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Fusion Protein:THSD4-ADAM10 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: THSD4-ADAM10 | FusionPDB ID: 90758 | FusionGDB2.0 ID: 90758 | Hgene | Tgene | Gene symbol | THSD4 | ADAM10 | Gene ID | 79875 | 102 |
| Gene name | thrombospondin type 1 domain containing 4 | ADAM metallopeptidase domain 10 | |
| Synonyms | ADAMTSL-6|ADAMTSL6|FVSY9334|PRO34005 | AD10|AD18|CD156c|CDw156|HsT18717|MADM|RAK|kuz | |
| Cytomap | 15q23 | 15q21.3 | |
| Type of gene | protein-coding | protein-coding | |
| Description | thrombospondin type-1 domain-containing protein 4A disintegrin and metalloproteinase with thrombospondin motifs-like protein 6ADAMTS-like protein 6thrombospondin, type I, domain containing 4 | disintegrin and metalloproteinase domain-containing protein 10a disintegrin and metalloprotease domain 10kuzbanian protein homologmammalian disintegrin-metalloprotease | |
| Modification date | 20200313 | 20200329 | |
| UniProtAcc | . | O14672 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000261862, ENST00000355327, ENST00000357769, ENST00000567838, | ENST00000558733, ENST00000396140, ENST00000402627, ENST00000561288, ENST00000260408, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 21 X 27 X 8=4536 | 12 X 10 X 8=960 |
| # samples | 31 | 13 | |
| ** MAII score | log2(31/4536*10)=-3.87108051966799 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(13/960*10)=-2.88452278258006 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: THSD4 [Title/Abstract] AND ADAM10 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | THSD4(71549054)-ADAM10(58957396), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | THSD4-ADAM10 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. THSD4-ADAM10 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. THSD4-ADAM10 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. THSD4-ADAM10 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 |
| Tgene | ADAM10 | GO:0006509 | membrane protein ectodomain proteolysis | 12714508|17557115|18355449|18419754|18676862|19114711 |
| Tgene | ADAM10 | GO:0007162 | negative regulation of cell adhesion | 12714508 |
| Tgene | ADAM10 | GO:0034612 | response to tumor necrosis factor | 11831872 |
| Tgene | ADAM10 | GO:0051089 | constitutive protein ectodomain proteolysis | 12714508 |
| Fusion gene breakpoints across THSD4 (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 ADAM10 (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-4444-01A | THSD4 | chr15 | 71549054 | - | ADAM10 | chr15 | 58957396 | - |
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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) |
| ENST00000355327 | THSD4 | chr15 | 71549054 | - | ENST00000260408 | ADAM10 | chr15 | 58957396 | - | 5255 | 1149 | 134 | 2911 | 925 |
| ENST00000261862 | THSD4 | chr15 | 71549054 | - | ENST00000260408 | ADAM10 | chr15 | 58957396 | - | 5200 | 1094 | 79 | 2856 | 925 |
| 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 |
| ENST00000355327 | ENST00000260408 | THSD4 | chr15 | 71549054 | - | ADAM10 | chr15 | 58957396 | - | 0.000255937 | 0.999744 |
| ENST00000261862 | ENST00000260408 | THSD4 | chr15 | 71549054 | - | ADAM10 | chr15 | 58957396 | - | 0.000243133 | 0.9997569 |
