Mucin 1 N-terminal subunit (MUC1-N) (MUC1-N)

Mucin 1 N-terminal subunit (MUC1-N) is the large, extracellular component of the MUC1 heterodimer, a transmembrane glycoprotein primarily expressed on the apical surface of epithelial cells. Following translation, MUC1 undergoes autoproteolysis at the GSVVV motif within the sea urchin sperm protein, enterokinase, and agrin (SEA) domain, resulting in the non-covalently linked MUC1-N and MUC1-C subunits. MUC1-N is characterized by a variable number of tandem repeats (VNTR) that are heavily O-glycosylated, providing a physical barrier and lubricating the cell surface. In many cancers, MUC1-N is overexpressed and loses its apical polarization, becoming distributed across the entire cell surface and often exhibiting aberrant glycosylation (e.g., Tn and sialyl-Tn antigens). This makes MUC1-N a significant target for monoclonal antibodies, antibody-drug conjugates (ADCs), and CAR-T cell therapies, although the shedding of MUC1-N into the bloodstream (detected as the CA 15-3 biomarker) can act as a decoy for these therapies.

Other names

Mucin 1, cell surface associatedCD227CA 15-3EpisialinH23AGPUMPEMEMAMUC-1/SECMUC-1/XMUC-1/Y

Monoclonal antibodies targeting MUC1-N typically act through antibody-dependent cellular cytotoxicity (ADCC) or by delivering cytotoxic payloads in the form of antibody-drug conjugates (ADCs). Some therapies aim to induce a T-cell response against the tumor-associated glycoforms of the MUC1-N tandem repeat domain.