Domain

Peptidase M12B, GON-ADAMTSs (IPR012314)

Short name: Pept_M12B_GON-ADAMTSs

Domain relationships

None.

Description

Over 50 metallopeptidase families have been identified to date. In these enzymes, a divalent cation, 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 and 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].

The ADAMTSs (a disintegrin and metalloproteinase domain with thrombospondin type-1 modules) are a family of zinc dependent metalloproteinases that play important roles in a variety of normal and pathological conditions. These enzymes show a complex domain organisation including signal sequence, propeptide, metalloproteinase domain (see PDOC50215), disintegrin-like domain (see PDOC00351), central TS-1 motif (see PDOC50092), cysteine-rich region, and a variable number of TS-like repeats at the C-terminal region. The GON domain is an approximately 200-residue module, whose presence is the hallmark of a subfamily of structurally and evolutionarily related ADAMTSs, called GON- ADAMTSs. The GON domain is characterised by the presence of several conserved cysteine residues and is likely to be globular [PMID: 12562771], [PMID: 12514189].

Some proteins known to contain a GON domain are listed below:

  • Mammalian ADAMTS-9
  • Mammalian ADAMTS-20
  • Caenorhabditis elegans gon-1, a protease required for gonadal morphogenesis

Proteins containing the GON domain belong to MEROPS peptidase subfamily M12B (adamalysin, clan MA).

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0004222 metalloendopeptidase activity
GO:0008270 zinc ion binding

Cellular Component

No terms assigned in this category.

Contributing signatures

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