Molecular cloning, expression, and characterization of a novel class of synaptotagmin (Syt XIV) conserved from Drosophila to humans

Synaptotagmins (Syts) represent a large family of putative membrane trafficking proteins found in various species from different phyla. In this study, I identified a novel class of Syt (named Syt XIV) conserved from Drosophila to humans and its highly related molecule, Strep14 (Syt XIV-related protein). Although both Syt XIV and Strep14 belong to the C-terminal-type (C-type) tandem C2 protein family, only Syt XIV has a single transmembrane domain at the N-terminus and a putative fatty-acylation site just downstream of the transmembrane domain. Biochemical analyses have indicated that Syt XIV is a Ca²⁺-independent Syt (e.g., Syts VIII, XII, and XIII) and that, like other Syt family proteins, it is capable of forming a Ca²⁺-independent oligomer. Unlike other Syt isoforms, however, expression of Syt XIV and Strep14 mRNA is highly restricted to mouse heart and testis and absent in the brain, where most other Syts are abundantly expressed, suggesting that Syt XIV and Strep14 may be involved in membrane trafficking in specific tissues outside the brain. I also identified all of the C-type tandem C2 proteins in humans, the mouse, the fruit fly, a nematode, a plant, and a yeast and discuss the molecular evolution of the C-type tandem C2 protein families, including the Syt family, the Syt-like protein (Slp) family, and the Doc2 family.