Gene Ontology annotation through association of InterPro records with GO terms
Gene Ontology annotation based on Enzyme Commission mapping
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Architecture of the human interactome defines protein communities and disease networks.
A reference map of the human binary protein interactome.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Structure of the human signal peptidase complex reveals the determinants for signal peptide cleavage.
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The human signal peptidase complex exists in two functional paralogs with distinct proteolytic subunits (SEC11A and SEC11C); the active site is formed by a catalytic triad abutting the ER membrane, where a transmembrane window thins the bilayer to generate specificity for signal peptides based on the length of their hydrophobic segments.
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SEC11C is the catalytic subunit of SPC-C (with accessory subunits SPCS1, SPCS2, SPCS3); Ser-68 is the catalytic nucleophile and the C-terminal short (CTS) helix is essential for catalytic activity.
Multimodal cell maps as a foundation for structural and functional genomics.
The human signal peptidase complex acts as a quality control enzyme for membrane proteins.
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Beyond canonical N-terminal signal peptide removal, the human SPC (catalytic core SEC11A/C with SPCS3) cleaves misfolded or unassembled membrane proteins at otherwise hidden "cryptic" cleavage sites abundant in the human membrane proteome; this post-translocational cleavage synergizes with ER-associated degradation (ERAD) to maintain membrane protein homeostasis. SEC11A knockdown did not abolish a noncanonical cleavage event, consistent with compensation by SEC11C.
The Natural Product Cavinafungin Selectively Interferes with Zika and Dengue Virus Replication by Inhibition of the Host Signal Peptidase.
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Genome-wide CRISPR/Cas9 chemogenomic profiling in human cells and resistance selection in yeast identified the catalytic subunit of the signal peptidase (SEC11; human SEC11A and SEC11C) as the conserved efficacy target of cavinafungin, which rapidly blocks signal-sequence cleavage of host and viral proteins.
Spc2 modulates substrate- and cleavage site-selection in the yeast signal peptidase complex.
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In yeast, the noncatalytic SPC subunit Spc2 (ortholog of human SPCS2) modulates SPC discrimination between substrates and cleavage-site selection; molecular dynamics indicates Spc2 contributes to the membrane thinning at the center of the SPC that underlies substrate recognition, informing the conserved mechanism by which accessory subunits support the SEC11 catalytic subunit.
Competitive Inhibition of the Endoplasmic Reticulum Signal Peptidase by Non-cleavable Mutant Preprotein Cargos.
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A non-cleavable variant preprotein (proline introduced immediately after the signal-peptide cleavage site) is translocated across the ER membrane where it binds the catalytic SPase subunit and inhibits signal peptidase activity in a dose-dependent manner; this work directly implicates SEC11A as the catalytic subunit and establishes eukaryotic SPase as a tractable antiviral target, informing the shared catalytic mechanism of the SEC11A/SEC11C signal peptidase paralogs.
Cleavage of the signal peptide of Preproghrelin
Signalase cleaves prM-E-NS1-NS2A
Signalase cleaves prepro-NS4B
UniProt entry Q9BY50 (SC11C_HUMAN), Signal peptidase complex catalytic subunit SEC11C
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SEC11C is the catalytic subunit of the signal peptidase complex paralog C (SPC-C) with SPCS1/2/3; cleaves N-terminal signal peptides (EC 3.4.21.89) from nascent proteins translocated into the ER lumen; single-pass type II ER membrane protein; peptidase S26B family; catalytic triad (Ser-68), selectivity for h-regions shorter than 18-20 residues via membrane thinning.