| Topic | Key finding (with numbers) | Evidence source (first author year) | DOI/URL | Publication date |
|---|---|---|---|---|
| Functional role in SPC | SEC11A/SPC18 is a catalytic subunit of the human ER-resident signal peptidase complex (SPC) that removes N-terminal signal peptides from secretory pre-proteins; the human SPC is estimated to process ~3,000 human signal peptides (pqac-00000000, pqac-00000001) | Liaci 2021 | https://doi.org/10.2139/ssrn.3778304 | 2021-01 |
| Complex composition / paralogs | Human SPC exists as 2 heterotetrameric paralogs: SPC-A contains SEC11A and SPC-C contains SEC11C; both also contain SPC12/SPCS1, SPC25/SPCS2, and SPC22/23/SPCS3; reconstituted complex is ~84 kDa (pqac-00000000, pqac-00000002, pqac-00000003) | Liaci 2021 | https://doi.org/10.2139/ssrn.3778304 | 2021-01 |
| Catalytic mechanism / triad | SEC11A/C functions as a serine protease with a catalytic Ser-His-Asp triad; the active site lies adjacent to the ER membrane and is stabilized by SPC22/23/SPCS3; the SPC is resistant to standard serine protease inhibitors (pqac-00000000, pqac-00000001, pqac-00000005) | Liaci 2021; Chung 2024 | https://doi.org/10.2139/ssrn.3778304 ; https://doi.org/10.1083/jcb.202211035 | 2021-01; 2024-11 |
| Signal peptide determinants / substrate specificity | SPC recognizes canonical signal peptides with a tripartite n/h/c architecture; h-regions are typically 7–15 aa, c-regions 3–7 aa, and efficient cleavage follows the -1/-3 rule requiring small, non-charged residues; eukaryotic SPC generally does not cleave substrates with h-regions >18–20 aa (pqac-00000000, pqac-00000002, pqac-00000003, pqac-00000005) | Liaci 2021; Chung 2024 | https://doi.org/10.2139/ssrn.3778304 ; https://doi.org/10.1083/jcb.202211035 | 2021-01; 2024-11 |
| Membrane thinning / TM window / lipid dependence | All SPC subunits form a ~15 Å transmembrane window that locally thins the bilayer from ~4 nm to ~2.3–2.6 nm, helping discriminate short signal-peptide h-regions from longer TM helices; phosphatidylcholine enrichment in the window and relipidation can restore activity in detergent systems (pqac-00000001, pqac-00000013) | Liaci 2021 | https://doi.org/10.2139/ssrn.3778304 | 2021-01 |
| Quality control / noncanonical cleavage | Beyond canonical signal peptide removal, 2023 work characterized the human SPC as a quality-control enzyme for membrane proteins; ~1,500 membrane proteins were predicted to contain putative cryptic SPC cleavage sites, and SPCS1 was proposed to recruit noncanonical substrates; SEC11A knockdown did not abolish cleavage of at least one noncanonical substrate (Cx32), consistent with compensation by SEC11C (pqac-00000004) | Zanotti 2023 | https://doi.org/10.11588/heidok.00033417 | 2023-01 |
| Clinical association: gastric cancer | In locally advanced gastric cancer, SEC11A mRNA was measured in n=253 patients (high n=127, low n=126). High expression associated with worse 5-year overall survival: 52.3% vs 75.9% (p<0.005). Multivariable HR for death: 2.010 (95% CI 1.303–3.100; p=0.002). Associations also seen with serosal invasion (p=0.002), lymph-node metastasis (p=0.002), venous invasion (p=0.019), and stage (p=0.015) (pqac-00000006, pqac-00000008, pqac-00000010) | Suematsu 2022 | https://doi.org/10.21873/anticanres.16097 | 2022-12 |
| Clinical association: HNSC (TCGA) | In TCGA HNSC, SEC11A was upregulated in primary tumors (n=518) vs adjacent normals (n=44). High-expression group had more PFS events 117/259 (22.6%) vs 80/259 (15.4%), p=0.001, and more DSS events 80/246 (16.3%) vs 50/246 (10.2%), p=0.003. Continuous-expression multivariable HRs: PFS 2.075 (95% CI 1.447–2.977; p<0.001) and DSS 2.023 (95% CI 1.284–3.187; p=0.002). Expression correlated with copy number, r=0.53 (p<0.001) (pqac-00000007, pqac-00000009, pqac-00000011) | Hu 2022 | https://doi.org/10.1371/journal.pone.0269166 | 2022-06 |


*Table: This table condenses the main mechanistic, structural, and clinical findings for human SEC11A/SPC18. It is useful as a quick reference linking SEC11A’s role in the signal peptidase complex to recent functional studies and quantitative cancer associations.*