PROSITE documentation PDOC00472Matrixins cysteine switch
Mammalian extracellular matrix metalloproteinases (EC 3.4.24.-), also known as matrixins [1] (see <PDOC00129>), are zinc-dependent enzymes. They are secreted by cells in an inactive form (zymogen) that differs from the mature enzyme by the presence of an N-terminal propeptide. A highly conserved octapeptide is found two residues downstream of the C-terminal end of the propeptide. This region has been shown to be involved in autoinhibition of matrixins [2,3]; a cysteine within the octapeptide chelates the active site zinc ion, thus inhibiting the enzyme. This region has been called the 'cysteine switch' or 'autoinhibitor region'.
A cysteine switch has been found in the following zinc proteases:
- MMP-1 (EC 3.4.24.7) (interstitial collagenase).
- MMP-2 (EC 3.4.24.24) (72 Kd gelatinase).
- MMP-3 (EC 3.4.24.17) (stromelysin-1).
- MMP-7 (EC 3.4.24.23) (matrilysin).
- MMP-8 (EC 3.4.24.34) (neutrophil collagenase).
- MMP-9 (EC 3.4.24.35) (92 Kd gelatinase).
- MMP-10 (EC 3.4.24.22) (stromelysin-2).
- MMP-11 (EC 3.4.24.-) (stromelysin-3).
- MMP-12 (EC 3.4.24.65) (macrophage metalloelastase).
- MMP-13 (EC 3.4.24.-) (collagenase 3).
- MMP-14 (EC 3.4.24.-) (membrane-type matrix metalliproteinase 1).
- MMP-15 (EC 3.4.24.-) (membrane-type matrix metalliproteinase 2).
- MMP-16 (EC 3.4.24.-) (membrane-type matrix metalliproteinase 3).
- Sea urchin hatching enzyme (EC 3.4.24.12) (envelysin) [4].
- Chlamydomonas reinhardtii gamete lytic enzyme (GLE) [5].
November 1997 / Pattern and text revised.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Woessner J.F. Jr. |
| Title | Matrix metalloproteinases and their inhibitors in connective tissue remodeling. | |
| Source | FASEB J. 5:2145-2154(1991). | |
| PubMed ID | 1850705 |
| 2 | Authors | Sanchez-Lopez R. Nicholson R. Gesnel M.C. Matrisian L.M. Breathnach R. |
| Source | J. Biol. Chem. 263:11892-11899(1988). |
| 3 | Authors | Park A.J. Matrisian L.M. Kells A.F. Pearson R. Yuan Z.Y. Navre M. |
| Title | Mutational analysis of the transin (rat stromelysin) autoinhibitor region demonstrates a role for residues surrounding the 'cysteine switch'. | |
| Source | J. Biol. Chem. 266:1584-1590(1991). | |
| PubMed ID | 1988438 |
| 4 | Authors | Lepage T. Gache C. |
| Title | Early expression of a collagenase-like hatching enzyme gene in the sea urchin embryo. | |
| Source | EMBO J. 9:3003-3012(1990). | |
| PubMed ID | 2167841 |
| 5 | Authors | Kinoshita T. Fukuzawa H. Shimada T. Saito T. Matsuda Y. |
| Title | Primary structure and expression of a gamete lytic enzyme in Chlamydomonas reinhardtii: similarity of functional domains to matrix metalloproteases. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 89:4693-4697(1992). | |
| PubMed ID | 1584806 |
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