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Kinase Fusion Gene:MDM2_DDR2 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: MDM2_DDR2 | KinaseFusionDB ID: KFG3740 | FusionGDB2.0 ID: KFG3740 | Hgene | Tgene | Gene symbol | MDM2 | DDR2 | Gene ID | 4193 | 4921 | |
| Gene name | MDM2 proto-oncogene | discoidin domain receptor tyrosine kinase 2 | ||||||||||
| Synonyms | ACTFS|HDMX|LSKB|hdm2 | MIG20a|NTRKR3|TKT|TYRO10|WRCN | ||||||||||
| Cytomap | 12q15 | 1q23.3 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | E3 ubiquitin-protein ligase Mdm2MDM2 oncogene, E3 ubiquitin protein ligaseMDM2 proto-oncogene, E3 ubiquitin protein ligaseMdm2, p53 E3 ubiquitin protein ligase homologMdm2, transformed 3T3 cell double minute 2, p53 binding proteindouble minute 2, hum | discoidin domain-containing receptor 2CD167 antigen-like family member Bcell migration-inducing protein 20discoidin domain receptor 2discoidin domain receptor family, member 2discoidin domain-containing receptor tyrosine kinase 2hydroxyaryl-protein | ||||||||||
| Modification date | 20240407 | 20240411 | ||||||||||
| UniProtAcc | Q00987 | Q16832 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000258148, ENST00000258149, ENST00000350057, ENST00000462284, ENST00000478070, ENST00000299252, ENST00000348801, ENST00000356290, ENST00000360430, ENST00000393410, ENST00000393412, ENST00000393413, ENST00000428863, ENST00000517852, ENST00000540827, ENST00000544125, ENST00000544561, ENST00000545204, | ENST00000367921, ENST00000367922, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: MDM2 [Title/Abstract] AND DDR2 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | MDM2(69214154)-DDR2(162625001), # 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 | MDM2 | GO:0000122 | negative regulation of transcription by RNA polymerase II | 9271120|17310983 |
| Hgene | MDM2 | GO:0006511 | ubiquitin-dependent protein catabolic process | 11278372|15314173|16173922|17310983 |
| Hgene | MDM2 | GO:0006915 | apoptotic process | 30879903 |
| Hgene | MDM2 | GO:0016567 | protein ubiquitination | 9450543|15878855|19656744|20153724 |
| Hgene | MDM2 | GO:0031648 | protein destabilization | 9529249|10360174|15314173 |
| Hgene | MDM2 | GO:0032436 | positive regulation of proteasomal ubiquitin-dependent protein catabolic process | 11278372 |
| Hgene | MDM2 | GO:0034504 | protein localization to nucleus | 10360174 |
| Hgene | MDM2 | GO:0042176 | regulation of protein catabolic process | 9153395 |
| Hgene | MDM2 | GO:0043518 | negative regulation of DNA damage response, signal transduction by p53 class mediator | 9529249|10360174 |
| Hgene | MDM2 | GO:0045184 | establishment of protein localization | 10360174 |
| Hgene | MDM2 | GO:0045892 | negative regulation of DNA-templated transcription | 9271120 |
| Hgene | MDM2 | GO:0051726 | regulation of cell cycle | 9529249 |
| Hgene | MDM2 | GO:0065003 | protein-containing complex assembly | 10608892|12915590 |
| Hgene | MDM2 | GO:0071480 | cellular response to gamma radiation | 16213212 |
| Hgene | MDM2 | GO:0072717 | cellular response to actinomycin D | 15314173 |
| Hgene | MDM2 | GO:1901797 | negative regulation of signal transduction by p53 class mediator | 16173922 |
| Tgene | DDR2 | GO:0018108 | peptidyl-tyrosine phosphorylation | 20004161 |
| Tgene | DDR2 | GO:0038063 | collagen-activated tyrosine kinase receptor signaling pathway | 16186108 |
| Tgene | DDR2 | GO:0046777 | protein autophosphorylation | 16186108 |
| Kinase Fusion gene breakpoints across MDM2 (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 DDR2 (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-DX-A1KU-01A | MDM2 | chr12 | 69214154 | DDR2 | chr1 | 162625001 |
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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/:69214154/:162625001) - 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 |
| MDM2 | DDR2 |
| FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome (PubMed:29681526). Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also a component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal degradation (PubMed:12821780, PubMed:15053880, PubMed:15195100, PubMed:15632057, PubMed:16337594, PubMed:17290220, PubMed:19098711, PubMed:19219073, PubMed:19837670, PubMed:19965871, PubMed:20173098, PubMed:20385133, PubMed:20858735, PubMed:22128911). Ubiquitinates DCX, leading to DCX degradation and reduction of the dendritic spine density of olfactory bulb granule cells (By similarity). Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor endocytosis (By similarity). Negatively regulates NDUFS1, leading to decreased mitochondrial respiration, marked oxidative stress, and commitment to the mitochondrial pathway of apoptosis (PubMed:30879903). Binds NDUFS1 leading to its cytosolic retention rather than mitochondrial localization resulting in decreased supercomplex assembly (interactions between complex I and complex III), decreased complex I activity, ROS production, and apoptosis (PubMed:30879903). {ECO:0000250|UniProtKB:P23804, ECO:0000269|PubMed:12821780, ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:15195100, ECO:0000269|PubMed:15632057, ECO:0000269|PubMed:16337594, ECO:0000269|PubMed:17290220, ECO:0000269|PubMed:19098711, ECO:0000269|PubMed:19219073, ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:19965871, ECO:0000269|PubMed:20173098, ECO:0000269|PubMed:20385133, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:22128911, ECO:0000269|PubMed:29681526, ECO:0000269|PubMed:30879903}. | FUNCTION: Tyrosine kinase involved in the regulation of tissues remodeling (PubMed:30449416). It functions as a cell surface receptor for fibrillar collagen and regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Required for normal bone development. Regulates osteoblast differentiation and chondrocyte maturation via a signaling pathway that involves MAP kinases and leads to the activation of the transcription factor RUNX2. Regulates remodeling of the extracellular matrix by up-regulation of the collagenases MMP1, MMP2 and MMP13, and thereby facilitates cell migration and tumor cell invasion. Promotes fibroblast migration and proliferation, and thereby contributes to cutaneous wound healing. {ECO:0000269|PubMed:16186104, ECO:0000269|PubMed:16186108, ECO:0000269|PubMed:17665456, ECO:0000269|PubMed:18201965, ECO:0000269|PubMed:20004161, ECO:0000269|PubMed:20564243, ECO:0000269|PubMed:20734453, ECO:0000269|PubMed:30449416, ECO:0000269|PubMed:9659899}. |
| 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 MDM2_DDR2 |
| 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 |
| 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 MDM2_DDR2 |
| 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 MDM2-DDR2 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 MDM2_DDR2 |
| 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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