Rhomboid protease GlpG (IPR023662)

Short name: Rhomboid_protease_GlpG

Overlapping homologous superfamilies

Family relationships


This entry consists of rhomboid protease GlpG and its homologues without the conserved peptidase active sites.

GlpG in E. coli is a rhomboid family intramembrane serine protease that has been extensively characterised as a proxy for rhomboid family proteases in animals. It efficiently cleaves eukaryote-derived model substrates. This multiple membrane-spanning protein excludes inappropriate substrates from access to its cleavage site, and shows activity against truncated versions, but not full-length versions, of the E. coli multidrug transporter MdfA. This finding suggests a housekeeping function in removing faulty proteins. In contrast, several eukaryotic rhomboid family proteases release peptide hormones for signaling functions, and the Shewanella and Vibrio protein rhombosortase appears to be part of a protein-sorting system, cleaving a C-terminal anchoring helix domain [PMID: 19919105].

GlpG belongs to the MEROPS peptidase family S54 (Rhomboid, clan ST).

The tertiary structure from the GlpG protein from E. coli has been determined [PMID: 21256137]. The GlpG protein six transmembrane domains (other members of the family are predicted to have seven), with the N- and C-terminal ends anchored in the cytoplasm. One transmembrane domain is shorter than the rest, creating an internal, aqueous cavity just below the membrane surface and it is here were proteolysis occurs. There is also a membrane-embedded loop between the first and second transmembrane domains which is postulated to act as a gate controlling substrate access to the active site. No other family of serine peptidases is known to have active site residues within transmembrane domains (although transmembrane active sites are known for aspartic peptidase and metallopeptidases), and the GlpG protein has the type structure for clan ST.

GO terms

Biological Process

GO:0006508 proteolysis

Molecular Function

GO:0004252 serine-type endopeptidase activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

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