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Transmembrane domain of ErbB3, a Protein Tyrosine Kinase ErbB3 (HER3) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane (TM) helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. ErbB receptors are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. ErbB3 contains an impaired tyr kinase domain, which lacks crucial residues for catalytic activity against exogenous substrates but is still able to bind ATP and autophosphorylate. ErbB3 binds the neuregulin ligands, NRG1 and NRG2, and it relies on its heterodimerization partners for activity following ligand binding. The ErbB2-ErbB3 heterodimer constitutes a high affinity co-receptor capable of potent mitogenic signaling. The TM domain not only serves as a membrane anchor, but also plays an important role in receptor dimerization and optimal activation. Mutations in the TM domain of ErbB receptors have been associated with increased breast cancer risk. ErbB3 participates in a signaling pathway involved in the proliferation, survival, adhesion, and motility of tumor cells. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",