PROSITE documentation PDOC00259
Cysteine proteases inhibitors signature


Inhibitors of cysteine proteases [1,2,3], which are found in the tissues and body fluids of animals, in the larva of the worm Onchocerca volvulus [4], as well as in plants, can be grouped into three distinct but related families:

  • Type 1 cystatins (or stefins), molecules of about 100 amino acid residues with neither disulfide bonds nor carbohydrate groups.
  • Type 2 cystatins, molecules of about 115 amino acid residues which contain one or two disulfide loops near their C-terminus.
  • Kininogens, which are multifunctional plasma glycoproteins. They are the precursor of the active peptide bradykinin and play a role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII. They are also inhibitors of cysteine proteases. Structurally, kininogens are made of three contiguous type-2 cystatin domains, followed by an additional domain (of variable length) which contains the sequence of bradykinin. The first of the three cystatin domains seems to have lost its inhibitory activity.

In all these inhibitors, there is a conserved region of five residues which has been proposed to be important for the binding to the cysteine proteases. Our pattern starts one residue before this conserved region.


This pattern is always twice in kininogens.


Members of the fetuin family (see <PDOC00966>) contain two copies of a cystatin-like domain.

Expert(s) to contact by email:

Turk B.

Last update:

April 2006 / Pattern revised.


Technical section

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

CYSTATIN, PS00287; Cysteine proteases inhibitors signature  (PATTERN)


1AuthorsBarrett A.J.
SourceTrends Biochem. Sci. 12:193-196(1987).

2AuthorsRawlings N.D. Barrett A.J.
TitleEvolution of proteins of the cystatin superfamily.
SourceJ. Mol. Evol. 30:60-71(1990).
PubMed ID2107324

3AuthorsTurk V. Bode W.
TitleThe cystatins: protein inhibitors of cysteine proteinases.
SourceFEBS Lett. 285:213-219(1991).
PubMed ID1855589

4AuthorsLustigman S. Brotman B. Huima T. Prince A.M.
TitleCharacterization of an Onchocerca volvulus cDNA clone encoding a genus specific antigen present in infective larvae and adult worms.
SourceMol. Biochem. Parasitol. 45:65-75(1991).
PubMed ID2052041

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