P-type trefoil domain (IPR000519)

Short name: P_trefoil_dom

Overlapping homologous superfamilies


Domain relationships



A cysteine-rich domain of approximately forty five amino-acid residues has been found in some extracellular eukaryotic proteins [PMID: 7820556, PMID: 9187350, PMID: 8518738, PMID: 8267796]. 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 [PMID: 7820556, PMID: 8518738, PMID: 8267796], 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 (EC: / EC:, a vertebrate membrane bound, multifunctional enzyme complex which hydrolyses sucrose, maltose and isomaltose
  • lysosomal alpha-glucosidase (EC:

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE profiles