Family I12


Summary Holotypes Alignment Tree Genomes Structure Literature

Summary for family I12

NameInhibitor family I12 (Bowman-Birk family)
Family type peptidaseI12.001 - Bowman-Birk inhibitor (Glycine-type) unit 1 (Glycine max), MEROPS Accession MER0018105 (inhibitor unit: 42-69)
Content of familyInhibitor family I12 contains inhibitors of serine endopeptidases in clan PA.
History Identifier created: MEROPS 6.1 (10 January 2003)
An inhibitor of trypsin (S01.151) and chymotrypsin (S01.001) was isolated from soybeans by Bowman (1946) and further characterised by Birk et al. (1963). In recognition of the pioneering contributions made by D. E. Bowman and Y. Birk to the study of inhibitor family I12, it is normally termed the 'Bowman-Birk family'. All of the early work on the family was done with double-headed inhibitors from the Leguminoseae (specifically, the Fabaceae), but more recently it has become clear that inhibitors of this family occur in other plants, and can contain one, four, five or more inhibitor units per molecule as well as two.
Peptidases inhibitedPeptidases inhibited belong mostly to family S1 (Laskowski & Kato, 1980) but also S3 (Murthy et al., 2000).
With Lys and Leu residues in unit 1 and unit 2, respectively, soybean Bowman-Birk inhibitor (LI12-001) inhibits one molecule of trypsin and one of chymotrypsin per molecule of inhibitor.
Mechanism of inhibitionInhibitors in family I12 inhibit serine peptidases by the Laskowski mechanism also termed the 'standard' mechanism (Laskowski & Kato, 1980).
Molecular structureThe family contains compound inhibitors with 1 (e.g. I12.002), 2 (e.g. LI12-001), 4 (e.g. LI12-002), 5 or 6 inhibitor units (Rawlings et al., 2004). The work of Odani & Ikenaka (1973) revealed the tightly-crosslinked covalent structure of soybean Bowman-Birk inhibitor (LI12-001), with a nine-residue disulfide loop containing a reactive site at each end of the molecule. Three-dimensional structures have been determined for sunflower cyclic inhibitor (I12.002), soybean inhibitor (LI12-001), barley seed inhibitor (LI12-002), wheat germ inhibitor (LI12-005), pea seed inhibitor (LI12-007) and peanut inhibitor (LI12-008).
Distribution of family Bacteria -  
Archaea -  
Protozoa -  
Fungi details  
Plants details  
Animals details  
Viruses -  
Biological functionsThe peptidase inhibitors of plants can contribute to their defences against predation by insects. By interfering with the digestion of proteins in the insect gut, they decrease the rate of growth and reproduction of the insects, and thus decrease the amount of plant material consumed. There is also selective pressure for the insect pests to diversify their digestive enzymes to evade this defence, however.
Pharmaceutical and biotech relevanceThe inhibitors of family I12 are amongst those that have aroused interest for their possible anti-cancer activities (reviewed by Troll et al., 1987). It is not certain whether any such activity is a direct consequence of the inhibition of peptidases, however.
Transgenic plants expressing peptidase inhibitors of the Bowman-Birk family, as well as others, show promise of increased resistance to pests (Azzouz et al., 2005).
ReviewsGood reviews include those of Ikenaka & Norioka (1986) and Qi et al. (2005).
Statistics for family I12Sequences:264
Identifiers with PDB entries:11
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Inhibitors and Homologues MEROPS ID Structure
Bowman-Birk inhibitor (Glycine-type) unit 1I12.001Yes
sunflower cyclic trypsin inhibitorI12.002Yes
Bowman-Birk trypsin inhibitor (Medicago-type) unit 1I12.003Yes
Bowman-Birk trypsin/chymotrypsin inhibitor (Arachis hypogaea) unit 1I12.006-
rice Bowman-Birk inhibitor inhibitor unit 1I12.007Yes
Bowman-Birk inhibitor (Glycine-type) unit 2I12.008Yes
Bowman-Birk inhibitor (Poaceae) inhibitor unit 1I12.009Yes
Bowman-Birk inhibitor (Poaceae) inhibitor unit 2I12.010Yes
rice Bowman-Birk trypsin inhibitor inhibitor unit 2I12.011-
rice Bowman-Birk trypsin inhibitor inhibitor unit 3I12.012-
rice Bowman-Birk trypsin inhibitor inhibitor unit 4I12.013-
Bowman-Birk peptidase inhibitor (Arachis hypogaea) inhibitor unit 2I12.017-
lupin Bowman-Birk trypsin inhibitorI12.018Yes
WRSI5 trypsin inhibitorI12.019-
Bowman-Birk inhibitor (Poaceae) inhibitor unit 4I12.950Yes
Bowman-Birk inhibitor (Poaceae) inhibitor unit 3I12.951Yes
rice Bowman-Birk trypsin inhibitor inhibitor unit 5I12.952-
family I12 unassigned peptidase inhibitor homologueshomologue-
family I12 unassigned peptidase inhibitorsunassignedYes