TXN2

TXN2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1UVZ, 1W4V, 1W89
Identifiers
Aliases	TXN2, MT-TRX, MTRX, TRX2, COXPD29, thioredoxin 2, TXN
External IDs	OMIM: 609063 MGI: 1929468 HomoloGene: 40849 GeneCards: TXN2
Gene location (Mouse) Chr. Chromosome 15 (mouse) Band 15|15 E1 Start 77,799,247 bp End 77,813,206 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Right adrenal gland Left adrenal gland right lobe of liver gastrocnemius muscle body of stomach left ventricle nucleus accumbens amygdala right lobe of thyroid gland left lobe of thyroid gland Top expressed in adrenal gland lip right ventricle brown adipose tissue proximal tubule soleus muscle skeletal muscle tissue superior frontal gyrus esophagus yolk sac More reference expression data BioGPS More reference expression data
Gene ontology Molecular function peptide-methionine (S)-S-oxide reductase activity peptide-methionine (R)-S-oxide reductase activity protein binding protein-disulfide reductase activity protein-containing complex binding Cellular component nucleolus mitochondrion mitochondrial matrix neuronal cell body dendrite Biological process response to hypoxia response to hormone cellular response to nutrient levels response to organic cyclic compound response to oxidative stress glycerol ether metabolic process response to axon injury response to glucose cell redox homeostasis sulfur amino acid catabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 25828 56551 Ensembl n/a ENSMUSG00000005354 UniProt Q99757 P97493 RefSeq (mRNA) NM_012473 NM_019913 RefSeq (protein) NP_036605 NP_064297 Location (UCSC) n/a Chr 15: 77.8 – 77.81 Mb PubMed search
Wikidata
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Thioredoxin, mitochondrial also known as thioredoxin-2 is a protein that in humans is encoded by the TXN2 gene on chromosome 22. This nuclear gene encodes a mitochondrial member of the thioredoxin family, a group of small multifunctional redox-active proteins. The encoded protein may play important roles in the regulation of the mitochondrial membrane potential and in protection against oxidant-induced apoptosis.

Structure

As a thioredoxin, TXN2 is a 12-kDa protein characterized by the redox active site Trp-Cys-Gly-Pro-Cys. In its oxidized (inactive) form, the two cysteines form a disulfide bond. This bond is then reduced by thioredoxin reductase and NADPH to a dithiol, which serves as a disulfide reductase. In contrast to TXN1, TXN2 contains a putative N-terminal mitochondrial targeting sequence, responsible for its mitochondria localization, and lacks structural cysteines. Two mRNA transcripts of the TXN2 gene differ by ~330 bp in the length of the 3′-untranslated region, and both are believed to exist in vivo.

Function

This nuclear gene encodes a mitochondrial member of the thioredoxin family, a group of small multifunctional redox-active proteins. The encoded protein is ubiquitously expressed in all prokaryotic and eukaryotic organisms, but demonstrates especially high expression in tissues with heavy metabolic activity, including the stomach, testis, ovary, liver, heart, neurons, and adrenal gland. It may play important roles in the regulation of the mitochondrial membrane potential and in protection against oxidant-induced apoptosis. Specifically, the ability of TXN2 to reduce disulfide bonds enables the protein to regulate mitochondrial redox and, thus, the production of reactive oxygen species (ROS). By extension, downregulation of TXN2 can lead to increased ROS generation and cell death. The antiapoptotic function of TXN2 is attributed to its involvement in GSH-dependent mechanisms to scavenge ROS, or its interaction with, and thus regulation of, thiols in the mitochondrial permeability transition pore component adenine nucleotide translocator (ANT).

Overexpression of TXN2 was shown to have attenuated hypoxia-induced HIF-1alpha accumulation, which is in direct opposition of the cytosolic TXN1, which enhanced HIF-1alpha levels. Moreover, although both TXN2 and TXN1 are able to reduce insulin, TXN2 does not depend on the oxidative status of the protein for this activity, a quality which may contribute to their difference in function.

Clinical Significance

It has been demonstrated that genetic polymorphisms in the TXN2 gene may be associated with the risk of spina bifida.

TXN2 is known to inhibit transforming growth factor (TGF)-β-stimulated ROS generation independent of Smad signaling. TGF-β is a pro-oncogenic cytokine that induces epithelial–mesenchymal transition (EMT), which is a crucial event in metastatic progression. In particular, TXN2 inhibits TGF-β-mediated induction of HMGA2, a central EMT mediator, and fibronectin, an EMT marker.

Interactions

TXN2 is shown to interact with ANT.

Further reading