{PDOC00026}
{PS51390; WAP}
{BEGIN}
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* WAP-type 'four-disulfide core' domain profile *
*************************************************

The 'four-disulfide core' or WAP domain comprises 8 cysteine residues involved
in  disulfide  bonds  in  a  conserved  arrangement  [1]. One or more of these
domains   occur   in   whey   acidic   protein   (WAP),   antileukoproteinase,
elastase-inhibitor  proteins and other structurally related proteins which are
listed below.

 - 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 [4].
 - 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'.
 - 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
   into spermatozoa.
 - 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 [7].
 - Waprins  from  snake  venom, such as omwaprin from Oxyuranus microlepidotus
   [8] 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>).

                           +---------------------+
                           |    +-----------+    |
                           |    |           |    |
         xxxxxxxCPxxxxxxxxxCxxxxCxxxxxCxxxxxCCxxxCxxxCxxxx
                |                     |      |       |
                |                     +--------------+
                |                            |
                +----------------------------+

         <------------------50-residues------------------>

'C': conserved cysteine involved in a disulfide bond.

We  developed  a  profile  that  covers  the  whole  structure of the WAP-type
'four-disulfide core' domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Expert(s) to contact by email:
           Claverie J.-M.; jmc@ir1cbm.cnrs-mrs.fr

-Last update: July 2008 / Pattern removed, profile added and text revised.

[ 1] Hennighausen L.G., Sippel A.E.
     "Mouse whey acidic protein is a novel member of the family of
     'four-disulfide core' proteins."
     Nucleic Acids Res. 10:2677-2684(1982).
     PubMed=6896234
[ 2] Wiedow O., Schroeder J.-M., Gregory H., Young J.A., Christophers E.
     "Elafin: an elastase-specific inhibitor of human skin. Purification,
     characterization, and complete amino acid sequence."
     J. Biol. Chem. 265:14791-14795(1990).
     PubMed=2394696
[ 3] Francart C., Dauchez M., Alix A.J., Lippens G.
     "Solution structure of R-elafin, a specific inhibitor of elastase."
     J. Mol. Biol. 268:666-677(1997).
     PubMed=9171290; DOI=10.1006/jmbi.1997.0983
[ 4] Araki K., Kuwada M., Ito O., Kuroki J., Tachibana S.
     "Four disulfide bonds' allocation of Na+, K(+)-ATPase inhibitor
     (SPAI)."
     Biochem. Biophys. Res. Commun. 172:42-46(1990).
     PubMed=2171523
[ 5] 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."
     Cell 67:423-435(1991).
     PubMed=1913827
[ 6] Hu Y., Sun Z., Eaton J.T., Bouloux P.M., Perkins S.J.
     "Extended and flexible domain solution structure of the extracellular
     matrix protein anosmin-1 by X-ray scattering, analytical
     ultracentrifugation and constrained modelling."
     J. Mol. Biol. 350:553-570(2005).
     PubMed=15949815; DOI=10.1016/j.jmb.2005.04.031
[ 7] Simpson K.J., Ranganathan S., Fisher J.A., Janssens P.A., Shaw D.C.,
     Nicholas K.R.
     "The gene for a novel member of the whey acidic protein family encodes
     three four-disulfide core domains and is asynchronously expressed
     during lactation."
     J. Biol. Chem. 275:23074-23081(2000).
     PubMed=10801834; DOI=10.1074/jbc.M002161200
[ 8] Nair D.G., Fry B.G., Alewood P., Kumar P.P., Kini R.M.
     "Antimicrobial activity of omwaprin, a new member of the waprin family
     of snake venom proteins."
     Biochem. J. 402:93-104(2007).
     PubMed=17044815; DOI=10.1042/BJ20060318

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