*****************************************************
* Kazal serine protease inhibitors family signature *
*****************************************************

The Kazal inhibitor family [1]  is  one of  the  numerous  families of  serine
proteinase  inhibitors.    The basic structure  of such a type of inhibitor is
shown in the following schematic representation:

                       +------------------+
                       |                  |
                       *******************|***
        xxxxxxxxCxxxxxxCx#xxxxxCxxxxxxxxxxCxxCxxxxxxxxxxxxxxxxxC
                |              |             |                 |
                |              +-------------|-----------------+
                +----------------------------+

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

The proteins known to belong to this family are:

 - Pancreatic secretory trypsin inhibitor (PSTI), whose physiological function
   is to prevent the trypsin-catalyzed premature activation of zymogens within
   the pancreas.
 - Mammalian seminal acrosin inhibitors.
 - Canidae and felidae submandibular gland double-headed protease  inhibitors,
   which contain  two  Kazal-type  domains, the first one inhibits trypsin and
   the second one elastase.
 - Avian ovomucoids, which consist of three Kazal-type domains.
 - Chicken ovoinhibitor [2], which consists of seven Kazal-type domains.
 - Bdellin B-3 [3], a leech trypsin inhibitor.
 - A mice prostatic  secretory  glycoprotein [4],  induced  by  androgens, and
   which exhibits anti-trypsin activity.
 - An eel peptide, which is probably a pancreatic  serine proteinase inhibitor
   [5].
 - An elastase inhibitor from a sea anemone [6].
 - Pig  intestinal  peptide  PEC-60 [7]. This protein, while highly similar to
   other members  of  the  Kazal  family,  does  not seem to act as a protease
   inhibitor. Its  exact biological function is not yet established, but it is
   known to  inhibit  the  glucose-induced  insulin  secretion  from  perfused
   pancreas and to play a role in the immune system.

The pattern  we  developed  to  pick  up  Kazal-type inhibitors spans a region
beginning with the second cysteine and ending with the fifth one.

-Consensus pattern: C-x(7)-C-x(6)-Y-x(3)-C-x(2,3)-C
                    [The four C's are involved in disulfide bonds]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for the sea anemone inhibitor which has six residues between the last two Cys
 of the pattern.
-Other sequence(s) detected in SWISS-PROT: yeast hypothetical protein YKL034w.

-Note: there are two residues between the last two cysteines in the pattern in
 all sequences except for that of bdellin B-3.
-Note: this pattern  will fail  to detect the first of the three Kazal domains
 in some of the ovomucoids.

-Last update: June 1994 / Text revised.

[ 1] Laskowski M., Kato I.
     Annu. Rev. Biochem. 49:593-626(1980).
[ 2] Scott M.J., Huckaby C.S., Kato I., Kohr W.J., Laskowski M. Jr.,
     Tsai M.-J., O'Malley B.W.
     J. Biol. Chem. 262:5899-5907(1987).
[ 3] Fink E., Rehm H., Gippner C., Bode W., Eulitz M., Machleidt W., Fritz H.
     Biol. Chem. Hoppe-Seyler 367:1235-1242(1986).
[ 4] Mills J.S., Needham M., Parker M.G.
     EMBO J. 6:3711-3717(1987).
[ 5] Conlon J.M., Thim L.
     Eur. J. Biochem. 174:149-153(1988).
[ 6] Tschesche H., Kolkenbrock H., Bode W.
     Biol. Chem. Hoppe-Seyler 368:1297-1304(1987).
[ 7] Liepinsh E., Berndt K.D., Sillard R., Mutt V., Otting G.
     J. Mol. Biol. 239:137-153(1994).