Nucleobindin contains multiple functional domains including a signal peptide on the N-terminal side, a leucine/isoleucine rich region, a DNA binding domain and a putative nuclear targeting signal. The second half of the protein contains two Ca²⁺-EF-hand motifs and a leucine zipper motif in the C-terminal region. To date, two nucleobindins have been identified, namely nucleobindin 1 and nucleobindin 2.

Nucleobindin 2 (NUCB2) can be found on the plasma membrane and in the cytoplasm. Putative post-translational processing of NUCB2 by the enzyme pro-hormone convertase (PC)-1/3 results in nesfatin-1, nesfatin-2 and nesfatin-3. So far, a biological activity has only been demonstrated for nesfatin-1 and its fragment, nesfatin-1_24–53¹.

The gene Nesfatin/NUCB2 encoding the protein is expressed in the appetite control hypothalamic nuclei such as the paraventricular nucleus (PVN), the supraoptic nucleus, the lateral hypothalamic area and the zona increta in rats. Nefstain-1 immunoreactivity is also detected in the brain stem nuclei such as the nucleus of the solitary tract and the dorsal nucleus of the vagus.

Nesfatin-1 has a substantial anorexigenic effect through the selective reduction of nesfatin/NUCB mRNA expression in the PVN of rats under starved conditions. Refeeding of rats was found to restore Nesfatin-1 reduction. A similar effect was not observed in other hypothalamic nuclei². In humans, Nesfatin-1 levels in the saliva and serum of epilepsy patients are reduced with the use of anti-epileptic medication, but are still higher than the amounts in normal subjects. In addition, nesfatin-1 levels are decreased in human subjects with type-2 diabetes and it has been hypothesized that the observed decrement might be associated with diabetic hyperphagia³.