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Kinase Fusion Gene:CNOT2_ERBB3 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: CNOT2_ERBB3 | KinaseFusionDB ID: KFG1369 | FusionGDB2.0 ID: KFG1369 | Hgene | Tgene | Gene symbol | CNOT2 | ERBB3 | Gene ID | 4848 | 2065 | |
| Gene name | CCR4-NOT transcription complex subunit 2 | erb-b2 receptor tyrosine kinase 3 | ||||||||||
| Synonyms | CDC36|HSPC131|IDNADFS|NOT2|NOT2H | ErbB-3|FERLK|HER3|LCCS2|MDA-BF-1|VSCN1|c-erbB-3|c-erbB3|erbB3-S|p180-ErbB3|p45-sErbB3|p85-sErbB3 | ||||||||||
| Cytomap | 12q15 | 12q13.2 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | CCR4-NOT transcription complex subunit 2CC chemokine receptor 4-negative regulator of transcription 2CCR4-associated factor 2negative regulator of transcription 2 | receptor tyrosine-protein kinase erbB-3human epidermal growth factor receptor 3proto-oncogene-like protein c-ErbB-3tyrosine kinase-type cell surface receptor HER3v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3 | ||||||||||
| Modification date | 20240403 | 20240411 | ||||||||||
| UniProtAcc | Q9NZN8 | P21860 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000229195, ENST00000418359, ENST00000548230, ENST00000551483, | ENST00000411731, ENST00000549832, ENST00000267101, ENST00000415288, ENST00000450146, ENST00000553131, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: CNOT2 [Title/Abstract] AND ERBB3 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | CNOT2(70672054)-ERBB3(56493958), # samples:2 | |||||||||||
| Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Hgene | CNOT2 | GO:0000122 | negative regulation of transcription by RNA polymerase II | 14707134|16712523 |
| Tgene | ERBB3 | GO:0007162 | negative regulation of cell adhesion | 7556068 |
| Tgene | ERBB3 | GO:0007165 | signal transduction | 10572067 |
| Tgene | ERBB3 | GO:0007169 | cell surface receptor protein tyrosine kinase signaling pathway | 7556068 |
| Tgene | ERBB3 | GO:0009968 | negative regulation of signal transduction | 11389077 |
| Tgene | ERBB3 | GO:0042127 | regulation of cell population proliferation | 11389077 |
| Tgene | ERBB3 | GO:0043491 | phosphatidylinositol 3-kinase/protein kinase B signal transduction | 7556068 |
| Tgene | ERBB3 | GO:0051048 | negative regulation of secretion | 10559227 |
| Kinase Fusion gene breakpoints across CNOT2 (5'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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| Kinase Fusion gene breakpoints across ERBB3 (3'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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Kinase Fusion Gene Sample Information |
| Kinase Fusion gene information. |
| Kinase Fusion gene information from four resources (ChiTars 5.0, ChimerDB 4.0, COSMIC, and CCLE) * All genome coordinats were lifted-over on hg19. * Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser. |
| Source | Sample | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp |
| ChimerDB4 | TCGA-06-5856-01A | CNOT2 | chr12 | 70672054 | ERBB3 | chr12 | 56493958 |
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Kinase Fusion ORF Analysis |
| Kinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB. |
| Henst | Tenst | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Seq length (transcript) | Seq length (amino acids) |
| ENST00000229195 | ENST00000267101 | CNOT2 | chr12 | 70672054 | ERBB3 | chr12 | 56493958 | 2977 | 328 |
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Kinase Fusion Amino Acid Sequences |
| For individual full-length fusion transcript sequence from KinaseFusionDB, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
| >Henst_Tenst_Hgene_Hchr_Hbp_Tgene_Tchr_Tbp_length(fusion AA)_AAseq >ENST00000229195_ENST00000267101_CNOT2_chr12_70672054_ERBB3_chr12_56493958_length(amino acids)=328 MIASGTVRKGHDSMVRTDGHTLSEKRNYQSQSLLSPSSGYMPMNQGNLGESCQESAVSGSSERCPRPVSLHPMPRGCLASESSEGHVTGS EAELQEKVSMCRSRSRSRSPRPRGDSAYHSQRHSLLTPVTPLSPPGLEEEDVNGYVMPDTHLKGTPSSREGTLSSVGLSSVLGTEEEDED EEYEYMNRRRRHSPPHPPRPSSLEELGYEYMDVGSDLSASLGSTQSCPLHPVPIMPTAGTTPDEDYEYMNRQRDGGGPGGDYAAMGACPA -------------------------------------------------------------- |
Multiple Sequence Alignment of All Fusion Protein Isoforms |
