Peptidase M48, protease HtpX, putative (IPR022919)

Short name: Pept_M48_protease_HtpX

Overlapping homologous superfamilies


Family relationships



Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation which is usually zinc, but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophillic role. Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site [PMID: 7674922]. The HEXXH motif is relatively common, but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases [PMID: 7674922].

This group of metallopeptidases belong to MEROPS peptidase family M48 (subfamily M48B). The members of this set of proteins are mostly described as probable protease htpX homologue (EC:3.4.24).

HtpX is a zinc-dependent endoprotease member of the membrane-localized proteolytic system in E. coli, which participates in the proteolytic quality control of membrane proteins in conjunction with FtsH, a membrane-bound and ATP-dependent protease. Biochemical characterisation revealed that HtpX undergoes self-degradation upon cell disruption or membrane solubilisation. It can also degraded casein and cleaves solubilised membrane proteins, for example, SecY [PMID: 16076848]. Expression of HtpX in the plasma membrane is under the control of CpxR, with the metalloproteinase active site of HtpX located on the cytosolic side of the membrane. This suggests a potential role for HtpX in the response to mis-folded proteins [PMID: 12081643].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0004222 metalloendopeptidase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

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