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Fusion Protein:LEF1-PAPSS1 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: LEF1-PAPSS1 | FusionPDB ID: 44424 | FusionGDB2.0 ID: 44424 | Hgene | Tgene | Gene symbol | LEF1 | PAPSS1 | Gene ID | 51176 | 9061 |
| Gene name | lymphoid enhancer binding factor 1 | 3'-phosphoadenosine 5'-phosphosulfate synthase 1 | |
| Synonyms | LEF-1|TCF10|TCF1ALPHA|TCF7L3 | ATPSK1|PAPSS|SK1 | |
| Cytomap | 4q25 | 4q25 | |
| Type of gene | protein-coding | protein-coding | |
| Description | lymphoid enhancer-binding factor 1T cell-specific transcription factor 1-alphaTCF1-alpha | bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 13-prime-phosphoadenosine 5-prime-phosphosulfate synthase 1PAPS synthase 1PAPSS 1SK 1adenylyl-sulfate kinasesulfate adenylyltransferasesulfurylase kinase 1 | |
| Modification date | 20200322 | 20200313 | |
| UniProtAcc | Q9UJU2 | . | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000265165, ENST00000379951, ENST00000438313, ENST00000510624, ENST00000512172, ENST00000503879, | ENST00000511304, ENST00000265174, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 2 X 2 X 2=8 | 10 X 9 X 6=540 |
| # samples | 2 | 10 | |
| ** MAII score | log2(2/8*10)=1.32192809488736 | log2(10/540*10)=-2.43295940727611 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: LEF1 [Title/Abstract] AND PAPSS1 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | LEF1(109084724)-PAPSS1(108581228), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | LEF1-PAPSS1 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. LEF1-PAPSS1 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. LEF1-PAPSS1 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. LEF1-PAPSS1 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. LEF1-PAPSS1 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF. LEF1-PAPSS1 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF. LEF1-PAPSS1 seems lost the major protein functional domain in Tgene partner, which is a cell metabolism 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 | LEF1 | GO:0006366 | transcription by RNA polymerase II | 23001182 |
| Hgene | LEF1 | GO:0008284 | positive regulation of cell proliferation | 19351848 |
| Hgene | LEF1 | GO:0010628 | positive regulation of gene expression | 16344550 |
| Hgene | LEF1 | GO:0030854 | positive regulation of granulocyte differentiation | 19620402 |
| Hgene | LEF1 | GO:0032696 | negative regulation of interleukin-13 production | 18445004 |
| Hgene | LEF1 | GO:0032713 | negative regulation of interleukin-4 production | 18445004 |
| Hgene | LEF1 | GO:0032714 | negative regulation of interleukin-5 production | 18445004 |
| Hgene | LEF1 | GO:0043392 | negative regulation of DNA binding | 18445004 |
| Hgene | LEF1 | GO:0043923 | positive regulation by host of viral transcription | 7657162 |
| Hgene | LEF1 | GO:0045892 | negative regulation of transcription, DNA-templated | 18794125 |
| Hgene | LEF1 | GO:0045893 | positive regulation of transcription, DNA-templated | 7657162|10644691|17063141|19620402|20128911 |
| Hgene | LEF1 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 11751639 |
| Hgene | LEF1 | GO:0060070 | canonical Wnt signaling pathway | 10644691|20123964 |
| Hgene | LEF1 | GO:0060326 | cell chemotaxis | 19576624 |
| Hgene | LEF1 | GO:0071353 | cellular response to interleukin-4 | 18579517 |
| Hgene | LEF1 | GO:0071899 | negative regulation of estrogen receptor binding | 18794125 |
| Tgene | PAPSS1 | GO:0000103 | sulfate assimilation | 14747722 |
| Tgene | PAPSS1 | GO:0050428 | 3'-phosphoadenosine 5'-phosphosulfate biosynthetic process | 14747722|23207770 |
| Fusion gene breakpoints across LEF1 (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 PAPSS1 (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 | STAD | TCGA-CG-4466-01A | LEF1 | chr4 | 109084724 | - | PAPSS1 | chr4 | 108581228 | - |
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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) |
| ENST00000379951 | LEF1 | chr4 | 109084724 | - | ENST00000265174 | PAPSS1 | chr4 | 108581228 | - | 3392 | 1603 | 631 | 2808 | 725 |
| ENST00000512172 | LEF1 | chr4 | 109084724 | - | ENST00000265174 | PAPSS1 | chr4 | 108581228 | - | 2020 | 231 | 21 | 1436 | 471 |
| 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 |
| ENST00000379951 | ENST00000265174 | LEF1 | chr4 | 109084724 | - | PAPSS1 | chr4 | 108581228 | - | 0.001055288 | 0.9989447 |
