ALDH2_RAT
ID ALDH2_RAT Reviewed; 519 AA.
AC P11884; Q6Q288; Q6Q289; Q6Q290; Q8K3V8; Q91ZD7;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 03-AUG-2022, entry version 184.
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=ALDH1;
DE Flags: Precursor;
GN Name=Aldh2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-29.
RC TISSUE=Liver;
RX PubMed=3342060; DOI=10.1016/0006-291x(88)90740-1;
RA Farres J., Guan K.-L., Weiner H.;
RT "Sequence of the signal peptide for rat liver mitochondrial aldehyde
RT dehydrogenase.";
RL Biochem. Biophys. Res. Commun. 150:1083-1087(1988).
RN [4]
RP PROTEIN SEQUENCE OF 1-19.
RC TISSUE=Liver;
RX PubMed=1898068; DOI=10.1016/0003-9861(91)90464-t;
RA Jeng J., Weiner H.;
RT "Purification and characterization of catalytically active precursor of rat
RT liver mitochondrial aldehyde dehydrogenase expressed in Escherichia coli.";
RL Arch. Biochem. Biophys. 289:214-222(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 10-519, AND VARIANTS ARG-86 AND LYS-498.
RC STRAIN=UChA, UChB, and Wistar; TISSUE=Liver;
RX PubMed=12893989; DOI=10.1097/01.fpc.0000054110.14659.62;
RA Sapag A., Tampier L., Valle-Prieto A., Quintanilla M.E., Moncada C.,
RA Israel Y.;
RT "Mutations in mitochondrial aldehyde dehydrogenase (ALDH2) change cofactor
RT affinity and segregate with voluntary alcohol consumption in rats.";
RL Pharmacogenetics 13:509-515(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 32-519.
RC STRAIN=Lewis;
RA Sapag A., Urra S., Gonzalez-Jara F., Moncada C., Israel Y.;
RT "Genomic structure and sequence of the mitochondrial aldehyde dehydrogenase
RT gene (ALDH2) of the Lewis rat.";
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 77-519.
RC STRAIN=Lewis; TISSUE=Liver;
RA Sapag A., Urra S., Gonzalez-Jara F., Moncada C., Israel Y.;
RT "Genomic structure and sequence of the mitochondrial aldehyde dehydrogenase
RT gene of the Lewis rat.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP PROTEIN SEQUENCE OF 162-174; 198-228; 260-340; 327-340; 358-370; 397-409
RP AND 495-508, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus, and Spinal cord;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [9]
RP PROTEIN SEQUENCE OF 327-340.
RX PubMed=1699808; DOI=10.1016/0014-5793(90)81088-6;
RA Diwan J.J., Paliwal R., Kaftan E., Bawa R.;
RT "A mitochondrial protein fraction catalyzing transport of the K+ analog
RT T1+.";
RL FEBS Lett. 273:215-218(1990).
RN [10]
RP STRUCTURE BY NMR OF 12-22.
RX PubMed=10721992; DOI=10.1016/s0092-8674(00)80691-1;
RA Abe Y., Shodai T., Muto T., Mihara K., Torii H., Nishikawa S., Endo T.,
RA Kohda D.;
RT "Structural basis of presequence recognition by the mitochondrial protein
RT import receptor Tom20.";
RL Cell 100:551-560(2000).
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 -!- INTERACTION:
CC P11884; Q02776: TIM50; Xeno; NbExp=3; IntAct=EBI-916402, EBI-30302;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; X14977; CAA33101.1; -; mRNA.
DR EMBL; BC062081; AAH62081.1; -; mRNA.
DR EMBL; M19030; AAA40719.1; -; mRNA.
DR EMBL; AY566467; AAS75813.1; -; mRNA.
DR EMBL; AY566468; AAS75814.1; -; mRNA.
DR EMBL; AY566469; AAS75815.1; -; mRNA.
DR EMBL; AF529165; AAM94394.2; -; mRNA.
DR EMBL; AY034137; AAK57732.1; -; Genomic_DNA.
DR PIR; S03564; S03564.
DR RefSeq; NP_115792.1; NM_032416.1.
DR PDB; 1OM2; NMR; -; B=12-20.
DR PDB; 2V1S; X-ray; 2.05 A; H/I/J/K/L/M/N=12-24.
DR PDB; 2V1T; X-ray; 1.92 A; C/D=12-22.
DR PDB; 3AWR; X-ray; 2.00 A; C/D=12-20.
DR PDB; 3AX2; X-ray; 1.90 A; B/D/F/H=12-20.
DR PDB; 3AX3; X-ray; 2.10 A; B/D/F/H=12-20.
DR PDB; 3AX5; X-ray; 2.20 A; B/D=12-20.
DR PDB; 5AZ8; X-ray; 1.70 A; B=12-24.
DR PDBsum; 1OM2; -.
DR PDBsum; 2V1S; -.
DR PDBsum; 2V1T; -.
DR PDBsum; 3AWR; -.
DR PDBsum; 3AX2; -.
DR PDBsum; 3AX3; -.
DR PDBsum; 3AX5; -.
DR PDBsum; 5AZ8; -.
DR AlphaFoldDB; P11884; -.
DR SMR; P11884; -.
DR BioGRID; 248173; 2.
DR IntAct; P11884; 3.
DR MINT; P11884; -.
DR STRING; 10116.ENSRNOP00000001816; -.
DR BindingDB; P11884; -.
DR ChEMBL; CHEMBL2812; -.
