PB0321 - Detailed phylogenetic analyses of Serpina10 Indicated Diverse Physiological roles of Protein Z Dependent Protease Inhibitor (ZPI)

Background: Protein Z dependent protease inhibitor (ZPI), a member of SERPIN (serine protease inhibitor) superfamily, inhibits the clotting functions of FXa and FXIa. Serpin family of proteins are excellent examples of proteins that have a common protein fold that can be used for different biological purposes other than acting as an anticoagulant. ZPI is coded by Serpina10 gene that belongs to clade A. Clade A is a multiple gene cluster consists of 13 serpins, that are involved in diverse physiological functions.

Aims: The present study is therefore aimed to provide insights into the evolutionary and biological roles of ZPI besides protease inhibition.

Methods: NCBI, Ensemble, InterPro, Genomics, Uniprot, were used to download and analyse amino acid as well as genomic sequences of the protein ZPI and the Serpina10 gene. Multiple Sequence alignment tools used were Clustal, Cobalt, etc. HMMER-3.3.2 – a probabilistic model-based sequence search software was used to identify remote homology. MEGA11 and IQ-TREE were the software used for phylogenetic tree building. Fig tree was used to view the graphical tree.

Results: Genome analyses revealed that serpina10 gene appeared first in Chondrichthyes. None of the serpins from organisms of taxa lower than the gnathostomes (jawed vertebrates) have homology with ZPI. Serpina10 gene showed clear paralogic conservation in higher metazoans. No plant serpins homologous to ZPI was observed. We also observed the presence of two sets of ZPI genes in zebra fish, in chromosome 20 and 17. Finally, it was very interesting to note that ZPI is completely absent in carnivores.

Conclusion(s): Phylogenetic arrangements of ZPI gene in evolutionarily important organisms clearly indicated that despite being a mild anticoagulant, ZPI may have other physiological functions in processes such as inflammation and infection.