Ask about this productRelated genes to: TMX2 antibody
- Gene:
- TMX2 NIH gene
- Name:
- thioredoxin related transmembrane protein 2
- Previous symbol:
- TXNDC14
- Synonyms:
- PDIA12
- Chromosome:
- 11q12.1
- Locus Type:
- gene with protein product
- Date approved:
- 2005-10-04
- Date modifiied:
- 2016-02-01
Related products to: TMX2 antibody
Related articles to: TMX2 antibody
- Ulcerative colitis (UC) remission is marked by gut microbiota restructuring, but how microbial metabolites influence immune-mediated tissue repair is unclear. Here, we demonstrate that oral vancomycin alleviates colitis symptoms in murine models, mirroring its clinical efficacy in inducing remission in patients with UC. Mechanistically, vancomycin's therapeutic effect is achieved by reducing deoxycholic acid (DCA). We reveal that DCA impairs mucosal repair driven by group 2 innate lymphoid cells (ILC2s) by inducing ER stress through direct binding to thioredoxin-related transmembrane protein 2 (TMX2). This interaction disrupts TMX2's role in protein folding, triggering unresolved unfolded protein response via hyperactivation of PERK/eIF2α signaling, which suppresses the production of pro-healing molecules by ILC2s. Pharmacological inhibition of PERK phosphorylation restores ILC2 function and accelerates colitis resolution. Our work uncovers a pathogenic microbiota/DCA/ILC2 axis that obstructs mucosal healing and positions vancomycin as a targeted strategy to eliminate DCA, thereby promoting UC remission. - Source: PubMed
Publication date: 2026/04/08
Tian QiuhengLiu HanGu XiangShen JingYuan XiZheng MengqiZhai YunjiaoChen YataiHan PenghuMa YangchunXin WeiMa HongyueLi YuWang SihanGuo LeiYuan DetianYu YanboLi Shiyang - Thioredoxin-related transmembrane proteins (TMXs) of the endoplasmic reticulum (ER) determine not only redox conditions within the ER lumen but also the formation and function of ER-mitochondria membrane contact sites (ERMCS). The presence of cytosolic, reactive oxygen species (ROS)-derived redox nanodomains at ERMCS suggests TMXs could also control these. The prime candidate for such a function is TMX2, the sole TMX family protein with a cytosolic thioredoxin domain. Indeed, TMX2 controls the extent of ERMCS through interaction with outer mitochondrial membrane proteins, including TOM70. Assisted by cytosolic peroxiredoxins, TMX2 moderates the sulfenylation of the TOM70 C residue. Thereby, TMX2 reduces mitochondrial Ca uptake and metabolism. Accordingly, mutation of the TMX2 gene in cells from a patient with a neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity (NEDMCMS) results in hyperactive mitochondria. In a fly in vivo NEDMCMS model, TMX2 knockdown manifests predominantly in glial cells, where it prevents seizure-like behavior. - Source: PubMed
Publication date: 2025/10/31
Chen JunshengYap Megan CBassot ArthurPascual Danielle MMakio TadashiZimmermann JannikMast HeatherBhat RakeshFleury Samuel GFan YuxiangBuzatto Adriana ZardiniMoore JackBallanyi KlausLi LiangOverduin MichaelLemieux M JoanneLemieux HélèneMancini Grazia M SMorgan BruceMarcogliese Paul CSimmen Thomas - Biallelic variants in thioredoxin-related transmembrane 2 protein (TMX2) can cause a malformation of brain cortical development characterized by microcephaly, polymicrogyria and pachygyria by an unknown mechanism. To investigate and visualize how TMX2 loss disrupts brain development in vivo, we generated zebrafish deficient for TMX2 ortholog tmx2b, which during the first two developmental days showed normal brain developmental hallmarks. From 3 days onwards, however, tmx2b mutants had no locomotor activity; this was accompanied by cell death in the brain, but not in other organs or in the spinal cord. Strikingly, cell death in tmx2b mutants occurred specifically in post-mitotic neurons within a ∼1.5-h timeframe, whereas neuronal progenitor and radial glial cells were preserved, and could be suppressed by inhibiting neuronal activity. In vivo calcium imaging showed a persistent ∼2-fold increase in calcium in neurons after the onset of cell death. This suggests that calcium homeostasis underlies the tmx2b mutant brain phenotype. Our results indicate that TMX2 is an evolutionarily conserved, protective regulator essential specifically for post-mitotic neurons after their differentiation in the vertebrate embryonic brain. - Source: PubMed
Publication date: 2025/09/18
Dekker JordyLam Wendyvan der Linde Herma COphorst Florisde Konink CharlotteSchot RachelKremers Gert-JanSanderson Leslie EBerdowski Woutje Mvan Woerden Geeske MMancini Grazia M Svan Ham Tjakko J - The aim of this study was to find potential drug targets of osteoporosis (OP) through systematic druggable genome-wide Mendelian randomization (MR) analysis. - Source: PubMed
Publication date: 2025/06/07
Sun ChiyunLiu RuikangHu JiamingFan WeimingSun ChuanruiShan PengchengWei Xu - Thioredoxin (TRX)-related transmembrane proteins (TMX), a subgroup of the protein disulfide isomerase (PDI) family, comprise a class of transmembrane proteins with diverse biological functions. Among these, TMX2 (PDIA12) remains one of the least characterized members. Recent studies have identified missense mutations in TMX2 associated with aberrant brain development and cerebellar malformations, highlighting its potential importance in developmental processes. Notably, Tmx2 mutant embryos exhibit developmental arrest at the E3.5 stage, suggesting a critical role in preimplantation embryogenesis. However, the precise molecular and cellular functions of Tmx2 in mammalian embryonic development remain largely unexplored. In this study, we provide novel insights into the essential role of Tmx2 during preimplantation embryonic development in mice. We demonstrate that TMX2 is specifically expressed in mouse embryos, with its subcellular localization closely associated with mitochondria during the two-cell to eight-cell stages. Knockdown of Tmx2 recapitulates the phenotypic defects observed in genetic mutants, revealing a pronounced impairment in blastomere proliferation, as confirmed by EdU incorporation assays. Furthermore, TUNEL assays indicate a significant increase in apoptotic signaling in Tmx2-deficient embryos, accompanied by elevated mRNA levels of the cell cycle inhibitors p21 and p53. Mechanistically, we show that Tmx2 knockdown disrupts mitochondrial function, leading to oxidative stress and impaired mitophagy and autophagy in developing embryos. These findings suggest that Tmx2 plays a pivotal role in maintaining mitochondrial integrity and cellular homeostasis during preimplantation embryogenesis. In summary, our study elucidates the critical role of Tmx2 in preimplantation embryonic development in mice, primarily through its regulation of mitochondrial function. These results advance our understanding of the molecular mechanisms governing preimplantation embryonic development and establish Tmx2 as a key regulator of mitochondrial dynamics and cellular survival during this critical developmental window. - Source: PubMed
Zhang ShangrongLiu QingWang SiyuZhang XiaoyuQin DingmeiBai RuisongChen JiMa ZijianLin ZhipengBi YuhengLiu HuanSun AoxueMo ZhongzhiWang HongchengWu XiaoqingLiu Yong