ALDH2
entrez
217
canonical
uniprot
P05091
canonical
ensembl
ENSG00000111275
resolver
ensp
ENSP00000261733
resolver
ensp
ENSP00000403349
resolver
genesymbol
ALDH2
resolver
genesymbol_syn
ALDM
resolver
hgnc
HGNC:404
resolver
uniprot
A0A384NPN7
resolver
uniprot
B4DW54
resolver
uniprot
E7EUE5
resolver
uniprot
Q03639
resolver
uniprot
Q6IB13
resolver
uniprot
Q6IV71
resolver
uniprot_entry
A0A384NPN7_HUMAN
resolver
uniprot_entry
ALDH2_HUMAN
resolver
uniprot_sec
B4DW54
resolver
uniprot_sec
E7EUE5
resolver
uniprot_sec
Q03639
resolver
uniprot_sec
Q6IB13
resolver
uniprot_sec
Q6IV71
resolver
activity_regulation
ACTIVITY REGULATION: Denitration activity toward nitroglycerin is inhibited by daizdin (PubMed:22988236). The aldehyde dehydrogenase activity toward 3,4-dihydroxyphenylacetaldehyde (DOPAL) is inhibited by 4-hydroxy-2-nonenal (4HNE) (PubMed:16956664). {ECO:0000269|PubMed:16956664, ECO:0000269|PubMed:22988236}.
uniprot
proteins
amino_acid_sequence
MLRAAARFGPRLGRRLLSAAATQAVPAPNQQPEVFCNQIFINNEWHDAVSRKTFPTVNPSTGEVICQVAEGDKEDVDKAVKAARAAFQLGSPWRRMDASHRGRLLNRLADLIERDRTYLAALETLDNGKPYVISYLVDLDMVLKCLRYYAGWADKYHGKTIPIDGDFFSYTRHEPVGVCGQIIPWNFPLLMQAWKLGPALATGNVVVMKVAEQTPLTALYVANLIKEAGFPPGVVNIVPGFGPTAGAAIASHEDVDKVAFTGSTEIGRVIQVAAGSSNLKRVTLELGGKSPNIIMSDADMDWAVEQAHFALFFNQGQCCCAGSRTFVQEDIYDEFVERSVARAKSRVVGNPFDSKTEQGPQVDETQFKKILGYINTGKQEGAKLLCGGGIAADRGYFIQPTVFGDVQDGMTIAKEEIFGPVMQILKFKTIEEVVGRANNSTYGLAAAVFTKDLDKANYLSQALQAGTVWVNCYDVFGAQSPFGGYKMSGSGRELGEYGLQAYTEVKTVTVKVPQKNS
uniprot
proteins
disease_involvement
DISEASE: AMED syndrome, digenic (AMEDS) [MIM:619151]: A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. AMEDS is an autosomal recessive, digenic form characterized by childhood onset of bone marrow failure resulting in aplastic anemia, in association with global developmental delay, intellectual disability, and poor overall growth with short stature. {ECO:0000269|PubMed:33355142}. Note=The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. AMEDS patients carry ADH5 biallelic variants and homozygous or heterozygous ALDH2 variant p.Glu504Lys, affecting protein activity. Cellular and animal studies demonstrate that the simultaneous loss of ALDH2 and ADH5 activities leads to an increase of cellular formaldehyde sensitivity and multisystem abnormalities including hematopoietic failure. {ECO:0000269|PubMed:33355142}.
