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PROSITE documentation PDOC00472
Matrixins cysteine switch


Description

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].
Last update:

November 1997 / Pattern and text revised.

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Technical section

PROSITE method (with tools and information) covered by this documentation:

CYSTEINE_SWITCH, PS00546; Matrixins cysteine switch  (PATTERN)


References

1AuthorsWoessner J.F. Jr.
TitleMatrix metalloproteinases and their inhibitors in connective tissue remodeling.
SourceFASEB J. 5:2145-2154(1991).
PubMed ID1850705

2AuthorsSanchez-Lopez R. Nicholson R. Gesnel M.C. Matrisian L.M. Breathnach R.
SourceJ. Biol. Chem. 263:11892-11899(1988).

3AuthorsPark A.J. Matrisian L.M. Kells A.F. Pearson R. Yuan Z.Y. Navre M.
TitleMutational analysis of the transin (rat stromelysin) autoinhibitor region demonstrates a role for residues surrounding the 'cysteine switch'.
SourceJ. Biol. Chem. 266:1584-1590(1991).
PubMed ID1988438

4AuthorsLepage T. Gache C.
TitleEarly expression of a collagenase-like hatching enzyme gene in the sea urchin embryo.
SourceEMBO J. 9:3003-3012(1990).
PubMed ID2167841

5AuthorsKinoshita T. Fukuzawa H. Shimada T. Saito T. Matsuda Y.
TitlePrimary structure and expression of a gamete lytic enzyme in Chlamydomonas reinhardtii: similarity of functional domains to matrix metalloproteases.
SourceProc. Natl. Acad. Sci. U.S.A. 89:4693-4697(1992).
PubMed ID1584806



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