QLGSPWRRMD ASERGRLLNR LADLIERDRT
YLAALETLDN GKPYIISYLV DLDMVLKCLR YYAGWADKYH GKTIPIDGDY FSYTRHEPVG
VCGQIIPWNF PLLMQAWKLG PALATGNVVV MKVAEQTPLT ALYVANLIKE AGFPPGVVNV
IPGFGPTAGA AIASHEDVDK VAFTGSTEVG HLIQVAAGKS NLKRVTLELG GKSPNIIMSD
ADMDWAVEQA HFALFFNQGQ CCCAGSRTFV QEDIYAEFVE RSVARAKSRV VGNPFDSRTE
QGPQVDETQF KKVLGYIKSG KEEGAKLLCG GGAAADRGYF IQPTVFGDVQ DGMTIAKEEI
FGPVMQILKF KSMEEVVGRA NNSKYGLAAA VFTKDLDKAN YLSQALQAGT VWVNCYDVFG
AQSPFGGYKL SGSGRELGEY GLQAYTEVKT VTVRVPQKNS
//
