| Functional axis | Key claims/definitions | Representative evidence (brief) | Key quantitative data (if any) | Primary sources (include DOI URLs and years) |
|---|---|---|---|---|
| ER translocation | Human SEC62 (UniProt Q99442) is an ER membrane component of the Sec61/Sec62/Sec63 machinery that supports substrate-specific protein import into the ER, especially when Sec61 channel opening is difficult; it acts with Sec63 and can promote Sec61 gating directly and/or via BiP recruitment. (pqac-00000002, pqac-00000007, pqac-00000008) | In intact human cells, loss of SEC62 impaired import of selected precursors such as pre-ERj3; disruption of Sec62/Sec63 function prevented productive signal-peptide insertion into Sec61, and BiP-dependent rescue experiments supported a channel-gating role. (pqac-00000007, pqac-00000008) | SEC62 knockdown significantly altered 329 proteins (208 down, 121 up; q < 0.05), with enrichment for cleavable signal peptide and N-glycosylated proteins among negatively affected proteins. (pqac-00000005) | Schorr et al., 2020, FEBS J., DOI: https://doi.org/10.1111/febs.15274 (2020); Zimmermann, 2025, Int J Mol Sci, DOI: https://doi.org/10.3390/ijms26188823 (2025) |
| Substrate specificity | SEC62/Sec63-dependent clients share signal peptides with comparatively longer but less hydrophobic hydrophobic regions and lower C-region polarity; dependence is strongly associated with slowly gating signal peptides plus downstream positively charged, translocation-disruptive clusters. (pqac-00000006, pqac-00000008) | Proteomics in human cells identified a shared signal-peptide signature among SEC62/Sec63 clients; for ERj3, these features also conferred BiP dependence and sensitivity to a Sec61 inhibitor. (pqac-00000006, pqac-00000008) | 22 novel SEC62/Sec63 substrates were identified; among affected SEC62-depletion substrates, 21 had cleavable signal peptides and 29 had TMHs; 22 precursors overlapped between SEC62 and SEC63 depletion datasets. (pqac-00000005, pqac-00000008) | Schorr et al., 2020, FEBS J., DOI: https://doi.org/10.1111/febs.15274 (2020); Schorr et al., 2019, bioRxiv, DOI: https://doi.org/10.1101/867762 (2019) |
| ER Ca2+ homeostasis | SEC62 helps regulate Sec61-mediated ER Ca2+ leak in cooperation with cytosolic calmodulin (CaM); a Ca2+-binding motif/EF-hand in SEC62 is required for this function, and SEC62 is proposed to sense local Ca2+ and facilitate Ca2+-CaM-dependent channel closure. (pqac-00000012, pqac-00000013, pqac-00000018) | Biacore/SPR and functional Ca2+ imaging supported a direct, Ca2+-sensitive interaction of Sec62 with the Sec61 complex; SEC62 silencing elevated basal cytosolic Ca2+ and increased thapsigargin-evoked Ca2+ release, while CaM antagonists phenocopied SEC62 depletion. A schematic model is available in Fig. 7. (pqac-00000014, pqac-00000017, pqac-00000019) | SEC62 depletion caused at least a two-fold increase in basal cytosolic Ca2+; assays used 1 μM thapsigargin for short-term Ca2+ imaging, 6–10 nM thapsigargin for proliferation assays, 4–8 μM TFP in functional assays. (pqac-00000014, pqac-00000017) | Linxweiler et al., 2013, BMC Cancer, DOI: https://doi.org/10.1186/1471-2407-13-574 (2013); Zimmermann et al., 2022, Front Physiol, DOI: https://doi.org/10.3389/fphys.2022.1014271 (2022); Parys & Van Coppenolle, 2022, Front Physiol, DOI: https://doi.org/10.3389/fphys.2022.991149 (2022) |
| recovER-phagy | SEC62 also functions as an ER-phagy receptor/adaptor during recovery from ER stress (“recovER-phagy”), linking ER protein import capacity to selective ER turnover and quality control. (pqac-00000003, pqac-00000009, pqac-00000010) | Recent reviews summarize SEC62 among ER-phagy receptors and specifically note its role in recovery-phase ER turnover rather than generic starvation-induced ER-phagy. (pqac-00000010) | No SEC62-specific 2023–2024 quantitative flux values were retrieved in context; available recent context is primarily review-level or cites the foundational 2016/2019 work. (pqac-00000009, pqac-00000010) | Knupp et al., 2023, FEBS J., DOI: https://doi.org/10.1111/febs.16986 (2023); Yasasilka & Lee, 2024, J Diabetes Investig., DOI: https://doi.org/10.1111/jdi.14184 (2024) |
| Cancer/clinical relevance | SEC62 is located on chromosome 3q/3q26, is frequently amplified/overexpressed in multiple tumors, and overexpression is associated with increased migration, invasion, stress tolerance, metastatic behavior, and poorer prognosis. (pqac-00000001, pqac-00000003, pqac-00000016, pqac-00000018) | SEC62 silencing inhibited cancer-cell migration across several tumor types, whereas overexpression stimulated migration and tumor growth-related phenotypes; reviews and mechanistic summaries describe SEC62 as a driver oncogene candidate in 3q26-amplified cancers. (pqac-00000011, pqac-00000015, pqac-00000016) | In a pan-cancer summary, SEC62 alterations were reported in 2,595 of >72,000 cancer patients, mostly amplifications; median survival was 54.2 months with SEC62 alterations vs 95.6 months without. In one NSCLC study, 70 patients (35 AC, 35 SCC) were analyzed by western blot/Kaplan-Meier using rSec62. (pqac-00000011, pqac-00000014) | Linxweiler et al., 2013, BMC Cancer, DOI: https://doi.org/10.1186/1471-2407-13-574 (2013); Linxweiler et al., 2017, Signal Transduct Target Ther, DOI: https://doi.org/10.1038/sigtrans.2017.2 (2017); Körner et al., 2022, Front Physiol, DOI: https://doi.org/10.3389/fphys.2022.880004 (2022); Zimmermann et al., 2022, Front Physiol, DOI: https://doi.org/10.3389/fphys.2022.1014271 (2022) |
| Pharmacological targeting | SEC62-overexpressing tumors may be functionally targeted by calmodulin antagonists, especially trifluoperazine (TFP), which phenocopy SEC62 silencing; SERCA-targeting agents such as thapsigargin analogs/mipsagargin have also been discussed in combination strategies focused on ER Ca2+ homeostasis. (pqac-00000012, pqac-00000013, pqac-00000018) | TFP and ophiobolin A inhibited migration and increased sensitivity to thapsigargin-induced ER stress similarly to SEC62 depletion; murine tumor models reviewed in 2022 showed TFP reduced tumor growth and metastatic potential. (pqac-00000012, pqac-00000018) | Experimental conditions included 8 μM TFP with 10 nM or 0.1 nM thapsigargin in PC3 cells and 4 μM TFP in migration assays; mipsagargin/G202 had entered phase II trials, though SEC62-overexpressing cells may be less responsive. (pqac-00000012, pqac-00000018) | Linxweiler et al., 2013, BMC Cancer, DOI: https://doi.org/10.1186/1471-2407-13-574 (2013); Zimmermann et al., 2022, Front Physiol, DOI: https://doi.org/10.3389/fphys.2022.1014271 (2022) |


*Table: This table summarizes the main experimentally supported functional axes of human SEC62/Q99442, including its roles in ER protein translocation, calcium homeostasis, recovER-phagy, and cancer relevance. It also highlights quantitative findings and source papers useful for downstream annotation or evidence review.*