N-terminal EF-hand calcium-binding protein 3 (NECAB3)

N-terminal EF-hand calcium-binding protein 3 (NECAB3) is a member of the NECAB family of neuronal calcium-binding proteins characterized by an N-terminal EF-hand calcium-binding domain and a C-terminal, poorly characterized antibiotic biosynthesis monooxygenase (ABM) domain[1][4][5]. NECAB3 is predominantly expressed in neurons but is also present in the heart and skeletal muscle[1]. Within cells, it localizes to the cytosol, endoplasmic reticulum, and Golgi apparatus[1][5]. NECAB3 regulates the association between the neuronal protein APBA2/X11L and the amyloid precursor protein (APP); it inhibits this association, abolishing the suppression of beta-amyloid generation and thereby potentially elevating beta-amyloid levels implicated in Alzheimer’s disease[1][5][6]. It also interacts with other proteins, such as NIMA-related kinase 2 (NEK2), HIF1AN, and Mint3, and modulates the activity of hypoxia-inducible factor 1 (HIF-1) to promote glycolysis and tumorigenicity in normoxic cancer cells[3][5]. While considered a functionally relevant protein in neuronal signaling and disease (notably Alzheimer’s and cancer), NECAB3 is not a classical therapeutic target (e.g., receptor or enzyme), and there are currently no drugs or clinical inhibitors specifically directed against it[1][3][5][6].

Other names

NECAB3APBA2BPNIP1SYTIP2XB51dJ63M2.4dJ63M2.5EFCBP3Amyloid-beta A4 protein-binding family A member 2-binding proteinNek2-interacting protein 1Neuronal calcium-binding protein 3X11L-binding protein 51Synaptotagmin interacting protein 2Synaptotagmin interacting protein STIP3

null (no direct drug targeting or mechanism established; effects are via protein-protein interactions with APBA2/X11L, HIF1AN, and Mint3)