SEC11C (SPC21, SEC11L3; EC 3.4.21.89) is a single-pass type II endoplasmic reticulum membrane protein and one of the two catalytic serine-endopeptidase subunits of the human signal peptidase complex (SPC). As the proteolytic subunit of the SPC-C paralog (with accessory subunits SPCS1, SPCS2 and SPCS3), SEC11C catalyzes cleavage of N-terminal signal (leader) peptides from secretory and membrane pre-proteins as they are translocated into the ER lumen. It belongs to peptidase family S26B and uses a Ser/His/Asp-type charge-relay catalytic system (Ser-68 nucleophile). Its active site abuts the ER membrane, where the complex locally thins the lipid bilayer, conferring selectivity for signal peptides whose hydrophobic h-region is shorter than ~18-20 residues. SEC11C is the paralog of the more broadly expressed SEC11A; the two catalytic subunits form distinct but functionally analogous SPC paralogs.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005787 signal peptidase complex | IBA GO_REF:0000033 | ACCEPT | Summary: SEC11C is the catalytic subunit of the signal peptidase complex (SPC-C paralog); membership in the SPC is its defining, conserved cellular component. Reason: Core cellular component; SEC11C is the proteolytic subunit of the signal peptidase complex. Supporting Evidence: file:human/SEC11C/SEC11C-uniprot.txt Component of the signal peptidase complex paralog C (SPC-C) |
| GO:0008233 peptidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: SEC11C is a peptidase; "peptidase activity" is a correct but generic parent of the specific serine-type endopeptidase/signal peptidase activity. Reason: Correct general molecular function; the specific serine-type endopeptidase activity (GO:0004252) better captures SEC11C's catalytic role. Supporting Evidence: file:human/SEC11C/SEC11C-uniprot.txt Belongs to the peptidase S26B family |
| GO:0004252 serine-type endopeptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: SEC11C is a serine-type endopeptidase that uses a Ser/His/Asp charge-relay catalytic triad to cleave signal peptides; this is its core molecular function. Reason: Core molecular function; experimentally established serine-endopeptidase (signal peptidase) activity, supported by IDA/EXP and the catalytic triad. Supporting Evidence: PMID:34388369 The active site is formed by a |
| GO:0005787 signal peptidase complex | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA electronic assignment of signal peptidase complex membership, redundant with the experimental IDA evidence. Reason: Correct core cellular component; redundant with IDA/IBA evidence. Supporting Evidence: file:human/SEC11C/SEC11C-uniprot.txt Component of the signal peptidase complex paralog C (SPC-C) |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic assignment of ER membrane localization from the UniProt subcellular location, consistent with the single-pass type II ER membrane topology. Reason: Correct core localization; SEC11C is a single-pass ER membrane protein. Supporting Evidence: file:human/SEC11C/SEC11C-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0008233 peptidase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based electronic assignment of peptidase activity; a generic parent of the specific serine-type endopeptidase activity. Reason: Correct general molecular function; GO:0004252 is the informative specific term. Supporting Evidence: file:human/SEC11C/SEC11C-uniprot.txt Belongs to the peptidase S26B family |
| GO:0009003 signal peptidase activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC-based electronic assignment of signal peptidase activity (EC 3.4.21.89); this is SEC11C's specific catalytic function and is experimentally supported (EXP). Reason: Core molecular function; SEC11C is the catalytic signal peptidase of the SPC-C complex (EC 3.4.21.89). Supporting Evidence: file:human/SEC11C/SEC11C-uniprot.txt EC=3.4.21.89 |
| GO:0016020 membrane | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: SEC11C is a membrane protein; "membrane" is a correct but generic parent of the specific ER membrane localization. Reason: Correct but generic; ER membrane (GO:0005789) is the specific and informative localization. Supporting Evidence: file:human/SEC11C/SEC11C-uniprot.txt Single-pass type II membrane protein |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: BioPlex (HCIP) high-throughput interactome capture; bare protein binding is uninformative for core function. Reason: High-throughput interactome interaction; uninformative bare term not elevated to core per guidelines. Supporting Evidence: file:human/SEC11C/SEC11C-uniprot.txt Q9BY50; P61009: SPCS3 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Binary interactome (HuRI) high-throughput capture; bare protein binding is uninformative. Reason: High-throughput interactome interaction; uninformative bare term not elevated to core. Supporting Evidence: file:human/SEC11C/SEC11C-uniprot.txt Q9BY50; P61009: SPCS3 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex proteome-scale interactome capture; bare protein binding is uninformative. Reason: High-throughput interactome interaction; uninformative bare term not elevated to core. Supporting Evidence: file:human/SEC11C/SEC11C-uniprot.txt Q9BY50; P61009: SPCS3 |
| GO:0005515 protein binding | IPI PMID:34388369 Structure of the human signal peptidase complex reveals the ... | KEEP AS NON CORE | Summary: SEC11C interacts with the SPC accessory subunits SPCS2 and SPCS3 within the signal peptidase complex; the bare protein binding term is uninformative, but the SPC assembly is captured better by the signal peptidase complex part_of annotation. Reason: Records genuine intra-complex interactions (SPCS2/SPCS3), but bare protein binding is uninformative; the functional content is captured by the signal peptidase complex CC. Supporting Evidence: file:human/SEC11C/SEC11C-uniprot.txt with SPCS2 and SPCS3 |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Multimodal cell-map (proteomics/imaging) high-throughput capture; bare protein binding is uninformative for core function. Reason: High-throughput interactome/cell-map interaction; uninformative bare term not elevated to core. Supporting Evidence: file:human/SEC11C/SEC11C-uniprot.txt Q9BY50; P61009: SPCS3 |
