ALDH2

Protein identityUniProt · HPA

UniProt accession

P05091

Gene

ALDH2

Ensembl

ENSG00000111275

Chromosome

12

Canonical length

517 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Quaternary structure

Homotetramer

OverviewNCBI Gene

This protein belongs to the aldehyde dehydrogenase family of proteins. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. Two major liver isoforms of aldehyde dehydrogenase, cytosolic and mitochondrial, can be distinguished by their electrophoretic mobilities, kinetic properties, and subcellular localizations. Most Caucasians have two major isozymes, while approximately 50% of East Asians have the cytosolic isozyme but not the mitochondrial isozyme. A remarkably higher frequency of acute alcohol intoxication among East Asians than among Caucasians could be related to the absence of a catalytically active form of the mitochondrial isozyme. The increased exposure to acetaldehyde in individuals with the catalytically inactive form may also confer greater susceptibility to many types of cancer. This gene encodes a mitochondrial isoform, which has a low Km for acetaldehydes, and is localized in mitochondrial matrix. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Nov 2016]

Canonical amino-acid sequenceUniProt

517 residues, UniProt reviewed canonical sequence.

>P05091|ALDH2
     1  MLRAAARFGP RLGRRLLSAA ATQAVPAPNQ QPEVFCNQIF INNEWHDAVS RKTFPTVNPS
    61  TGEVICQVAE GDKEDVDKAV KAARAAFQLG SPWRRMDASH RGRLLNRLAD LIERDRTYLA
   121  ALETLDNGKP YVISYLVDLD MVLKCLRYYA GWADKYHGKT IPIDGDFFSY TRHEPVGVCG
   181  QIIPWNFPLL MQAWKLGPAL ATGNVVVMKV AEQTPLTALY VANLIKEAGF PPGVVNIVPG
   241  FGPTAGAAIA SHEDVDKVAF TGSTEIGRVI QVAAGSSNLK RVTLELGGKS PNIIMSDADM
   301  DWAVEQAHFA LFFNQGQCCC AGSRTFVQED IYDEFVERSV ARAKSRVVGN PFDSKTEQGP
   361  QVDETQFKKI LGYINTGKQE GAKLLCGGGI AADRGYFIQP TVFGDVQDGM TIAKEEIFGP
   421  VMQILKFKTI EEVVGRANNS TYGLAAAVFT KDLDKANYLS QALQAGTVWV NCYDVFGAQS
   481  PFGGYKMSGS GRELGEYGLQ AYTEVKTVTV KVPQKNS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ALDH2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.23

Highest tissue expression

801 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ALDH2.

Disease | AllUniProt

Conditions ALDH2 is implicated in, by any mechanism.

• AMED syndrome, digenic (AMEDS) MIM:619151

ReferencesPubMed · IEDB

Publications for ALDH2 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.09

gnomAD pLI

0

gnomAD missense Z

1.32

DepMap mean gene effect

-0.11

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• alcohol metabolic process
• aldehyde catabolic process
• carbohydrate metabolic process
• cellular detoxification of aldehyde
• ethanol catabolic process
• ethanol metabolic process
• nitroglycerin metabolic process
• regulation of dopamine biosynthetic process
• regulation of serotonin biosynthetic process

Molecular functions

• aldehyde dehydrogenase (NAD+) activity
• aldehyde dehydrogenase [NAD(P)+] activity
• carboxylesterase activity
• electron transfer activity
• NAD binding
• phenylacetaldehyde dehydrogenase (NAD+) activity

Cellular components

• extracellular exosome
• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Aldehyde dehydrogenase domain
• Aldehyde dehydrogenase, cysteine active site
• Aldehyde/histidinol dehydrogenase
• Aldehyde dehydrogenase, N-terminal
• Aldehyde dehydrogenase, C-terminal
• Aldehyde dehydrogenase, glutamic acid active site
• Aldehyde dehydrogenase family

KeywordsUniProt

• Acetylation
• Dwarfism
• Intellectual disability
• Mitochondrion
• NAD
• Oxidoreductase
• Transit peptide
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of ALDH2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ALDH1A1