A cysteine-rich domain of approximately forty five amino-acid residues has
been found in some extracellular eukaryotic proteins [1,2,3,4,5]. This domain
is known as either the 'P', 'trefoil' or 'TFF' domain. It contains six
cysteines that are linked by three disulfide bonds in a 1-5, 2-4, and 3-6
configuration. 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
β-sheet, which is capped by an irregular loop and forms a central hairpin
(loop 3). The β-sheet is preceded by a short α-helix, with majority of
the remainder of the domain contained in two loops, which lie on either side
of the central hairpin (see <PDB:1E9T>) .
Proteins known to contain this domain are:
Protein pS2 (TFF1), a protein secreted by the stomach mucosa, whose gene is
induced by estrogen. The exact function of pS2 is not known. It is a
protein of about 65 residues and it contains a copy of the 'P' domain.
Spasmolytic polypeptide (SP) (TFF2), a protein of about 115 residues that
inhibits gastrointestinal motility and gastric acid secretion. SP could be
a growth factor. It contains two tandem copies of the 'P' domain.
Intestinal trefoil factor (ITF) (TFF3), an intestinal protein of about 60
residues which may have a role in promoting cell migration. It contains a
copy of the 'P' domain.
Xenopus integumentary mucins A.1 (FIM-A.1 or preprospasmolysin) and C.1
(FIM-C.1). These proteins could be involved in defense against microbial
infections by protecting the epithelia from external environment. They are
large proteins (400 residues for A.1; more than 660 residues for C.1 whose
sequence is only partially known) that contain multiple copies of the 'P'
domain interspersed with tandem repeats of threonine-rich, O-glycosylated
Xenopus skin protein xp2 (or APEG) a protein that contains two 'P' domains
and which exists in two alternative spliced forms that differ from the
inclusion of a N-terminal region of 320 residues that consist of 33 tandem
repeats of a G-[GE]-[AP](2,4)-A-E motif.
Zona pellucida sperm-binding protein B (ZP-B) (also known as ZP-X in rabbit
and ZP-3 α in pig). This protein is a receptor-like glycoprotein whose
extracellular region contains a 'P' domain followed by a ZP domain (see
Intestinal sucrase-isomaltase (EC 184.108.40.206 / EC 220.127.116.11), a vertebrate
membrane-bound, multifunctional enzyme complex which hydrolyzes sucrose,
maltose and isomaltose (see <PDOC00120>).
Lysosomal α-glucosidase (EC 18.104.22.168) (acid maltase), a vertebrate
extracellular glycosidase (see <PDOC00120>).
Structurally the P-type domain can be represented as shown below.
Lemercinier X. Muskett F.W. Cheeseman B. McIntosh P.B. Thim L. Carr M.D.
High-resolution solution structure of human intestinal trefoil factor and functional insights from detailed structural comparisons with the other members of the trefoil family of mammalian cell motility factors.
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and
distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives
(CC BY-NC-ND 4.0) License, see prosite_license.html.