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Kinase Fusion Protein Functional Features |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr12:70672054/chr12:56493958) - FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels. - How to search 1. Put your fusion gene symbol. 2. Press the tab key until there will be shown the breakpoint information filled. 4. Go down and press 'Search' tab twice. 4. Go down to have the hyperlink of the search result. 5. Click the hyperlink. 6. See the FGviewer result for your fusion gene. |
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| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| CNOT2 | ERBB3 |
| FUNCTION: Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Required for the CCR4-NOT complex structural integrity. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may specifically involve the N-Cor repressor complex containing HDAC3, NCOR1 and NCOR2. Involved in the maintenance of embryonic stem (ES) cell identity. {ECO:0000269|PubMed:14707134, ECO:0000269|PubMed:16712523, ECO:0000269|PubMed:21299754, ECO:0000269|PubMed:22367759}. | 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 (PubMed:20682778). May also be activated by CSPG5 (PubMed:15358134). Involved in the regulation of myeloid cell differentiation (PubMed:27416908). {ECO:0000269|PubMed:15358134, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:27416908}. |
| Retention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained domain in the 5'-partner of fusion protein (protein functional feature from UniProt). |
| Partner | Hgeneene | Hbp | Tgeneene | Tbp | ENST | BPexon | TotalExon | Protein feature loci | BPloci | TotalLen | Feature | Note |
| - Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt). |
| Partner | Hgeneene | Hbp | Tgeneene | Tbp | ENST | BPexon | TotalExon | Protein feature loci | BPloci | TotalLen | Feature | Note |
| Tgene | CNOT2 | 70672054 | ERBB3 | 56493958 | ENST00000229195 | 0 | 3 | 709_966 | 0 | 184 | Domain | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Tgene | CNOT2 | 70672054 | ERBB3 | 56493958 | ENST00000229195 | 11 | 15 | 709_966 | 400 | 700 | Domain | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
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Kinase Fusion Protein Structures |
| CIF files of the predicted kinase fusion proteins * Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| Kinase Fusion protein CIF link (fusion AA seq ID in KinaseFusionDB) | Henst | Tenst | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | AA seq | Len(AA seq) |
| PDB file >>>115_CNOT2_ERBB3 | ENST00000229195 | ENST00000267101 | CNOT2 | chr12 | 70672054 | ERBB3 | chr12 | 56493958 | MIASGTVRKGHDSMVRTDGHTLSEKRNYQSQSLLSPSSGYMPMNQGNLGESCQESAVSGSSERCPRPVSLHPMPRGCLASESSEGHVTGS EAELQEKVSMCRSRSRSRSPRPRGDSAYHSQRHSLLTPVTPLSPPGLEEEDVNGYVMPDTHLKGTPSSREGTLSSVGLSSVLGTEEEDED EEYEYMNRRRRHSPPHPPRPSSLEELGYEYMDVGSDLSASLGSTQSCPLHPVPIMPTAGTTPDEDYEYMNRQRDGGGPGGDYAAMGACPA | 328 |
| 3D view using mol* of 115_CNOT2_ERBB3 | ||||||||||
| PDB file >>>TKFP_195_CNOT2_ERBB3 | ENST00000229195 | ENST00000267101 | CNOT2 | chr12 | 70672054 | ERBB3 | chr12 | 56493958 | MIASGTVRKGHDSMVRTDGHTLSEKRNYQSQSLLSPSSGYMPMNQGNLGESCQESAVSGSSERCPRPVSLHPMPRGCLASESSEGHVTGS EAELQEKVSMCRSRSRSRSPRPRGDSAYHSQRHSLLTPVTPLSPPGLEEEDVNGYVMPDTHLKGTPSSREGTLSSVGLSSVLGTEEEDED EEYEYMNRRRRHSPPHPPRPSSLEELGYEYMDVGSDLSASLGSTQSCPLHPVPIMPTAGTTPDEDYEYMNRQRDGGGPGGDYAAMGACPA | 328_CNOT2_ERBB3 |
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Comparison of Fusion Protein Isoforms |
| Superimpose the 3D Structures Among All Fusion Protein Isoforms * Download the pdb file and open it from the molstar online viewer. |
| Comparison of the Secondary Structures of Fusion Protein Isoforms |
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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB |
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pLDDT score distribution |
| pLDDT score distribution of the predicted fusion protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. * The blue color at the bottom marks the best active site residues. |
| 115_CNOT2_ERBB3.png |
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| 115_CNOT2_ERBB3.png |
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Potential Active Site Information |
| The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite. |
| Kinase Fusion AA seq ID in KinaseFusionDB | Site score | Size | Dscore | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
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Ramachandran Plot of Kinase Fusion Protein Structure |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide. |
