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Fusion Protein:EZH1-FOXK2 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: EZH1-FOXK2 | FusionPDB ID: 28092 | FusionGDB2.0 ID: 28092 | Hgene | Tgene | Gene symbol | EZH1 | FOXK2 | Gene ID | 2145 | 3607 |
| Gene name | enhancer of zeste 1 polycomb repressive complex 2 subunit | forkhead box K2 | |
| Synonyms | KMT6B | ILF|ILF-1|ILF1|nGTBP | |
| Cytomap | 17q21.2 | 17q25.3 | |
| Type of gene | protein-coding | protein-coding | |
| Description | histone-lysine N-methyltransferase EZH1ENX-2enhancer of zeste homolog 1 | forkhead box protein K2FOXK1G/T-mismatch specific binding proteincellular transcription factor ILF-1interleukin enhancer-binding factor 1 | |
| Modification date | 20200315 | 20200313 | |
| UniProtAcc | Q92800 | Q01167 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000415827, ENST00000428826, ENST00000435174, ENST00000585893, ENST00000590078, ENST00000592743, ENST00000590783, | ENST00000529652, ENST00000335255, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 8 X 12 X 6=576 | 10 X 15 X 9=1350 |
| # samples | 12 | 16 | |
| ** MAII score | log2(12/576*10)=-2.26303440583379 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(16/1350*10)=-3.07681559705083 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: EZH1 [Title/Abstract] AND FOXK2 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | EZH1(40855757)-FOXK2(80543779), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | EZH1-FOXK2 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. EZH1-FOXK2 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. EZH1-FOXK2 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. EZH1-FOXK2 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. EZH1-FOXK2 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF. EZH1-FOXK2 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. EZH1-FOXK2 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF. EZH1-FOXK2 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF. EZH1-FOXK2 seems lost the major protein functional domain in Tgene partner, which is a transcription factor due to the frame-shifted ORF. | ||
| * DoF score (Degree of Frequency) = # partners X # break points X # cancer types ** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10) |
| 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 |
| Tgene | FOXK2 | GO:0045892 | negative regulation of transcription, DNA-templated | 20810654|25451922 |
| Tgene | FOXK2 | GO:0045893 | positive regulation of transcription, DNA-templated | 22083952 |
| Tgene | FOXK2 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 9065434 |
| Fusion gene breakpoints across EZH1 (5'-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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| Fusion gene breakpoints across FOXK2 (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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Fusion Gene Sample Information |
| Fusion gene information from FusionGDB2.0. |
| Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0) * 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 | Disease | Sample | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| ChimerDB4 | ESCA | TCGA-LN-A9FO | EZH1 | chr17 | 40855757 | - | FOXK2 | chr17 | 80543779 | + |
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Fusion ORF Analysis |
| Fusion information from ORFfinder translation from full-length transcript sequence from FusionPDB. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | Seq length (transcript) | BP loci (transcript) | Predicted start (transcript) | Predicted stop (transcript) | Seq length (amino acids) |
| ENST00000435174 | EZH1 | chr17 | 40855757 | - | ENST00000335255 | FOXK2 | chr17 | 80543779 | + | 5814 | 2002 | 321 | 2705 | 794 |
| DeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | No-coding score | Coding score |
| ENST00000435174 | ENST00000335255 | EZH1 | chr17 | 40855757 | - | FOXK2 | chr17 | 80543779 | + | 0.00069242 | 0.99930763 |
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Fusion Amino Acid Sequences |
| For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
