Open Access Articles- Top Results for ERBB4


SymbolsERBB4 ; ALS19; HER4; p180erbB4
External IDsOMIM600543 MGI104771 HomoloGene21084 IUPHAR: 1799 ChEMBL: 3009 GeneCards: ERBB4 Gene
EC number2.7.10.1
RNA expression pattern
File:PBB GE ERBB4 206794 at tn.png
More reference expression data
RefSeq (mRNA)NM_001042599NM_010154
RefSeq (protein)NP_001036064NP_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

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. PMID 17018285. doi:10.1016/j.cell.2006.07.037. 
  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. PMID 16402353. doi:10.1002/ajmg.b.30275. 
  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. PMC 3824132. PMID 24119685. doi:10.1016/j.ajhg.2013.09.008. 
  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. PMC 16285. PMID 10725395. doi:10.1073/pnas.070042497. 
  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. PMID 10839362. doi:10.1016/S0896-6273(00)81176-9. 
  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. PMC 2172499. PMID 15534001. doi:10.1083/jcb.200403155. 
  9. ^ Schulze WX, Deng L, Mann M (2005). "Phosphotyrosine interactome of the ErbB-receptor kinase family". Molecular Systems Biology 1 (1): 2005.0008. PMC 1681463. PMID 16729043. doi:10.1038/msb4100012. 
  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. PMID 15023535. doi:10.1016/j.yexcr.2003.12.002. 

Further reading


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