Neuregulin 3 (NRG3)

Neuregulin 3 (NRG3) is a neural tissue-enriched member of the neuregulin family of growth factors, structurally related to neuregulin 1 (NRG1), and encoded by the **NRG3** gene on chromosome 10q22-q23[2][4][5]. NRG3 is characterized by an extracellular epidermal growth factor (EGF)-like domain, a transmembrane segment, and an intracellular domain. Uniquely, NRG3 lacks the immunoglobulin-like and kringle domains found in other neuregulins, instead possessing glycosylation-rich mucin-like regions[1][3]. Its primary role is as a direct and high-affinity ligand for the ERBB4 (HER4) receptor tyrosine kinase, where binding promotes receptor phosphorylation and downstream signaling, influencing neural proliferation, differentiation, migration, and survival—especially in oligodendrocytes and during neurodevelopment[1][3][4]. NRG3 signaling through ERBB4 also participates in mammary gland development during embryogenesis and is implicated in neurodevelopmental and psychiatric disorders, particularly schizophrenia and Hirschsprung disease[2][4][6]. NRG3 is mainly expressed in the central nervous system, with restricted expression outside neural tissues[1][3][4]. No approved drugs are known to directly target NRG3, but its ligand-receptor interaction may present opportunities and risks for therapeutic modulation in oncology or neuropsychiatric disease[4][7].

Other names

Pro-neuregulin-3Neuregulin-3NRG3Pro-NRG3NRG-3HRG3pro-neuregulin-3neuregulin-3-like polypeptide

Ligand-induced activation of ERBB4 (HER4) receptor tyrosine kinase signaling, leading to receptor dimerization, tyrosine phosphorylation, and downstream cellular effects[1][2][3][4]. Initiation of PKC signaling and downstream proteolytic cleavage of ERBB4[2].