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Fusion Protein:SMAD3-MAP2K1 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: SMAD3-MAP2K1 | FusionPDB ID: 83799 | FusionGDB2.0 ID: 83799 | Hgene | Tgene | Gene symbol | SMAD3 | MAP2K1 | Gene ID | 4088 | 5604 |
| Gene name | SMAD family member 3 | mitogen-activated protein kinase kinase 1 | |
| Synonyms | HSPC193|HsT17436|JV15-2|LDS1C|LDS3|MADH3 | CFC3|MAPKK1|MEK1|MKK1|PRKMK1 | |
| Cytomap | 15q22.33 | 15q22.31 | |
| Type of gene | protein-coding | protein-coding | |
| Description | mothers against decapentaplegic homolog 3MAD homolog 3MAD, mothers against decapentaplegic homolog 3SMA- and MAD-related protein 3SMAD, mothers against DPP homolog 3hMAD-3hSMAD3mad homolog JV15-2mad protein homologmad3mothers against DPP homolog | dual specificity mitogen-activated protein kinase kinase 1ERK activator kinase 1MAPK/ERK kinase 1MAPKK 1MEK 1protein kinase, mitogen-activated, kinase 1 (MAP kinase kinase 1) | |
| Modification date | 20200329 | 20200327 | |
| UniProtAcc | . | Q02750 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000327367, ENST00000439724, ENST00000537194, ENST00000540846, ENST00000559092, | ENST00000566326, ENST00000307102, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 17 X 13 X 12=2652 | 5 X 6 X 4=120 |
| # samples | 30 | 6 | |
| ** MAII score | log2(30/2652*10)=-3.14404636961671 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(6/120*10)=-1 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: SMAD3 [Title/Abstract] AND MAP2K1 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | SMAD3(67358698)-MAP2K1(66727365), # samples:2 | ||
| Anticipated loss of major functional domain due to fusion event. | SMAD3-MAP2K1 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. SMAD3-MAP2K1 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. SMAD3-MAP2K1 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. SMAD3-MAP2K1 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. | ||
| * 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 | SMAD3 | GO:0000122 | negative regulation of transcription by RNA polymerase II | 8774881 |
| Hgene | SMAD3 | GO:0006357 | regulation of transcription by RNA polymerase II | 21947082 |
| Hgene | SMAD3 | GO:0007179 | transforming growth factor beta receptor signaling pathway | 9732876|18548003|21947082 |
| Hgene | SMAD3 | GO:0007183 | SMAD protein complex assembly | 9111321|10823886 |
| Hgene | SMAD3 | GO:0010628 | positive regulation of gene expression | 21307346 |
| Hgene | SMAD3 | GO:0010718 | positive regulation of epithelial to mesenchymal transition | 21307346 |
| Hgene | SMAD3 | GO:0030308 | negative regulation of cell growth | 8774881 |
| Hgene | SMAD3 | GO:0045429 | positive regulation of nitric oxide biosynthetic process | 27038547 |
| Hgene | SMAD3 | GO:0045599 | negative regulation of fat cell differentiation | 19816956 |
| Hgene | SMAD3 | GO:0045893 | positive regulation of transcription, DNA-templated | 9111321|9311995|9732876 |
| Hgene | SMAD3 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 8774881|18832382 |
| Hgene | SMAD3 | GO:0051481 | negative regulation of cytosolic calcium ion concentration | 27038547 |
| Hgene | SMAD3 | GO:0071560 | cellular response to transforming growth factor beta stimulus | 12902338 |
| Hgene | SMAD3 | GO:1901203 | positive regulation of extracellular matrix assembly | 21307346 |
| Tgene | MAP2K1 | GO:0000187 | activation of MAPK activity | 10644344 |
| Tgene | MAP2K1 | GO:0006468 | protein phosphorylation | 28166211 |
| Tgene | MAP2K1 | GO:0008285 | negative regulation of cell proliferation | 9765203 |
| Tgene | MAP2K1 | GO:0071902 | positive regulation of protein serine/threonine kinase activity | 8388392 |
| Fusion gene breakpoints across SMAD3 (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 MAP2K1 (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 | OV | TCGA-59-2351-01A | SMAD3 | chr15 | 67358698 | + | MAP2K1 | chr15 | 66727365 | + |
| ChimerDB4 | OV | TCGA-59-2351 | SMAD3 | chr15 | 67358698 | + | MAP2K1 | chr15 | 66727364 | + |
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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) |
| ENST00000327367 | SMAD3 | chr15 | 67358698 | + | ENST00000307102 | MAP2K1 | chr15 | 66727365 | + | 3315 | 516 | 310 | 1617 | 435 |
| ENST00000327367 | SMAD3 | chr15 | 67358698 | + | ENST00000307102 | MAP2K1 | chr15 | 66727364 | + | 3315 | 516 | 310 | 1617 | 435 |
