ERBB4

ERBB4
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2AHX, 2L2T, 2LCX, 2R4B, 3BBT, 3BBW, 3BCE, 3U2P, 3U7U, 3U9U
Identifiers
Aliases	ERBB4, ALS19, HER4, p180erbB4, erb-b2 receptor tyrosine kinase 4
External IDs	OMIM: 600543; MGI: 104771; HomoloGene: 21084; GeneCards: ERBB4; OMA:ERBB4 - orthologs
Gene location (Human)
Chr.	Chromosome 2 (human)
End	212,538,841 bp
Gene location (Mouse)
Chr.	Chromosome 1 (mouse)
End	69,147,218 bp
RNA expression pattern
	Top expressed in
	endothelial cell; ; secondary oocyte; ; optic nerve; ; middle temporal gyrus; ; buccal mucosa cell; ; Brodmann area 23; ; entorhinal cortex; ; Brodmann area 46; ; orbitofrontal cortex; ; right uterine tube;
	Top expressed in
	dentate gyrus of hippocampal formation granule cell; ; superior frontal gyrus; ; interventricular septum; ; visual cortex; ; primary visual cortex; ; Cardiac muscle tissue of myocardium; ; cardiac muscle tissue of left ventricle; ; corneal stroma; ; plantaris muscle; ; gray matter layer of cerebellum;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	transferase activity; nucleotide binding; protein kinase activity; protein homodimerization activity; epidermal growth factor receptor binding; kinase activity; protein binding; transmembrane receptor protein tyrosine kinase activity; ATP binding; protein tyrosine kinase activity; phosphatidylinositol-4,5-bisphosphate 3-kinase activity; receptor tyrosine kinase; transmembrane signaling receptor activity;
Cellular component	integral component of membrane; cytosol; membrane; receptor complex; plasma membrane; nucleoplasm; extracellular region; mitochondrial matrix; basolateral plasma membrane; mitochondrion; nucleus; postsynaptic membrane; glutamatergic synapse; GABA-ergic synapse; integral component of presynaptic membrane; integral component of postsynaptic density membrane; cytoplasm; integral component of plasma membrane; basal plasma membrane;
Biological process	mitochondrial fragmentation involved in apoptotic process; negative regulation of neuron migration; cell fate commitment; positive regulation of protein phosphorylation; regulation of cell migration; regulation of transcription, DNA-templated; olfactory bulb interneuron differentiation; embryonic pattern specification; phosphorylation; transmembrane receptor protein tyrosine kinase signaling pathway; central nervous system morphogenesis; mammary gland alveolus development; transcription, DNA-templated; nervous system development; mammary gland epithelial cell differentiation; MAPK cascade; positive regulation of phosphatidylinositol 3-kinase activity; positive regulation of transcription, DNA-templated; multicellular organism development; heart development; protein phosphorylation; positive regulation of cardiac muscle cell proliferation; neural crest cell migration; positive regulation of ERK1 and ERK2 cascade; positive regulation of protein localization to cell surface; protein autophosphorylation; cardiac muscle tissue regeneration; positive regulation of phosphatidylinositol 3-kinase signaling; peptidyl-tyrosine phosphorylation; lactation; cell population proliferation; cell migration; signal transduction; negative regulation of cell population proliferation; apoptotic process; ERBB2 signaling pathway; phosphatidylinositol phosphate biosynthetic process; peptidyl-tyrosine autophosphorylation; positive regulation of cell population proliferation; positive regulation of apoptotic process; regulation of cell motility; negative regulation of apoptotic process; cellular response to epidermal growth factor stimulus; positive regulation of tyrosine phosphorylation of STAT protein; positive regulation of protein kinase B signaling; positive regulation of receptor signaling pathway via JAK-STAT; synapse assembly; negative regulation of signal transduction; cell differentiation;
	Sources:Amigo / QuickGO
Orthologs
	2066
	13869
	ENSG00000178568
	ENSMUSG00000062209
	Q15303
	Q61527
	NM_001042599; NM_005235
	NM_010154
	NP_001036064; NP_005226
	NP_034284
	Wikidata
View/Edit Human	View/Edit Mouse

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]

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

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000178568 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000062209 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ 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.
^ ^a ^b ^c "Entrez Gene: ERBB4 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian)".
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.

External links

Overview of all the structural information available in the PDB for UniProt: Q15303 (Receptor tyrosine-protein kinase erbB-4) at the PDBe-KB.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000178568 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[pmid7700649-5] 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.

[pmid17018285-6] 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.

[entrez-7] "Entrez Gene: ERBB4 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian)".

[pmid16402353-8] 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.

[pmid24119685-9] 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.

[pmid10725395-10] 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.

[pmid10839362-11] 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.

[pmid15534001-12] 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.

[pmid16729043-13] 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.

[pmid15023535-14] 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.

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v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

Function

Clinical significance

Interactions

References

Further reading

External links