Molecular cloning of bullfrog saxiphilin: a unique relative of the transferrin family that binds saxitoxin

Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2478-82. doi: 10.1073/pnas.91.7.2478.


Plasma and tissue of certain vertebrates contain a protein called saxiphilin that specifically binds the neurotoxin saxitoxin with nanomolar affinity. We describe the isolation of a cDNA clone of saxiphilin from liver of the North American bullfrog (Rana catesbeiana). The cDNA sequence encodes a protein that is evolutionarily related to members of the transferrin family of Fe(3+)-binding proteins. Pairwise sequence alignment of saxiphilin with various transferrins reveals amino acid identity as high as 51% and predicts 14 disulfide bonds that are highly conserved. The larger size of saxiphilin (91 kDa) versus serum transferrin (approximately 78 kDa) is primarily due to a unique insertion of 144 residues. This insertion contains a 49-residue domain classified as a type 1 repetitive element of thyroglobulin, which is shared by a variety of membrane, secreted, and extracellular matrix proteins. Saxiphilin also differs from transferrins in 9 of 10 highly conserved amino acids in the two homologous Fe3+/HCO3-binding sites of transferrin. Identification of saxiphilin implies that transferrin-like proteins comprise a diverse superfamily with functions other than iron binding.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amphibian Proteins
  • Animals
  • Base Sequence
  • Carrier Proteins*
  • Cloning, Molecular
  • DNA Transposable Elements / genetics
  • Molecular Sequence Data
  • RNA, Messenger / biosynthesis
  • Ranidae / genetics*
  • Repetitive Sequences, Nucleic Acid / genetics
  • Saxitoxin / metabolism
  • Sequence Homology, Amino Acid
  • Sodium Channels / genetics*
  • Tissue Distribution
  • Transferrin / genetics*


  • Amphibian Proteins
  • Carrier Proteins
  • DNA Transposable Elements
  • RNA, Messenger
  • Sodium Channels
  • Transferrin
  • saxitoxin-binding protein, Rana catesbeiana
  • Saxitoxin

Associated data

  • GENBANK/U05246