Multiple forms of α2-macroglobulin from a bony fish, the common carp (Cyprinus carpio): Striking sequence diversity in functional sites

Junichi Mutsuro, Miki Nakao, Kazuhiro Fujiki, Tomoki Yano

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41 Citations (Scopus)


Unlike mammals, bony fish possess multiple genes encoding the complement component C3, a member of the α2-macroglobulin (α2M) protein family, presumably expanding the diversity of immune recognition. To examine whether the α2M gene has also duplicated and diverged in the bony fish lineage, cDNA cloning of α2M from a pseudotetraploid teleost, the common carp (Cyprinus carpio), was conducted and resulted in the isolation of three distinct α2M sequences from a single individual, indicating the presence of multiple α2M genes in this species. The deduced amino acid sequences contained a post-translational cleavage signal, predicting a C3-like two-chain structure, as in lamprey α2M. Two distinct α2M proteins were purified from carp serum; both proved to be M(r) 380,000 dimers, the subunits of which are composed of disulfide-linked α chains (M(r) 93,000) and β chains (M(r) 85,000), as reported for the α2M from plaice, another teleost species. The presence of an internal thioester in the a chain was demonstrated by its autolytic fragmentation and direct incorporation of [14C]methylamine. Interestingly, the three forms of carp α2M exhibited outstanding sequence diversity in the bait region which displays target sequences for various proteases, and in the C-terminal region of the α chain assigned as the receptor-binding domain, while an Asn residue at the position corresponding to the catalytic His in C3 was completely conserved in the carp α2Ms, as in most α2Ms of other animals. The possible functional significance of the sequence diversity is discussed.

Original languageEnglish
Pages (from-to)847-855
Number of pages9
Issue number10
Publication statusPublished - Jan 1 2000

All Science Journal Classification (ASJC) codes

  • Immunology
  • Genetics

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