| Category | Key findings (1-3 bullets) | Evidence/source | Publication (author year, DOI/URL) |
|---|---|---|---|
| Identity/domain | • Human TXNDC12 corresponds to ERp18, a small PDI/thioredoxin-like ER protein. <br>• Reported as 172 aa, with a single thioredoxin-fold catalytic domain and ER-retention signal EDEL. <br>• Family-level reviews place TXNDC12/ERp18 among PDI-family proteins that mediate thiol-disulfide exchange in ER proteostasis. | Pierre 2023 thesis; PDI family review (pqac-00000002, pqac-00000001) | Pierre 2023, https://doi.org/10.5525/gla.thesis.83614; Powell & Foster 2021, https://doi.org/10.1002/cam4.3836 |
| Enzymatic activity | • Recombinant human ERp18 shows disulfide reductase activity in a Di-E-GSSG assay; catalytic mutant loses activity. <br>• Thesis evidence also reports in vitro reductase activity and insulin reduction assay framework. <br>• ERp18 is described as capable of catalyzing disulfide bond formation, reduction, and isomerization. | Recombinant-protein assay and thesis biochemical analyses (pqac-00000000, pqac-00000004, pqac-00000002) | He et al. 2024, https://doi.org/10.1186/s12959-024-00678-5; Pierre 2023, https://doi.org/10.5525/gla.thesis.83614 |
| Active-site motif | • ERp18 contains a single CGAC catalytic motif. <br>• Mutation of CGAC to SGAS abolishes reductase activity and fails to support the pro-thrombotic function seen with WT protein. <br>• PDI-family reviews note catalytic CXXC motifs as the basis for thiol-disulfide exchange activity. | Catalytic-motif experiment and family review (pqac-00000000, pqac-00000015, pqac-00000001) | He et al. 2024, https://doi.org/10.1186/s12959-024-00678-5; Powell & Foster 2021, https://doi.org/10.1002/cam4.3836 |
| Localization | • ERp18 is ER-resident/ER-localized in cell-based studies. <br>• In thrombosis work, ERp18 is detected in endothelial cells, leukocytes, and platelets; present on resting platelet surfaces and surface exposure increases with activation. <br>• Activated platelets/endothelial cells can release or externalize ERp18, indicating extracellular activity in vascular settings. | Cell localization and vascular-cell expression studies (pqac-00000004, pqac-00000000, pqac-00000015) | Pierre 2023, https://doi.org/10.5525/gla.thesis.83614; He et al. 2024, https://doi.org/10.1186/s12959-024-00678-5 |
| UPR/ATF6 mechanism | • ERp18 interacts with ATF6α during ER stress and regulates ATF6α redox state and ER-to-Golgi trafficking. <br>• ERp18 reductase activity antagonizes the monomer→467D disulfide-linked dimer shift; knockout enhances this shift and causes dysregulated/non-canonical ATF6α processing. <br>• Substrate-trapping evidence supports mixed-disulfide formation with ATF6α, biased toward C467, consistent with ERp18 acting as a redox quality-control checkpoint in early ATF6 activation. | ATF6-focused thesis experiments (pqac-00000003, pqac-00000006, pqac-00000008, pqac-00000009) | Pierre 2023, https://doi.org/10.5525/gla.thesis.83614 |
| Thrombosis findings | • ERp18 knockout mice develop reduced venous thrombosis in the IVC stenosis model, with lower thrombus weight, length, and incidence. <br>• WT recombinant ERp18, but not inactive SGAS mutant, supports pro-thrombotic effects, indicating catalytic activity is required. <br>• ERp18 deficiency lowers local plasma/thrombus vWF after stenosis while basal vWF is unchanged, suggesting regulation of vWF release/exocytosis rather than biosynthesis. | In vivo mouse model, enzymatic rescue, and vWF analyses (pqac-00000015, pqac-00000000, pqac-00000010) | He et al. 2024, https://doi.org/10.1186/s12959-024-00678-5 |
| Cancer/ferroptosis associations | • In osteosarcoma, TXNDC12 is one of five genes in an ER-stress prognostic signature; higher TXNDC12 expression was associated with better overall survival in that cohort. <br>• In hepatocarcinoma-cell proteomic analysis, TXNDC12 is discussed as an antioxidant/redox protein and cited as a factor that may inhibit lipid peroxidation and ferroptosis. <br>• These 2024 sources provide association/mechanistic hypotheses rather than definitive TXNDC12-specific clinical implementation. | Prognostic-signature study and oxidative-stress/ferroptosis discussion (pqac-00000014, pqac-00000013) | Chen et al. 2024, https://doi.org/10.1186/s12967-023-04794-0; Shukla et al. 2024, https://doi.org/10.3390/cancers16020292 |


*Table: This table summarizes the experimentally supported identity, molecular function, localization, UPR role, and disease associations of human TXNDC12/ERp18 using only the retrieved evidence snippets. It is useful as a compact evidence map for building the full research report.*