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- ***************************************************
- * WAP-type 'four-disulfide core' domain signature *
- ***************************************************
-
- Small proteins that contain 8 cysteine residues involved in disulfide bonds
- have been called 'four-disulfide core' proteins [1]. It is probable that these
- proteins share the same tertiary structure folding pattern, but many of them
- are not related at the sequence level. There is, however, a group of such
- structurally related proteins which are listed below.
-
- - Whey acidic protein (WAP). WAP is a major component of milk whey whose
- exact function is not yet known. It consists of two 'four-disulfide core'
- domains.
- - 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].
- - Sodium/potassium ATPase inhibitors SPAI-1, -2, and -3 from pig [3].
- - 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
- domain'.
- - WDNM1 protein [4], involved in the metastatic potential of adenocarcinomas
- in rats.
- - Caltrin-like protein II from guinea pig [5], which inhibits calcium
- transport into spermatozoa.
- - Kallmann syndrome protein (ADML-X or KALIG-1) [6]. This protein may be a
- secreted adhesion-like molecule with anti-protease activity. It contains a
- a 'four-disulfide core domain' in its N-terminal part.
-
- The following schematic representation shows the position of the conserved
- cysteines for that category of 'four-disulfide core' domain and the location
- of the signature pattern for such a domain.
-
- +---------------------+
- | +-----------+ |
- | | | |
- xxxxxCPxxxxxxxxxxCxxxxCxxxxxCxxxxxCCxxxCxxxCxxxxx
- | ******|******| |
- | +--------------+
- | |
- +-----------------------------+
-
- <------------------50-residues------------------>
-
- 'C': conserved cysteine involved in a disulfide bond.
- '*': position of the pattern.
-
- -Consensus pattern: C-x-{C}-[DN]-x(2)-C-x(5)-C-C
- [The four C's are involved in disulfide bonds]
- -Sequences known to belong to this class detected by the pattern: ALL.
- -Other sequence(s) detected in SWISS-PROT: chicken vasotocin-neurophysin, rice
- oryzain beta and Caenorhabditis elegans K04H4.3.
-
- -Expert(s) to contact by email: Claverie J.-M.
- jmc@ncbi.nlm.nih.gov
-
- -Last update: December 1992 / Text revised.
-
- [ 1] Hennighausen L.G., Sippel A.E.
- Nucleic Acids Res. 10:2677-2684(1982).
- [ 2] Wiedow O., Schroeder J.-M., Gregory H., Young J.A., Christophers E.
- J. Biol. Chem. 265:14791-14795(1990).
- [ 3] Araki K., Kuwada M., Ito O., Kuroki J., Tachibana S.
- Biochem. Biophys. Res. Commun. 172:42-46(1990).
- [ 4] Dear T.N., Ramshaw I.A., Kefford R.F.
- Cancer Res. 48:5203-5209(1988).
- [ 5] Coronel C.E., San Agustin J., Lardy H.A.
- J. Biol. Chem. 265:6854-6859(1990).
- [ 6] 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.
- Cell 67:423-435(1991).
-