| ENST00000512172 | ENST00000265174 | LEF1 | chr4 | 109084724 | - | PAPSS1 | chr4 | 108581228 | - | 0.000389879 | 0.9996101 |
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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 >44424_44424_1_LEF1-PAPSS1_LEF1_chr4_109084724_ENST00000379951_PAPSS1_chr4_108581228_ENST00000265174_length(amino acids)=725AA_BP=1 MHLLLGQTGPFCPDPLSFLGKQTTKSASGVTTVERVSAETRRRTLLCTLGRRAPSRTGVLRAQIPATRGRGVAAGAASSSARRADAPGVA SYRSPRRPVPFGLGGGRLRRSPRSGKARRPPGFGRRGSCSGCRPAAPRSPAPLPPAVLLHEPFQLSFPPPPLSYPSVFPAVARVLPQRSG DYRAAGMPQLSGGGGGGGGDPELCATDEMIPFKDEGDPQKEKIFAEISHPEEEGDLADIKSSLVNESEIIPASNGHEVARQAQTSQEPYH DKAREHPDDGKHPDGGLYNKGPSYSSYSGYIMMPNMNNDPYMSNGSLSPPIPRTDIVPVDASYEVKELYVPENKLHLAKTDAETLPALKI NKVDMQWVQVLAEGWATPLNGFMREREYLQCLHFDCLLDGGVINLSVPIVLTATHEDKERLDGCTAFALMYEGRRVAILRNPEFFEHRKE ERCARQWGTTCKNHPYIKMVMEQGDWLIGGDLQVLDRVYWNDGLDQYRLTPTELKQKFKDMNADAVFAFQLRNPVHNGHALLMQDTHKQL LERGYRRPVLLLHPLGGWTKDDDVPLMWRMKQHAAVLEEGVLNPETTVVAIFPSPMMYAGPTEVQWHCRARMVAGANFYIVGRDPAGMPH PETGKDLYEPSHGAKVLTMAPGLITLEIVPFRVAAYNKKKKRMDYYDSEHHEDFEFISGTRMRKLAREGQKPPEGFMAPKAWTVLTEYYK -------------------------------------------------------------- >44424_44424_2_LEF1-PAPSS1_LEF1_chr4_109084724_ENST00000512172_PAPSS1_chr4_108581228_ENST00000265174_length(amino acids)=471AA_BP=3 MAEVARQAQTSQEPYHDKAREHPDDGKHPDGGLYNKGPSYSSYSGYIMMPNMNNDPYMSNGSLSPPIPRTDIVPVDASYEVKELYVPENK LHLAKTDAETLPALKINKVDMQWVQVLAEGWATPLNGFMREREYLQCLHFDCLLDGGVINLSVPIVLTATHEDKERLDGCTAFALMYEGR RVAILRNPEFFEHRKEERCARQWGTTCKNHPYIKMVMEQGDWLIGGDLQVLDRVYWNDGLDQYRLTPTELKQKFKDMNADAVFAFQLRNP VHNGHALLMQDTHKQLLERGYRRPVLLLHPLGGWTKDDDVPLMWRMKQHAAVLEEGVLNPETTVVAIFPSPMMYAGPTEVQWHCRARMVA GANFYIVGRDPAGMPHPETGKDLYEPSHGAKVLTMAPGLITLEIVPFRVAAYNKKKKRMDYYDSEHHEDFEFISGTRMRKLAREGQKPPE -------------------------------------------------------------- |
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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/chr4:109084724/chr4:108581228) - 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 |
| LEF1 | . |
| FUNCTION: Transcription factor that binds DNA in a sequence-specific manner (PubMed:2010090). Participates in the Wnt signaling pathway (By similarity). Activates transcription of target genes in the presence of CTNNB1 and EP300 (By similarity). PIAG antagonizes both Wnt-dependent and Wnt-independent activation by LEF1 (By similarity). TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by LEF1 and CTNNB1 (PubMed:11266540). Regulates T-cell receptor alpha enhancer function (PubMed:19653274). Required for IL17A expressing gamma-delta T-cell maturation and development, via binding to regulator loci of BLK to modulate expression (By similarity). May play a role in hair cell differentiation and follicle morphogenesis (By similarity). {ECO:0000250|UniProtKB:P27782, ECO:0000269|PubMed:11266540, ECO:0000269|PubMed:19653274, ECO:0000269|PubMed:2010090}.; FUNCTION: [Isoform 1]: Transcriptionally activates MYC and CCND1 expression and enhances proliferation of pancreatic tumor cells. {ECO:0000269|PubMed:19653274}.; FUNCTION: [Isoform 3]: Lacks the CTNNB1 interaction domain and may therefore be an antagonist for Wnt signaling. {ECO:0000269|PubMed:11326276}.; FUNCTION: [Isoform 5]: Transcriptionally activates the fibronectin promoter, binds to and represses transcription from the E-cadherin promoter in a CTNNB1-independent manner, and is involved in reducing cellular aggregation and increasing cell migration of pancreatic cancer cells. {ECO:0000269|PubMed:19653274}. | 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. |
| 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 | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000265165 | - | 3 | 12 | 14_52 | 138.0 | 504.3333333333333 | Compositional bias | Note=Asp/Glu-rich (acidic) |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000265165 | - | 3 | 12 | 6_13 | 138.0 | 504.3333333333333 | Compositional bias | Note=Poly-Gly |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000379951 | - | 3 | 10 | 14_52 | 138.0 | 387.0 | Compositional bias | Note=Asp/Glu-rich (acidic) |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000379951 | - | 3 | 10 | 6_13 | 138.0 | 387.0 | Compositional bias | Note=Poly-Gly |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000438313 | - | 3 | 11 | 14_52 | 138.0 | 393.6666666666667 | Compositional