PROSITE documentation PDOC00260
Tissue inhibitors of metalloproteinases signature

Description

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.

Last update:

May 2004 / Text revised.

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Technical section

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

TIMP, PS00288; Tissue inhibitors of metalloproteinases signature (PATTERN)

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 in UniProtKB/Swiss-Prot known to belong to this class: 39
- detected by PS00288: 33 (true positives)
- undetected by PS00288: 6 (4 false negatives and 2 'partials')
Other sequence(s) in UniProtKB/Swiss-Prot detected by PS00288:
NONE.
Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
Clustal format, color, condensed view / Clustal format, color / Clustal format, plain text / Fasta format
Retrieve the sequence logo from the alignment
Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00288
Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00288
Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS00288
View ligand binding statistics of PS00288
Matching PDB structures: 1BQQ 1BR9 1BUV 1D2B ... [ALL]

References

1	Authors	Stetler-Stevenson W.G. Krutzsch H.C. Liotta L.A.
1	Source	J. Biol. Chem. 264:17374-17378(1989).

2	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

3	Authors	Pavloff N. Staskus P.W. Kishnani N.S. Hawkes S.P.
	Title	A new inhibitor of metalloproteinases from chicken: ChIMP-3. A third member of the TIMP family.
	Source	J. Biol. Chem. 267:17321-17326(1992).
	PubMed ID	1512267

4	Authors	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.
	Title	Disulphide bond assignment in human tissue inhibitor of metalloproteinases (TIMP).
	Source	Biochem. J. 268:267-274(1990).
	PubMed ID	2163605

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PROSITE documentation PDOC00260Tissue inhibitors of metalloproteinases signature

PROSITE documentation PDOC00260
Tissue inhibitors of metalloproteinases signature