Secretogranin-3 is a family of vertebrate proteins that is one of the granin family. Granins are rich in acidic amino acids, exhibit aggregation at low pH, and possess a high capacity for calcium binding. Because granins are restricted in their localisation to secretory granules of neuroendocrine cells, two interesting characteristics of their sorting mechanisms have been observed. These are, first, that they aggregate on low pH/high calcium concentrations and second that two of them carry an N-terminal disulfide loop, mutations in which lead to mis-sorting. Thus, granins are thought to be essential for the sorting of secretory proteins at the trans-Golgi network. Chromogranin A (CgA) binds to SGIII in secretory granules of endocrine cells []. SGIII directly binds to cholesterol components of the secretory granule membrane and targets CgA to secretory granules in pituitary and pancreatic endocrine cells []. Mutations in the SGIII gene may influence the risk of obesity through possible regulation of hypothalamic neuropeptide secretion [].Secretogranin-3 interacts with cromogranin A; this interaction is optimal in conditions mimicking the lumenal milieu of the trans-Golgi network, i.e. pH 5.5 and 10 mM Ca(+2) [].
