Nucleobindin-1 (NUCB1)

Nucleobindin-1 (NUCB1) is a multidomain calcium-binding protein featuring two EF-hand motifs, a leucine zipper, a DNA-binding region, and a nuclear localization signal[1][3][5][6]. NUCB1 is found in the Golgi apparatus, ER, nucleus, and cytoplasm, where it acts as a calcium sensor, participates in protein trafficking, and regulates signaling pathways—including functioning as a calcium-dependent guanine nucleotide dissociation inhibitor for Gαi subunits of heterotrimeric G proteins[1][3]. NUCB1 also binds to protofibrillar amyloid aggregates from proteins such as Aβ42, α-synuclein, islet amyloid polypeptide, and transthyretin, stabilizing their soluble intermediates and preventing toxic fibril formation—which implicates NUCB1 in neurodegenerative and metabolic diseases as a natural chaperone-like amyloid binding protein[2][3]. In the ER and Golgi, NUCB1 negatively regulates the unfolded protein response, impacting cellular stress reactions[3]. Its structure and multiple interaction domains enable both nucleic acid and protein binding, with emerging evidence of enzymatic activities (e.g., serine protease-like) regulated by interactions with metal ions and G proteins[3][4][6].

Other names

CalnucNUCnucleobindin-1

N/A—no drugs act directly on NUCB1. Its actions involve protein-protein interactions, inhibitory capping of amyloid protofibrils, and regulation of nucleotide release from Gαi subunits[1][2].