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The 'four-disulfide core' or WAP domain comprises 8 cysteine residues involved
in disulfide bonds in a conserved arrangement . One or more of these
domains occur in whey acidic protein (WAP), antileukoproteinase,
elastase-inhibitor proteins and other structurally related proteins which are
Whey acidic protein (WAP). WAP is a major component of milk whey whose
function might be that of a protease inhibitor. WAP consists of two
'four-disulfide core' domains in most mammals.
Antileukoproteinase 1 (HUSI), a mucous fluid serine proteinase inhibitor.
HUSI consists of two 'four-disulfide core' domains.
Elafin, an elastase-specific inhibitor from human skin [2,3].
Sodium/potassium ATPase inhibitors SPAI-1, -2, and -3 from pig .
Chelonianin, a protease inhibitor from the eggs of red sea turtle. This
inhibitor consists of two domains: an N-terminal domain which inhibits
trypsin and belongs to the BPTI/Kunitz family of inhibitors, and a
C-terminal domain which inhibits subtilisin and is a 'four-disulfide core
Extracellular peptidase inhibitor (WDNM1 protein), involved in the
metastatic potential of adenocarcinomas in rats.
Caltrin-like protein 2 from guinea pig, which inhibits calcium transport
Kallmann syndrome protein (Anosmin-1 or KALIG-1) [5,6]. This secreted
protein may be a adhesion-like molecule with anti-protease activity. It
contains a 'four-disulfide core domain' in its N-terminal part.
Whey acidic protein (WAP) from the tammar wallaby, which consists of three
'four-disulfide core' domains .
Waprins from snake venom, such as omwaprin from Oxyuranus microlepidotus
 which has antibacterial activity against Gram-positive bacteria.
The following schematic representation shows the position of the conserved
cysteines that form the 'four-disulfide core' WAP domain (see <PDB:2REL>).
Legouis R., Hardelin J.-P., Levilliers J., Claverie J.-M., Compain S., Wunderle V., Millasseau P., Le Paslier D., Cohen D., Caterina D. Bougueleret L., Delemarre-Van de Waal H., Lutfalla G., Weissenbach J., Petit C.
The candidate gene for the X-linked Kallmann syndrome encodes a protein related to adhesion molecules.
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