4-trimethylaminobutyraldehyde dehydrogenase (ALDH9A1)

The protein contains 494 amino acids for an estimated molecular weight of 53802 Da.

 

Converts gamma-trimethylaminobutyraldehyde into gamma-butyrobetaine with high efficiency (in vitro). Can catalyze the irreversible oxidation of a broad range of aldehydes to the corresponding acids in an NAD-dependent reaction, but with low efficiency. (updated: July 3, 2019)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 100%
Model score: 71

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VariantDescription
allele ALDH9A1*2

The reference OMIM entry for this protein is 602733

Aldehyde dehydrogenase, family 9, subfamily a, member 1; aldh9a1
Aldehyde dehydrogenase 9; aldh9
E3

DESCRIPTION

The aldehyde dehydrogenases (EC 1.2.1.3) are a family of isozymes that catalyze the oxidation of a broad range of aldehydes and the dehydrogenation of aldehyde metabolites of compounds such as corticosteroids and biogenic amines. The aldehyde dehydrogenase E3 catalyzes the dehydrogenation of gamma-aminobutyraldehyde to gamma-aminobutyric acid (GABA) (summary by Kurys et al., 1989).

CLONING

Kurys et al. (1989) identified a liver aldehyde dehydrogenase isozyme, which they called E3, that catalyzes the dehydrogenation of gamma-aminobutyraldehyde to gamma-aminobutyric acid. By SDS-PAGE and gradient gel electrophoresis, they found that E3 is a tetramer of identical 54-kD subunits. Using antibodies against E3 to screen a liver cDNA library, Kurys et al. (1993) isolated partial E3 cDNAs. Lin et al. (1996) isolated cDNAs containing the complete ALDH9 coding region, and found that the gene encodes a predicted 493-amino acid protein. These authors stated that their nucleotide sequence differs from that of Kurys et al. (1993) in 3 positions. By sequence analysis of the ALDH9 locus in several unrelated individuals, Lin et al. (1996) determined that 2 of the differences were due to polymorphism. They attributed the third difference to a misprint in Kurys et al. (1993). Northern blot analysis revealed that ALDH9 is expressed as a 2.4-kb mRNA in a variety of tissues, with the highest levels of expression in liver, skeletal muscle, and kidney. To study the role of E3 in the synthesis of the central nervous system inhibitory neurotransmitter GABA, Kikonyogo and Pietruszko (1996) characterized the E3 expression pattern in brain. By Northern blot analysis, they found that E3 is expressed as a 2.9-kb mRNA in all regions of the brain, with the highest levels in the spinal cord.

GENE STRUCTURE

Lin et al. (1996) reported that the ALDH9 gene contains 10 exons and spans approximately 45 kb.

MAPPING

By analysis of a somatic cell hybrid panel, McPherson et al. (1994) localized the E3 gene to chromosome 1. Using fluorescence in situ hybridization, Lin et al. (1996) mapped the ALDH9 gene to 1q22-q23.

NOMENCLATURE

Vasiliou et al. (1999) discussed the eukaryotic aldehyde dehydrogenases, tabulated all known human polymorphisms, and recommended nomenclature based on divergent evolution and chromosomal mapping. They suggested that the symbol ALDH9 (the 'trivial' designation) be changed to ALDH9A1. ... More on the omim web site

Subscribe to this protein entry history

July 4, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 15, 2016: Protein entry updated
Automatic update: OMIM entry 602733 was added.