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Kinase Fusion Gene:MKI67_DYRK3 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: MKI67_DYRK3 | KinaseFusionDB ID: KFG3873 | FusionGDB2.0 ID: KFG3873 | Hgene | Tgene | Gene symbol | MKI67 | DYRK3 | Gene ID | 4288 | 8444 | |
| Gene name | marker of proliferation Ki-67 | dual specificity tyrosine phosphorylation regulated kinase 3 | ||||||||||
| Synonyms | KIA|MIB-|MIB-1|PPP1R105 | DYRK5|RED|REDK|hYAK3-2 | ||||||||||
| Cytomap | 10q26.2 | 1q32.1 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | proliferation marker protein Ki-67Molecular Immunology Borstel antibody 1antigen Ki67antigen identified by monoclonal antibody Ki-67proliferation-related Ki-67 antigenprotein phosphatase 1, regulatory subunit 105 | dual specificity tyrosine-phosphorylation-regulated kinase 3dual specificity tyrosine-(Y)-phosphorylation regulated kinase 3dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 5protein kinase Dyrk3regulatory erythroid kinase | ||||||||||
| Modification date | 20240407 | 20240403 | ||||||||||
| UniProtAcc | P46013 | O43781 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000368653, ENST00000368654, ENST00000484853, | ENST00000367106, ENST00000367108, ENST00000367109, ENST00000489878, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: MKI67 [Title/Abstract] AND DYRK3 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | MKI67(129893319)-DYRK3(206852116), # samples:1 | |||||||||||
| 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 | MKI67 | GO:0007088 | regulation of mitotic nuclear division | 27362226 |
| Hgene | MKI67 | GO:0051983 | regulation of chromosome segregation | 27362226 |
| Tgene | DYRK3 | GO:0006468 | protein phosphorylation | 10779429|29634919|29973724 |
| Tgene | DYRK3 | GO:0030218 | erythrocyte differentiation | 10779429 |
| Tgene | DYRK3 | GO:0035063 | nuclear speck organization | 29973724 |
| Tgene | DYRK3 | GO:0035617 | stress granule disassembly | 29973724 |
| Tgene | DYRK3 | GO:1902751 | positive regulation of cell cycle G2/M phase transition | 29973724 |
| Tgene | DYRK3 | GO:1903008 | organelle disassembly | 29973724 |
| Kinase Fusion gene breakpoints across MKI67 (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 DYRK3 (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 |
| ChiTaRS5.0 | FN167197 | MKI67 | chr10 | 129893319 | DYRK3 | chr1 | 206852116 |
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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/:129893319/:206852116) - 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 |
| MKI67 | DYRK3 |
| FUNCTION: Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). Associates with the surface of the mitotic chromosome, the perichromosomal layer, and covers a substantial fraction of the chromosome surface (PubMed:27362226). Prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization (PubMed:24867636). It is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in maintaining mitotic chromosomes dispersed (Probable). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226}. | FUNCTION: Dual-specificity protein kinase that promotes disassembly of several types of membraneless organelles during mitosis, such as stress granules, nuclear speckles and pericentriolar material (PubMed:29973724). Dual-specificity tyrosine-regulated kinases (DYRKs) autophosphorylate a critical tyrosine residue in their activation loop and phosphorylate their substrate on serine and threonine residues (PubMed:9748265, PubMed:29634919). Acts as a central dissolvase of membraneless organelles during the G2-to-M transition, after the nuclear-envelope breakdown: acts by mediating phosphorylation of multiple serine and threonine residues in unstructured domains of proteins, such as SRRM1 and PCM1 (PubMed:29973724). Does not mediate disassembly of all membraneless organelles: disassembly of P-body and nucleolus is not regulated by DYRK3 (PubMed:29973724). Dissolution of membraneless organelles at the onset of mitosis is also required to release mitotic regulators, such as ZNF207, from liquid-unmixed organelles where they are sequestered and keep them dissolved during mitosis (PubMed:29973724). Regulates mTORC1 by mediating the dissolution of stress granules: during stressful conditions, DYRK3 partitions from the cytosol to the stress granule, together with mTORC1 components, which prevents mTORC1 signaling (PubMed:23415227). When stress signals are gone, the kinase activity of DYRK3 is required for the dissolution of stress granule and mTORC1 relocation to the cytosol: acts by mediating the phosphorylation of the mTORC1 inhibitor AKT1S1, allowing full reactivation of mTORC1 signaling (PubMed:23415227). Also acts as a negative regulator of EPO-dependent erythropoiesis: may place an upper limit on red cell production during stress erythropoiesis (PubMed:10779429). Inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells (PubMed:10779429). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1: this in turn inhibits p53/TP53 activity and apoptosis (PubMed:20167603). {ECO:0000269|PubMed:10779429, ECO:0000269|PubMed:20167603, ECO:0000269|PubMed:23415227, ECO:0000269|PubMed:29634919, ECO:0000269|PubMed:29973724, ECO:0000269|PubMed:9748265}. |
| 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 MKI67_DYRK3 |
| 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 |
| DYRK3 | O43781 | human | H3-3A | P84243 | T45 | PHryrPGtVALrEIR | Histone |
| DYRK3 | O43781 | human | AKT1S1 | Q96B36 | T246 | LPRPRLNtsDFQkLK | PRAS |
| DYRK3 | O43781 | human | NCOA3 | Q9Y6Q9 | S1330 | PAFGRVSsPPNAMMS | DUF1518 |
| 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 |
| DYRK3 | ID | Description | 0.00e+00 |
| DYRK3 | GO:0043696 | dedifferentiation | 3.85e-02 |
| DYRK3 | GO:0043697 | cell dedifferentiation | 3.85e-02 |
| DYRK3 | GO:2000035 | regulation of stem cell division | 3.85e-02 |
| DYRK3 | GO:0060623 | regulation of chromosome condensation | 3.85e-02 |
| DYRK3 | GO:0140719 | constitutive heterochromatin formation | 3.85e-02 |
| DYRK3 | GO:0045618 | positive regulation of keratinocyte differentiation | 3.85e-02 |
| DYRK3 | GO:0048011 | neurotrophin TRK receptor signaling pathway | 3.85e-02 |
| DYRK3 | GO:0045606 | positive regulation of epidermal cell differentiation | 3.85e-02 |
| DYRK3 | GO:0034508 | centromere complex assembly | 3.85e-02 |
| DYRK3 | GO:0017145 | stem cell division | 3.85e-02 |
| DYRK3 | GO:2000273 | positive regulation of signaling receptor activity | 3.85e-02 |
| DYRK3 | GO:0045684 | positive regulation of epidermis development | 3.85e-02 |
| DYRK3 | GO:0001556 | oocyte maturation | 3.85e-02 |
| DYRK3 | GO:0071392 | cellular response to estradiol stimulus | 3.85e-02 |
| DYRK3 | GO:0038179 | neurotrophin signaling pathway | 3.85e-02 |
| DYRK3 | GO:0045616 | regulation of keratinocyte differentiation | 3.85e-02 |
| DYRK3 | GO:0030261 | chromosome condensation | 3.97e-02 |
| DYRK3 | GO:1904262 | negative regulation of TORC1 signaling | 3.97e-02 |
| DYRK3 | GO:1902459 | positive regulation of stem cell population maintenance | 3.97e-02 |
| DYRK3 | GO:0007566 | embryo implantation | 4.21e-02 |
| DYRK3 | GO:0045604 | regulation of epidermal cell differentiation | 4.21e-02 |
| DYRK3 | GO:0048599 | oocyte development | 4.21e-02 |
| DYRK3 | GO:0009994 | oocyte differentiation | 4.21e-02 |
| DYRK3 | GO:0045682 | regulation of epidermis development | 4.21e-02 |
| DYRK3 | GO:0030858 | positive regulation of epithelial cell differentiation | 4.21e-02 |
| DYRK3 | GO:0032007 | negative regulation of TOR signaling | 4.21e-02 |
| DYRK3 | GO:2000036 | regulation of stem cell population maintenance | 4.21e-02 |
| DYRK3 | GO:0031507 | heterochromatin formation | 4.79e-02 |
| DYRK3 | GO:1903432 | regulation of TORC1 signaling | 4.79e-02 |
| DYRK3 | GO:2001251 | negative regulation of chromosome organization | 4.79e-02 |
| DYRK3 | GO:0038202 | TORC1 signaling | 4.79e-02 |
| DYRK3 | GO:0070828 | heterochromatin organization | 4.79e-02 |
| DYRK3 | GO:0010469 | regulation of signaling receptor activity | 4.95e-02 |
| DYRK3 | GO:0048477 | oogenesis | 4.95e-02 |
| DYRK3 | GO:0032355 | response to estradiol | 4.95e-02 |
| DYRK3 | GO:0006334 | nucleosome assembly | 4.97e-02 |
| DYRK3 | GO:0045814 | negative regulation of gene expressio | 1.90e-02 |
| DYRK3 | GO:0006997 | nucleus organization | 5.01e-02 |
| DYRK3 | GO:0032006 | regulation of TOR signaling | 5.01e-02 |
| DYRK3 | GO:0035264 | multicellular organism growth | 5.01e-02 |
| DYRK3 | GO:0008584 | male gonad development | 5.01e-02 |
| DYRK3 | GO:0046546 | development of primary male sexual characteristics | 5.01e-02 |
| DYRK3 | GO:0007292 | female gamete generation | 5.01e-02 |
| DYRK3 | GO:0030307 | positive regulation of cell growth | 5.01e-02 |
| DYRK3 | GO:0007338 | single fertilization | 5.01e-02 |
| DYRK3 | GO:0031929 | TOR signaling | 5.01e-02 |
| DYRK3 | GO:0030856 | regulation of epithelial cell differentiation | 5.01e-02 |
| DYRK3 | GO:0046661 | male sex differentiation | 5.01e-02 |
| DYRK3 | GO:0030216 | keratinocyte differentiation | 5.01e-02 |
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Related Drugs to MKI67_DYRK3 |
| 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 MKI67-DYRK3 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 MKI67_DYRK3 |
| 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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