| 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 |
| ENST00000327367 | ENST00000307102 | SMAD3 | chr15 | 67358698 | + | MAP2K1 | chr15 | 66727365 | + | 0.001349738 | 0.99865025 |
| ENST00000327367 | ENST00000307102 | SMAD3 | chr15 | 67358698 | + | MAP2K1 | chr15 | 66727364 | + | 0.001349738 | 0.99865025 |
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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 >83799_83799_1_SMAD3-MAP2K1_SMAD3_chr15_67358698_ENST00000327367_MAP2K1_chr15_66727364_ENST00000307102_length(amino acids)=435AA_BP=68 MSSILPFTPPIVKRLLGWKKGEQNGQEEKWCEKAVKSLVKKLKKTGQLDELEKAITTQNVNTKCITIPRTNLEALQKKLEELELDEQQRK RLEAFLTQKQKVGELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGE ISICMEHMDGGSLDQVLKKAGRIPEQILGKVSIAVIKGLTYLREKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRS YMSPERLQGTHYSVQSDIWSMGLSLVEMAVGRYPIPPPDAKELELMFGCQVEGDAAETPPRPRTPGRPLSSYGMDSRPPMAIFELLDYIV -------------------------------------------------------------- >83799_83799_2_SMAD3-MAP2K1_SMAD3_chr15_67358698_ENST00000327367_MAP2K1_chr15_66727365_ENST00000307102_length(amino acids)=435AA_BP=68 MSSILPFTPPIVKRLLGWKKGEQNGQEEKWCEKAVKSLVKKLKKTGQLDELEKAITTQNVNTKCITIPRTNLEALQKKLEELELDEQQRK RLEAFLTQKQKVGELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGE ISICMEHMDGGSLDQVLKKAGRIPEQILGKVSIAVIKGLTYLREKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRS YMSPERLQGTHYSVQSDIWSMGLSLVEMAVGRYPIPPPDAKELELMFGCQVEGDAAETPPRPRTPGRPLSSYGMDSRPPMAIFELLDYIV -------------------------------------------------------------- |
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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/chr15:67358698/chr15:66727365) - 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 |
| . | MAP2K1 |
| FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes. | FUNCTION: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126). Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis. {ECO:0000269|PubMed:14737111, ECO:0000269|PubMed:17101779, ECO:0000269|PubMed:29433126}. |
| 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 |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727364 | ENST00000307102 | 0 | 11 | 262_307 | 26.666666666666668 | 394.0 | Compositional bias | Note=Pro-rich | |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727365 | ENST00000307102 | 0 | 11 | 262_307 | 26.666666666666668 | 394.0 | Compositional bias | Note=Pro-rich | |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727364 | ENST00000307102 | 0 | 11 | 68_361 | 26.666666666666668 | 394.0 | Domain | Protein kinase | |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727365 | ENST00000307102 | 0 | 11 | 68_361 | 26.666666666666668 | 394.0 | Domain | Protein kinase | |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727364 | ENST00000307102 | 0 | 11 | 143_146 | 26.666666666666668 | 394.0 | Nucleotide binding | ATP | |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727364 | ENST00000307102 | 0 | 11 | 150_153 | 26.666666666666668 | 394.0 | Nucleotide binding | ATP | |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727364 | ENST00000307102 | 0 | 11 | 192_195 | 26.666666666666668 | 394.0 | Nucleotide binding | ATP | |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727364 | ENST00000307102 | 0 | 11 | 74_82 | 26.666666666666668 | 394.0 | Nucleotide binding | ATP | |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727365 | ENST00000307102 | 0 | 11 | 143_146 | 26.666666666666668 | 394.0 | Nucleotide binding | ATP | |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727365 | ENST00000307102 | 0 | 11 | 150_153 | 26.666666666666668 | 394.0 | Nucleotide binding | ATP | |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727365 | ENST00000307102 | 0 | 11 | 192_195 | 26.666666666666668 | 394.0 | Nucleotide binding | ATP | |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727365 | ENST00000307102 | 0 | 11 | 74_82 | 26.666666666666668 | 394.0 | Nucleotide binding | ATP | |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727364 | ENST00000307102 | 0 | 11 | 144_146 | 26.666666666666668 | 394.0 | Region | Note=Inhibitor binding | |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727364 | ENST00000307102 | 0 | 11 | 208_212 | 26.666666666666668 | 394.0 | Region | Note=Inhibitor binding | |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727364 | ENST00000307102 | 0 | 11 | 270_307 | 26.666666666666668 | 394.0 | Region | RAF1-binding | |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727364 | ENST00000307102 | 0 | 11 | 77_78 | 26.666666666666668 | 394.0 | Region | Note=Inhibitor binding | |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727365 | ENST00000307102 | 0 | 11 | 144_146 | 26.666666666666668 | 394.0 | Region | Note=Inhibitor binding | |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727365 | ENST00000307102 | 0 | 11 | 208_212 | 26.666666666666668 | 394.0 | Region | Note=Inhibitor binding | |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727365 | ENST00000307102 | 0 | 11 | 270_307 | 26.666666666666668 | 394.0 | Region | RAF1-binding | |
