Domain

Peptidase M10A, catalytic domain (IPR033739)

Short name: M10A_MMP

Domain relationships

Description

This entry represents the matrix metalloproteinase (MMP) sub-family M10A catalytic domain. MMPs are responsible for a great deal of pericellular proteolysis of extracellular matrix and cell surface molecules, playing crucial roles in morphogenesis, cell fate specification, cell migration, tissue repair, tumorigenesis, gain or loss of tissue-specific functions, and apoptosis [PMID: 16720377, PMID: 12784993, PMID: 11686860, PMID: 11485970, PMID: 11433375]. In many instances, they are anchored to cell membranes via trans-membrane domains, and their activity is controlled via TIMPs (tissue inhibitors of metalloproteinases) [PMID: 10356396, PMID: 9737711, PMID: 9724659, PMID: 8939664].

Sequences having this domain are extracellular metalloproteases, such as collagenase and stromelysin, which degrade the extracellular matrix, are known as matrixins. They are zinc-dependent, calcium-activated proteases synthesised as inactive precursors(zymogens), which are proteolytically cleaved to yield the active enzyme [PMID: 2551898, PMID: 2167841].

All MMPs possess an N-terminal domain and a zinc-binding catalytic domain. The N-terminal domain peptide, cleaved during the activation step, includes a conserved PRCGVPDV octapeptide, known as the cysteine switch, whose Cys residue chelates the active site zinc atom, rendering the enzyme inactive [PMID: 2841336, PMID: 1988438]. The catalytic domain contains a zinc ion, which is responsible for the peptide hydrolysis reaction. Another zinc ion and one to three calcium ions are present in the catalytic domain with a structural role [PMID: 9785958]. All but two of the human MMPs (MMP-7 and MMP-26) also have a C-terminal hemopexin-like domain, and two MMPs (MMP-2 and MMP-9) contain fibronectin insertions into their catalytic domains [PMID: 15095982].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0008237 metallopeptidase 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.
CDD