Receptor tyrosine-protein kinase erbB-3

Function

Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. Binds to neuregulin-1 (NRG1) and is activated by it; ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase. May also be activated by CSPG5. Involved in the regulation of myeloid cell differentiation.

Classification

Family (Pfam)

PF00757 Furin-like, PF14843 GF_recep_IV, PF07714 PK_Tyr_Ser-Thr, PF01030 Recep_L_domain

InterPro

Furin-like_Cys-rich_dom, Furin_repeat, GF_recep_IV, Growth_fac_rcpt_cys_sf, Kinase-like_dom_sf, Prot_kinase_dom, Rcpt_L-dom, Rcpt_L-dom_sf, RTK, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_EGF/ERB/XmrK_rcpt

Functional cluster

Secreted Growth Factors & Cytokines

Experimental structures · PDB · 23

• 1M6B X-ray 2.60A
• 2L9U NMR
• 3KEX X-ray 2.80A
• 3LMG X-ray 2.80A
• 3P11 X-ray 3.70A
• 4LEO X-ray 2.64A
• 4P59 X-ray 3.40A
• 4RIW X-ray 3.10A
• 4RIX X-ray 3.10A
• 4RIY X-ray 2.98A
• 5CUS X-ray 3.20A
• 5O4O X-ray 3.40A
• … and 11 more

A predicted model is available from AlphaFold.

Gene Ontology · 46

• GO:0016324 apical plasma membrane
• GO:0009925 basal plasma membrane
• GO:0016323 basolateral plasma membrane
• GO:0038143 ERBB3:ERBB2 complex
• GO:0005615 extracellular space
• GO:0016328 lateral plasma membrane
• GO:0005886 plasma membrane
• GO:0045211 postsynaptic membrane
• GO:0043235 receptor complex
• GO:0005524 ATP binding
• GO:0043125 ErbB-3 class receptor binding
• GO:0019838 growth factor binding
• GO:0042802 identical protein binding
• GO:0038132 neuregulin binding
• GO:0038131 neuregulin receptor activity
• GO:0046982 protein heterodimerization activity
• GO:0004672 protein kinase activity
• GO:0030296 protein tyrosine kinase activator activity
• GO:0004888 transmembrane signaling receptor activity
• GO:0031625 ubiquitin protein ligase binding
• GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
• GO:0021545 cranial nerve development
• GO:0007173 epidermal growth factor receptor signaling pathway
• GO:0038133 ERBB2-ERBB3 signaling pathway
• GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand
• GO:0007507 heart development
• GO:0042552 myelination
• GO:0043066 negative regulation of apoptotic process
• GO:0007162 negative regulation of cell adhesion
• GO:0043524 negative regulation of neuron apoptotic process
• GO:0051048 negative regulation of secretion
• GO:0009968 negative regulation of signal transduction
• GO:0007528 neuromuscular junction development
• GO:0051402 neuron apoptotic process
• GO:0030182 neuron differentiation
• GO:0007422 peripheral nervous system development
• GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction
• GO:0050679 positive regulation of epithelial cell proliferation
• GO:0046330 positive regulation of JNK cascade
• GO:0043410 positive regulation of MAPK cascade
• GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• GO:0042127 regulation of cell population proliferation
• GO:0014044 Schwann cell development
• GO:0014037 Schwann cell differentiation
• GO:0007165 signal transduction
• GO:0042060 wound healing

Disease associations

• erythroleukemia, familial, susceptibility to MONDO:0007573
• visceral neuropathy, familial, 1, autosomal recessive MONDO:8000011
• lethal congenital contracture syndrome 2 MONDO:0011868

Drugs targeting this protein · 4

• SAPITINIB inhibitor
• VANDETANIB inhibitor
• POZIOTINIB inhibitor
• TARLOXOTINIB inhibitor

Related proteins · sequence + function similarity

• Receptor tyrosine-protein kinase erbB-3 1.00
• Receptor tyrosine-protein kinase erbB-3 0.99
• Receptor tyrosine-protein kinase erbB-3 0.99
• Receptor tyrosine-protein kinase erbB-2 0.93
• Receptor tyrosine-protein kinase erbB-2 0.92
• Receptor tyrosine-protein kinase erbB-2 0.92
• Receptor tyrosine-protein kinase erbB-2 0.90
• Receptor tyrosine-protein kinase erbB-2 0.90
• Melanoma receptor tyrosine-protein kinase 0.87
• Epidermal growth factor receptor 0.77
• Epidermal growth factor receptor 0.76
• Epidermal growth factor receptor 0.76

Co-cited proteins · studied together in the literature

• Proliferation-associated protein 2G4 2 shared papers
• Chondroitin sulfate proteoglycan 5 1 shared papers
• Proliferation-associated protein 2G4 1 shared papers
• Receptor tyrosine-protein kinase erbB-2 2 shared papers
• Receptor tyrosine-protein kinase erbB-4 2 shared papers
• Growth factor receptor-bound protein 7 1 shared papers
• RAC-alpha serine/threonine-protein kinase 1 shared papers
• Mucin-1 1 shared papers
• Pro-neuregulin-1, membrane-bound isoform 1 shared papers
• Integrin beta-4 1 shared papers
• Integrin alpha-6 1 shared papers
• Integrin alpha-V 1 shared papers

Literature · 23 cited papers

• Dysregulation of the NRG1/ERBB pathway causes a developmental disorder with gastrointestinal dysmotility in humans. J. Clin. Invest. · 2021
• A germline ERBB3 variant is a candidate for predisposition to erythroid MDS/erythroleukemia. Leukemia · 2016
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Spatial structure and dimer-monomer equilibrium of the ErbB3 transmembrane domain in DPC micelles. Biochim. Biophys. Acta · 2011
• Direct binding of the EGF-like domain of neuregulin-1 to integrins ({alpha}v{beta}3 and {alpha}6{beta}4) is involved in neuregulin-1/ErbB signaling. J. Biol. Chem. · 2010
• ErbB3/HER3 intracellular domain is competent to bind ATP and catalyze autophosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2010
• Structural analysis of the catalytically inactive kinase domain of the human EGF receptor 3. Proc. Natl. Acad. Sci. U.S.A. · 2009
• Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
• Lethal congenital contractural syndrome type 2 (LCCS2) is caused by a mutation in ERBB3 (Her3), a modulator of the phosphatidylinositol-3-kinase/Akt pathway. Am. J. Hum. Genet. · 2007
• Patterns of somatic mutation in human cancer genomes. Nature · 2007
• Ebp1 isoforms distinctively regulate cell survival and differentiation. Proc. Natl. Acad. Sci. U.S.A. · 2006
• … and 11 more in the literature graph