Peptidase S1C (IPR001940)

Short name: Peptidase_S1C

Overlapping homologous superfamilies

Family relationships


This group of serine peptidases and non-peptidase homologues belong to the MEROPS peptidase family S1, subfamily S1C (protease Do subfamily, clan PS(S)). A type example is the protease Do from Escherichia coli.

Other members of this group include the E. coli htrA gene product (HrtA or DegP protein), which is essential for bacterial survival at temperatures above 42 degrees [PMID: 3057437, PMID: 2180903] and for digesting misfolded protein in the periplasm. Mature DegP from E. coli has 448 residues, of which His105, Asp135, and Ser210 form the catalytic triad [PMID: 3057437]. The protein has an N-terminal sequence typical of a leader peptide. Structural analysis indicates that bacterial HtrA is a serine protease belonging to the family of age-forming proteases and that only unfolded polypeptides can be threaded in extended conformation into the cage to access the proteolytic sites. Disulphide bonds of partially unfolded substrates impede protein breakdown and represent a conformational constraint for entering the inner cavity. This preference for unfolded polypeptides might be also a reason for the ATP-independent mode of action and for the increased proteolytic activity at higher temperatures [PMID: 12408815].

The HtrA family shares a modular architecture composed of an N-terminal segment believed to have regulatory functions, a conserved trypsin-like protease domain, and one or two PDZ domains which mediate specific protein-protein interactions and bind preferentially to the C-terminal three to four residues of the target protein. HtrA belongs to the trypsin clan SA. SA proteases have a two-domain structure with each domain forming a six-stranded barrel. The active site cleft is located at the interface of the two perpendicularly arranged barrel domains. The active site is constructed by several loops located at the C-terminal side of both barrel domains. The functional unit of HtrA appears to be a trimer, which is stabilised exclusively by residues of the protease domains. The basic trimer has a funnel-like shape with the protease domains located at its top and the PDZ domains protruding to the outside. Once substrates have been bound, they have to be delivered into the interior of the funnel and the proteolytic sites. In contrast to other protease-chaperone systems, ATP does not drive binding and release of substrates [PMID: 12408815].

The degQ and degS genes of E. coli encode proteins of 455 and 355 residues that are homologues of the DegP protease [PMID: 8576051]. Purified DegQ protein has the properties of a serine endopeptidase, and is processed by the removal of a 27-residue N-terminal signal sequence. Deletion studies suggest that DegQ, like DegP, functions as a periplasmic protease in vivo [PMID: 8576051].

An example of a non-peptidase homologue in this entry is the anti-sigma-I factor RsgI9 from Clostridium thermocellum, which has the catalytic serine replaced with threonine.

GO terms

Biological Process

GO:0006508 proteolysis

Molecular Function

GO:0004252 serine-type endopeptidase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.