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Kinase Fusion Gene:ZWILCH_MAP2K1 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: ZWILCH_MAP2K1 | KinaseFusionDB ID: KFG7318 | FusionGDB2.0 ID: KFG7318 | Hgene | Tgene | Gene symbol | ZWILCH | MAP2K1 | Gene ID | 55055 | 5604 | |
| Gene name | zwilch kinetochore protein | mitogen-activated protein kinase kinase 1 | ||||||||||
| Synonyms | KNTC1AP|hZwilch | CFC3|MAPKK1|MEK1|MEL|MKK1|PRKMK1 | ||||||||||
| Cytomap | 15q22.31 | 15q22.31 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | protein zwilch homologZwilch, kinetochore associated, homologhomolog of Drosophila Zwilch | dual specificity mitogen-activated protein kinase kinase 1ERK activator kinase 1MAPK/ERK kinase 1MAPKK 1MEK 1protein kinase, mitogen-activated, kinase 1 (MAP kinase kinase 1) | ||||||||||
| Modification date | 20240305 | 20240407 | ||||||||||
| UniProtAcc | Q9H900 | Q02750 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000535141, ENST00000307897, ENST00000446801, ENST00000565627, ENST00000565960, | ENST00000307102, ENST00000566326, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: ZWILCH [Title/Abstract] AND MAP2K1 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | ||||||||||||
| 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 | MAP2K1 | GO:0006468 | protein phosphorylation | 28166211 |
| Tgene | MAP2K1 | GO:0008285 | negative regulation of cell population proliferation | 9765203 |
| Tgene | MAP2K1 | GO:0071902 | positive regulation of protein serine/threonine kinase activity | 8388392 |
| Kinase Fusion gene breakpoints across ZWILCH (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 MAP2K1 (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 |
| CCLE | SNU-46 | ZWILCH | chr15 | 66832548 | MAP2K1 | chr15 | 66783043 |
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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/:/:) - 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 |
| ZWILCH | MAP2K1 |
| FUNCTION: Essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. Required for the assembly of the dynein-dynactin and MAD1-MAD2 complexes onto kinetochores. Its function related to the spindle assembly machinery is proposed to depend on its association in the mitotic RZZ complex (PubMed:15824131). {ECO:0000269|PubMed:15824131}. | FUNCTION: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126). Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis. {ECO:0000269|PubMed:14737111, ECO:0000269|PubMed:17101779, ECO:0000269|PubMed:29433126}. |
| 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 ZWILCH_MAP2K1 |
| 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 |
| MAP2K1 | Q02750 | human | XRCC6 | P12956 | S77 | VYISKIIssDRDLLA | Ku_N |
| MAP2K1 | Q02750 | human | TARDBP | Q13148 | T153 | GFGFVRFtEyETQVk | RRM_1 |
| MAP2K1 | Q02750 | human | MAPK3 | P27361 | T207 | FLtEyVAtRWyrAPE | Pkinase |
| MAP2K1 | Q02750 | human | MLXIP | Q9HAP2 | Y222 | IEIVIREyHKWRTYF | |
| MAP2K1 | Q02750 | human | GSK3B | P49841 | Y216 | RGEPNVsyICsRyyR | Pkinase |
| MAP2K1 | Q02750 | human | KRT8 | P05787 | S74 | tVNQsLLsPLVLEVD | Keratin_2_head |
| MAP2K1 | Q02750 | human | TARDBP | Q13148 | Y155 | GFVRFtEyETQVkVM | RRM_1 |
| MAP2K1 | Q02750 | human | MACC1 | Q6ZN28 | Y793 | KPAYDFLyTWSAHYG | |
| MAP2K1 | Q02750 | human | MACC1 | Q6ZN28 | Y673 | VLADVLGySHLSLED | |
| MAP2K1 | Q02750 | human | MAPK1 | P28482 | T185 | HDHtGFLtEyVAtRW | Pkinase |
| MAP2K1 | Q02750 | human | MAPK3 | P27361 | Y210 | EyVAtRWyrAPEIML | Pkinase |
| MAP2K1 | Q02750 | human | MACC1 | Q6ZN28 | Y695 | KESEKVSyVIKKLKE | |
| MAP2K1 | Q02750 | human | MAPK3 | P27361 | T202 | HDHtGFLtEyVAtRW | Pkinase |
| MAP2K1 | Q02750 | human | TAL1 | P17542 | S122 | DGRMVQLsPPALAAP | |
| MAP2K1 | Q02750 | human | MAPK1 | P28482 | Y187 | HtGFLtEyVAtRWyr | Pkinase |
| MAP2K1 | Q02750 | human | HSF1 | Q00613 | S326 | ssVDtLLsPTALIDs | Vert_HS_TF |
| MAP2K1 | Q02750 | human | XRCC6 | P12956 | S78 | YISKIIssDRDLLAV | Ku_N |
| MAP2K1 | Q02750 | human | RAF1 | P04049 | S338 | RPRGQRDssyyWEIE | |
| MAP2K1 | Q02750 | human | MAPK3 | P27361 | Y204 | HtGFLtEyVAtRWyr | Pkinase |
| MAP2K1 | Q02750 | human | PGR | P06401 | S294 | APMAPGRsPLATTVM | Prog_receptor |
| 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 |
| MAP2K1 | ID | Description | 0.00e+00 |
| MAP2K1 | GO:0071375 | cellular response to peptide hormone stimulus | 2.29e-04 |
| MAP2K1 | GO:0008286 | insulin receptor signaling pathway | 2.29e-04 |
| MAP2K1 | GO:0030878 | thyroid gland development | 2.29e-04 |
| MAP2K1 | GO:0035270 | endocrine system development | 2.36e-04 |
| MAP2K1 | GO:0071276 | cellular response to cadmium ion | 2.36e-04 |
| MAP2K1 | GO:1901653 | cellular response to peptide | 2.75e-04 |
| MAP2K1 | GO:0048538 | thymus development | 3.35e-04 |
| MAP2K1 | GO:0043434 | response to peptide hormone | 3.35e-04 |
| MAP2K1 | GO:0048009 | insulin-like growth factor receptor signaling pathway | 3.35e-04 |
| MAP2K1 | GO:0060324 | face development | 3.35e-04 |
| MAP2K1 | GO:0046686 | response to cadmium ion | 4.17e-04 |
| MAP2K1 | GO:0032869 | cellular response to insulin stimulus | 4.17e-04 |
| MAP2K1 | GO:0048863 | stem cell differentiation | 7.75e-04 |
| MAP2K1 | GO:0071216 | cellular response to biotic stimulus | 7.97e-04 |
| MAP2K1 | GO:0032868 | response to insulin | 7.97e-04 |
| MAP2K1 | GO:0048708 | astrocyte differentiation | 7.97e-04 |
| MAP2K1 | GO:0050847 | progesterone receptor signaling pathway | 7.97e-04 |
| MAP2K1 | GO:0060020 | Bergmann glial cell differentiation | 7.97e-04 |
| MAP2K1 | GO:0060439 | trachea morphogenesis | 7.97e-04 |
| MAP2K1 | GO:0072584 | caveolin-mediated endocytosis | 7.97e-04 |
| MAP2K1 | GO:0061517 | macrophage proliferation | 1.03e-03 |
| MAP2K1 | GO:0048534 | hematopoietic or lymphoid organ development | 1.03e-03 |
| MAP2K1 | GO:0062197 | cellular response to chemical stress | 1.11e-03 |
| MAP2K1 | GO:0048308 | organelle inheritance | 1.11e-03 |
| MAP2K1 | GO:0048313 | Golgi inheritance | 1.11e-03 |
| MAP2K1 | GO:0061307 | cardiac neural crest cell differentiation involved in heart development | 1.11e-03 |
| MAP2K1 | GO:0061308 | cardiac neural crest cell development involved in heart development | 1.11e-03 |
| MAP2K1 | GO:2001252 | positive regulation of chromosome organization | 1.11e-03 |
| MAP2K1 | GO:0032386 | regulation of intracellular transport | 1.12e-03 |
| MAP2K1 | GO:1900034 | regulation of cellular response to heat | 1.12e-03 |
| MAP2K1 | GO:1903358 | regulation of Golgi organization | 1.12e-03 |
| MAP2K1 | GO:1904355 | positive regulation of telomere capping | 1.23e-03 |
| MAP2K1 | GO:0010759 | positive regulation of macrophage chemotaxis | 1.41e-03 |
| MAP2K1 | GO:0060438 | trachea development | 1.41e-03 |
| MAP2K1 | GO:2000641 | regulation of early endosome to late endosome transport | 1.41e-03 |
| MAP2K1 | GO:0031331 | positive regulation of cellular catabolic process | 1.80e-03 |
| MAP2K1 | GO:0031333 | negative regulation of protein-containing complex assembly | 2.05e-03 |
| MAP2K1 | GO:0043254 | regulation of protein-containing complex assembly | 2.12e-03 |
| MAP2K1 | GO:0034614 | cellular response to reactive oxygen species | 2.23e-03 |
| MAP2K1 | GO:0000723 | telomere maintenance | 2.23e-03 |
| MAP2K1 | GO:1904353 | regulation of telomere capping | 2.23e-03 |
| MAP2K1 | GO:1905523 | positive regulation of macrophage migration | 2.23e-03 |
| MAP2K1 | GO:0048732 | gland development | 2.30e-03 |
| MAP2K1 | GO:0071480 | cellular response to gamma radiation | 2.30e-03 |
| MAP2K1 | GO:0010758 | regulation of macrophage chemotaxis | 2.37e-03 |
| MAP2K1 | GO:0048568 | embryonic organ development | 2.37e-03 |
| MAP2K1 | GO:1902042 | negative regulation of extrinsic apoptotic signaling pathway via death domain receptors | 2.85e-03 |
| MAP2K1 | GO:1903649 | regulation of cytoplasmic transport | 2.97e-03 |
| MAP2K1 | GO:0032200 | telomere organization | 3.10e-03 |
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Related Drugs to ZWILCH_MAP2K1 |
| 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 ZWILCH-MAP2K1 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 ZWILCH_MAP2K1 |
| 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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