Secretory granule neuroendocrine protein 1 7B2 protein
Known variously as APPG, 7B2 and neuroendocrine protein I, Secretogranin V was originally isolated from porcine pituitary in 1983. It soon became evident that Secretogranin V-like immunoreactants were present in many cell types from a variety of species, and it is now recognised to be widely distributed in neural and endocrine tissues. In the early 1990s full length (27kDa) Secretogranin V was shown to be a potent inhibitor of prohormone convertase PC2 activity, a subtilisin-like enzyme responsible for the proteolytic cleavage of many neuroendocrine precursor molecules, including proenkephalin, POMC and gastrin-17. mRNA distribution analysis revealed that in adult rat brain, expression of Secretogranin V mRNA was pan-neuronal, whereas PC2 mRNA was exclusively neuronal, but more restricted. PC2+/Secretogranin V- cells were not encountered in the adult, but were common in developing rat brain. These findings suggest that Secretogranin V may have intracellular functions other than PC2 maturation in certain cells, although some recent work shows a discordancy between mRNA expression and enzymic activity.
The mechanism for PC2 maturation appears to involve pro-Secretogranin V binding to inactive pro-PC2 via its polyproline motif (116 PPNPCP 121) in the endoplasmic reticulum and chaperoning pro-PC2 to a later secretory pathway compartment where maturation of PC2 proceeds once pro-Secretogranin V is proteolytically processed by a furin-like convertase into a 21kDa fragment and a C-terminal peptide. It is the C-terminal peptide that potently inhibits maturation of pro-PC2 until the complex is subjected to a decreasing pH gradient along the secretory pathway. It seems likely that mature PC2 then cleaves the CT peptide at its internal lys-lys site.
Secretogranin V knockout mice develop a severe Cushings-like phenotype and exhibit multiple metabolic and hormonal abnormalities, indicating that Secretogranin V is required for activation of PC2 in vivo. Conversely, PC2-null mice appear to be viable.
Neuroendocrine and endocrine secretory granules.
SDS-PAGE - Secretogranin V protein (ab100887)
ab100887 (3 µg) on an SDS-PAGE gel (15 %).
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