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Kinase Fusion Gene:MUC4_TNK2 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: MUC4_TNK2 | KinaseFusionDB ID: KFG3992 | FusionGDB2.0 ID: KFG3992 | Hgene | Tgene | Gene symbol | MUC4 | TNK2 | Gene ID | 4585 | 10188 | |
| Gene name | mucin 4, cell surface associated | tyrosine kinase non receptor 2 | ||||||||||
| Synonyms | ASGP|HSA276359|MUC-4 | ACK|ACK-1|ACK1|p21cdc42Hs | ||||||||||
| Cytomap | 3q29 | 3q29 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | mucin-4ascites sialoglycoproteinmucin 4, tracheobronchialpancreatic adenocarcinoma mucintestis mucintracheobronchial mucin | activated CDC42 kinase 1activated Cdc42-associated kinase 1activated p21cdc42Hs kinasetyrosine kinase non-receptor protein 2 | ||||||||||
| Modification date | 20240407 | 20240411 | ||||||||||
| UniProtAcc | Q99102 | Q07912 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000346145, ENST00000349607, ENST00000463781, ENST00000475231, ENST00000478685, | ENST00000468819, ENST00000316664, ENST00000333602, ENST00000381916, ENST00000392400, ENST00000428187, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: MUC4 [Title/Abstract] AND TNK2 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | MUC4(195495893)-TNK2(195610180), # 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 |
| Tgene | TNK2 | GO:0016310 | phosphorylation | 20333297|20979614 |
| Tgene | TNK2 | GO:0050731 | positive regulation of peptidyl-tyrosine phosphorylation | 10587647 |
| Tgene | TNK2 | GO:2000369 | regulation of clathrin-dependent endocytosis | 18262180 |
| Kinase Fusion gene breakpoints across MUC4 (5'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Kinase Fusion gene breakpoints across TNK2 (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-C5-A8XK-01A | MUC4 | chr3 | 195495893 | TNK2 | chr3 | 195610180 |
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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) |
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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 |
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/:195495893/:195610180) - 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 |
| MUC4 | TNK2 |
| FUNCTION: Membrane-bound mucin, a family of highly glycosylated proteins that constitute the major component of the mucus, the slimy and viscous secretion covering epithelial surfaces (PubMed:10880978). These glycoproteins play important roles in the protection of the epithelium and are implicated in epithelial renewal and differentiation (PubMed:10880978). Regulates cellular behavior through both anti-adhesive effects on cell-cell and cell-extracellular matrix interactions and its ability to act as an intramembrane ligand for ERBB2. Plays an important role in proliferation and differentiation of epithelial cells by inducing specific phosphorylation of ERBB2. In polarized epithelial cells, segregates ERBB2 and other ERBB receptors and prevents ERBB2 from acting as a coreceptor. The interaction with ERBB2 leads to enhanced expression of CDKN1B. The formation of a MUC4-ERBB2-ERBB3-NRG1 complex leads to down-regulation of CDKN1B, resulting in repression of apoptosis and stimulation of proliferation. Its ability to promote tumor growth may be mainly due to repression of apoptosis as opposed to proliferation. {ECO:0000269|PubMed:12102554, ECO:0000269|PubMed:16049287, ECO:0000269|PubMed:16814944, ECO:0000269|PubMed:16914178, ECO:0000303|PubMed:10880978}. | FUNCTION: Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR. Phosphorylates WASP (PubMed:20110370). {ECO:0000269|PubMed:10652228, ECO:0000269|PubMed:11278436, ECO:0000269|PubMed:16247015, ECO:0000269|PubMed:16257963, ECO:0000269|PubMed:16472662, ECO:0000269|PubMed:17038317, ECO:0000269|PubMed:18262180, ECO:0000269|PubMed:18435854, ECO:0000269|PubMed:19815557, ECO:0000269|PubMed:20110370, ECO:0000269|PubMed:20333297, ECO:0000269|PubMed:20383201}. |
| 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 |
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Kinase-Substrate Information of MUC4_TNK2 |
| 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 |
| TNK2 | Q07912 | human | AR | P10275 | Y365 | AyQSRDyyNFPLALA | Androgen_recep |
| TNK2 | Q07912 | human | TNK2 | Q07912 | Y860 | KVsstHyyLLPERPs | |
| TNK2 | Q07912 | human | AKT1 | P31749 | S473 | RPHFPQFsysAsGtA | Pkinase_C |
| TNK2 | Q07912 | human | AR | P10275 | Y269 | QLRGDCMyAPLLGVP | Androgen_recep |
| TNK2 | Q07912 | human | TNK2 | Q07912 | Y284 | LPQNDDHyVMQEHRK | PK_Tyr_Ser-Thr |
| TNK2 | Q07912 | human | H4C1 | P62805 | Y88 | VtAMDVVyALkRQGR | CENP-T_C |
| TNK2 | Q07912 | human | CDKN1B | P46527 | Y88 | kGsLPEFyyRPPRPP | |
