title: The gene for a novel member of the whey acidic protein family encodes three four-disulfide core domains and is asynchronously expressed during lactation.
abstract: Secretion of whey acidic protein (WAP) in milk throughout lactation has previously been reported for a limited number of species, including the mouse, rat, rabbit, camel, and pig. We report here the isolation of WAP from the milk of a marsupial, the tammar wallaby (Macropus eugenii). Tammar WAP (tWAP) was isolated by reverse-phase HPLC and migrates in SDS-polyacrylamide gel electrophoresis at 29.9 kDa. tWAP is the major whey protein, but in contrast to eutherians, secretion is asynchronous and occurs only from approximately days 130 through 240 of lactation. The full-length cDNA codes for a mature protein of 191 amino acids, which is comprised of three four-disulfide core domains, contrasting with the two four-disulfide core domain arrangement in all other known WAPs. A three-dimensional model for tWAP has been constructed and suggests that the three domains have little interaction and could function independently. Analysis of the amino acid sequence suggests the protein belongs to a family of protease inhibitors; however, the predicted active site of these domains is dissimilar to the confirmed active site for known protease inhibitors. This suggests that any putative protease ligand may be unique to either the mammary gland, milk, or gut of the pouch young. Examination of the endocrine regulation of the tWAP gene showed consistently that the gene is prolactin-responsive but that the endocrine requirements for induction and maintenance of tWAP gene expression are different during lactation.
authors.affiliation: Victorian Institute of Animal Science, 475 Mickleham Rd., Attwood, Victoria 3049, Australia. k.simpson@biochemistry.unimelb.edu.au
authors.forename: K J
authors.initials: KJ
authors.lastname: Simpson
authors.forename: S
authors.initials: S
authors.lastname: Ranganathan
authors.forename: J A
authors.initials: JA
authors.lastname: Fisher
authors.forename: P A
authors.initials: PA
authors.lastname: Janssens
authors.forename: D C
authors.initials: DC
authors.lastname: Shaw
authors.forename: K R
authors.initials: KR
authors.lastname: Nicholas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D018076:DNA, Complementary; D004220:Disulfides / Q000737:chemistry*; D004702:Endocrine Glands / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D007774:Lactation / Q000235:genetics*; D008394:Marsupialia; D051379:Mice; D008894:Milk Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011817:Rabbits; D051381:Rats; D017386:Sequence Homology, Amino Acid
chemical_list: D018076:DNA, Complementary; D004220:Disulfides; D008894:Milk Proteins; C024471:whey acidic proteins