Spectrin repeat-containing nuclear envelope protein 3 (SYNE3)

Spectrin repeat-containing nuclear envelope protein 3 (SYNE3, also known as Nesprin-3) is a structural protein localized at the outer nuclear membrane. It serves as a crucial component of the LINC (linker of nucleoskeleton and cytoskeleton) complex, where it connects the nuclear lamina to the cytoskeleton by interacting with cytoskeletal linker proteins such as plectin, BPAG1, and MACF. Unlike other nesprins, nesprin-3 lacks an actin-binding domain and connects to the cytoskeleton indirectly by binding proteins with actin-binding domains rather than interacting directly with actin filaments. It plays a vital role in maintaining nuclear morphology, enabling nuclear positioning, regulating cell shape, centrosome positioning, and mechanotransduction, particularly in 3D cell migration and vascular endothelial cell function. In cancer, SYNE3 expression is associated with apoptosis and possibly tumor suppressor functions, potentially via p53 signaling and its interactions with key cell cycle and apoptosis regulators (CDK1, CASP8, CCNB1, LMNA, LMNB1/2). SYNE3 is highly conserved in mammals and appears essential for tissue homeostasis and cellular architecture. Currently, there are no known drugs, clinical biomarkers, or therapeutic safety concerns specifically associated with SYNE3 as a target, and it is not established as a classical therapeutic target (e.g., not a receptor, enzyme, or transporter).

Other names

Nesprin-3C14orf139C14orf49LINC00341KASH3FLJ25605NET53Nesp3NCRNA00341uncharacterized protein C14orf113