| >FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP >28092_28092_1_EZH1-FOXK2_EZH1_chr17_40855757_ENST00000435174_FOXK2_chr17_80543779_ENST00000335255_length(amino acids)=794AA_BP=560 MEEASCPTCSVNEACEWTPFSQKEMIPGSVLISDAVFLELVDALNQYSDEEEEGHNDTSDGKQDDSKEDLPVTRKRKRHAIEGNKKSSKK QFPNDMIFSAIASMFPENGVPDDMKERYRELTEMSDPNALPPQCTPNIDGPNAKSVQREQSLHSFHTLFCRRCFKYDCFLHPFHATPNVY KRKNKEIKIEPEPCGTDCFLLLEGAKEYAMLHNPRSKCSGRRRRRHHIVSASCSNASASAVAETKEGDSDRDTGNDWASSSSEANSRCQT PTKQKASPAPPQLCVVEAPSEPVEWTGAEESLFRVFHGTYFNNFCSIARLLGTKTCKQVFQFAVKESLILKLPTDELMNPSQKKKRKHRL WAAHCRKIQLKKDNSSTQVYNYQPCDHPDRPCDSTCPCIMTQNFCEKFCQCNPDCQNRFPGCRCKTQCNTKQCPCYLAVRECDPDLCLTC GASEHWDCKVVSCKNCSIQRGLKKHLLLAPSDVAGWGTFIKESVQKNEFISEYCGELISQDEADRRGKVYDKYMSSFLFNLNNDFVVDAT RKGNKIRFANHSVNPNCYAKGSPLSSQPVLITVQRQLPQAIKPVTYTVATPVTTSTSQPPVVQTVHVVHQIPAVSVTSVAGLAPANTYTV SGQAVVTPAAVLAPPKAEAQENGDHREVKVKVEPIPAIGHATLGTASRIIQTAQTTPVQTVTIVQQAPLGQHQLPIKTVTQNGTHVASVP -------------------------------------------------------------- |
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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/chr17:40855757/chr17:80543779) - 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 |
| EZH1 | FOXK2 |
| FUNCTION: Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH1 complex, which methylates 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Required for embryonic stem cell derivation and self-renewal, suggesting that it is involved in safeguarding embryonic stem cell identity. Compared to EZH2-containing complexes, it is less abundant in embryonic stem cells, has weak methyltransferase activity and plays a less critical role in forming H3K27me3, which is required for embryonic stem cell identity and proper differentiation. {ECO:0000269|PubMed:19026781}. | FUNCTION: Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis and autophagy (By similarity). Recognizes and binds the forkhead DNA sequence motif (5'-GTAAACA-3') and can both act as a transcription activator or repressor, depending on the context (PubMed:22083952, PubMed:25451922). Together with FOXK1, acts as a key regulator of metabolic reprogramming towards aerobic glycolysis, a process in which glucose is converted to lactate in the presence of oxygen (By similarity). Acts by promoting expression of enzymes for glycolysis (such as hexokinase-2 (HK2), phosphofructokinase, pyruvate kinase (PKLR) and lactate dehydrogenase), while suppressing further oxidation of pyruvate in the mitochondria by up-regulating pyruvate dehydrogenase kinases PDK1 and PDK4 (By similarity). Probably plays a role in gluconeogenesis during overnight fasting, when lactate from white adipose tissue and muscle is the main substrate (By similarity). Together with FOXK1, acts as a negative regulator of autophagy in skeletal muscle: in response to starvation, enters the nucleus, binds the promoters of autophagy genes and represses their expression, preventing proteolysis of skeletal muscle proteins (By similarity). In addition to the 5'-GTAAACA-3' DNA motif, also binds the 5'-TGANTCA-3' palindromic DNA motif, and co-associates with JUN/AP-1 to activate transcription (PubMed:22083952). Also able to bind to a minimal DNA heteroduplex containing a G/T-mismatch with 5'-TRT[G/T]NB-3' sequence (PubMed:20097901). Binds to NFAT-like motifs (purine-rich) in the IL2 promoter (PubMed:1339390). Positively regulates WNT/beta-catenin signaling by translocating DVL proteins into the nucleus (PubMed:25805136). Also binds to HIV-1 long terminal repeat. May be involved in both positive and negative regulation of important viral and cellular promoter elements (PubMed:1909027). {ECO:0000250|UniProtKB:Q3UCQ1, ECO:0000269|PubMed:1339390, ECO:0000269|PubMed:1909027, ECO:0000269|PubMed:20097901, ECO:0000269|PubMed:22083952, ECO:0000269|PubMed:25451922, ECO:0000269|PubMed:25805136}. |
