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Kinase Fusion Gene:TIMP2_FLT4 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: TIMP2_FLT4 | KinaseFusionDB ID: KFG6548 | FusionGDB2.0 ID: KFG6548 | Hgene | Tgene | Gene symbol | TIMP2 | FLT4 | Gene ID | 7077 | 2324 | |
| Gene name | TIMP metallopeptidase inhibitor 2 | fms related receptor tyrosine kinase 4 | ||||||||||
| Synonyms | CSC-21K|DDC8 | CHTD7|FLT-4|FLT41|LMPH1A|LMPHM1|PCL|VEGFR-3|VEGFR3 | ||||||||||
| Cytomap | 17q25.3 | 5q35.3 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | metalloproteinase inhibitor 2testicular secretory protein Li 57tissue inhibitor of metalloproteinases 2 | vascular endothelial growth factor receptor 3Feline McDonough Sarcoma (FMS)-like tyrosine kinase 4VEGF receptor-3fms related tyrosine kinase 4fms-like tyrosine kinase 4primary congenital lymphedematyrosine-protein kinase receptor FLT4 | ||||||||||
| Modification date | 20240416 | 20240416 | ||||||||||
| UniProtAcc | P16035 | P35916 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000262768, ENST00000536189, ENST00000585421, ENST00000586057, | ENST00000261937, ENST00000393347, ENST00000502649, ENST00000424276, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: TIMP2 [Title/Abstract] AND FLT4 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | TIMP2(76849995)-FLT4(180052936), # 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 | TIMP2 | GO:1905049 | negative regulation of metallopeptidase activity | 9573338 |
| Tgene | FLT4 | GO:0018108 | peptidyl-tyrosine phosphorylation | 7898938 |
| Tgene | FLT4 | GO:0035924 | cellular response to vascular endothelial growth factor stimulus | 9435229 |
| Tgene | FLT4 | GO:0038084 | vascular endothelial growth factor signaling pathway | 23878260 |
| Tgene | FLT4 | GO:0046777 | protein autophosphorylation | 7675451|9435229|23878260 |
| Tgene | FLT4 | GO:0048010 | vascular endothelial growth factor receptor signaling pathway | 9012504 |
| Kinase Fusion gene breakpoints across TIMP2 (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 FLT4 (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 | AA368924 | TIMP2 | chr17 | 76849995 | FLT4 | chr5 | 180052936 |
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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/:76849995/:180052936) - 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 |
| TIMP2 | FLT4 |
| FUNCTION: Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-13, MMP-14, MMP-15, MMP-16 and MMP-19. {ECO:0000269|PubMed:11710594, ECO:0000269|PubMed:2554304, ECO:0000269|PubMed:2793861}. | FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'. {ECO:0000269|PubMed:11532940, ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:15474514, ECO:0000269|PubMed:16076871, ECO:0000269|PubMed:16452200, ECO:0000269|PubMed:17210781, ECO:0000269|PubMed:19610651, ECO:0000269|PubMed:19779139, ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:20431062, ECO:0000269|PubMed:20445537, ECO:0000269|PubMed:21273538, ECO:0000269|PubMed:7675451, ECO:0000269|PubMed:8700872, ECO:0000269|PubMed:9435229}. |
| 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 TIMP2_FLT4 |
| 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 |
| FLT4 | P35916 | human | GLO1 | Q04760 | Y136 | GIAVPDVysACkRFE | Glyoxalase |
| 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 |
| FLT4 | ID | Description | 0.00e+00 |
| FLT4 | GO:0006749 | glutathione metabolic process | 1.11e-02 |
| FLT4 | GO:0006081 | cellular aldehyde metabolic process | 1.11e-02 |
| FLT4 | GO:0030316 | osteoclast differentiation | 1.12e-02 |
| FLT4 | GO:0042180 | cellular ketone metabolic process | 1.49e-02 |
| FLT4 | GO:0002573 | myeloid leukocyte differentiation | 1.49e-02 |
| FLT4 | GO:0030099 | myeloid cell differentiation | 2.28e-02 |
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Related Drugs to TIMP2_FLT4 |
| 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 TIMP2-FLT4 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 TIMP2_FLT4 |
| 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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