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V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4
Protein ERBB4 PDB 2ahx.png
PDB rendering based on 2ahx.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols ERBB4 ; ALS19; HER4; p180erbB4
External IDs OMIM600543 MGI104771 HomoloGene21084 IUPHAR: 1799 ChEMBL: 3009 GeneCards: ERBB4 Gene
EC number
RNA expression pattern
PBB GE ERBB4 206794 at tn.png
More reference expression data
Species Human Mouse
Entrez 2066 13869
Ensembl ENSG00000178568 ENSMUSG00000062209
UniProt Q15303 Q61527
RefSeq (mRNA) NM_001042599 NM_010154
RefSeq (protein) NP_001036064 NP_034284
Location (UCSC) Chr 2:
212.24 – 213.4 Mb
Chr 1:
68.03 – 69.11 Mb
PubMed search [1] [2]

Receptor tyrosine-protein kinase erbB-4 is an enzyme that in humans is encoded by the ERBB4 gene.[1][2] Alternatively spliced variants that encode different protein isoforms have been described; however, not all variants have been fully characterized.[3]


Receptor tyrosine-protein kinase erbB-4 is a receptor tyrosine kinase that is a member of the epidermal growth factor receptor subfamily. 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 and -3, 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.[3]

Clinical significance[edit]

Mutations in this gene have been associated with cancer.[3] Other single-nucleotide polymorphisms and a risk haplotype have been linked to schizophrenia.[4] Single-nucleotide polymorphisms in ERBB4 have also been found in a study of patients with familial Amyotrophic lateral sclerosis type 19 [5]


ERBB4 has been shown to interact with:


  1. ^ Zimonjic DB, Alimandi M, Miki T, Popescu NC, Kraus MH (Mar 1995). "Localization of the human HER4/erbB-4 gene to chromosome 2". Oncogene 10 (6): 1235–7. PMID 7700649. 
  2. ^ Sardi SP, Murtie J, Koirala S, Patten BA, Corfas G (Oct 2006). "Presenilin-dependent ErbB4 nuclear signaling regulates the timing of astrogenesis in the developing brain". Cell 127 (1): 185–97. doi:10.1016/j.cell.2006.07.037. PMID 17018285. 
  3. ^ a b c "Entrez Gene: ERBB4 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian)". 
  4. ^ Silberberg G, Darvasi A, Pinkas-Kramarski R, Navon R (Mar 2006). "The involvement of ErbB4 with schizophrenia: association and expression studies". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : The Official Publication of the International Society of Psychiatric Genetics 141B (2): 142–8. doi:10.1002/ajmg.b.30275. PMID 16402353. 
  5. ^ Takahashi Y, Fukuda Y, Yoshimura J, Toyoda A, Kurppa K, Moritoyo H et al. (Nov 2013). "ERBB4 mutations that disrupt the neuregulin-ErbB4 pathway cause amyotrophic lateral sclerosis type 19". American Journal of Human Genetics 93 (5): 900–5. doi:10.1016/j.ajhg.2013.09.008. PMC 3824132. PMID 24119685. 
  6. ^ Garcia RA, Vasudevan K, Buonanno A (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 97 (7): 3596–601. doi:10.1073/pnas.070042497. PMC 16285. PMID 10725395. 
  7. ^ Huang YZ, Won S, Ali DW, Wang Q, Tanowitz M, Du QS et al. (May 2000). "Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses". Neuron 26 (2): 443–55. doi:10.1016/S0896-6273(00)81176-9. PMID 10839362. 
  8. ^ Williams CC, Allison JG, Vidal GA, Burow ME, Beckman BS, Marrero L et al. (Nov 2004). "The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone". The Journal of Cell Biology 167 (3): 469–78. doi:10.1083/jcb.200403155. PMC 2172499. PMID 15534001. 
  9. ^ Schulze WX, Deng L, Mann M (2005). "Phosphotyrosine interactome of the ErbB-receptor kinase family". Molecular Systems Biology 1 (1): 2005.0008. doi:10.1038/msb4100012. PMC 1681463. PMID 16729043. 
  10. ^ Omerovic J, Puggioni EM, Napoletano S, Visco V, Fraioli R, Frati L et al. (Apr 2004). "Ligand-regulated association of ErbB-4 to the transcriptional co-activator YAP65 controls transcription at the nuclear level". Experimental Cell Research 294 (2): 469–79. doi:10.1016/j.yexcr.2003.12.002. PMID 15023535. 

Further reading[edit]