Molecular cloning of bullfrog saxiphilin: a unique relative of the transferrin family that binds saxitoxin.
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.
Morabito
M A
MA
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.
Moczydlowski
E
E
D000595:Amino Acid Sequence; D029845:Amphibian Proteins; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins; D003001:Cloning, Molecular; D004251:DNA Transposable Elements / Q000235:genetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D011898:Ranidae / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D012530:Saxitoxin / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015222:Sodium Channels / Q000235:genetics*; D014018:Tissue Distribution; D014168:Transferrin / Q000235:genetics*
D029845:Amphibian Proteins; D002352:Carrier Proteins; D004251:DNA Transposable Elements; D012333:RNA, Messenger; D015222:Sodium Channels; D014168:Transferrin; C027525:saxitoxin-binding protein, Rana catesbeiana; D012530:Saxitoxin