| 115_CNOT2_ERBB3_ramachandran.png |
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Virtual Screening Results |
| Distribution of the average docking score across all approved kinase inhibitors. Distribution of the number of occurrence across all approved kinase inhibitors. |
| 5'-kinase fusion protein case |
| 3'-kinase fusion protein case |
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| Drug information from DrugBank of the top 20 interacting small molecules. * The detailed information of individual kinase inhibitors are available in the download page. |
| Fusion gene name info | Drug | Docking score | Glide g score | Glide energy |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Tofacitinib | -3.4376800000000003 | -3.44918 | -21.544 |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Tofacitinib | -3.4376800000000003 | -3.44918 | -21.544 |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Abrocitinib | -3.13279 | -3.1438900000000003 | -22.8268 |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Abrocitinib | -3.13279 | -3.1438900000000003 | -22.8268 |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Tofacitinib | -3.08828 | -3.09978 | -20.9931 |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Tofacitinib | -3.08828 | -3.09978 | -20.9931 |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Ruxolitinib | -3.0374 | -3.0374 | -21.4094 |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Abrocitinib | -3.01608 | -3.02718 | -24.78 |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Abrocitinib | -3.01608 | -3.02718 | -24.78 |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Upadacitinib | -2.97416 | -2.97516 | -24.0738 |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Upadacitinib | -2.7972599999999996 | -2.79826 | -21.355 |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Tofacitinib | -2.77115 | -2.78265 | -18.9684 |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Tofacitinib | -2.77115 | -2.78265 | -18.9684 |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Upadacitinib | -2.73385 | -2.73485 | -24.0563 |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Tofacitinib | -2.7225900000000003 | -2.73409 | -15.8063 |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Tofacitinib | -2.7225900000000003 | -2.73409 | -15.8063 |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Larotrectinib | -2.58901 | -2.58901 | -22.0976 |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Larotrectinib | -2.5815 | -2.5815 | -22.9249 |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Larotrectinib | -2.56608 | -2.56608 | -24.576999999999998 |
| 115_CNOT2_ERBB3-DOCK_HTVS_1-001 | Capmatinib | -2.52123 | -2.52683 | -23.9372 |
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Kinase-Substrate Information of CNOT2_ERBB3 |
| Phosphorylation target of the kinase (phosphosite, 03-17-2024) |
| Kinase | Kinase UniProt Acc | Kinase species | Substrate | Substrate UniProt Acc | Substrate phosphorylated residues | Substrate phosphorylated sites (+/-7AA) | Domain |
| Biological Network Integration of This Kinase and Substrates (GeneMANIA website) |
| Enriched GO biological processes of the phosphorylation target genes of the kinase |
| Kinase | GOID | GO term | P.adjust |
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Related Drugs to CNOT2_ERBB3 |
| Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Drug | Source | PMID |
| Distribution of the number of studies mentioning CNOT2-ERBB3 and kinase inhibitors the PubMed Abstract (04-01-2024) |
| Fusion gene - drug pair 1 | Fusion gene - drug pair 2 | PMID | Publication date | DOI | Study title |
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Related Diseases to CNOT2_ERBB3 |
| Diseases that have this fusion gene. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Disease | Source | PMID |
| Related diseases from the literature mentioned this fusion gene and drug. (PubMed, 04-01-2024) |
| MeSH ID | MeSH term |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
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Clinical Trials of the Found Drugs/Small Molecules |
| Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024) |
| Clinical Trials from clinicaltrials.gov (06-17-2024) |
| Fusion Gene | Kinase Inhibitor | NCT ID | Study Status | Phases | Disease | # Enrolment | Date |
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