ERBB4

Function

Receptor tyrosine-protein kinase erbB-4 is a receptor tyrosine kinase that is a member of the epidermal growth factor receptor family. ERBB4 is a single-pass type I transmembrane protein with multiple furin-like cysteine rich domains, a tyrosine kinase domain, a phosphotidylinositol-3 kinase binding site and a PDZ domain binding motif. The protein binds to and is activated by neuregulins-2, -3 and -4, heparin-binding EGF-like growth factor and betacellulin. Ligand binding induces a variety of cellular responses including mitogenesis and differentiation. Multiple proteolytic events allow for the release of a cytoplasmic fragment and an extracellular fragment.

Clinical significance

Mutations in this gene have been associated with cancer. Other single-nucleotide polymorphisms and a risk haplotype have been linked to schizophrenia. Single-nucleotide polymorphisms in ERBB4 have also been found in a study of patients with familial amyotrophic lateral sclerosis type 19.

Interactions

ERBB4 has been shown to interact with:

• DLG4
• NRG1,
• STAT5A, and
• YAP1.

References

References

1. (Mar 1995). "Localization of the human HER4/erbB-4 gene to chromosome 2". Oncogene.
2. (Oct 2006). "Presenilin-dependent ErbB4 nuclear signaling regulates the timing of astrogenesis in the developing brain". Cell.
3. "Entrez Gene: ERBB4 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian)".
4. (Mar 2006). "The involvement of ErbB4 with schizophrenia: association and expression studies". American Journal of Medical Genetics Part B.
5. (Nov 2013). "ERBB4 mutations that disrupt the neuregulin-ErbB4 pathway cause amyotrophic lateral sclerosis type 19". American Journal of Human Genetics.
6. (Mar 2000). "The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses". Proceedings of the National Academy of Sciences of the United States of America.
7. (May 2000). "Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses". Neuron.
8. (Nov 2004). "The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone". The Journal of Cell Biology.
9. (2005). "Phosphotyrosine interactome of the ErbB-receptor kinase family". Molecular Systems Biology.
10. (Apr 2004). "Ligand-regulated association of ErbB-4 to the transcriptional co-activator YAP65 controls transcription at the nuclear level". Experimental Cell Research.