A phylogenetic analysis of MCTP proteins: from amino acid sequence to function

MCTPs (Multiple C2 domain proteins with two transmembrane regions) are evolutionarily and structurally related to other C2 proteins which play fundamental roles in exocytosis and membrane trafficking, however their specific role has been little studied. This work points out possible functional implications of MCTPs by comparing their primary amino acid sequence and functional domains. MCTP amino acid sequences were identified in non-chordates and chordates. The primary sequences grouped in three classes: MCTP, MCTP-1 and MCTP-2. MCTP is present only in non-chordates, while MCTP-1 and MCTP-2 are present in chordates. MCTP genes emerged early in metazoan evolution and are well conserved across species including humans. Genomic analysis of diverse species of representative phyla showed that the three C2 domains (C2A-C2C) and transmembrane regions (TMR) are well conserved. The C2 domains have eight {beta} strands as well as aspartate residues known to bind calcium. Interestingly, we identified a lysine-rich cluster, also known as polybasic cluster in C2A and C2B, which is known to bind lipids in other proteins. We also describe the phylogenetic distribution of MCTPs and analyze conserved domains and their predicted secondary structure in metazoans. We highlight important motifs that have not been previously described in MCTPs C2A and C2B domains that suggest MCTPs potentially bind phospholipids. Our observations show MCTPs are proteins widely distributed in eukaryotic organisms and may play an important role in membrane fusion or exocytosis.