{PDOC00472}
{PS00546; CYSTEINE_SWITCH}
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* Matrixins cysteine switch *
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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].

-Consensus pattern: P-R-C-[GN]-x-P-[DR]-[LIVSAPKQ]
                    [C chelates the zinc ion]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for cat MMP-7 and mouse MMP-11.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: November 1997 / Pattern and text revised.

[ 1] Woessner J.F. Jr.
     "Matrix metalloproteinases and their inhibitors in connective tissue
     remodeling."
     FASEB J. 5:2145-2154(1991).
     PubMed=1850705
[ 2] Sanchez-Lopez R., Nicholson R., Gesnel M.C., Matrisian L.M.,
     Breathnach R.
     J. Biol. Chem. 263:11892-11899(1988).
[ 3] Park A.J., Matrisian L.M., Kells A.F., Pearson R., Yuan Z.Y., Navre M.
     "Mutational analysis of the transin (rat stromelysin) autoinhibitor
     region demonstrates a role for residues surrounding the 'cysteine
     switch'."
     J. Biol. Chem. 266:1584-1590(1991).
     PubMed=1988438
[ 4] Lepage T., Gache C.
     "Early expression of a collagenase-like hatching enzyme gene in the
     sea urchin embryo."
     EMBO J. 9:3003-3012(1990).
     PubMed=2167841
[ 5] Kinoshita T., Fukuzawa H., Shimada T., Saito T., Matsuda Y.
     "Primary structure and expression of a gamete lytic enzyme in
     Chlamydomonas reinhardtii: similarity of functional domains to matrix
     metalloproteases."
     Proc. Natl. Acad. Sci. U.S.A. 89:4693-4697(1992).
     PubMed=1584806

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