Comparative Functional Analysis of 12 Mammalian IFN-?4 Orthologs

Paquin, Ashley; Onabajo, Olusegun O.; Tang, Wei; Prokunina-Olsson, Ludmila

Protein sequence alignment of IFN-l4 orthologs showed high similarity between primates, while more diversity was observed among nonprimate species (Fig. 1) . All orthologs were predicted to have a leader peptide, with a cleavage site located between amino acids 22 and 23 in most cases and between 21 and 22 or 23 and 24 in some cases. Interestingly, the lowest leader peptide prediction score was for human IFN-l4 (0.56), followed by marmoset (0.67); all other orthologs had higher prediction scores (0.77-0.87) (Table 1) . However, a swap of leader peptides between the poorly secreted IFN-l4 and highly secreted IFN-l3 did not affect the secretion of IFN-l4 (Hamming and others 2013), suggesting that the predicted strength of the leader peptide might not be relevant for IFN-l4 secretion. The most diverse area in IFN-l4 is the sequence immediately after the predicted leader peptide-the 7 amino acid fragment was missing in all primates and this sequence was different in all nonprimates (Fig. 1) . This fragment did not seem to affect the leader peptide prediction scores and its functional significance is unclear.