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Mouse Txn1 encodes thioredoxin-1 (Trx1), the cytosolic thioredoxin isoform in
mammals, distinct from the mitochondrial paralog Txn2/Trx2.
"The target protein is **thioredoxin-1 (Trx1)** encoded by **Txn1** (often denoted TXN1/Trx1), the **cytosolic** thioredoxin isoform in mammals, and is distinct from **Txn2/Trx2**, the mitochondrial paralog."
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Trx1 is a thiol-disulfide oxidoreductase that catalyzes reduction of oxidized
cysteine residues and protein disulfide bonds via its Cys32/Cys35 catalytic pair,
forming a transient mixed-disulfide intermediate followed by thiol-disulfide exchange.
"Trx1 catalyzes the **reduction of oxidized cysteine residues and protein disulfide bonds** in target proteins (i.e., converting a disulfide to two thiols), via its **Cys32/Cys35** catalytic pair"
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Oxidized Trx1 is regenerated by thioredoxin reductase (TrxR/TXNRD1) using reducing
equivalents from NADPH; the canonical electron flow is NADPH to TrxR to Trx1 to
substrate disulfide.
"Oxidized Trx1 is regenerated by **thioredoxin reductase (TrxR; cytosolic TXNRD1 in mammals)** using reducing equivalents ultimately derived from **NADPH**. Thus, the canonical electron flow is **NADPH → TrxR → Trx1 → substrate disulfide**"
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Trx1 acts as a broadly acting disulfide reductase and donates electrons to
peroxiredoxins, supporting peroxide detoxification via peroxiredoxin regeneration;
it has low intrinsic affinity for H2O2 itself.
"it is also described as reducing oxidized **peroxiredoxins** (i.e., supporting peroxide detox/redox cycling indirectly through peroxiredoxin regeneration)"
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Trx1 is mainly cytoplasmic but can translocate to the nucleus under oxidative/
nitrosative stress, associate with membranes, and be secreted via a leaderless
secretory pathway with extracellular signaling/chemotaxis roles.
"Trx1 is described as **mainly cytoplasmic**, but capable of **nuclear translocation** under oxidative/nitrosative stress; it can also associate with membranes and be **secreted via a leaderless secretory pathway**, with extracellular roles including signaling/chemotaxis"
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Thioredoxin binds and inhibits ASK1 (MAP3K5) under basal conditions; TXNIP binds
reduced thioredoxin and displaces/inactivates it, promoting oxidative-stress
signaling, apoptosis, and inflammasome-linked responses.
"Thioredoxin is described as binding and inhibiting **ASK1** under basal conditions; displacement or inactivation of thioredoxin (e.g., by TXNIP) promotes oxidative stress signaling and downstream outcomes (e.g., apoptosis/inflammasome-linked signaling)"
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Thioredoxin is required for NF-kB binding to DNA, consistent with a role in
maintaining transcription factor cysteines in a reduced, DNA-binding-competent state.
"thioredoxin is also noted as required for **NF-κB binding to DNA**, pointing to a mechanistic role in transcriptional redox regulation"
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Global Txn1 loss in mouse is embryonic lethal, with growth retardation around the
blastocyst stage (~E3.5) and trophoblast/hatching defects, indicating a nonredundant
developmental requirement.
"Mouse genetic loss of **Txn1** is described as causing **early embryonic lethality**; embryos show growth retardation around the **blastocyst stage (~E3.5)** and defects in trophoblast formation/hatching, indicating a nonredundant requirement for Trx1 during early development"