ERBB3

Receptor tyrosine-protein kinase erbB-3, also known as HER3 (human epidermal growth factor receptor 3), is a membrane bound protein that in humans is encoded by the ERBB3 gene.

ErbB3 is a member of the epidermal growth factor receptor (EGFR/ERBB) family of receptor tyrosine kinases. The kinase-impaired ErbB3 is known to form active heterodimers with other members of the ErbB family, most notably the ligand binding-impaired ErbB2.

Gene and expression

The human ERBB3 gene is located on the long arm of chromosome 12 (12q13). It is encoded by 23,651 base pairs and translates into 1342 amino acids.

During human development, ERBB3 is expressed in skin, bone, muscle, nervous system, heart, lungs, and intestinal epithelium.ERBB3 is expressed in normal adult human gastrointestinal tract, reproductive system, skin, nervous system, urinary tract, and endocrine system.

Structure

ErbB3, like the other members of the ErbB receptor tyrosine kinase family, consists of an extracellular domain, a transmembrane domain, and an intracellular domain. The extracellular domain contains four subdomains (I-IV). Subdomains I and III are leucine-rich and are primarily involved in ligand binding. Subdomains II and IV are cysteine-rich and most likely contribute to protein conformation and stability through the formation of disulfide bonds. Subdomain II also contains the dimerization loop required for dimer formation. The cytoplasmic domain contains a juxtamembrane segment, a kinase domain, and a C-terminal domain.