| TNK2 | Q07912 | human | ATP5F1A | P25705 | Y243 | SDEkkkLyCIyVAIG | ATP-synt_ab |
| TNK2 | Q07912 | human | TNK2 | Q07912 | Y859 | KKVsstHyyLLPERP | |
| TNK2 | Q07912 | human | ATP5F1A | P25705 | Y246 | kkkLyCIyVAIGQKR | ATP-synt_ab |
| TNK2 | Q07912 | human | WWOX | Q9NZC7 | Y287 | LSPTKNDyWAMLAYN | |
| TNK2 | Q07912 | human | AR | P10275 | Y535 | MDSYSGPyGDMRLET | |
| TNK2 | Q07912 | human | KDM3A | Q9Y4C1 | Y1114 | ITPEDRKyGTTNLHL | |
| TNK2 | Q07912 | human | WAS | P42768 | Y291 | AEtsKLIyDFIEDQG | PBD |
| 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 |
| TNK2 | ID | Description | 0.00e+00 |
| TNK2 | GO:0060768 | regulation of epithelial cell proliferation involved in prostate gland development | 3.61e-03 |
| TNK2 | GO:0060767 | epithelial cell proliferation involved in prostate gland development | 3.61e-03 |
| TNK2 | GO:1901655 | cellular response to ketone | 3.61e-03 |
| TNK2 | GO:0050678 | regulation of epithelial cell proliferation | 5.15e-03 |
| TNK2 | GO:2001236 | regulation of extrinsic apoptotic signaling pathway | 6.55e-03 |
| TNK2 | GO:0050673 | epithelial cell proliferation | 6.55e-03 |
| TNK2 | GO:0050680 | negative regulation of epithelial cell proliferation | 6.60e-03 |
| TNK2 | GO:0072331 | signal transduction by p53 class mediator | 6.60e-03 |
| TNK2 | GO:0071383 | cellular response to steroid hormone stimulus | 8.82e-03 |
| TNK2 | GO:1901654 | response to ketone | 8.82e-03 |
| TNK2 | GO:0071241 | cellular response to inorganic substance | 9.77e-03 |
| TNK2 | GO:0097191 | extrinsic apoptotic signaling pathway | 9.77e-03 |
| TNK2 | GO:2001239 | regulation of extrinsic apoptotic signaling pathway in absence of ligand | 1.33e-02 |
| TNK2 | GO:0030521 | androgen receptor signaling pathway | 1.36e-02 |
| TNK2 | GO:0030850 | prostate gland development | 1.36e-02 |
| TNK2 | GO:0048009 | insulin-like growth factor receptor signaling pathway | 1.38e-02 |
| TNK2 | GO:0046686 | response to cadmium ion | 1.53e-02 |
| TNK2 | GO:0060135 | maternal process involved in female pregnancy | 1.53e-02 |
| TNK2 | GO:0048638 | regulation of developmental growth | 1.53e-02 |
| TNK2 | GO:0048545 | response to steroid hormone | 1.53e-02 |
| TNK2 | GO:0061180 | mammary gland epithelium development | 1.53e-02 |
| TNK2 | GO:0001655 | urogenital system development | 1.53e-02 |
| TNK2 | GO:0038034 | signal transduction in absence of ligand | 1.53e-02 |
| TNK2 | GO:0097192 | extrinsic apoptotic signaling pathway in absence of ligand | 1.53e-02 |
| TNK2 | GO:0043536 | positive regulation of blood vessel endothelial cell migration | 1.89e-02 |
| TNK2 | GO:0000079 | regulation of cyclin-dependent protein serine/threonine kinase activity | 2.11e-02 |
| TNK2 | GO:1904029 | regulation of cyclin-dependent protein kinase activity | 2.12e-02 |
| TNK2 | GO:2001233 | regulation of apoptotic signaling pathway | 2.12e-02 |
| TNK2 | GO:2001237 | negative regulation of extrinsic apoptotic signaling pathway | 2.63e-02 |
| TNK2 | GO:0048732 | gland development | 2.63e-02 |
| TNK2 | GO:0071901 | negative regulation of protein serine/threonine kinase activity | 2.63e-02 |
| TNK2 | GO:1903076 | regulation of protein localization to plasma membrane | 2.97e-02 |
| TNK2 | GO:0030518 | intracellular steroid hormone receptor signaling pathway | 3.67e-02 |
| TNK2 | GO:0010595 | positive regulation of endothelial cell migration | 4.03e-02 |
| TNK2 | GO:0030879 | mammary gland development | 4.10e-02 |
| TNK2 | GO:1904375 | regulation of protein localization to cell periphery | 4.17e-02 |
| TNK2 | GO:0043401 | steroid hormone mediated signaling pathway | 4.17e-02 |
| TNK2 | GO:0001890 | placenta development | 4.85e-02 |
| TNK2 | GO:0043535 | regulation of blood vessel endothelial cell migration | 4.85e-02 |
| TNK2 | GO:0036294 | cellular response to decreased oxygen levels | 5.04e-02 |
| TNK2 | GO:0007009 | plasma membrane organization | 5.16e-02 |
| TNK2 | GO:0048660 | regulation of smooth muscle cell proliferation | 5.16e-02 |
| TNK2 | GO:0071453 | cellular response to oxygen levels | 5.16e-02 |
| TNK2 | GO:0048659 | smooth muscle cell proliferation | 5.16e-02 |
| TNK2 | GO:0010634 | positive regulation of epithelial cell migration | 5.16e-02 |
| TNK2 | GO:0035265 | organ growth | 5.16e-02 |
| TNK2 | GO:0006469 | negative regulation of protein kinase activity | 5.16e-02 |
| TNK2 | GO:0001936 | regulation of endothelial cell proliferation | 5.16e-02 |
| TNK2 | GO:0007219 | Notch signaling pathway | 5.16e-02 |
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Related Drugs to MUC4_TNK2 |
| 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 MUC4-TNK2 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 MUC4_TNK2 |
| 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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