Synaptotagmin-9 (SYT9) belongs to the synaptotagmin family, which is a group of membrane-trafficking proteins that contain two C-terminal C2 domains (known as C2A and C2B domains). Most of the synaptotagmins have a unique N-terminal domain that is involved in membrane anchoring or specific ligand binding.Synaptotagmin 1 (originally called p65) was the first member of the synaptotagmin family identified [, ]. It has been shown to function as a Ca2+ sensor on the synaptic vesicle surface, therefore to regulate Ca2+ dependent neurotransmitter release [, ]. SYT9 shares high degree of protein sequence similarity with SYT1. However, unlike SYT1, the C2 domain of SYT9 does not form Ca2+/phospholipid complexes and the endogenous SYT9 does not associate with SNARE complexes in the absence or presence of Ca2+. The C2 domain of SYT9 has low Ca2+ affinity and may have a modulatory Ca2+-dependent function []. SYT9 is involved in endocrine secretion such as insulin release from large dense core vesicles in pancreatic beta-cells [].
