Bacterial type I secretion

A species-neutral module for one-step export of a cytoplasmic protein across both membranes of a diderm bacterium through a tripartite type I secretion conduit. An inner-membrane ABC transporter recognizes an uncleaved secretion signal in its substrate and hydrolyzes ATP; a periplasmic membrane-fusion adaptor anchored in the inner membrane bridges to, and opens, an oligomeric outer-membrane exit duct. Because the three components form a continuous channel, the substrate never appears as a folded periplasmic intermediate. Substrate maturation before export, folding and cofactor acquisition after release, Sec- and Tat-dependent routes, and small-molecule efflux through the same family of outer-membrane ducts are outside this module.

## Boundary The module begins when an ABC transporter engages a cytoplasmic substrate bearing an uncleaved type I secretion signal and ends when that substrate leaves the outer-membrane duct. Only the three conserved machinery parts are admitted. Cargo proteins are deliberately excluded, in line with the sibling type II and type VI modules, because the same conduit serves unrelated substrate classes; the cargo-dependent features that do belong to the machinery are captured as an ABC-transporter subclass variant. Two things commonly conflated with this module are excluded on structural grounds. First, outer-membrane factors of the TolC family are shared with resistance-nodulation-division and major-facilitator efflux pumps, so the presence of a TolC-like duct is not evidence of protein secretion. Second, substrate acylation or other maturation performed by dedicated accessory enzymes acts on the substrate before engagement and is not part of the transport step. Ontology and curation gaps are recorded in these notes rather than as `knowledge_gaps`, which CLAUDE.md reserves for biological unknowns that only new experiments could close. None of the items below is a biological unknown: a term request or a curator would resolve each one. ## Ontology gap: the duct's molecular function cannot distinguish its two uses The molecular function asserted for the outer-membrane duct cannot distinguish protein cargo from small-molecule cargo. The efflux transporter term is what every outer-membrane factor carries, and its definition does cover a protein substrate, but using one term for both uses makes type I protein secretion indistinguishable from drug efflux to anything reading the annotations. **Asserted instead.** Use the family-wide efflux transporter term and keep the two uses separate in prose and in the module's part structure, rather than asserting a protein-transporter term that no outer-membrane factor carries. This gap is now a formal term request in `genes/ECOLI/tolC/tolC-ai-review.yaml` under `proposed_new_terms`. ## Ontology gap: no term for the membrane-fusion protein role No GO molecular-function term expresses the membrane-fusion protein role, so the periplasmic adaptor is annotated with the generic structural molecule activity. This loses the specific claim that the protein couples two membrane components and gates a shared channel. **Asserted instead.** Keep structural molecule activity as a placeholder on the adaptor rather than substituting a transporter term it does not deserve, and record the adaptor role in prose until a suitable term exists.