Calcium-binding protein which may have a role in calcium homeostasis (By similarity). Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein (G-protein) alpha subunit GNAI3 (PubMed:21653697). 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 (PubMed:21653697). Preferentially interacts with inactive rather than active GNAI3 (PubMed:21653697). Interaction with GNAI3 is inhibited when NUCB2 binds calcium, probably due to a conformational change which renders the GBA motif inaccessible (PubMed:21653697). Binds to the postmitotic growth suppressor NDN; coexpression abolishes NUCB2 secretion (By similarity). The GBA (G-alpha binding and activating) motif mediates binding to the alpha subunits of guanine nucleotide-binding proteins (G proteins). NEFA stands for N=DNA-binding; EF=EF-hand; A=Acidic region. Belongs to the nucleobindin family.