| GO:0005787 signal peptidase complex | IPI PMID:34388369 Structure of the human signal peptidase complex reveals the ... | ACCEPT | Summary: The cryo-EM structure identifies SEC11C within the assembled signal peptidase complex (SPC-C) with SPCS1/2/3; defining cellular component. Reason: Core cellular component; SEC11C is the catalytic subunit of the structurally resolved SPC-C complex. Supporting Evidence: file:human/SEC11C/SEC11C-uniprot.txt Component of the signal peptidase complex paralog C (SPC-C) |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:34388369 Structure of the human signal peptidase complex reveals the ... | ACCEPT | Summary: The SPC structure places SEC11C in the ER membrane, with the active site abutting the bilayer; direct experimental localization. Reason: Core localization with direct experimental support; SEC11C acts at the ER membrane. Supporting Evidence: file:human/SEC11C/SEC11C-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0016485 protein processing | IDA PMID:34388369 Structure of the human signal peptidase complex reveals the ... | ACCEPT | Summary: SEC11C processes pre-proteins by cleaving their signal peptides; "protein processing" is a correct but generic parent of the specific signal peptide processing. Reason: Correct biological process; the specific signal peptide processing (GO:0006465) better captures SEC11C's role. Supporting Evidence: PMID:34388369 it removes signal peptides (SPs) from a large |
| GO:0005789 endoplasmic reticulum membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity (ISS) transfer of ER membrane localization, consistent with the experimental IDA evidence. Reason: Correct core localization; redundant with IDA/IEA ER membrane evidence. Supporting Evidence: file:human/SEC11C/SEC11C-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0009003 signal peptidase activity | EXP PMID:34388369 Structure of the human signal peptidase complex reveals the ... | ACCEPT | Summary: Experimental demonstration (structure + catalytic-activity/mutagenesis of the catalytic triad including Ser-68) that SEC11C is a catalytic signal peptidase of the SPC. This is the core molecular function. Reason: Core molecular function with direct experimental support; SEC11C is a catalytic signal peptidase subunit of the SPC. Supporting Evidence: PMID:34388369 human SPC exists in two functional paralogs with distinct proteolytic subunits |
| GO:0004252 serine-type endopeptidase activity | IDA PMID:34388369 Structure of the human signal peptidase complex reveals the ... | ACCEPT | Summary: Direct experimental demonstration of SEC11C serine-type endopeptidase (signal peptidase) activity via the resolved catalytic triad and catalytic-activity assays; core molecular function. Reason: Core molecular function with direct experimental (IDA) support. Supporting Evidence: PMID:34388369 The active site is formed by a |
| GO:0005787 signal peptidase complex | IDA PMID:34388369 Structure of the human signal peptidase complex reveals the ... | ACCEPT | Summary: Direct structural demonstration that SEC11C is the catalytic subunit within the assembled SPC-C; defining cellular component. Reason: Core cellular component with direct experimental (IDA) support. Supporting Evidence: file:human/SEC11C/SEC11C-uniprot.txt Component of the signal peptidase complex paralog C (SPC-C) |
| GO:0051604 protein maturation | IDA PMID:34388369 Structure of the human signal peptidase complex reveals the ... | ACCEPT | Summary: By cleaving signal peptides from pre-proteins, SEC11C contributes to maturation of secretory/membrane proteins; "protein maturation" is a correct but generic parent of the specific signal peptide processing. Reason: Correct biological process; the specific signal peptide processing (GO:0006465) better captures SEC11C's role. Supporting Evidence: PMID:34388369 it removes signal peptides (SPs) from a large |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-422051 | ACCEPT | Summary: Reactome curation of SEC11C ER membrane localization (preproghrelin signal peptide cleavage). Reason: Correct core localization; redundant with experimental ER membrane evidence. Supporting Evidence: file:human/SEC11C/SEC11C-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9918795 | ACCEPT | Summary: Reactome curation of SEC11C ER membrane localization (flaviviral polyprotein signalase cleavage). Reason: Correct core localization; redundant with experimental ER membrane evidence. Supporting Evidence: file:human/SEC11C/SEC11C-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9918871 | ACCEPT | Summary: Reactome curation of SEC11C ER membrane localization (NS4B signalase cleavage). Reason: Correct core localization; redundant with experimental ER membrane evidence. Supporting Evidence: file:human/SEC11C/SEC11C-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
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Download this section (compressed HTML)Q: What distinguishes the substrate specificity of the SEC11C (SPC-C) versus SEC11A (SPC-A) paralogous signal peptidase complexes, and do they serve distinct subsets of the secretory proteome or distinct tissues?
Q: How does the SPC's local thinning of the ER membrane mechanistically couple signal-peptide h-region length to catalytic engagement by SEC11C?
Experiment: Reconstitute purified SPC-C (SEC11C + SPCS1/2/3) and assay cleavage of a panel of signal peptides varying in h-region length to quantify SEC11C's length-dependent specificity, comparing wild-type Ser-68 to the catalytic-dead S68A mutant.
Experiment: Acute degron depletion of SEC11C versus SEC11A followed by N-terminomics (e.g. TAILS) to define the paralog-specific repertoire of cleaved signal-peptide substrates in human cells.
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