| 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 protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000428826 | - | 19 | 21 | 524_606 | 699.3333333333334 | 748.0 | Compositional bias | Note=Cys-rich |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000585893 | - | 18 | 20 | 524_606 | 659.3333333333334 | 708.0 | Compositional bias | Note=Cys-rich |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000590078 | - | 18 | 20 | 524_606 | 629.3333333333334 | 678.0 | Compositional bias | Note=Cys-rich |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000592743 | - | 18 | 20 | 524_606 | 699.3333333333334 | 748.0 | Compositional bias | Note=Cys-rich |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000428826 | - | 19 | 21 | 504_606 | 699.3333333333334 | 748.0 | Domain | CXC |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000585893 | - | 18 | 20 | 504_606 | 659.3333333333334 | 708.0 | Domain | CXC |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000590078 | - | 18 | 20 | 504_606 | 629.3333333333334 | 678.0 | Domain | CXC |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000592743 | - | 18 | 20 | 504_606 | 699.3333333333334 | 748.0 | Domain | CXC |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000428826 | - | 19 | 21 | 491_496 | 699.3333333333334 | 748.0 | Motif | Nuclear localization signal |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000435174 | - | 17 | 19 | 491_496 | 560.3333333333334 | 609.0 | Motif | Nuclear localization signal |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000585893 | - | 18 | 20 | 491_496 | 659.3333333333334 | 708.0 | Motif | Nuclear localization signal |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000590078 | - | 18 | 20 | 491_496 | 629.3333333333334 | 678.0 | Motif | Nuclear localization signal |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000592743 | - | 18 | 20 | 491_496 | 699.3333333333334 | 748.0 | Motif | Nuclear localization signal |
| - Not-retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000435174 | - | 17 | 19 | 524_606 | 560.3333333333334 | 609.0 | Compositional bias | Note=Cys-rich |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000428826 | - | 19 | 21 | 613_728 | 699.3333333333334 | 748.0 | Domain | SET |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000435174 | - | 17 | 19 | 504_606 | 560.3333333333334 | 609.0 | Domain | CXC |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000435174 | - | 17 | 19 | 613_728 | 560.3333333333334 | 609.0 | Domain | SET |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000585893 | - | 18 | 20 | 613_728 | 659.3333333333334 | 708.0 | Domain | SET |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000590078 | - | 18 | 20 | 613_728 | 629.3333333333334 | 678.0 | Domain | SET |
| Hgene | EZH1 | chr17:40855757 | chr17:80543779 | ENST00000592743 | - | 18 | 20 | 613_728 | 699.3333333333334 | 748.0 | Domain | SET |
| Tgene | FOXK2 | chr17:40855757 | chr17:80543779 | ENST00000335255 | 5 | 9 | 10_93 | 426.3333333333333 | 661.0 | Compositional bias | Note=Gly-rich | |
| Tgene | FOXK2 | chr17:40855757 | chr17:80543779 | ENST00000335255 | 5 | 9 | 258_353 | 426.3333333333333 | 661.0 | DNA binding | Fork-head | |
| Tgene | FOXK2 | chr17:40855757 | chr17:80543779 | ENST00000335255 | 5 | 9 | 54_128 | 426.3333333333333 | 661.0 | Domain | FHA | |
| Tgene | FOXK2 | chr17:40855757 | chr17:80543779 | ENST00000335255 | 5 | 9 | 300_318 | 426.3333333333333 | 661.0 | Region | DNA-binding%3B major groove | |
| Tgene | FOXK2 | chr17:40855757 | chr17:80543779 | ENST00000335255 | 5 | 9 | 328_332 | 426.3333333333333 | 661.0 | Region | DNA-binding%3B minor groove | |
| Tgene | FOXK2 | chr17:40855757 | chr17:80543779 | ENST00000335255 | 5 | 9 | 348_353 | 426.3333333333333 | 661.0 | Region | DNA-binding%3B minor groove |
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Fusion Protein-Protein Interaction |
| Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in |
| Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160) |
| Gene | PPI interactors |
| Protein-protein interactors based on sequence similarity (STRING) |
| Gene | STRING network |
| EZH1 | |
| FOXK2 |
| - Retained interactions in fusion protein (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
| - Lost interactions due to fusion (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
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Related Drugs to EZH1-FOXK2 |
| Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Drug | Source | PMID |
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Related Diseases to EZH1-FOXK2 |
| Diseases that have this fusion gene. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Disease | Source | PMID |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
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