| Claim/Topic | Key findings (1-2 sentences) | Evidence type | Primary source (first author, journal) | Pub year/month | DOI URL |
|---|---|---|---|---|---|
| Identity | SEC11C matches UniProt Q9BY50 as the human signal peptidase complex catalytic subunit also called SPC21; it is one of two alternative proteolytic SPC subunits, the other being SEC11A, and belongs to the conserved Sec11/S26 signal peptidase family (pqac-00000000, pqac-00000001, pqac-00000002). | Cryo-EM, proteomics, review/background | Liaci, SSRN Electronic Journal | 2021/01 | https://doi.org/10.2139/ssrn.3778304 |
| Complex composition | Human SPC forms two heterotetrameric paralogs, SPC-A and SPC-C, each composed of SPC12, SPC22/23, SPC25, and either SEC11A or SEC11C; co-expression and affinity purification from HEK293 cells recovered near-stoichiometric complexes for each paralog (pqac-00000001, pqac-00000002, pqac-00000009). | Cryo-EM, affinity purification, MS | Liaci, SSRN Electronic Journal | 2021/01 | https://doi.org/10.2139/ssrn.3778304 |
| Catalytic mechanism | SEC11C is the catalytic protease of the ER SPC (EC 3.4.21.89). Structural analysis supports a Ser-His-Asp catalytic triad positioned in a c-region binding pocket adjacent to the membrane, with signal-peptide scissile bonds modeled near the catalytic residues (pqac-00000000, pqac-00000002, pqac-00000009). | Cryo-EM, modeling, structural proteomics | Liaci, SSRN Electronic Journal | 2021/01 | https://doi.org/10.2139/ssrn.3778304 |
| Localization/topology | SEC11C acts in the endoplasmic reticulum membrane with its catalytic domain exposed on the luminal side near the membrane surface, whereas its C terminus lies on the cytosolic side; the luminal domain of SPCS3 helps stabilize and position the catalytic core (pqac-00000000, pqac-00000001, pqac-00000007). | Cryo-EM, topology inference, comparative analysis | Liaci, SSRN Electronic Journal | 2021/01 | https://doi.org/10.2139/ssrn.3778304 |
| Substrate recognition | The SPC creates a locally thinned membrane window that acts as a molecular ruler favoring shorter hydrophobic h-regions typical of signal peptides over longer transmembrane helices. Both SEC11A- and SEC11C-containing complexes cleaved a pre-β-lactamase substrate with similar efficiency in vitro (pqac-00000001, pqac-00000002, pqac-00000009). | Cryo-EM, molecular dynamics, in vitro cleavage assay | Liaci, SSRN Electronic Journal | 2021/01 | https://doi.org/10.2139/ssrn.3778304 |
| Quality-control role | Beyond canonical signal peptide removal, the human SPC can cleave cryptic sites in misfolded or surplus membrane proteins, promoting their degradation and membrane proteostasis. SEC11C is part of this catalytic machinery, and the 2023 characterization proposed SEC11C may provide backup catalytic capacity when SEC11A is limiting (pqac-00000003, pqac-00000004). | Cell biology, genetic/knockdown interpretation, thesis synthesis | Zanotti, Science; Zanotti, thesis | 2022/12; 2023/01 | https://doi.org/10.1126/science.abo5672 ; https://doi.org/10.11588/heidok.00033417 |
| Inhibitor/antiviral relevance | Eukaryotic SPase is a plausible antiviral target because inhibition impairs maturation of secretory and viral proteins. Cavinafungin inhibits host signal peptidase by targeting SEC11-containing SPC, and reviews note the complex contains SEC11A and SEC11C; the 2023 thesis states cavinafungin should in principle also bind SEC11C (pqac-00000003, pqac-00000008). | Small-molecule inhibition, virology, review/background | Cui, JBC; Zanotti, thesis | 2015/11; 2023/01 | https://doi.org/10.1074/jbc.m115.692350 ; https://doi.org/10.11588/heidok.00033417 |
| Quantitative data | Cryo-EM structures were determined at about 4.9 Å resolution for the human paralogs, and membrane thickness near the active site was reported to decrease from ~4 nm to ~2.3 nm. In yeast, loss of Spc2 reduced Sec11 abundance by ~10%, supporting accessory-subunit effects on catalytic-subunit stability (pqac-00000001, pqac-00000007, pqac-00000009). | Cryo-EM, molecular dynamics, quantitative MS | Liaci, SSRN Electronic Journal; Chung, Journal of Cell Biology | 2021/01; 2024/11 | https://doi.org/10.2139/ssrn.3778304 ; https://doi.org/10.1083/jcb.202211035 |


*Table: This table summarizes functional annotation evidence for human SEC11C (UniProt Q9BY50), covering identity, complex membership, catalytic mechanism, localization, substrate recognition, quality-control function, and translational relevance. It is designed to support a concise, citation-backed report using only validated context IDs from the gathered literature.*