{PDOC00252}
{PS00280; BPTI_KUNITZ_1}
{PS50279; BPTI_KUNITZ_2}
{BEGIN}
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* 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-alpha-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 beta-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  alpha(3)  chain  of type VI
   collagen.
 - A domain at the C-terminal  extremity  of  the  alpha(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.

-Consensus pattern: F-x(2)-{I}-G-C-x(6)-[FY]-x(5)-C
                    [The 2 C's are involved in disulfide bonds]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for trypsin inhibitor IV from the sea anemone Radianthus macrodactylus  which
 has Asp instead of Phe/Tyr.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Expert(s) to contact by email:
           Ikeo K.; kikeo@genes.nig.ac.jp

-Last update: April 2006 / Pattern revised.

[ 1] Laskowski M. Jr., Kato I.
     "Protein inhibitors of proteinases."
     Annu. Rev. Biochem. 49:593-626(1980).
     PubMed=6996568; DOI=10.1146/annurev.bi.49.070180.003113
[ 2] Salier J.-P.
     "Inter-alpha-trypsin inhibitor: emergence of a family within the
     Kunitz-type protease inhibitor superfamily."
     Trends Biochem. Sci. 15:435-439(1990).
     PubMed=1703675
[ 3] Ikeo K., Takahashi K., Gojobori T.
     "Evolutionary origin of a Kunitz-type trypsin inhibitor domain
     inserted in the amyloid beta precursor protein of Alzheimer's
     disease."
     J. Mol. Evol. 34:536-543(1992).
     PubMed=1593645
[ 4] Sprecher C.A., Kisiel W., Mathewes S., Foster D.C.
     "Molecular cloning, expression, and partial characterization of a
     second human tissue-factor-pathway inhibitor."
     Proc. Natl. Acad. Sci. U.S.A. 91:3353-3357(1994).
     PubMed=8159751
[ 5] Papayannopoulos I.A., Biemann K.
     "Amino acid sequence of a protease inhibitor isolated from Sarcophaga
     bullata determined by mass spectrometry."
     Protein Sci. 1:278-288(1992).
     PubMed=1304909

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