Receptor tyrosine-protein kinase erbB-2 (extracellular domain IV) (HER2 (ERBB2))

HER2/ERBB2 is a cell-surface receptor tyrosine kinase and a member of the epidermal growth factor receptor family. The extracellular region (ECD) comprises four domains (I-IV): domain IV lies nearest the surface of the cell membrane and is implicated in stabilizing the protein-protein interaction between HER2 and its dimerization partners, such as EGFR and HER3. HER2 lacks a direct ligand-binding pocket but serves as a preferred partner for dimerization, facilitating potent signal transduction pathways driving cell proliferation and survival. Overexpression or mutation of HER2 leads to uncontrolled dimerization and constitutive signaling, strongly associated with aggressive forms of breast and other cancers. Domain IV is a target for monoclonal antibody therapies (e.g., trastuzumab), which bind near this region to block dimerization and downstream signaling, making it a validated site for therapeutic intervention.

Other names

HER2ERBB2NeuHER2/neuReceptor tyrosine-protein kinase erbB-2extracellular domain IVdomain IVDIVC-terminal ECD of HER2

Monoclonal antibodies (e.g., trastuzumab, pertuzumab) bind to extracellular domains (including domain IV) to prevent receptor dimerization, disrupt signaling, and induce antibody-dependent cellular cytotoxicity (ADCC) Tyrosine kinase inhibitors (e.g., lapatinib) block kinase activity Antibody-drug conjugates (e.g., T-DM1) deliver cytotoxic agents to HER2-overexpressing cells