The nucleotide and deduced amino acid structures of sheep and pig fetuin

Abstract

This study was initiated to gain further insight into the structural features of the mammalian fetuin family. The cDNA structures of sheep and pig fetuin were determined. The cDNA insert encoding sheep (pig) fetuin comprised 1550 (1470) nucleotides, including 54 (46) nucleotides encoding a signal peptide of 18 (15) residues and 1038 (1041) nucleotides encoding the 346 (347) amino acids of the mature plasma protein. The predicted amino‐terminal sequence of the mature pig fetuin was confirmed by the amino‐terminal sequence of the purified protein. However, two alternative sheep amino‐terminal sequences were found in fetuin purified from the plasma of a single sheep fetus; the minor product was the one predicted by comparison with other fetuin sequences while the major product was two amino acids longer. Comparison of the deduced amino acid sequences of sheep and pig fetuin showed an extensive sequence identity between them (75%) and with other proteins of the mammalian fetuin family, i. e. human α₂‐HS glycoprotein, and bovine and rat fetuins. Twelve cysteine residues were found at invariant positions in all fetuin sequences, suggesting strongly that the arrangement of disulphide bridges identified in human α₂‐HS glycoprotein is common to the members of the family. Further sequence comparisons revealed that the structures of mammalian fetuins are organised in three domains: two cystatin‐like domains (D1 and D2) and a complex carboxyl‐terminal domain (D3). The proposed three‐domain structure of the protein is reflected in the organisation of the rat fetuin structural gene which has recently been published.