title: Phylogeny of whey acidic protein (WAP) four-disulfide core proteins and their role in lower vertebrates and invertebrates.
abstract: Proteins containing WAP (whey acidic protein) domains with a characteristic WFDC (WAP four-disulfide core) occur not only in mammals (including marsupials and monotremes) but also in birds, reptiles, amphibians and fish. In addition, they are present in numerous invertebrates, from cnidarians to urochordates. Many of those from non-mammalian groups are poorly understood with respect to function or phylogeny. Those well characterized so far are waprins from snakes, perlwapins from bivalves and crustins from decapod crustaceans. Waprins are venom proteins with a single WAP domain at the C-terminus. They display antimicrobial, rather than proteinase inhibitory, activities. Perlwapins, in contrast, possess three WAP domains at the C-terminus and are expressed in the shell nacre of abalones. They participate in shell formation by inhibiting the growth of calcium crystals in the shell. The crustin group is the largest of all WFDC-containing proteins in invertebrates with the vast majority being highly expressed in the haemocytes. Most have a single WAP domain at the C-terminus. The presence and type of the domains between the signal sequence and the C-terminus WAP domain separate the different crustin types. Most of the Type I and II crustins are antimicrobial towards Gram-positive bacteria, whereas the Type III crustins tend to display protease inhibition. Expression studies show that at least some crustins have other important biological effects, as levels change with physiological stress, wound repair, tissue regeneration or ecdysis. Thus WAP domains are widely distributed and highly conserved, serving in diverse physiological processes (proteinase inhibition, bacterial killing or inhibition of calcium transport).
authors.affiliation: Scottish Oceans Institute, Gatty Laboratory, University of St Andrews, St Andrews, Scotland KY16 8LB, UK. vjs1@st-andrews.ac.uk
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Smith
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006801:Humans; D007448:Invertebrates / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D011506:Proteins / Q000145:classification* / Q000235:genetics*; D016415:Sequence Alignment; D014714:Vertebrates / Q000235:genetics*
chemical_list: D011506:Proteins; C484310:WFDC1 protein, human