Thioredoxin reductase 1, cytoplasmic (TXNRD1)
The protein contains 649 amino acids for an estimated molecular weight of 70906 Da.
Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a combination of interferon-beta and retinoic acid. (updated: April 1, 2015)
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:rs1127954 |
Biological Process
Cell population proliferation
Cell redox homeostasis
Cellular lipid metabolic process
Cellular response to oxidative stress
Mesoderm formation
Nucleobase-containing small molecule interconversion
Nucleobase-containing small molecule metabolic process
Regulation of lipid metabolic process
Regulation of metabolic process
Response to oxygen radical
Response to reactive oxygen species
Selenium compound metabolic process
Signal transduction
Small molecule metabolic process
Cellular Component
Cytoplasm
Cytosol
Extracellular exosome
Fibrillar center
Mitochondrion
Nucleolus
Nucleoplasm
Obsolete cell
The reference OMIM entry for this protein is 601112
Thioredoxin reductase 1; txnrd1
Txnr
Tr1
CLONING
Thioredoxin reductase (EC 1.6.4.5) is a key enzyme in the regulation of the intracellular redox environment. Gasdaska et al. (1995) purified human thioredoxin reductase from placenta and obtained amino acid sequence from tryptic peptides. Based on protein sequence data, the authors designed degenerate PCR primers and used them to screen a human placenta cDNA library. The authors obtained a 3.8-kb cDNA encoding a predicted 495-amino acid protein that is 40% identical to glutathione reductase (GSR; 138300) and 24% identical to thioredoxin reductase from E. coli. The protein has a predicted FAD-binding domain, but this activity could not be demonstrated with recombinantly expressed enzyme. By Northern blot analysis, Gasdaska et al. (1996) found that thioredoxin reductase was expressed in all tissues examined, but at varying levels. The authors found no correlation between the relative expression levels of thioredoxin and thioredoxin reductase. Tamura and Stadtman (1996) purified a selenocysteine-containing enzyme from a human lung adenocarcinoma cell line. The protein was purified as a homodimer of 57-kD subunits with no detectable N-linked oligosaccharides. Tamura and Stadtman (1996) identified a prosthetic FAD group in the protein, and they found that the protein catalyzed NADPH-dependent reduction of insulin in the presence of thioredoxin. The subunit composition and catalytic properties of the selenoprotein were similar to those of mammalian thioredoxin reductase, but it failed to crossreact with anti-rat liver thioredoxin reductase polyclonal antibodies in immunoblot assays. Selenium has been indirectly implicated in immunologic function and numerous nutritional studies over many years. Furthermore, human immunodeficiency virus (HIV)-infected persons have been reported to have decreased levels of plasma selenium and selenium-containing glutathione peroxidase (e.g., 138321). For this reason, Gladyshev et al. (1996) initiated studies on selenium metabolism in human T cells. They identified one of the selenoproteins detected in T cells as thioredoxin reductase and demonstrated that the location of selenocysteine in this protein corresponds to a TGA codon in the cloned placental gene. The finding that T-cell thioredoxin reductase is a selenoenzyme that contains selenium in a conserved C-terminal region provides another example of the role of selenium in the major antioxidant enzyme system (i.e., thioredoxin-thioredoxin reductase), in addition to the well-known glutathione peroxidase enzyme system. Dammeyer et al. (2008) stated that there are at least 3 TXNRD1 splice variants with different 5-prime ends that encode TXNRD1 isoforms with unique N-terminal domains. They studied variant-3 (v3), which includes alternative exons upstream of the core promoter that encode an atypical N-terminal monothiol glutaredoxin (GRX, or GLRX; 600443) domain fused to the thioredoxin module. Northern blot analysis detected a 4.5-kb v3 transcript in testis only. PCR analysis also showed v3 expression in ovary, spleen, heart, liver, kidney, pancreas, and some cancer cell lines of various tissue origin. Immunohistochemical analysis of human testis detected v3 predominantly in Leydig cells. Dammeyer et al. (2008) stated that orthologs of v3 are found in chimpanzee and dog, but not in mouse or rat.GENE FUNCTION
Gorlatov and Stadtman (1998) demonstrated the essential role of selenocysteine in thioredoxin reductase isolated from HeLa ce ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for TXNRD1
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601112 was added.