DR DrugCentral; P11884; -.
DR GuidetoPHARMACOLOGY; 2595; -.
DR CarbonylDB; P11884; -.
DR iPTMnet; P11884; -.
DR PhosphoSitePlus; P11884; -.
DR World-2DPAGE; 0004:P11884; -.
DR jPOST; P11884; -.
DR PaxDb; P11884; -.
DR PRIDE; P11884; -.
DR GeneID; 29539; -.
DR KEGG; rno:29539; -.
DR UCSC; RGD:69219; rat.
DR CTD; 217; -.
DR RGD; 69219; Aldh2.
DR eggNOG; KOG2450; Eukaryota.
DR InParanoid; P11884; -.
DR OrthoDB; 153834at2759; -.
DR PhylomeDB; P11884; -.
DR BRENDA; 1.2.1.3; 5301.
DR BRENDA; 1.2.1.5; 5301.
DR Reactome; R-RNO-380612; Metabolism of serotonin.
DR Reactome; R-RNO-71384; Ethanol oxidation.
DR SABIO-RK; P11884; -.
DR UniPathway; UPA00780; UER00768.
DR EvolutionaryTrace; P11884; -.
DR PRO; PR:P11884; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0070404; F:NADH binding; IDA:RGD.
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; IMP:RGD.
DR GO; GO:0046185; P:aldehyde catabolic process; ISS:UniProtKB.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; IEP:RGD.
DR GO; GO:0048149; P:behavioral response to ethanol; IMP:RGD.
DR GO; GO:0110095; P:cellular detoxification of aldehyde; IMP:RGD.
DR GO; GO:0071398; P:cellular response to fatty acid; IEP:RGD.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IEP:RGD.
DR GO; GO:1904639; P:cellular response to resveratrol; IEP:RGD.
DR GO; GO:0006068; P:ethanol catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006067; P:ethanol metabolic process; IEP:RGD.
DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; IMP:RGD.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
DR GO; GO:1903179; P:regulation of dopamine biosynthetic process; ISS:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; IMP:RGD.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IMP:RGD.
DR GO; GO:1902882; P:regulation of response to oxidative stress; IEP:RGD.
DR GO; GO:1905627; P:regulation of serotonin biosynthetic process; ISS:UniProtKB.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0009408; P:response to heat; IEP:RGD.
DR GO; GO:0055093; P:response to hyperoxia; IEP:RGD.
DR GO; GO:0002931; P:response to ischemia; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0035094; P:response to nicotine; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IMP:RGD.
DR GO; GO:0032570; P:response to progesterone; IEP:RGD.
DR GO; GO:0033574; P:response to testosterone; IEP:RGD.
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 3D-structure; Acetylation; Direct protein sequencing; Mitochondrion; NAD;
KW Oxidoreductase; Reference proteome; Transit peptide.
FT TRANSIT 1..19
FT /note="Mitochondrion"
FT CHAIN 20..519
FT /note="Aldehyde dehydrogenase, mitochondrial"
FT /id="PRO_0000007170"
FT ACT_SITE 287
FT /note="Proton acceptor"
FT ACT_SITE 321
FT /note="Nucleophile"
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:0000250|UniProtKB:P47738"
FT MOD_RES 75
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47738"
FT MOD_RES 80
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47738"
FT MOD_RES 161
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47738"
FT MOD_RES 370
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47738"
FT MOD_RES 377
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47738"
FT MOD_RES 385
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47738"
FT MOD_RES 409
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 430
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47738"
FT MOD_RES 443
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47738"
FT MOD_RES 453
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47738"
FT VARIANT 86
FT /note="Q -> R (in allele Aldh2*2 and allele Aldh2*3; in
FT strains UChA and UChB)"
FT /evidence="ECO:0000269|PubMed:12893989"
FT VARIANT 498
FT /note="E -> K (in allele Aldh2*3; in strain: UChB)"
FT /evidence="ECO:0000269|PubMed:12893989"
FT HELIX 13..15
FT /evidence="ECO:0007829|PDB:2V1T"
FT HELIX 16..18
FT /evidence="ECO:0007829|PDB:5AZ8"
SQ SEQUENCE 519 AA; 56488 MW; 75C748202F1333E5 CRC64;
MLRAALSTAR RGPRLSRLLS AAATSAVPAP NQQPEVFCNQ IFINNEWHDA VSKKTFPTVN
PSTGEVICQV AEGNKEDVDK AVKAAQAAFQ LGSPWRRMDA SDRGRLLYRL ADLIERDRTY
LAALETLDNG KPYVISYLVD LDMVLKCLRY YAGWADKYHG KTIPIDGDFF SYTRHEPVGV
CGQIIPWNFP LLMQAWKLGP ALATGNVVVM KVAEQTPLTA LYVANLIKEA GFPPGVVNIV
PGFGPTAGAA IASHEDVDKV AFTGSTEVGH LIQVAAGSSN LKRVTLELGG KSPNIIMSDA
DMDWAVEQAH FALFFNQGQC CCAGSRTFVQ EDVYDEFVER SVARAKSRVV GNPFDSRTEQ
GPQVDETQFK KILGYIKSGQ QEGAKLLCGG GAAADRGYFI QPTVFGDVKD GMTIAKEEIF
GPVMQILKFK TIEEVVGRAN NSKYGLAAAV FTKDLDKANY LSQALQAGTV WINCYDVFGA
QSPFGGYKMS GSGRELGEYG LQAYTEVKTV TVKVPQKNS