| Tgene | MAP2K1 | chr15:67358698 | chr15:66727365 | ENST00000307102 | 0 | 11 | 77_78 | 26.666666666666668 | 394.0 | Region | Note=Inhibitor binding |
| - 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 | SMAD3 | chr15:67358698 | chr15:66727364 | ENST00000327367 | + | 1 | 9 | 10_136 | 68.66666666666667 | 426.0 | Domain | MH1 |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727364 | ENST00000327367 | + | 1 | 9 | 232_425 | 68.66666666666667 | 426.0 | Domain | MH2 |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727364 | ENST00000439724 | + | 1 | 9 | 10_136 | 0 | 382.0 | Domain | MH1 |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727364 | ENST00000439724 | + | 1 | 9 | 232_425 | 0 | 382.0 | Domain | MH2 |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727364 | ENST00000537194 | + | 1 | 7 | 10_136 | 0 | 231.0 | Domain | MH1 |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727364 | ENST00000537194 | + | 1 | 7 | 232_425 | 0 | 231.0 | Domain | MH2 |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727364 | ENST00000540846 | + | 1 | 9 | 10_136 | 0 | 321.0 | Domain | MH1 |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727364 | ENST00000540846 | + | 1 | 9 | 232_425 | 0 | 321.0 | Domain | MH2 |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727365 | ENST00000327367 | + | 1 | 9 | 10_136 | 68.66666666666667 | 426.0 | Domain | MH1 |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727365 | ENST00000327367 | + | 1 | 9 | 232_425 | 68.66666666666667 | 426.0 | Domain | MH2 |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727365 | ENST00000439724 | + | 1 | 9 | 10_136 | 0 | 382.0 | Domain | MH1 |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727365 | ENST00000439724 | + | 1 | 9 | 232_425 | 0 | 382.0 | Domain | MH2 |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727365 | ENST00000537194 | + | 1 | 7 | 10_136 | 0 | 231.0 | Domain | MH1 |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727365 | ENST00000537194 | + | 1 | 7 | 232_425 | 0 | 231.0 | Domain | MH2 |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727365 | ENST00000540846 | + | 1 | 9 | 10_136 | 0 | 321.0 | Domain | MH1 |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727365 | ENST00000540846 | + | 1 | 9 | 232_425 | 0 | 321.0 | Domain | MH2 |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727364 | ENST00000327367 | + | 1 | 9 | 137_231 | 68.66666666666667 | 426.0 | Region | Note=Linker |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727364 | ENST00000439724 | + | 1 | 9 | 137_231 | 0 | 382.0 | Region | Note=Linker |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727364 | ENST00000537194 | + | 1 | 7 | 137_231 | 0 | 231.0 | Region | Note=Linker |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727364 | ENST00000540846 | + | 1 | 9 | 137_231 | 0 | 321.0 | Region | Note=Linker |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727365 | ENST00000327367 | + | 1 | 9 | 137_231 | 68.66666666666667 | 426.0 | Region | Note=Linker |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727365 | ENST00000439724 | + | 1 | 9 | 137_231 | 0 | 382.0 | Region | Note=Linker |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727365 | ENST00000537194 | + | 1 | 7 | 137_231 | 0 | 231.0 | Region | Note=Linker |
| Hgene | SMAD3 | chr15:67358698 | chr15:66727365 | ENST00000540846 | + | 1 | 9 | 137_231 | 0 | 321.0 | Region | Note=Linker |
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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 |
| SMAD3 | |
| MAP2K1 |
| - 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 SMAD3-MAP2K1 |
| 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 SMAD3-MAP2K1 |
| 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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