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Fusion Protein:MAP3K2-IWS1 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: MAP3K2-IWS1 | FusionPDB ID: 51293 | FusionGDB2.0 ID: 51293 | Hgene | Tgene | Gene symbol | MAP3K2 | IWS1 | Gene ID | 10746 | 55677 |
| Gene name | mitogen-activated protein kinase kinase kinase 2 | interacts with SUPT6H, CTD assembly factor 1 | |
| Synonyms | MEKK2|MEKK2B | - | |
| Cytomap | 2q14.3 | 2q14.3 | |
| Type of gene | protein-coding | protein-coding | |
| Description | mitogen-activated protein kinase kinase kinase 2MAP/ERK kinase kinase 2MAPK/ERK kinase kinase 2MEK kinase 2MEKK 2 | protein IWS1 homologIWS1 homologIWS1, SUPT6H interacting proteinIWS1-like proteininteracts with Spt6 | |
| Modification date | 20200329 | 20200313 | |
| UniProtAcc | Q5TCX8 | Q96ST2 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000344908, ENST00000409947, | ENST00000455721, ENST00000486662, ENST00000295321, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 10 X 8 X 3=240 | 3 X 4 X 2=24 |
| # samples | 9 | 4 | |
| ** MAII score | log2(9/240*10)=-1.41503749927884 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(4/24*10)=0.736965594166206 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: MAP3K2 [Title/Abstract] AND IWS1 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | MAP3K2(128093446)-IWS1(128238751), # samples:2 | ||
| Anticipated loss of major functional domain due to fusion event. | MAP3K2-IWS1 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. MAP3K2-IWS1 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. MAP3K2-IWS1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. MAP3K2-IWS1 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. MAP3K2-IWS1 seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF. MAP3K2-IWS1 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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 |
| Hgene | MAP3K2 | GO:0045893 | positive regulation of transcription, DNA-templated | 14515274 |
| Fusion gene breakpoints across MAP3K2 (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 IWS1 (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 | BRCA | TCGA-AC-A2BM-01A | MAP3K2 | chr2 | 128093446 | - | IWS1 | chr2 | 128238751 | - |
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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) |
| ENST00000409947 | MAP3K2 | chr2 | 128093446 | - | ENST00000295321 | IWS1 | chr2 | 128238751 | - | 917 | 547 | 271 | 678 | 135 |
| 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 |
| ENST00000409947 | ENST00000295321 | MAP3K2 | chr2 | 128093446 | - | IWS1 | chr2 | 128238751 | - | 0.008261735 | 0.99173826 |
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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 >51293_51293_1_MAP3K2-IWS1_MAP3K2_chr2_128093446_ENST00000409947_IWS1_chr2_128238751_ENST00000295321_length(amino acids)=135AA_BP=92 MFAIMDDQQALNSIMQDLAVLHKASRPALSLQETRKAKSSSPKKQNDVRVKFEHRGEKRILQFPRPVKLEDLRSKAKIAFGQSMDLHYTN -------------------------------------------------------------- |
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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/chr2:128093446/chr2:128238751) - 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 |
| MAP3K2 | IWS1 |
| FUNCTION: Negative regulator of TLR4 signaling. Does not activate JNK1/MAPK8 pathway, p38/MAPK14, nor ERK2/MAPK1 pathways. {ECO:0000269|PubMed:21602844}. | FUNCTION: Transcription factor which plays a key role in defining the composition of the RNA polymerase II (RNAPII) elongation complex and in modulating the production of mature mRNA transcripts. Acts as an assembly factor to recruit various factors to the RNAPII elongation complex and is recruited to the complex via binding to the transcription elongation factor SUPT6H bound to the C-terminal domain (CTD) of the RNAPII subunit RPB1 (POLR2A). The SUPT6H:IWS1:CTD complex recruits mRNA export factors (ALYREF/THOC4, EXOSC10) as well as histone modifying enzymes (such as SETD2) to ensure proper mRNA splicing, efficient mRNA export and elongation-coupled H3K36 methylation, a signature chromatin mark of active transcription. {ECO:0000269|PubMed:17184735, ECO:0000269|PubMed:17234882, ECO:0000269|PubMed:19141475}. |
| 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 |
| - 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 | MAP3K2 | chr2:128093446 | chr2:128238751 | ENST00000344908 | - | 4 | 16 | 357_617 | 88.0 | 620.0 | Domain | Protein kinase |
| Hgene | MAP3K2 | chr2:128093446 | chr2:128238751 | ENST00000344908 | - | 4 | 16 | 43_122 | 88.0 | 620.0 | Domain | PB1 |
| Hgene | MAP3K2 | chr2:128093446 | chr2:128238751 | ENST00000409947 | - | 5 | 17 | 357_617 | 88.0 | 620.0 | Domain | Protein kinase |
| Hgene | MAP3K2 | chr2:128093446 | chr2:128238751 | ENST00000409947 | - | 5 | 17 | 43_122 | 88.0 | 620.0 | Domain | PB1 |
| Hgene | MAP3K2 | chr2:128093446 | chr2:128238751 | ENST00000344908 | - | 4 | 16 | 362_371 | 88.0 | 620.0 | Nucleotide binding | ATP |
| Hgene | MAP3K2 | chr2:128093446 | chr2:128238751 | ENST00000409947 | - | 5 | 17 | 362_371 | 88.0 | 620.0 | Nucleotide binding | ATP |
| Tgene | IWS1 | chr2:128093446 | chr2:128238751 | ENST00000295321 | 12 | 14 | 83_509 | 776.0 | 820.0 | Compositional bias | Note=Glu-rich | |
| Tgene | IWS1 | chr2:128093446 | chr2:128238751 | ENST00000295321 | 12 | 14 | 614_692 | 776.0 | 820.0 | Domain | TFIIS N-terminal | |
| Tgene | IWS1 | chr2:128093446 | chr2:128238751 | ENST00000295321 | 12 | 14 | 469_495 | 776.0 | 820.0 | Motif | Integrase domain-binding motif (IBM) | |
| Tgene | IWS1 | chr2:128093446 | chr2:128238751 | ENST00000295321 | 12 | 14 | 235_296 | 776.0 | 820.0 | Region | Note=3 X approximate tandem repeats | |
| Tgene | IWS1 | chr2:128093446 | chr2:128238751 | ENST00000295321 | 12 | 14 | 235_260 | 776.0 | 820.0 | Repeat | Note=1 | |
| Tgene | IWS1 | chr2:128093446 | chr2:128238751 | ENST00000295321 | 12 | 14 | 261_286 | 776.0 | 820.0 | Repeat | Note=2 | |
| Tgene | IWS1 | chr2:128093446 | chr2:128238751 | ENST00000295321 | 12 | 14 | 287_296 | 776.0 | 820.0 | Repeat | Note=3%3B half-length |
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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 |
| MAP3K2 | |
| IWS1 |
| - 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 |
| Tgene | IWS1 | chr2:128093446 | chr2:128238751 | ENST00000295321 | 12 | 14 | 523_819 | 776.0 | 820.0 | SUPT6H and ALYREF |
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Related Drugs to MAP3K2-IWS1 |
| 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 MAP3K2-IWS1 |
| 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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