PROSITE documentation PDOC00252

Pancreatic trypsin inhibitor (Kunitz) family signature and profile

The pancreatic trypsin inhibitor (Kunitz) family [1,2,3] 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:

            +-----------------------+
            |  +--------+           |
            |  |      **|*******    |
          xxCxxC#xxxCxxxCxxxxxxCxxxxCxx
                    |          |
                    +----------+

            <------50 residues------>

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

In addition to the prototype sequence for this type of inhibitor - the bovine pancreatic trypsin inhibitor (BPTI) (also known as basic protease inhibitor (BPI)) - this family also includes many other members which are listed below (references are only provided for recently determined sequences):

• Mammalian inter-α-trypsin inhibitors (ITI). ITI's contain two inhibitory domains.
• Tissue factor pathway inhibitor precursor (TFPI) (previously known as lipoprotein-associated coagulation inhibitor (LACI)), which inhibits factor X (Xa) directly and, in a Xa-dependent way, inhibits VIIa / Tissue factor activity. TFPI contains three inhibitory domains.
• TFPI-2 [4] (also known as placental protein 5), a protein that contains two inhibitory domains.
• Bovine colostrum, serum and spleen trypsin inhibitors.
• Trypstatin, a rat mast cell inhibitor of trypsin.
• A number of venom basic protease inhibitors (including dendrotoxins) from snakes.
• Isoinhibitor K from garden snail.
• Protease inhibitor from the hemocytes of horseshoe crab.
• Basic protease inhibitor from red sea turtle.
• Sea anemone protease inhibitor 5 II.
• Chymotrypsin inhibitors SCI-I,- II, and -III from silk moth.
• Trypsin inhibitors A and B from the hemolymph of the tobacco hornworm.
• Trypsin inhibitor from the hemolymph of the flesh fly [5].
• Acrosin inhibitor from the male accessory gland of Drosophila.
• A domain found in one of the alternatively spliced forms of Alzheimer's amyloid β-protein (APP) (also known as protease nexin II) as well as the closely related amyloid-like protein 2 (or APPH).
• A domain at the C-terminal extremity of the α(3) chain of type VI collagen.
• A domain at the C-terminal extremity of the α(1) chain of type VII collagen.

We developed a pattern which will only pick up sequences belonging to this family of inhibitors. It spans a region starting after the third cysteine and ending with the fifth one. We also developed a profile that spans the complete domain.