bias | Note=Asp/Glu-rich (acidic) |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000438313 | - | 3 | 11 | 6_13 | 138.0 | 393.6666666666667 | Compositional bias | Note=Poly-Gly |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000510624 | - | 3 | 11 | 14_52 | 70.0 | 183.0 | Compositional bias | Note=Asp/Glu-rich (acidic) |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000510624 | - | 3 | 11 | 6_13 | 70.0 | 183.0 | Compositional bias | Note=Poly-Gly |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000265165 | - | 3 | 12 | 1_62 | 138.0 | 504.3333333333333 | Region | CTNNB1-binding |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000379951 | - | 3 | 10 | 1_62 | 138.0 | 387.0 | Region | CTNNB1-binding |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000438313 | - | 3 | 11 | 1_62 | 138.0 | 393.6666666666667 | Region | CTNNB1-binding |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000510624 | - | 3 | 11 | 1_62 | 70.0 | 183.0 | Region | CTNNB1-binding |
| Tgene | PAPSS1 | chr4:109084724 | chr4:108581228 | ENST00000265174 | 4 | 12 | 419_422 | 223.0 | 625.0 | Nucleotide binding | ATP 2 | |
| Tgene | PAPSS1 | chr4:109084724 | chr4:108581228 | ENST00000265174 | 4 | 12 | 521_525 | 223.0 | 625.0 | Nucleotide binding | ATP 2 | |
| Tgene | PAPSS1 | chr4:109084724 | chr4:108581228 | ENST00000265174 | 4 | 12 | 234_624 | 223.0 | 625.0 | Region | Sulfate adenylyltransferase |
| - 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 | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000265165 | - | 3 | 12 | 374_379 | 138.0 | 504.3333333333333 | Compositional bias | Note=Poly-Lys |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000265165 | - | 3 | 12 | 77_273 | 138.0 | 504.3333333333333 | Compositional bias | Note=Pro-rich |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000379951 | - | 3 | 10 | 374_379 | 138.0 | 387.0 | Compositional bias | Note=Poly-Lys |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000379951 | - | 3 | 10 | 77_273 | 138.0 | 387.0 | Compositional bias | Note=Pro-rich |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000438313 | - | 3 | 11 | 374_379 | 138.0 | 393.6666666666667 | Compositional bias | Note=Poly-Lys |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000438313 | - | 3 | 11 | 77_273 | 138.0 | 393.6666666666667 | Compositional bias | Note=Pro-rich |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000510624 | - | 3 | 11 | 374_379 | 70.0 | 183.0 | Compositional bias | Note=Poly-Lys |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000510624 | - | 3 | 11 | 77_273 | 70.0 | 183.0 | Compositional bias | Note=Pro-rich |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000265165 | - | 3 | 12 | 299_367 | 138.0 | 504.3333333333333 | DNA binding | HMG box |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000379951 | - | 3 | 10 | 299_367 | 138.0 | 387.0 | DNA binding | HMG box |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000438313 | - | 3 | 11 | 299_367 | 138.0 | 393.6666666666667 | DNA binding | HMG box |
| Hgene | LEF1 | chr4:109084724 | chr4:108581228 | ENST00000510624 | - | 3 | 11 | 299_367 | 70.0 | 183.0 | DNA binding | HMG box |
| Tgene | PAPSS1 | chr4:109084724 | chr4:108581228 | ENST00000265174 | 4 | 12 | 62_67 | 223.0 | 625.0 | Nucleotide binding | ATP 1 | |
| Tgene | PAPSS1 | chr4:109084724 | chr4:108581228 | ENST00000265174 | 4 | 12 | 106_109 | 223.0 | 625.0 | Region | Adenylyl sulfate binding | |
| Tgene | PAPSS1 | chr4:109084724 | chr4:108581228 | ENST00000265174 | 4 | 12 | 132_133 | 223.0 | 625.0 | Region | Adenylyl sulfate binding | |
| Tgene | PAPSS1 | chr4:109084724 | chr4:108581228 | ENST00000265174 | 4 | 12 | 184_185 | 223.0 | 625.0 | Region | Adenylyl sulfate binding | |
| Tgene | PAPSS1 | chr4:109084724 | chr4:108581228 | ENST00000265174 | 4 | 12 | 1_225 | 223.0 | 625.0 | Region | Adenylyl-sulfate kinase | |
| Tgene | PAPSS1 | chr4:109084724 | chr4:108581228 | ENST00000265174 | 4 | 12 | 89_92 | 223.0 | 625.0 | Region | Adenylyl sulfate binding |
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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 |
| LEF1 | |
| PAPSS1 |
| - 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 LEF1-PAPSS1 |
| 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 LEF1-PAPSS1 |
| 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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