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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 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 (May 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 (October 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 (2006). "The involvement of ErbB4 with schizophrenia: association and expression studies". Am J Med Genet B Neuropsychiatr Genet 141 (B2): 142–8. doi:10.1002/ajmg.b.30275. PMID 16402353. 
  5. ^ Takahashi Y, Fukuda Y, Yoshimura J, Toyoda A, Kurppa K, Moritoyo H, Belzil VV, Dion PA, Higasa K, Doi K, Ishiura H, Mitsui J, Date H, Ahsan B, Matsukawa T, Ichikawa Y, Moritoyo T, Ikoma M, Hashimoto T, Kimura F, Murayama S, Onodera O, Nishizawa M, Yoshida M, Atsuta N, Sobue G, Fifita JA, Williams KL, Blair IP, Nicholson GA, Gonzalez-Perez P, Brown RH, Nomoto M, Elenius K, Rouleau GA, Fujiyama A, Morishita S, Goto J, Tsuji S (2013). "ERBB4 mutations that disrupt the neuregulin-ErbB4 pathway cause amyotrophic lateral sclerosis type 19". Am. J. Hum. Genet. 93 (5): 900–5. doi:10.1016/j.ajhg.2013.09.008. PMC 3824132. PMID 24119685. 
  6. ^ Garcia, R A; Vasudevan K; Buonanno A (March 2000). "The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (7): 3596–601. doi:10.1073/pnas.070042497. ISSN 0027-8424. PMC 16285. PMID 10725395. 
  7. ^ Huang, Y Z; Won S, Ali D W, Wang Q, Tanowitz M, Du Q S, Pelkey K A, Yang D J, Xiong W C, Salter M W, Mei L (May 2000). "Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses". Neuron (UNITED STATES) 26 (2): 443–55. doi:10.1016/S0896-6273(00)81176-9. ISSN 0896-6273. PMID 10839362. 
  8. ^ Williams, Christopher C; Allison June G; Vidal Gregory A; Burow Matthew E; Beckman Barbara S; Marrero Luis; Jones Frank E (November 2004). "The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone". J. Cell Biol. (United States) 167 (3): 469–78. doi:10.1083/jcb.200403155. ISSN 0021-9525. PMC 2172499. PMID 15534001. 
  9. ^ Schulze, Waltraud X; Deng Lei; Mann Matthias (2005). "Phosphotyrosine interactome of the ErbB-receptor kinase family". Mol. Syst. Biol. (England) 1 (1): 2005.0008. doi:10.1038/msb4100012. PMC 1681463. PMID 16729043. 
  10. ^ Omerovic, Jasminka; Puggioni Eleonora M R; Napoletano Silvia; Visco Vincenzo; Fraioli Rocco; Frati Luigi; Gulino Alberto; Alimandi Maurizio (April 2004). "Ligand-regulated association of ErbB-4 to the transcriptional co-activator YAP65 controls transcription at the nuclear level". Exp. Cell Res. (United States) 294 (2): 469–79. doi:10.1016/j.yexcr.2003.12.002. ISSN 0014-4827. PMID 15023535. 

Further reading[edit]