uniprot
proteins
ec_number
1.2.1.19
uniprot
proteins
ec_number
1.2.1.24
uniprot
proteins
ec_number
1.2.1.3
uniprot
proteins
ec_number
1.2.1.36
uniprot
proteins
ec_number
1.2.1.46
uniprot
proteins
ec_number
1.7.1.-
uniprot
proteins
function
FUNCTION: Mitochondrial aldehyde dehydrogenase with broad substrate specificity which participates in the detoxification of ethanol-derived acetaldehyde and endogenous aldehydes, including those arising from lipid peroxidation (PubMed:16956664, PubMed:22339434, PubMed:33355142, PubMed:39075523). The reaction mechanism involves a nucleophilic attack on the aldehyde substrate, resulting in formation of a thiohemiacetal intermediate. Subsequent hydride transfer to NAD+, yields a thioester intermediate which is hydrolyzed to the carboxylic acid product through activation of a water molecule by the catalytic glutamate (PubMed:19506075). In vivo, ALDH2 is required for the clearance of formaldehyde, a cytotoxic and carcinogenic endogenous metabolite that induces DNA damage (PubMed:33355142). It also catalyzes the oxidation of 3,4-dihydroxyphenylacetaldehyde (DOPAL), a reactive intermediate of dopamine catabolism, to 3,4-dihydroxyphenylacetate (DOPAC) (PubMed:16956664). ALDH2 may also catalyze the oxidation of 4-aminobutanal (gamma-aminobutyraldehyde) to 4-aminobutanoate (GABA), representing an alternative route for GABA biosynthesis from polyamine catabolism (By similarity). In vitro, ALDH2 catalyzes the oxidation of acrolein, malondialdehyde, and 4-hydroxynonenal (4-HNE) (PubMed:22339434). It also exhibits esterase activity that is enhanced by NAD+ but does not require it, although the physiological relevance of this activity remains unclear (PubMed:19506075). {ECO:0000250|UniProtKB:P20000, ECO:0000269|PubMed:16956664, ECO:0000269|PubMed:19506075, ECO:0000269|PubMed:22339434, ECO:0000269|PubMed:33355142, ECO:0000269|PubMed:39075523}.; FUNCTION: ALDH2 also bioactivates the antianginal drug nitroglycerin through denitration, generating nitric oxide (NO) by a mechanism that remains incompletely understood. The generated NO activates the soluble guanylate cyclase/cGMP signaling pathway, which in turn leads to vasorelaxation and relief of angina pectoris. {ECO:0000269|PubMed:16440063, ECO:0000269|PubMed:19506075, ECO:0000269|PubMed:22988236, ECO:0000269|PubMed:25413692}.
uniprot
proteins
mass_dalton
56381
uniprot
proteins
mutagenesis
MUTAGEN 220; /note="Y->H: Decreased aldehyde dehydrogenase (NAD+) activity."; /evidence="ECO:0000269|PubMed:10631996"; MUTAGEN 285; /note="E->Q: Loss of acetaldehyde dehydrogenase (NAD+) activity. Decreased oxidoreductase activity toward nitroglycerin. Loss of in vitro esterase activity."; /evidence="ECO:0000269|PubMed:19506075"; MUTAGEN 319; /note="C->S: Loss of acetaldehyde dehydrogenase (NAD+) activity. Loss of oxidoreductase activity toward nitroglycerin. Loss of in vitro esterase activity."; /evidence="ECO:0000269|PubMed:19506075
uniprot
proteins
pathway_participation
PATHWAY: Alcohol metabolism; ethanol degradation; acetate from ethanol: step 2/2. {ECO:0000269|PubMed:39075523}.
uniprot
proteins
post_translational_modification
PTM: In response to mitochondrial stress, the precursor protein is ubiquitinated by the SIFI complex in the cytoplasm before mitochondrial import, leading to its degradation (PubMed:38297121). {ECO:0000269|PubMed:38297121}.
uniprot
proteins
protein_family
Aldehyde dehydrogenase family
uniprot
proteins
pubmed
10631996
uniprot
proteins
pubmed
12795606
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15242332
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15983043
uniprot
proteins
pubmed
16440063
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
16956664
uniprot
proteins
pubmed
19506075
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22339434
uniprot
proteins
pubmed
22988236
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25413692
uniprot
proteins
pubmed
2838413
uniprot
proteins
pubmed
2987944
uniprot
proteins
pubmed
33355142
uniprot
proteins
pubmed
3562250
uniprot
proteins
pubmed
3582651
uniprot
proteins
pubmed
3610592
uniprot
proteins
pubmed
3653404
uniprot
proteins
pubmed
38297121
uniprot
proteins
pubmed
39075523
uniprot
proteins
pubmed
4015823
uniprot
proteins
pubmed
4065146
uniprot
proteins
pubmed
6582480
uniprot
proteins
pubmed
8561277
uniprot
proteins
sequence_length
517
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:16440063, ECO:0000269|PubMed:4065146}.
uniprot
proteins