| 2004 |
TMX1 (TMX) is a transmembrane oxidoreductase localized to the ER membrane with its N-terminal thioredoxin-like domain (CPAC active site) facing the ER lumen; recombinant TMX showed PDI-like refolding activity on scrambled RNase in vitro. |
Subcellular fractionation, membrane topology analysis, in vitro refolding assay (scrambled RNase) |
Archives of biochemistry and biophysics |
Medium |
14871470
|
| 2011 |
Palmitoylation of cysteine residue(s) adjacent to the transmembrane domain of TMX1 is required for its enrichment on the mitochondria-associated membrane (MAM); mutation of the palmitoylation site or chemical interference with palmitoylation disrupts MAM localization. |
Palmitoylation site mutagenesis, chemical inhibition of palmitoylation, subcellular fractionation/immunofluorescence |
The EMBO journal |
High |
22045338
|
| 2015 |
TMX1 forms functional complexes with the ER lectin calnexin and preferentially acts on cysteine-containing, membrane-anchored client proteins during folding, while ignoring the same cysteine-containing ectodomains when not membrane-tethered; TMX1 is the first topology-specific client protein redox catalyst in living cells. |
Co-immunoprecipitation (TMX1–calnexin complex), substrate specificity assays comparing membrane-anchored vs. soluble ectodomains, KD/KO with defined folding phenotype |
Molecular biology of the cell |
High |
26246604
|
| 2016 |
TMX1 regulates ER-to-mitochondria Ca²⁺ flux at the MAM; its thioredoxin (CPAC) motif and palmitoylation-dependent MAM targeting are both required for this function. Low TMX1 reduces ER-mitochondria contacts, decreases mitochondrial Ca²⁺ uptake, shifts bioenergetics away from mitochondria, and reduces apoptosis progression. |
TMX1 knockout/knockdown, CPAC active-site mutant, palmitoylation mutant; Ca²⁺ imaging, mitochondrial ATP measurements, ER-mitochondria contact site quantification |
The Journal of cell biology |
High |
27502484
|
| 2017 |
TMX1 is reversibly oxidized in response to ER protein overload (brefeldin A-induced protein accumulation); oxidation precedes the classical ER stress marker BiP induction, and glutathione is involved in maintaining TMX1 in its reduced (basal) state. |
Redox state analysis (alkylation-based trapping), BFA treatment and washout, glutathione depletion experiments |
FEBS open bio |
Medium |
29123984
|
| 2018 |
TMX1 acts as a topology-specific reductase in ERAD, preferentially reducing disulfide bonds of membrane-tethered misfolded polypeptides to facilitate their dislocation, while ignoring the same misfolded ectodomains when soluble. |
ERAD substrate degradation assays, membrane-anchored vs. soluble substrate comparisons, TMX1 knockdown with defined ERAD phenotype |
Biochemical and biophysical research communications |
Medium |
29932915
|
| 2018 |
TMX1 is expressed on the platelet surface and acts as an oxidase toward the αIIbβ3 integrin; TMX1-deficient platelets have increased free thiols on the β3 subunit, and recombinant extracellular TMX1 inhibits platelet aggregation, ATP release, αIIbβ3 activation, and P-selectin expression, making it the first identified negative (inhibitory) extracellular thiol isomerase regulator of platelet function. |
TMX1 knockout mouse model, recombinant extracellular domain protein (rTMX1) addition, anti-TMX1 antibody, thiol-labeling of αIIbβ3, platelet aggregation and ATP release assays, FeCl3 mesenteric arterial injury thrombosis model |
Blood |
High |
30425049
|
| 2012 |
TMX1-deficient mice are highly susceptible to LPS/d-galactosamine-induced inflammatory liver injury, with enhanced p53-signaling pathway activation in the liver; TNF-α neutralization suppressed the toxic phenotype, indicating TMX1 protects against oxidative inflammatory damage downstream of TNF-α signaling. |
TMX1 knockout mouse model, LPS/GalN and thioacetamide liver injury models, liver transcriptional profiling, TNF-α neutralization |
Antioxidants & redox signaling |
Medium |
22924822
|
| 2024 |
TMX1 directly engages the CxxC motif of CD3δ (a TCR complex subunit); loss of TMX1 decreases surface TCR expression and destabilizes CD3ζ, impairing TCR assembly and T cell cytotoxicity as well as NFAT, NFκB, and AP1 signaling. Overexpression of CD3ζ rescues the phenotype, indicating TMX1 is required for TCR assembly but not for CD3ζ function per se. |
APEX2 proximity labeling screen (CD8α bait), CRISPR TMX1 deletion, CD3ζ overexpression rescue, surface TCR expression assays, T cell signaling readouts |
bioRxivpreprint |
Medium |
39386445
|
| 2024 |
TMX1 oxidizes ERp46 (inhibiting its reductase activity) and also re-oxidizes the αIIbβ3 disulfides that ERp46 reduces, thereby counterbalancing ERp46-mediated platelet activation; TMX1 deficiency increases free thiols on ERp46 in platelets, an effect reversed by addition of wild-type but not catalytically inactive TMX1. |
ERp46- and TMX1-deficient platelets, wild-type vs. inactive TMX1 protein addition, thiol labeling, reductase activity assays, platelet aggregation and clot retraction assays |
Research and practice in thrombosis and haemostasis |
Medium |
39247212
|
| 2025 |
TMX1 binds FABP5 and competitively blocks interaction between FABP5 and the E3 ubiquitin ligase NEDD4, preventing K48-linked ubiquitination and degradation of FABP5, thereby enhancing FABP5-mediated inhibition of ferroptosis in hepatocellular carcinoma cells. |
Co-immunoprecipitation (TMX1–FABP5 interaction), ubiquitination assays, TMX1 KD/OE with FABP5 KD rescue, in vivo xenograft model |
Cellular signalling |
Medium |
41482143
|
| 2025 |
CCT2 recruits TRIM28 to catalyze SUMO2 modification of TMX1, which inhibits TMX1 ubiquitination and stabilizes the protein; this stabilized TMX1 promotes ROS clearance, conferring resistance to third-generation EGFR tyrosine kinase inhibitors in NSCLC. |
CRISPR/Cas9 genome-wide screen, TMT proteomics, SUMO2 modification assays, ubiquitination assays, TMX1 KD with ROS measurements, xenograft models |
Cell death and differentiation |
Medium |
41168408
|