Thioredoxin (TXN)
The protein contains 105 amino acids for an estimated molecular weight of 11737 Da.
Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions (PubMed:2176490, PubMed:17182577, PubMed:19032234). Plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity (PubMed:16408020, PubMed:17606900). Induces the FOS/JUN AP-1 DNA-binding activity in ionizing radiation (IR) cells through its oxidation/reduction status and stimulates AP-1 transcriptional activity (PubMed:9108029, PubMed:11118054).', 'ADF augments the expression of the interleukin-2 receptor TAC (IL2R/P55). (updated: Feb. 26, 2020)
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.
- 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.
- 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.
- 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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Biological Process
Activation of protein kinase B activity
Cell population proliferation
Cell redox homeostasis
Cell-cell signaling
Cellular oxidant detoxification
Cellular response to oxidative stress
Glycerol ether metabolic process
Innate immune response
Movement of cell or subcellular component
Negative regulation of hydrogen peroxide-induced cell death
Negative regulation of protein export from nucleus
Negative regulation of transcription by RNA polymerase II
Nucleobase-containing small molecule interconversion
Nucleobase-containing small molecule metabolic process
Nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
Oxidation-reduction process
Positive regulation of DNA binding
Positive regulation of peptidyl-cysteine S-nitrosylation
Positive regulation of peptidyl-serine phosphorylation
Positive regulation of protein kinase B signaling
Protein repair
Purinergic nucleotide receptor signaling pathway
Regulation of protein import into nucleus, translocation
Response to nitric oxide
Response to radiation
Response to reactive oxygen species
Signal transduction
Small molecule metabolic process
Transcription, DNA-templated
Cellular Component
Cytoplasm
Cytosol
Extracellular exosome
Extracellular region
Mitochondrion
Nucleoplasm
Nucleus
Obsolete cell
Molecular Function
Oxidoreductase activity, acting on a sulfur group of donors, disulfide as acceptor
Peptide disulfide oxidoreductase activity
Poly(A) RNA binding
Protein homodimerization activity
Protein-disulfide reductase (NAD(P)) activity
Protein-disulfide reductase activity
RNA binding
Thioredoxin-disulfide reductase activity
The reference OMIM entry for this protein is 187700
Thioredoxin; txn
Trx
Trx1
DESCRIPTION
Thioredoxin is a 12-kD oxidoreductase enzyme containing a dithiol-disulfide active site. It is ubiquitous and found in many organisms from plants and bacteria to mammals. Multiple in vitro substrates for thioredoxin have been identified, including ribonuclease, choriogonadotropins, coagulation factors, glucocorticoid receptor, and insulin. Reduction of insulin is classically used as an activity test.CLONING
Wollman et al. (1988) identified a full-length cDNA clone encoding human thioredoxin. The open reading frame codes for a protein of 104 amino acids, excluding the initial methionine. This protein possesses the highly conserved enzymatic active site common to plant and bacterial thioredoxins: trp-cys-gly-pro-cys (amino acids 30 to 34).GENE FUNCTION
By yeast 2-hybrid analysis of a human brain cDNA library, Saitoh et al. (1998) identified TRX and ASK1 (MAP3K5; 602448) as interacting partners. TRX associated with the N-terminal portion of ASK1 in vitro and in vivo, and the interaction between TRX and ASK1 was highly dependent on the redox status of TRX. Expression of TRX inhibited ASK1 kinase activity and ASK1-dependent apoptosis. Inhibition of TRX resulted in activation of endogenous ASK1 activity. Saitoh et al. (1998) concluded that TRX is a physiologic inhibitor of ASK1 and may be involved in redox regulation of the apoptosis signal transduction pathway. Junn et al. (2000) found that the C-terminal half of mouse Vdup1 (TXNIP; 606599) interacted with the redox-active center of Trx. Mutation of 2 critical cysteines in the Trx active center abrogated the interaction with Vdup1. Transfection of mouse Vdup1 into human embryonic kidney cells reduced the endogenous reducing activity of TRX or the activity of cotransfected TRX. Overexpression of Vdup1 inhibited interaction between Trx and a thiol-specific antioxidant, Pag (PRDX1; 176763), and it inhibited interaction between Trx and Ask1. Treatment of mouse fibroblasts and T-cell hybridoma cells with various stress stimuli, such as hydrogen peroxide or heat shock, induced Vdup1 expression. Exposure of mouse fibroblasts overexpressing Vdup1 to stress resulted in reduced cell proliferation and elevated apoptotic cell death. Junn et al. (2000) concluded that VDUP1 functions as an oxidative stress mediator by inhibiting TRX activity. Wang et al. (2002) found that biomechanical strain or hydrogen peroxide downregulated expression of Vdup1, but not Trx, in rat cardiomyocytes. The rapid response occurred through transcriptional control and led to increased Trx activity. Adenovirus-mediated overexpression of Vdup1 suppressed Trx activity and induced cardiomyocyte apoptosis. Furthermore, Vdup1 overexpression sensitized cells to hydrogen peroxide-induced apoptosis, whereas Trx overexpression protected cells against injury. Wang et al. (2002) concluded that VDUP1 is a key stress-responsive inhibitor of thioredoxin activity in cardiomyocytes. Adriamycin (ADR) is an anticancer drug that causes severe cardiac toxicity by generating free radicals. Shioji et al. (2002) found that Trx1 was dose-dependently increased concomitant with formation of hydroxyl radicals in ADR-treated neonatal rat cardiomyocytes. Treatment with recombinant human TRX1 suppressed cardiomyocyte injury in ADR-treated cells. Electron microscopy revealed better maintenance of cardiac mitochondria and cellular architecture in ADR-treated TRX1-expressing transgenic mice than in ADR-treated wild ... More on the omim web site
March 3, 2020: 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 187700 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed