Receptor tyrosine-protein kinase erbB-2
Also known as: ERBB2, HER2, MLN19, NEU, NGL
Function
Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization.
Classification
- Family (Pfam)
- PF00757 Furin-like, PF14843 GF_recep_IV, PF07714 PK_Tyr_Ser-Thr, PF01030 Recep_L_domain, PF21314 TM_ErbB1
- InterPro
- Furin-like_Cys-rich_dom, Furin_repeat, GF_recep_IV, Growth_fac_rcpt_cys_sf, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, Rcpt_L-dom, Rcpt_L-dom_sf, RTK, Ser-Thr/Tyr_kinase_cat_dom, TM_ErbB1, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_EGF/ERB/XmrK_rcpt
- Functional cluster
- Secreted Growth Factors & Cytokines
Experimental structures · PDB · 59
- 1MFG X-ray 1.25A
- 1MFL X-ray 1.88A
- 1MW4 NMR
- 1N8Z X-ray 2.52A
- 1QR1 X-ray 2.40A
- 1S78 X-ray 3.25A
- 2A91 X-ray 2.50A
- 2JWA NMR
- 2KS1 NMR
- 2L4K NMR
- 2N2A NMR
- 3BE1 X-ray 2.90A
- … and 47 more
A predicted model is available from AlphaFold.
Gene Ontology · 65
- GO:0016324 apical plasma membrane
- GO:0009925 basal plasma membrane
- GO:0016323 basolateral plasma membrane
- GO:0005829 cytosol
- GO:0005769 early endosome
- GO:0010008 endosome membrane
- GO:0038143 ERBB3:ERBB2 complex
- GO:0016020 membrane
- GO:0043209 myelin sheath
- GO:0031594 neuromuscular junction
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0048471 perinuclear region of cytoplasm
- GO:0005886 plasma membrane
- GO:0045211 postsynaptic membrane
- GO:0042734 presynaptic membrane
- GO:0043235 receptor complex
- GO:0032587 ruffle membrane
- GO:0002116 semaphorin receptor complex
- GO:0005524 ATP binding
- GO:0015026 coreceptor activity
- GO:0043125 ErbB-3 class receptor binding
- GO:0042802 identical protein binding
- GO:0046982 protein heterodimerization activity
- GO:0004713 protein tyrosine kinase activity
- GO:0030971 receptor tyrosine kinase binding
- GO:0001042 RNA polymerase I core binding
- GO:0005102 signaling receptor binding
- GO:0004714 transmembrane receptor protein tyrosine kinase activity
- GO:0004888 transmembrane signaling receptor activity
- GO:0008283 cell population proliferation
- GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
- GO:0007166 cell surface receptor signaling pathway
- GO:0071364 cellular response to epidermal growth factor stimulus
- GO:0071363 cellular response to growth factor stimulus
- GO:0006351 DNA-templated transcription
- GO:0007167 enzyme-linked receptor protein signaling pathway
- GO:0007173 epidermal growth factor receptor signaling pathway
- GO:0038134 ERBB2-EGFR signaling pathway
- GO:0038133 ERBB2-ERBB3 signaling pathway
- GO:0038135 ERBB2-ERBB4 signaling pathway
- GO:0035556 intracellular signal transduction
- GO:0043066 negative regulation of apoptotic process
- GO:0030182 neuron differentiation
- GO:0099645 neurotransmitter receptor localization to postsynaptic specialization membrane
- GO:0018108 peptidyl-tyrosine phosphorylation
- GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction
- GO:0045785 positive regulation of cell adhesion
- GO:0030307 positive regulation of cell growth
- GO:0050679 positive regulation of epithelial cell proliferation
- GO:0046330 positive regulation of JNK cascade
- GO:0043406 positive regulation of MAP kinase activity
- GO:0043410 positive regulation of MAPK cascade
- GO:0090314 positive regulation of protein targeting to membrane
- GO:0035025 positive regulation of Rho protein signal transduction
- GO:0045943 positive regulation of transcription by RNA polymerase I
- GO:0045727 positive regulation of translation
- GO:0006468 protein phosphorylation
- GO:0045765 regulation of angiogenesis
- GO:0070372 regulation of ERK1 and ERK2 cascade
- GO:0032886 regulation of microtubule-based process
- GO:0014044 Schwann cell development
- GO:0071526 semaphorin-plexin signaling pathway
- GO:0007165 signal transduction
- GO:0042060 wound healing
Disease associations
- glioma susceptibility 1 MONDO:0024498
- ovarian cancer MONDO:0008170
- lung cancer MONDO:0008903
- gastric cancer MONDO:0001056
- visceral neuropathy, familial, 2, autosomal recessive MONDO:0030399
Drugs targeting this protein · 27
- LAPATINIB DITOSYLATE inhibitor
- MUBRITINIB inhibitor
- TAK-285 inhibitor
- AC-480 inhibitor
- NERATINIB inhibitor
- ALLITINIB inhibitor
- VARLITINIB inhibitor
- AFATINIB DIMALEATE inhibitor
- DACOMITINIB inhibitor
- DACOMITINIB ANHYDROUS inhibitor
- SAPITINIB inhibitor
- VANDETANIB inhibitor
- JNJ-26483327 inhibitor
- MASOPROCOL inhibitor
- TESEVATINIB inhibitor
- POZIOTINIB inhibitor
- BMS-690514 inhibitor
- PYROTINIB inhibitor
- TUCATINIB inhibitor
- NERATINIB MALEATE inhibitor
- TARLOXOTINIB inhibitor
- TUXOBERTINIB negative allosteric modulator
- CP-724714 inhibitor
- CANERTINIB DIHYDROCHLORIDE inhibitor
- AEE-788 inhibitor
- CUDC-101 inhibitor
- AV-412 inhibitor
Related proteins · sequence + function similarity
- Receptor tyrosine-protein kinase erbB-2 0.99
- Receptor tyrosine-protein kinase erbB-2 0.99
- Receptor tyrosine-protein kinase erbB-2 0.99
- Receptor tyrosine-protein kinase erbB-2 0.98
- Receptor tyrosine-protein kinase erbB-3 0.90
- Receptor tyrosine-protein kinase erbB-3 0.90
- Receptor tyrosine-protein kinase erbB-3 0.89
- Receptor tyrosine-protein kinase erbB-3 0.89
- Epidermal growth factor receptor 0.80
- Epidermal growth factor receptor 0.80
- Melanoma receptor tyrosine-protein kinase 0.79
- Epidermal growth factor receptor 0.77
Co-cited proteins · studied together in the literature
- Receptor tyrosine-protein kinase erbB-2 1 shared papers
- Protein MEMO1 2 shared papers
- Adapter SH3BGRL 1 shared papers
- Receptor tyrosine-protein kinase erbB-3 2 shared papers
- Receptor tyrosine-protein kinase erbB-4 3 shared papers
- Cyclin-dependent kinase 12 1 shared papers
- Tyrosine-protein phosphatase non-receptor type 12 1 shared papers
- Erbin 1 shared papers
- Growth factor receptor-bound protein 7 1 shared papers
- Plexin-B1 1 shared papers
- SH3 domain-binding glutamic acid-rich-like protein 3 1 shared papers
- Protein-tyrosine kinase 6 1 shared papers
Literature · 50 cited papers
- IGFBP5 is an ROR1 ligand promoting glioblastoma invasion via ROR1/HER2-CREB signaling axis. Nat. Commun. · 2023
- SH3BGRL3 binds to myosin 1c in a calcium dependent manner and modulates migration in the MDA-MB-231 cell line. BMC Mol. Cell Biol. · 2021
- Dysregulation of the NRG1/ERBB pathway causes a developmental disorder with gastrointestinal dysmotility in humans. J. Clin. Invest. · 2021
- SH3BGRL confers innate drug resistance in breast cancer by stabilizing HER2 activation on cell membrane. J. Exp. Clin. Cancer Res. · 2020
- SORLA regulates endosomal trafficking and oncogenic fitness of HER2. Nat. Commun. · 2019
- Crystal structure and substrate specificity of PTPN12. Cell Rep. · 2016
- Client proteins and small molecule inhibitors display distinct binding preferences for constitutive and stress-induced HSP90 isoforms and their conformationally restricted mutants. PLoS ONE · 2015
- Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism. Nat. Commun. · 2014
- 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
- Nuclear ErbB2 enhances translation and cell growth by activating transcription of ribosomal RNA genes. Cancer Res. · 2011
- Structural analysis of the mechanism of inhibition and allosteric activation of the kinase domain of HER2 protein. J. Biol. Chem. · 2011
- … and 38 more in the literature graph