ERBB4

Receptor tyrosine-protein kinase erbB-4 is an enzyme that in humans is encoded by the ERBB4 gene.[5][6] Alternatively spliced variants that encode different protein isoforms have been described; however, not all variants have been fully characterized.[7]

ERBB4
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesERBB4, ALS19, HER4, p180erbB4, erb-b2 receptor tyrosine kinase 4
External IDsOMIM: 600543 MGI: 104771 HomoloGene: 21084 GeneCards: ERBB4
Orthologs
SpeciesHumanMouse
Entrez

2066

13869

Ensembl

ENSG00000178568

ENSMUSG00000062209

UniProt

Q15303

Q61527

RefSeq (mRNA)

NM_001042599
NM_005235

NM_010154

RefSeq (protein)

NP_001036064
NP_005226

NP_034284

Location (UCSC)Chr 2: 211.38 – 212.54 MbChr 1: 68.07 – 69.15 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[7]

Clinical significance

Mutations in this gene have been associated with cancer.[7] Other single-nucleotide polymorphisms and a risk haplotype have been linked to schizophrenia.[8] Single-nucleotide polymorphisms in ERBB4 have also been found in a study of patients with familial amyotrophic lateral sclerosis type 19.[9]

Interactions

ERBB4 has been shown to interact with:

References
  1. GRCh38: Ensembl release 89: ENSG00000178568 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000062209 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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.
  6. 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. S2CID 18779079.
  7. "Entrez Gene: ERBB4 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian)".
  8. 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. 141B (2): 142–8. doi:10.1002/ajmg.b.30275. PMID 16402353. S2CID 23553550.
  9. 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.
  10. 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.
  11. Huang YZ, Won S, Ali DW, Wang Q, Tanowitz M, Du QS, Pelkey KA, Yang DJ, Xiong WC, Salter MW, Mei L (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. S2CID 1429113.
  12. Williams CC, Allison JG, Vidal GA, Burow ME, Beckman BS, Marrero L, Jones FE (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.
  13. 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.
  14. Omerovic J, Puggioni EM, Napoletano S, Visco V, Fraioli R, Frati L, Gulino A, Alimandi M (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
  • Overview of all the structural information available in the PDB for UniProt: Q15303 (Receptor tyrosine-protein kinase erbB-4) at the PDBe-KB.


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