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	PROSITE documentation PDOC00252 [for PROSITE entry PS00280]

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.

Expert(s) to contact by email:

Ikeo K.

Last update:

April 2006 / Pattern revised.

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

BPTI_KUNITZ_1, PS00280; Pancreatic trypsin inhibitor (Kunitz) family signature  (PATTERN)

• Consensus pattern:
  F-x(2)-{I}-G-C-x(6)-[FY]-x(5)-C
  The 2 C's are involved in disulfide bonds
• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 375
  • detected by PS00280: 294 (true positives)
  • undetected by PS00280: 81 (61 false negatives and 20 'partials')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS00280:
  6 false positives.
• 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 PS00280
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00280
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS00280
• View ligand binding statistics of PS00280
• Matching PDB structures: 1AAP 1ADZ 1B0C 1BF0 ... [ALL]

BPTI_KUNITZ_2, PS50279; Pancreatic trypsin inhibitor (Kunitz) family profile  (MATRIX)

• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 376
  • detected by PS50279: 355 (true positives)
  • undetected by PS50279: 21 (4 false negatives and 17 'partials')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS50279:
  NONE.
• Domain architecture view of Swiss-Prot proteins matching PS50279
  
• 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 PS50279
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS50279
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS50279
• View ligand binding statistics of PS50279
• Matching PDB structures: 1AAL 1AAP 1ADZ 1B0C ... [ALL]

1	Authors	Laskowski M. Jr., Kato I.
	Title	Protein inhibitors of proteinases.
	Source	Annu. Rev. Biochem. 49:593-626(1980).
	PubMed ID	6996568
	DOI	10.1146/annurev.bi.49.070180.003113

2	Authors	Salier J.-P.
	Title	Inter-alpha-trypsin inhibitor: emergence of a family within the Kunitz-type protease inhibitor superfamily.
	Source	Trends Biochem. Sci. 15:435-439(1990).
	PubMed ID	1703675

3	Authors	Ikeo K., Takahashi K., Gojobori T.
	Title	Evolutionary origin of a Kunitz-type trypsin inhibitor domain inserted in the amyloid beta precursor protein of Alzheimer's disease.
	Source	J. Mol. Evol. 34:536-543(1992).
	PubMed ID	1593645

4	Authors	Sprecher C.A., Kisiel W., Mathewes S., Foster D.C.
	Title	Molecular cloning, expression, and partial characterization of a second human tissue-factor-pathway inhibitor.
	Source	Proc. Natl. Acad. Sci. U.S.A. 91:3353-3357(1994).
	PubMed ID	8159751

5	Authors	Papayannopoulos I.A., Biemann K.
	Title	Amino acid sequence of a protease inhibitor isolated from Sarcophaga bullata determined by mass spectrometry.
	Source	Protein Sci. 1:278-288(1992).
	PubMed ID	1304909

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