InterPro domain: IPR044913

A cysteine-rich domain of approximately forty five amino-acid residues has been found in some extracellular eukaryotic proteins [ 1 , 2 , 3 , 4 ]. It is known as either the 'P', 'trefoil' or 'TFF' domain, and contains six cysteines linked by three disulphide bonds with connectivity 1-5, 2-4, 3-6. This leads to a characteristic three leafed structure ('trefoil'). The P-type domain is clearly composed of three looplike regions. The central core of the domain consists of a short two-stranded antiparallel beta-sheet, which is capped by an irregular loop and forms a central hairpin (loop 3). The beta-sheet is preceded by a short alpha-helix, with majority of the remainder of the domain contained in two loops, which lie on either side of the central hairpin.

This domain has been found in a variety of extracellular eukaryotic proteins [ 5 , 5 , 5 ], including:

• Protein pS2 (TFF1), a protein secreted by the stomach mucosa
• Spasmolytic polypeptide (SP) (TFF2), a protein of about 115 residues that inhibits gastrointestinal motility and gastric acid secretion
• Intestinal trefoil factor (ITF) (TFF3)
• Xenopus laevis stomach proteins xP1 and xP4
• Xenopus integumentary mucins A.1 (FIM-A.1 or preprospasmolysin) and C.1 (FIM-C.1), proteins which may be involved in defence against microbial infections by protecting the epithelia from the external environment
• Xenopus skin protein xp2 (or APEG)
• Zona pellucida sperm-binding protein B (ZP-B)
• Intestinal sucrase-isomaltase ( 3.2.1.48 / 3.2.1.10 ), a vertebrate membrane bound, multifunctional enzyme complex which hydrolyses sucrose, maltose and isomaltose
• Lysosomal alpha-glucosidase ( 3.2.1.20 )

1. Trefoil peptides. Coming up clover. Curr. Biol. 4, 835-8
2. Rolling in the clover: trefoil factor family (TFF)-domain peptides, cell migration and cancer. FEBS Lett. 408, 121-3
3. A trefoil domain in the major rabbit zona pellucida protein. Protein Sci. 2, 669-70
4. The P-domain or trefoil motif: a role in renewal and pathology of mucous epithelia? Trends Biochem. Sci. 18, 239-43