Calcium-binding protein which may have a role in calcium homeostasis (PubMed:10915798). Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein (G-protein) alpha subunit GNAI3 (By similarity). Anorexigenic peptide, seems to play an important role in hypothalamic pathways regulating food intake and energy homeostasis, acting in a leptin-independent manner. May also exert hypertensive roles and modulate blood pressure through directly acting on peripheral arterial resistance. Interacts (via GBA motif) with guanine nucleotide-binding protein G(i) alpha subunit GNAI3 (By similarity). Preferentially interacts with inactive rather than active GNAI3 (By similarity). Interaction with GNAI3 is inhibited when NUCB2 binds calcium, probably due to a conformational change which renders the GBA motif inaccessible (By similarity). Binds to the postmitotic growth suppressor NDN; coexpression abolishes NUCB2 secretion (PubMed:10915798). In dendrites and perikarya of brain neurons. Abundant in the ER cisternae and nuclear envelope, but not detected in Golgi, mitochondria or nucleoplasm in neurons. In cell culture, cytoplasmic and secreted. Found in liver, heart, thymus, muscle, intestine, kidney, lung, spleen and throughout the brain, in cerebral cortex, hippocampus, hypothalamus and medulla oblongata. Nucb2 and necdin levels were higher in postmitotic neurons. The GBA (G-alpha binding and activating) motif mediates binding to the alpha subunits of guanine nucleotide-binding proteins (G proteins). Belongs to the nucleobindin family.