Receptor tyrosine-protein kinase erbB-4 (ERBB4) (ERBB4)

Receptor tyrosine-protein kinase erbB-4 (ERBB4), also known as HER4, is a member of the epidermal growth factor receptor (EGFR) subfamily of receptor tyrosine kinases [UniProt: Q15303]. It is unique among the ErbB family for its ability to undergo regulated intramembrane proteolysis, releasing an intracellular domain that can translocate to the nucleus to function as a transcriptional co-regulator [PMID: 11533492]. ErbB-4 is essential for normal development, particularly in the heart, central nervous system, and mammary glands, where it mediates signals from neuregulins and other growth factors [NCBI Gene: 2066]. In the context of human disease, ErbB-4 is frequently implicated in various cancers, where it can act as either an oncogene or a tumor suppressor depending on the specific tissue and isoform [PMID: 24519125]. Beyond oncology, genetic variants and signaling abnormalities in ErbB-4 are strongly associated with neuropsychiatric disorders like schizophrenia and neurodegenerative conditions such as amyotrophic lateral sclerosis [PMID: 25135911]. Therapeutic targeting of ErbB-4 is primarily achieved through multi-kinase inhibitors like afatinib and lapatinib that also target EGFR and HER2 [DrugBank: DB08916].

Other names

HER4Human epidermal growth factor receptor 4Proto-oncogene-like protein c-ErbB-4Tyrosine kinase-type cell surface receptor HER4

Inhibition of the intracellular tyrosine kinase domain by competing with ATP binding, thereby preventing autophosphorylation and downstream signaling cascades [DrugBank: DB08916].