{PDOC00260}
{PS00288; TIMP}
{BEGIN}
*****************************************************
* Tissue inhibitors of metalloproteinases signature *
*****************************************************

Tissue inhibitors of metalloproteinases (TIMP)  are a family of proteins [1,2,
3] that can form complexes with extracellular matrix metalloproteinases  (such
as collagenases)  and irreversibly  inactivate them.   TIMP's  are proteins of
about 200 amino acid residues, 12 of which are cysteines involved in disulfide
bonds [4].    The  basic structure of such a type of inhibitor is shown in the
following schematic representation:

          +-----------------------------+         +--------------+
        **|**                           |         |              |
        CxCxCxxxxxxxxxxxxxxxxxCxxxxxxxxxCxxxxxxxCxCxCxCxCxxxxxCxxCxxx
        |   |                 |                 |   | | |     |
        |   +-----------------|-----------------+   +-+ +-----+
        +---------------------+

'C': conserved cysteine involved in a disulfide bond.
'*': position of the pattern.

As a signature pattern for TIMP's, we chose  the N-terminal extremity of these
proteins, which includes three conserved cysteines.

-Consensus pattern: C-x-C-x-P-x-H-P-Q-x(2)-[FIV]-C
                    [The 3 C's are involved in disulfide bonds]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: May 2004 / Text revised.

[ 1] Stetler-Stevenson W.G., Krutzsch H.C., Liotta L.A.
     J. Biol. Chem. 264:17374-17378(1989).
[ 2] Woessner J.F. Jr.
     "Matrix metalloproteinases and their inhibitors in connective tissue
     remodeling."
     FASEB J. 5:2145-2154(1991).
     PubMed=1850705
[ 3] Pavloff N., Staskus P.W., Kishnani N.S., Hawkes S.P.
     "A new inhibitor of metalloproteinases from chicken: ChIMP-3. A third
     member of the TIMP family."
     J. Biol. Chem. 267:17321-17326(1992).
     PubMed=1512267
[ 4] Williamson R.A., Marston F.A.O., Angal S., Koklitis P., Panico M.,
     Morris H.R., Carne A.F., Smith B.J., Harris T.J.R., Freedman R.B.
     "Disulphide bond assignment in human tissue inhibitor of
     metalloproteinases (TIMP)."
     Biochem. J. 268:267-274(1990).
     PubMed=2163605

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{END}