Retinal dehydrogenase 1 (ALDH1A1)
The protein contains 501 amino acids for an estimated molecular weight of 54862 Da.
Can convert/oxidize retinaldehyde to retinoic acid. Binds free retinal and cellular retinol-binding protein-bound retinal (By similarity). May have a broader specificity and oxidize other aldehydes in vivo (PubMed:19296407, PubMed:26373694, PubMed:25450233). (updated: Nov. 22, 2017)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- 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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
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| Variant | Description |
|---|---|
| dbSNP:rs1049981 | |
| dbSNP:rs11554423 | |
| dbSNP:rs8187929 |
No binding partner found
Biological Process
Cellular aldehyde metabolic process
Ethanol oxidation
Fructose catabolic process to hydroxyacetone phosphate and glyceraldehyde-3-phosphate
Negative regulation of cold-induced thermogenesis
Oxidation-reduction process
Retinoid metabolic process
Retinol metabolic process
Small molecule metabolic process
Xenobiotic metabolic process
The reference OMIM entry for this protein is 100640
Aldehyde dehydrogenase 1 family, member a1; aldh1a1
Aldehyde dehydrogenase 1; aldh1
Acetaldehyde dehydrogenase 1
Aldh, liver cytosolic
Retinal dehydrogenase 1; raldh1
DESCRIPTION
The ALDH1A1 gene encodes a liver cytosolic isoform of acetaldehyde dehydrogenase (EC 1.2.1.3), an enzyme involved in the major pathway of alcohol metabolism after alcohol dehydrogenase (ADH, see 103700). See also liver mitochondrial ALDH2 (100650), variation in which has been implicated in different responses to alcohol ingestion. ALDH1 is associated with a low Km for NAD, a high Km for acetaldehyde, and is strongly inactivated by disulfiram. ALDH2 is associated with a high Km for NAD, and low Km for acetaldehyde, and is insensitive to inhibition by disulfiram (Hsu et al., 1985).CLONING
Inoue et al. (1979) purified and partially characterized aldehyde dehydrogenase from human erythrocytes: this was the cytosolic form, present in only low concentration in red cells. Using isoelectric focusing, Thomas et al. (1982) showed that the cytosolic and mitochondrial ALDHs are distinct isozymes. Hempel et al. (1984) determined the amino acid sequence of the cytosolic ALDH isoform. The monomer is composed of 500 residues and contains 11 cysteine residues. Hsu et al. (1985) reported cloning of the ALDH1 and ALDH2 genes. The 2 proteins showed 69% homology at the protein level. The ALDH1 gene encodes a 501-residue protein (Hsu et al., 1989).MAPPING
With cDNA probes for Southern blot analysis of somatic cell hybrids, Hsu et al. (1985, 1986) assigned the ALDH1 locus to chromosome 9q and the ALDH2 locus to chromosome 12.GENE STRUCTURE
Hsu et al. (1989) found that the ALDH1 gene is about 53 kb long and is divided into 13 exons. A similar intron-exon organization was found in ALDH2, which also has 13 exons with 9 of the 12 introns interrupting the coding sequence at positions homologous to those in ALDH1. Thus, the 2 isozymes appear to have evolved after duplication of a common ancestral gene.MOLECULAR GENETICS
Thomas et al. (1982) found low cytosolic ALDH in the liver of alcoholic patients with fatty liver; mitochondrial ALDH was normal. Abstaining alcoholics showed persistently low cytosolic ALDH. Eckey et al. (1986) reported a variant of cytosolic ALDH in a Chinese autopsy liver specimen. While the major isozyme band was nearly absent, several additional minor bands were observed on isoelectric focusing gel. Rabbit antibodies showed immunological cross-reactivity for the variant enzyme bands. The existence of additional minor bands indicated the presence of tetramer hybrid forms made up of normal and variant monomers. The observed abnormality may represent a heterozygous form of cytosolic ALDH variation. A similar variant was also detected in erythrocytes of a male Thai student. Yoshida et al. (1989) demonstrated that among Caucasians alcohol flushing can be related to abnormalities of ALDH1. In 9 unrelated Caucasian alcohol flushers, they found 1 who exhibited low activity (10-20% of normal) and another who exhibited moderately low activity (60%) and altered kinetic properties. The electrophoretic mobilities of these 2 samples were not altered. Immunologic quantitation indicated that the amount of protein in the 2 samples was not reduced in parallel with the enzyme deficiency. In the first case, the daughter of the proposita also had very low enzyme activity and alcohol flushing.ANIMAL MODEL
Retinaldehyde is generated by ADH1 (103700) from retinol, and its concentration is determined in large part by its subsequent catabolism by RALDH1 to retinoic acid. Ziouzenkova et al ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
Feb. 10, 2018: 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 100640 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed