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Kinase Fusion Gene:MKNK2_ISG15 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: MKNK2_ISG15 | KinaseFusionDB ID: KFG3883 | FusionGDB2.0 ID: KFG3883 | Hgene | Tgene | Gene symbol | MKNK2 | ISG15 | Gene ID | 2872 | 9636 | |
| Gene name | MAPK interacting serine/threonine kinase 2 | ISG15 ubiquitin like modifier | ||||||||||
| Synonyms | GPRK7|MNK2 | G1P2|IFI15|IMD38|IP17|UCRP|hUCRP | ||||||||||
| Cytomap | 19p13.3 | 1p36.33 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | MAP kinase-interacting serine/threonine-protein kinase 2G protein-coupled receptor kinase 7MAP kinase interacting serine/threonine kinase 2MAP kinase signal-integrating kinase 2MAPK signal-integrating kinase 2 | ubiquitin-like protein ISG15interferon, alpha-inducible protein (clone IFI-15K)interferon-induced 17-kDa/15-kDa proteininterferon-stimulated protein, 15 kDaubiquitin cross-reactive protein | ||||||||||
| Modification date | 20240305 | 20240305 | ||||||||||
| UniProtAcc | Q9HBH9 | P05161 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000591142, ENST00000591601, ENST00000309340, ENST00000250896, ENST00000541165, ENST00000591588, ENST00000588014, | ENST00000379389, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: MKNK2 [Title/Abstract] AND ISG15 [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 | MKNK2 | GO:0006468 | protein phosphorylation | 11463832 |
| Hgene | MKNK2 | GO:0030097 | hemopoiesis | 21149447 |
| Hgene | MKNK2 | GO:0035556 | intracellular signal transduction | 11463832 |
| Hgene | MKNK2 | GO:0071243 | cellular response to arsenic-containing substance | 18299328 |
| Tgene | ISG15 | GO:0007229 | integrin-mediated signaling pathway | 29100055 |
| Tgene | ISG15 | GO:0009615 | response to virus | 33727702 |
| Tgene | ISG15 | GO:0031397 | negative regulation of protein ubiquitination | 18305167 |
| Tgene | ISG15 | GO:0032020 | ISG15-protein conjugation | 16122702|16407192|21543490|33727702 |
| Tgene | ISG15 | GO:0032461 | positive regulation of protein oligomerization | 33727702 |
| Tgene | ISG15 | GO:0032728 | positive regulation of interferon-beta production | 33727702 |
| Tgene | ISG15 | GO:0032729 | positive regulation of type II interferon production | 29100055 |
| Tgene | ISG15 | GO:0032733 | positive regulation of interleukin-10 production | 29100055 |
| Tgene | ISG15 | GO:0034340 | response to type I interferon | 22859821 |
| Tgene | ISG15 | GO:0045071 | negative regulation of viral genome replication | 33727702 |
| Tgene | ISG15 | GO:0045087 | innate immune response | 28724761 |
| Tgene | ISG15 | GO:0051607 | defense response to virus | 33727702 |
| Tgene | ISG15 | GO:0070585 | protein localization to mitochondrion | 33727702 |
| Kinase Fusion gene breakpoints across MKNK2 (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 ISG15 (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 | NCI-H446 | MKNK2 | chr19 | 2041839 | ISG15 | chr1 | 943574 |
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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 |
| MKNK2 | ISG15 |
| FUNCTION: Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal. {ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11463832, ECO:0000269|PubMed:12897141, ECO:0000269|PubMed:16111636, ECO:0000269|PubMed:17965020, ECO:0000269|PubMed:18299328, ECO:0000269|PubMed:20823271, ECO:0000269|PubMed:20927323, ECO:0000269|PubMed:21149447}. | FUNCTION: Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated protein (PubMed:27564865). ISGylation involves a cascade of enzymatic reactions involving E1, E2, and E3 enzymes which catalyze the conjugation of ISG15 to a lysine residue in the target protein (PubMed:33727702). Its target proteins include IFIT1, MX1/MxA, PPM1B, UBE2L6, UBA7, CHMP5, CHMP2A, CHMP4B and CHMP6. Isgylation of the viral sensor IFIH1/MDA5 promotes IFIH1/MDA5 oligomerization and triggers activation of innate immunity against a range of viruses, including coronaviruses, flaviviruses and picornaviruses (PubMed:33727702). Can also isgylate: EIF2AK2/PKR which results in its activation, RIGI which inhibits its function in antiviral signaling response, EIF4E2 which enhances its cap structure-binding activity and translation-inhibition activity, UBE2N and UBE2E1 which negatively regulates their activity, IRF3 which inhibits its ubiquitination and degradation and FLNB which prevents its ability to interact with the upstream activators of the JNK cascade thereby inhibiting IFNA-induced JNK signaling. Exhibits antiviral activity towards both DNA and RNA viruses, including influenza A, HIV-1 and Ebola virus. Restricts HIV-1 and ebola virus via disruption of viral budding. Inhibits the ubiquitination of HIV-1 Gag and host TSG101 and disrupts their interaction, thereby preventing assembly and release of virions from infected cells. Inhibits Ebola virus budding mediated by the VP40 protein by disrupting ubiquitin ligase activity of NEDD4 and its ability to ubiquitinate VP40. ISGylates influenza A virus NS1 protein which causes a loss of function of the protein and the inhibition of virus replication. The secreted form of ISG15 can: induce natural killer cell proliferation, act as a chemotactic factor for neutrophils and act as a IFN-gamma-inducing cytokine playing an essential role in antimycobacterial immunity. The secreted form acts through the integrin ITGAL/ITGB2 receptor to initiate activation of SRC family tyrosine kinases including LYN, HCK and FGR which leads to secretion of IFNG and IL10; the interaction is mediated by ITGAL (PubMed:29100055). {ECO:0000269|PubMed:1373138, ECO:0000269|PubMed:16009940, ECO:0000269|PubMed:16112642, ECO:0000269|PubMed:16428300, ECO:0000269|PubMed:16434471, ECO:0000269|PubMed:16872604, ECO:0000269|PubMed:18305167, ECO:0000269|PubMed:19270716, ECO:0000269|PubMed:19357168, ECO:0000269|PubMed:2005397, ECO:0000269|PubMed:20133869, ECO:0000269|PubMed:20308324, ECO:0000269|PubMed:20639253, ECO:0000269|PubMed:21543490, ECO:0000269|PubMed:22693631, ECO:0000269|PubMed:22859821, ECO:0000269|PubMed:23229543, ECO:0000269|PubMed:27564865, ECO:0000269|PubMed:29100055, ECO:0000269|PubMed:33727702, ECO:0000269|PubMed:7526157, ECO:0000269|PubMed:8550581}. |
| 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 MKNK2_ISG15 |
| 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 |
| MKNK2 | Q9HBH9 | human | SFPQ | P23246 | S283 | EGFkANLsLLRRPGE | |
| MKNK2 | Q9HBH9 | human | SFPQ | P23246 | S8 | MSRDRFrsrGGGGGG | |
| MKNK2 | Q9HBH9 | human | SPRY2 | O43597 | S112 | APLSRSIsTVssGsR | |
| MKNK2 | Q9HBH9 | human | EIF4E | P06730 | S209 | DtATksGsttKNRFV | |
| MKNK2 | Q9HBH9 | human | PLEC | Q15149 | S4642 | RAGsRrGsFDAtGsG | |
| MKNK2 | Q9HBH9 | human | SPRY2 | O43597 | S121 | VssGsRSsTRtSTSs |
| 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 MKNK2_ISG15 |
| 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 MKNK2-ISG15 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 MKNK2_ISG15 |
| 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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