Thioredoxin (TXN)

Thioredoxin (TXN) participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. Thioredoxin plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Thioredoxin nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity. Thioredoxin 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.

Thioredoxin (TXN) Related Areas

Enzyme>>Oxidoreductase>>Thioredoxin/TXN

Thioredoxin (TXN) Alternative Names

Thioredoxin, TXN, RP11-427L11.1, DKFZp686B1993, MGC61975, TRX, TRX1 [Homo sapiens]

Thioredoxin, Txn, Txn1, RP23-332H16.1, ADF, AW550880, Trx1 [Mus musculus]

Summaries for Thioredoxin (TXN)

Entrez Gene summary for Thioredoxin (TXN):

The protein encoded by TXN gene acts as a homodimer and is involved in many redox reactions. The encoded protein is active in the reversible S-nitrosylation of cysteines in certain proteins, which is part of the response to intracellular nitric oxide. This protein is found in the cytoplasm. Two transcript variants encoding different isoforms have been found for TXN gene. [provided by RefSeq, Oct 2011]

OMIM - description for Thioredoxin (TXN):

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.

Wikipedia summary for Thioredoxin (TXN):

Thioredoxin is a class of small redox proteins known to be present in all organisms. It plays a role in many important biological processes, including redox signaling. In humans, it is encoded by the TXN gene.Loss-of-function mutation of either of the two human thioredoxin genes is lethal at the four-cell stage of the developing embryo. Although not entirely understood, thioredoxin plays a central role in humans and is increasingly linked to medicine through their response to reactive oxygen species (ROS). In plants, thioredoxins perform a spectrum of critical functions, ranging from photosynthesis to growth, flowering and the development and germination of seeds. It has also recently been found to play a role in cell-to-cell communication.

Human Thioredoxin (TXN) Protein General Information

 

• Protein names: Thioredoxin
  Short name=TXN
• Sequence length: 105 AA.
• Domain: Redox-active center
• Sequence similarities: Belongs to the thioredoxin family.
  Contains 1 thioredoxin domain.
• Post-translational modification: In the fully reduced protein, both Cys-69 and Cys-73 are nitrosylated in response to nitric oxide (NO). When two disulfide bonds are present in the protein, only Cys-73 is nitrosylated. Cys-73 can serve as donor for nitrosylation of target proteins.
  In case of infection, ubiquitinated by S.typhimurium protein slrP, leading to its degradation.
• Subunit structure: Homodimer; disulfide-linked. Interacts with TXNIP through the redox-active site. Interacts with MAP3K5 and CASP3. In case of infection, interacts with S.typhimurium protein slrP. Interacts with APEX1; the interaction stimulates the FOS/JUN AP-1 DNA-binding activity in a redox-dependent manner.
• Subcellular location: Nucleus. Cytoplasm. Secreted. Note: Secreted by a leaderless secretory pathway. Predominantly in the cytoplasm in non irradiated cells. Radiation induces translocation of TRX from the cytoplasm to the nucleus.
• Induction: Up-regulated by ionizing radiation.

General information above from UniProt

Function for Thioredoxin (TXN) Protein

UniProtKB:

Thioredoxin (TXN) participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. Thioredoxin plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Thioredoxin nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity. Thioredoxin 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.

Genatlas:

• Thioredoxin has a dithiol-disulfide oxidoreductase activity
• Thioredoxin participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide
• Thioredoxin catalyzes dithiol-disulfide exchange reactions
• Thioredoxin is implicated in thioredoxin system may be an effective defense system protecting the lens against oxidative stress
• Thioredoxin has a little role in apoptosis of malignant mesothelioma cells
• Thioredoxin is enhanced HIF-1alpha protein amount and facilitated synthesis of HIF-1alpha by activating Akt, p70S6K, and eIF-4E, known to control cap-dependent translation
• Thioredoxin affects CD30-dependent changes in lymphocyte effector function
• Thioredoxin is IFN-gamma-induced factor that may play a role in developing Th1 immunity and in the maintenance of immune homeostasis upon infection, radiation, and oxidative stress
• Thioredoxin is multifunctional thiol protein that is critically involved in maintaining cellular redox homeostasis
• Thioredoxin has a role in suppressing senescence in normal cells in addition to its function as a redox-protective protein
• Thioredoxin reduces disulfide bonds and other thiol modifications in all cells using a CXXC motif
• Antiapoptotic and oncogenic potential of (secreted) TXN suggesting that it may exert effects in Tregs beyond redox regulation
• TXN and TXN2 regulate the proliferation and survival of adipose tissue-derived mesenchymal stem cells, and these processes are mediated by the activation of ERK1/2
• Thioredoxin is an important antioxidative enzyme in endothelial cells, required for apoptosis inhibition
• Thioredoxin is denitrosylase that reverses NO inhibition of exocytosis
• Thioredoxin might regulate exocytosis in a variety of physiological settings, such as vascular inflammation, thrombosis, and insulin release
• Thioredoxin is highly specific activator of oxidized human TGM2

Homology for human Thioredoxin (TXN)

• homolog to C.elegans B0228.5
• homolog to rattus Txn1 (90.29 pc)
• homolog to murine Txn1 (89.32 pc)

Drugs for Thioredoxin (TXN)

Target	Drug Name	Disease	Drug Status
Thioredoxin (TXN)	PX-12	Gastric Cancer	Phase Ib
Thioredoxin (TXN)	PX-12	Pancreatic Cancer	Phase II

Drugs for Thioredoxin (TXN) from TTD (Therapeutic Targets Database)