Aldo-keto reductase family 1 member A1 (AKR1A1)
The protein contains 325 amino acids for an estimated molecular weight of 36573 Da.
Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. Displays enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosaccharides and bile acids, with a preference for negatively charged substrates, such as glucuronate and succinic semialdehyde (PubMed:10510318). Functions as a detoxifiying enzyme by reducing a range of toxic aldehydes. Reduces methylglyoxal and 3-deoxyglucosone, which are present at elevated levels under hyperglycemic conditions and are cytotoxic. Involved also in the detoxification of lipid-derived aldehydes like acrolein (By similarity). Plays a role in the activation of procarcinogens, such as polycyclic aromatic hydrocarbon trans-dihydrodiols, and in the metabolism of various xenobiotics and drugs, including the anthracyclines doxorubicin (DOX) and daunorubicin (DAUN) (PubMed:18276838, PubMed:11306097). Displays no reductase activity towards retinoids (By similarity). (updated: May 8, 2019)
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.
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.
This protein is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| Reduced activity towards daunorubicin | |
| Reduced activity towards daunorubicin |
Biological Process
Aldehyde catabolic process
Cellular aldehyde metabolic process
Cellular detoxification of aldehyde
D-glucuronate catabolic process
Daunorubicin metabolic process
Doxorubicin metabolic process
Glucose metabolic process
Glucuronate catabolic process to xylulose 5-phosphate
Glutathione derivative biosynthetic process
L-ascorbic acid biosynthetic process
Molecular Function
Alcohol dehydrogenase (NADP+) activity
Alditol:NADP+ 1-oxidoreductase activity
Aldo-keto reductase (NADP) activity
Allyl-alcohol dehydrogenase activity
D-threo-aldose 1-dehydrogenase activity
Electron transfer activity
Glucuronolactone reductase activity
Glycerol dehydrogenase [NADP+] activity
L-glucuronate reductase activity
Methylglyoxal reductase (NADPH-dependent, acetol producing)
Oxidoreductase activity
The reference OMIM entry for this protein is 103830
Aldo-keto reductase family 1, member a1; akr1a1
Aldehyde reductase; alr
DESCRIPTION
Aldehyde reductase (EC 1.1.1.2) and aldose reductase (EC 1.1.1.21; 103880) are monomeric NADPH-dependent oxidoreductases having wide substrate specificities for carbonyl compounds (summary by Bohren et al., 1989).CLONING
Petrash et al. (1981) studied aldose reductase (AR), aldose reductase M (ARM), and aldehyde reductase (ALR) in a variety of human tissues. Lens aldose reductase is composed of a single subunit with molecular weight 35 kD, and liver aldehyde reductase is composed of a single subunit of molecular weight 32 kD. Liver aldose reductase M is composed of 2 nonidentical subunits of molecular weights 35 kD and 42 kD. Lens has only AR, liver has ARM and ALR, red cells have only ALR, while brain and placenta have all 3 enzymes. Petrash et al. (1981) suggested that 3 loci--alpha, beta, and delta--code for these enzymes, and that AR is a monomer of alpha polypeptide, ARM a dimer of alpha and beta subunits, and ALR a monomer of delta polypeptide. By screening a liver library with degenerate oligonucleotide primers based on the protein sequence of liver aldehyde reductase, Bohren et al. (1989) isolated aldehyde reductase cDNAs. The predicted protein contains 325 amino acids. Aldose reductase and aldehyde reductase share 3 homology domains and are 51% identical overall.MAPPING
By fluorescence in situ hybridization, Fujii et al. (1999) mapped the AKR1A1 gene to chromosome 1p33-p32. ... More on the omim web site
May 11, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 22, 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 103830 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed