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Kinase Fusion Gene:MLKL_KARS |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: MLKL_KARS | KinaseFusionDB ID: KFG3902 | FusionGDB2.0 ID: KFG3902 | Hgene | Tgene | Gene symbol | MLKL | KARS | Gene ID | 197259 | 3735 | |
| Gene name | mixed lineage kinase domain like pseudokinase | lysyl-tRNA synthetase 1 | ||||||||||
| Synonyms | hMLKL | CMTRIB|DEAPLE|DFNB89|KARS|KARS2|KRS|LEPID | ||||||||||
| Cytomap | 16q23.1 | 16q23.1 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | mixed lineage kinase domain-like protein | lysine--tRNA ligaselysRSlysine tRNA ligase | ||||||||||
| Modification date | 20240411 | 20240407 | ||||||||||
| UniProtAcc | Q8NB16 | Q15046 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000306247, ENST00000308807, | ENST00000319410, ENST00000302445, ENST00000568378, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: MLKL [Title/Abstract] AND KARS [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 |
| Hgene | MLKL | GO:0070207 | protein homotrimerization | 24316671 |
| Hgene | MLKL | GO:0097528 | execution phase of necroptosis | 24316671 |
| Tgene | KARS | GO:0002863 | positive regulation of inflammatory response to antigenic stimulus | 15851690 |
| Tgene | KARS | GO:0006430 | lysyl-tRNA aminoacylation | 9278442|10952987|23159739 |
| Tgene | KARS | GO:0015966 | diadenosine tetraphosphate biosynthetic process | 23159739 |
| Tgene | KARS | GO:0043032 | positive regulation of macrophage activation | 15851690 |
| Kinase Fusion gene breakpoints across MLKL (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 KARS (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 | FU-OV-1 | MLKL | chr16 | 74734351 | KARS | chr16 | 75675621 |
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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 |
| MLKL | KARS |
| FUNCTION: Pseudokinase that plays a key role in TNF-induced necroptosis, a programmed cell death process (PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:24316671). Does not have protein kinase activity (PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:24316671). Activated following phosphorylation by RIPK3, leading to homotrimerization, localization to the plasma membrane and execution of programmed necrosis characterized by calcium influx and plasma membrane damage (PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:24316671). In addition to TNF-induced necroptosis, necroptosis can also take place in the nucleus in response to orthomyxoviruses infection: following activation by ZBP1, MLKL is phosphorylated by RIPK3 in the nucleus, triggering disruption of the nuclear envelope and leakage of cellular DNA into the cytosol.following ZBP1 activation, which senses double-stranded Z-RNA structures, nuclear RIPK3 catalyzes phosphorylation and activation of MLKL, promoting disruption of the nuclear envelope and leakage of cellular DNA into the cytosol (By similarity). Binds to highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which is essential for its necroptotic function (PubMed:29883610). {ECO:0000250|UniProtKB:Q9D2Y4, ECO:0000269|PubMed:22265413, ECO:0000269|PubMed:22265414, ECO:0000269|PubMed:22421439, ECO:0000269|PubMed:24316671, ECO:0000269|PubMed:29883610}. | FUNCTION: Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA (PubMed:9278442, PubMed:18029264, PubMed:18272479). When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages (PubMed:15851690). Catalyzes the synthesis of the signaling molecule diadenosine tetraphosphate (Ap4A), and thereby mediates disruption of the complex between HINT1 and MITF and the concomitant activation of MITF transcriptional activity (PubMed:5338216, PubMed:14975237, PubMed:19524539, PubMed:23159739). {ECO:0000269|PubMed:14975237, ECO:0000269|PubMed:15851690, ECO:0000269|PubMed:18029264, ECO:0000269|PubMed:19524539, ECO:0000269|PubMed:28887846, ECO:0000269|PubMed:5338216, ECO:0000269|PubMed:9278442}.; FUNCTION: (Microbial infection) Interacts with HIV-1 virus GAG protein, facilitating the selective packaging of tRNA(3)(Lys), the primer for reverse transcription initiation. {ECO:0000269|PubMed:15220430}. |
| 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 MLKL_KARS |
| 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 |
| MLKL | Q8NB16 | human | CNR2 | P34972 | S352 | kITPWPDsRDLDLSD |
| 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 |
| MLKL | ID | Description | 0.00e+00 |
| MLKL | GO:0033004 | negative regulation of mast cell activation | 9.03e-03 |
| MLKL | GO:0001975 | response to amphetamine | 9.03e-03 |
| MLKL | GO:0032228 | regulation of synaptic transmissio | 1.85e-03 |
| MLKL | GO:0014075 | response to amine | 9.03e-03 |
| MLKL | GO:0050805 | negative regulation of synaptic transmission | 9.03e-03 |
| MLKL | GO:0007187 | G protein-coupled receptor signaling pathwa | 2.97e-03 |
| MLKL | GO:0045576 | mast cell activation | 9.51e-03 |
| MLKL | GO:0001508 | action potential | 1.81e-02 |
| MLKL | GO:0007189 | adenylate cyclase-activating G protein-coupled receptor signaling pathway | 1.81e-02 |
| MLKL | GO:0002695 | negative regulation of leukocyte activation | 2.01e-02 |
| MLKL | GO:0050866 | negative regulation of cell activation | 2.01e-02 |
| MLKL | GO:0030595 | leukocyte chemotaxis | 2.01e-02 |
| MLKL | GO:0002274 | myeloid leukocyte activation | 2.01e-02 |
| MLKL | GO:0007188 | adenylate cyclase-modulating G protein-coupled receptor signaling pathway | 2.01e-02 |
| MLKL | GO:0060326 | cell chemotaxis | 2.49e-02 |
| MLKL | GO:0032496 | response to lipopolysaccharide | 2.52e-02 |
| MLKL | GO:0002237 | response to molecule of bacterial origin | 2.54e-02 |
| MLKL | GO:0050900 | leukocyte migration | 2.60e-02 |
| MLKL | GO:0042391 | regulation of membrane potential | 2.60e-02 |
| MLKL | GO:0006935 | chemotaxis | 2.60e-02 |
| MLKL | GO:0042330 | taxis | 2.60e-02 |
| MLKL | GO:0050804 | modulation of chemical synaptic transmission | 2.60e-02 |
| MLKL | GO:0099177 | regulation of trans-synaptic signaling | 2.60e-02 |
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Related Drugs to MLKL_KARS |
| 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 MLKL-KARS 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 MLKL_KARS |
| 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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