Aldo-keto reductase family 1 member B1 (AKR1B1)
The protein contains 316 amino acids for an estimated molecular weight of 35853 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, monosacharides, bile acids and xenobiotics substrates. Key enzyme in the polyol pathway, catalyzes reduction of glucose to sorbitol during hyperglycemia (PubMed:1936586). Reduces steroids and their derivatives and prostaglandins. Displays low enzymatic activity toward all-trans-retinal, 9-cis-retinal, and 13-cis-retinal (PubMed:12732097, PubMed:19010934, PubMed:8343525). Catalyzes the reduction of diverse phospholipid aldehydes such as 1-palmitoyl-2-(5-oxovaleroyl)-sn -glycero-3-phosphoethanolamin (POVPC) and related phospholipid aldehydes that are generated from the oxydation of phosphotidylcholine and phosphatdyleethanolamides (PubMed:17381426). Plays a role in detoxifying dietary and lipid-derived unsaturated carbonyls, such as crotonaldehyde, 4-hydroxynonenal, trans-2-hexenal, trans-2,4-hexadienal and their glutathione-conjugates carbonyls (GS-carbonyls) (PubMed:21329684). (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.
- 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.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
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.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs5054 | |
| dbSNP:rs5056 | |
| dbSNP:rs5057 | |
| dbSNP:rs2229542 | |
| dbSNP:rs5061 | |
| dbSNP:rs5062 |
Biological Process
C21-steroid hormone biosynthetic process
Carbohydrate metabolic process
Cellular hyperosmotic salinity response
Cellular response to methylglyoxal
Cellular response to peptide
Daunorubicin metabolic process
Doxorubicin metabolic process
Epithelial cell maturation
Fructose biosynthetic process
Inner medullary collecting duct development
Maternal process involved in female pregnancy
Metanephric collecting duct development
Naphthalene metabolic process
Negative regulation of apoptotic process
Norepinephrine metabolic process
Oxidation-reduction process
Positive regulation of receptor signaling pathway via JAK-STAT
Positive regulation of smooth muscle cell proliferation
Regulation of urine volume
Renal water homeostasis
Response to stress
Response to thyroid hormone
Response to water deprivation
Retinoid metabolic process
Small molecule metabolic process
Sorbitol biosynthetic process
Steroid metabolic process
Stress-activated protein kinase signaling cascade
Tissue homeostasis
Cellular Component
Cytoplasm
Cytosol
Extracellular exosome
Extracellular space
Mast cell granule
Nucleoplasm
Paranodal junction
Perinuclear region of cytoplasm
Plasma membrane bounded cell projection cytoplasm
Schmidt-Lanterman incisure
Schwann cell microvillus
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
Glyceraldehyde oxidoreductase activity
Glycerol dehydrogenase [NADP+] activity
NADP-retinol dehydrogenase activity
Oxidoreductase activity
Prostaglandin H2 endoperoxidase reductase activity
Retinal dehydrogenase activity
The reference OMIM entry for this protein is 103880
Aldo-keto reductase family 1, member b1; akr1b1
Aldose reductase; ar
Aldehyde reductase 1; aldr1
DESCRIPTION
See aldehyde reductase (103830). Aldose reductase (EC 1.1.1.21) is a member of the monomeric, NADPH-dependent aldo-keto reductase family and participates in glucose metabolism and osmoregulation. It is believed to play a protective role against toxic aldehydes derived from lipid peroxidation and steroidogenesis that could affect cell growth/differentiation when accumulated (Lefrancois-Martinez et al., 2004). It is the first enzyme of the polyol pathway of sugar metabolism, is most abundantly expressed in adrenal gland, and has been implicated in diabetic complications (Shah et al., 1997).CLONING
Chung and LaMendola (1989) cloned and sequenced the aldose reductase gene from a human placental cDNA library using antibodies against the bovine lens aldose reductase. The deduced amino acid sequence indicated that maturation of aldose reductase involves removal of the N-terminal methionine. Nishimura et al. (1990) also cloned the aldose reductase gene using synthetic oligonucleotide probes based on partial amino acid sequences of purified human psoas muscle aldose reductase. Bohren et al. (1989) isolated aldose reductase and aldehyde reductase cDNAs. They reported that the 2 proteins are 51% identical. Northern blot analysis revealed that aldose reductase was expressed as an approximately 1.4-kb mRNA in placenta. Graham et al. (1991) determined the sequence of the ALDR1 gene by analysis of cDNA and genomic clones. The gene codes for a 316-amino acid protein with a molecular mass of 35,858 Da. A major site of transcription initiation in liver was mapped to an adenine residue 31 nucleotides upstream from the A of the ATG initiation codon.GENE STRUCTURE
Graham et al. (1991) determined that the ALDR1 gene extends over approximately 18 kb and consists of 10 exons, giving rise to a 1,384 nucleotide mRNA, excluding the poly(A) tail. The exons range in size from 82 to 168 bp, whereas the introns range from 325 to about 7,160 bp. The promoter region of the gene contains a TATA (TATTTA) box and a CCAAT box, located 37 and 104 nucleotides upstream, respectively, from the transcription initiation site. Graham et al. (1991) found 4 Alu elements in the ALDR1 gene: 2 in intron 1 and 1 each in introns 4 and 9.GENE FUNCTION
Using specific antibodies, Northern blot analysis, and enzymatic assays, Lefrancois-Martinez et al. (2004) presented evidence that AKR1B1 detectable in 15-week-old fetal glands is regulated by cAMP in human adrenocortical cells and thus that AKR1B1 is functionally related to the ACTH-responsive murine akr1b7/mvdp (mouse vas deferens protein) gene rather than to its direct ortholog, the mouse aldose reductase akr1b3 gene.BIOCHEMICAL FEATURES
Aldose reductase catalyzes the reduction of a number of aldehydes, including the aldehyde form of glucose, which is reduced to the corresponding sugar alcohol, sorbitol (Chung and LaMendola, 1989). Sorbitol is subsequently metabolized to fructose by sorbitol dehydrogenase. Under normal conditions, this pathway plays a minor role in glucose metabolism in most tissues. In diabetic hyperglycemia, however, cells undergoing insulin-independent uptake of glucose produce significant quantities of sorbitol. The sorbitol accumulates in cells because of its poor penetration across cellular membranes and its slow metabolism by sorbitol dehydrogenase. The resulting hyperosmotic stress to cells may be a cause of diabetic complications such as neur ... More on the omim web site
May 11, 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 103880 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed