{"uniprot":"P0C7V7","gene":"SEC11B","name":"Putative signal peptidase complex catalytic subunit SEC11B","organism":"Homo sapiens (Human)","status":"dark","length":166,"sequence":"MNKWRLYYQVLNFGMIVSSALMIWKGLMVITGSESPIVLLSGSMEPAFHRGYLLFLTNRVEDPIRVGEIAVLRIEGRKIPIVHRVLKIHEKQNGHIKFLTKGDNNAVDDRGLYKQDQHWLEKKDVVGRARGFVPYIGIGTSLMNDYPKHKYEVLFLLGLFVLVHRE","function_summary":"A membrane-embedded serine endopeptidase in human cells that resides in the endoplasmic reticulum and executes essential maturation cleavages for secretory and membrane proteins. It removes signal peptides and performs specific processing reactions that generate the mature form of the ER chaperone BiP and trim the precursor of the inflammatory caspase-1 zymogen. Anchored by multiple transmembrane segments and operating within ER peptidase assemblies, it couples substrate recognition and hydrolysis to the ribosome–translocon pathway to ensure efficient signal peptide processing and protein biogenesis.","plain_language":"SEC11B has barely been studied. The model's best guess: A membrane-embedded serine endopeptidase in human cells that resides in the endoplasmic reticulum and executes essential maturation cleavages for secretory and membrane proteins. It removes signal peptides and performs specific processing reactions that generate the mature form of the ER chaperone BiP and trim the precursor of the inflammatory caspase-1 zymogen.","uniprot_summary":"Endopeptidase which plays a crucial role in the processing of secretory and membrane precursor proteins. Involved in the maturation of the HSPA5/BiP ER chaperone and the cleavage of the caspase-1 precursor protein.","go_terms":{"molecular_function":[{"id":"GO:0004252","label":"serine-type endopeptidase activity"},{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0006465","label":"signal peptide processing"}],"cellular_component":[{"id":"GO:0005789","label":"endoplasmic reticulum membrane"},{"id":"GO:1905368","label":"peptidase complex"}]},"interpro":[{"id":"IPR036286","name":"LexA/Signal peptidase-like superfamily","type":"homologous_superfamily","start":37,"end":108},{"id":"IPR019533","name":"Peptidase S26","type":"domain","start":35,"end":129},{"id":"IPR001733","name":"Peptidase S26B","type":"family","start":5,"end":166},{"id":"IPR019758","name":"Peptidase S26A, signal peptidase I, conserved site","type":"conserved_site","start":98,"end":111}],"reasoning":"I begin with the InterPro architecture. The sequence is dominated by peptidase S26 signatures: IPR001733 (Peptidase S26B family, residues 5–166) frames the full-length enzyme and establishes membership in the ER-resident signal peptidase II lineage. Nested within this, IPR019533 (Peptidase S26 domain, residues 35–129) defines the catalytic core typical of signal peptidases that cleave signal peptides from nascent secretory and membrane proteins. The core is further contextualized by IPR036286 (LexA/Signal peptidase-like superfamily, residues 37–108), indicating a conserved serine-protease-like fold that stabilizes the active-site geometry. Critically, IPR019758 (Peptidase S26A, signal peptidase I, conserved site, residues 98–111) marks a conserved catalytic region that, in this enzyme class, supports serine-type endopeptidase chemistry. The ordered layout—an N-terminal S26B family envelope, a central S26 catalytic domain, and a conserved active-site motif—causally dictates a membrane-associated serine endopeptidase that executes precise endoproteolytic cleavage events.\n\nThis domain architecture drives the molecular function. The S26 fold and conserved site together produce GO:0004252 serine-type endopeptidase activity, with the membrane-anchored catalytic module positioned to cleave signal peptides and specific post-translational junctions. The presence of broad interaction surfaces and the need to assemble with ribosome–translocon machinery necessitate GO:0005515 protein binding, enabling assembly into larger processing complexes.\n\nFrom function to process, the catalytic profile of S26B family members is specialized for signal peptide removal and defined maturation cleavages. This directly instantiates GO:0006465 signal peptide processing: the enzyme’s architecture and membrane context cause efficient hydrolysis of signal sequences as polypeptides enter the ER lumen. The same catalytic logic explains its role in generating the mature form of the ER chaperone BiP and in trimming the propeptide of the caspase-1 precursor—both consequences of the enzyme’s capacity to cleave within signal/stromal regions.\n\nCellular location follows from both topology and complex membership. The S26B family is membrane-associated, and the catalytic core is peripherally disposed relative to multiple transmembrane segments, matching a multi-pass ER membrane protein. This places the enzyme in GO:0005789 endoplasmic reticulum membrane and, functionally, within GO:1905368 peptidase complex—ER-resident proteolytic assemblies that coordinate with the signal peptidase I machinery and the ribosome–translocon apparatus.\n\nMechanistically, the enzyme operates as a membrane-tethered serine endopeptidase that recognizes and cleaves signal peptides and defined internal junctions during secretory pathway maturation. It likely binds and positions substrates emerging from the Sec61 channel, using transient protein–protein interactions to couple cleavage with translocation and chaperone handoff. I therefore hypothesize interactions with the Sec61 translocon and ribosome-associated factors, with signal peptidase I and BiP as immediate partners; these assemblies would channel substrates from the ER entry site to downstream folding and trafficking pathways.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-P0C7V7.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/P0C7V7"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/P0C7V7/entry","atlas":"/p/P0C7V7"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}