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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 >90758_90758_1_THSD4-ADAM10_THSD4_chr15_71549054_ENST00000261862_ADAM10_chr15_58957396_ENST00000260408_length(amino acids)=925AA_BP=338 MVSHFMGSLSVLCFLLLLGFQFVCPQPSTQHRKVPQRMAAEGAPEDDGGGGAPGVWGAWGPWSACSRSCSGGVMEQTRPCLPRSYRLRGG QRPGAPARAFADHVVSAVRTSVPLHRSRDETPALAGTDASRQGPTVLRGSRHPQPQGLEVTGDRRSRTRGTIGPGKYGYGKAPYILPLQT DTAHTPQRLRRQKLSSRHSRSQGASSARHGYSSPAHQVPQHGPLYQSDSGPRSGLQAAEAPIYQLPLTHDQGYPAASSLFHSPETSNNHG VGTHGATQSFSQPARSTAISCIGAYRQYKLCNTNVCPESSRSIREVQCASYNNKPFMGRFYEWEPFAEDYPHKYGPQGGCADHSVFERMR KYQMTGVEEVTQIPQEEHAANGPELLRKKRTTSAEKNTCQLYIQTDHLFFKYYGTREAVIAQISSHVKAIDTIYQTTDFSGIRNISFMVK RIRINTTADEKDPTNPFRFPNIGVEKFLELNSEQNHDDYCLAYVFTDRDFDDGVLGLAWVGAPSGSSGGICEKSKLYSDGKKKSLNTGII TVQNYGSHVPPKVSHITFAHEVGHNFGSPHDSGTECTPGESKNLGQKENGNYIMYARATSGDKLNNNKFSLCSIRNISQVLEKKRNNCFV ESGQPICGNGMVEQGEECDCGYSDQCKDECCFDANQPEGRKCKLKPGKQCSPSQGPCCTAQCAFKSKSEKCRDDSDCAREGICNGFTALC PASDPKPNFTDCNRHTQVCINGQCAGSICEKYGLEECTCASSDGKDDKELCHVCCMKKMDPSTCASTGSVQWSRHFSGRTITLQPGSPCN DFRGYCDVFMRCRLVDADGPLARLKKAIFSPELYENIAEWIVAHWWAVLLMGIALIMLMAGFIKICSVHTPSSNPKLPPPKPLPGTLKRR -------------------------------------------------------------- >90758_90758_2_THSD4-ADAM10_THSD4_chr15_71549054_ENST00000355327_ADAM10_chr15_58957396_ENST00000260408_length(amino acids)=925AA_BP=338 MVSHFMGSLSVLCFLLLLGFQFVCPQPSTQHRKVPQRMAAEGAPEDDGGGGAPGVWGAWGPWSACSRSCSGGVMEQTRPCLPRSYRLRGG QRPGAPARAFADHVVSAVRTSVPLHRSRDETPALAGTDASRQGPTVLRGSRHPQPQGLEVTGDRRSRTRGTIGPGKYGYGKAPYILPLQT DTAHTPQRLRRQKLSSRHSRSQGASSARHGYSSPAHQVPQHGPLYQSDSGPRSGLQAAEAPIYQLPLTHDQGYPAASSLFHSPETSNNHG VGTHGATQSFSQPARSTAISCIGAYRQYKLCNTNVCPESSRSIREVQCASYNNKPFMGRFYEWEPFAEDYPHKYGPQGGCADHSVFERMR KYQMTGVEEVTQIPQEEHAANGPELLRKKRTTSAEKNTCQLYIQTDHLFFKYYGTREAVIAQISSHVKAIDTIYQTTDFSGIRNISFMVK RIRINTTADEKDPTNPFRFPNIGVEKFLELNSEQNHDDYCLAYVFTDRDFDDGVLGLAWVGAPSGSSGGICEKSKLYSDGKKKSLNTGII TVQNYGSHVPPKVSHITFAHEVGHNFGSPHDSGTECTPGESKNLGQKENGNYIMYARATSGDKLNNNKFSLCSIRNISQVLEKKRNNCFV ESGQPICGNGMVEQGEECDCGYSDQCKDECCFDANQPEGRKCKLKPGKQCSPSQGPCCTAQCAFKSKSEKCRDDSDCAREGICNGFTALC PASDPKPNFTDCNRHTQVCINGQCAGSICEKYGLEECTCASSDGKDDKELCHVCCMKKMDPSTCASTGSVQWSRHFSGRTITLQPGSPCN DFRGYCDVFMRCRLVDADGPLARLKKAIFSPELYENIAEWIVAHWWAVLLMGIALIMLMAGFIKICSVHTPSSNPKLPPPKPLPGTLKRR -------------------------------------------------------------- |
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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/chr15:71549054/chr15:58957396) - 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 |
| . | ADAM10 |
| 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: Cleaves the membrane-bound precursor of TNF-alpha at '76-Ala-|-Val-77' to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface (PubMed:20592283). Responsible for the proteolytic release of several other cell-surface proteins, including heparin-binding epidermal growth-like factor, ephrin-A2, CD44, CDH2 and for constitutive and regulated alpha-secretase cleavage of amyloid precursor protein (APP) (PubMed:26686862, PubMed:11786905, PubMed:29224781). Contributes to the normal cleavage of the cellular prion protein (PubMed:11477090). Involved in the cleavage of the adhesion molecule L1 at the cell surface and in released membrane vesicles, suggesting a vesicle-based protease activity (PubMed:12475894). Controls also the proteolytic processing of Notch and mediates lateral inhibition during neurogenesis (By similarity). Responsible for the FasL ectodomain shedding and for the generation of the remnant ADAM10-processed FasL (FasL APL) transmembrane form (PubMed:17557115). Also cleaves the ectodomain of the integral membrane proteins CORIN and ITM2B (PubMed:19114711, PubMed:21288900). Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3 (By similarity). Mediates the proteolytic cleavage of IL6R and IL11RA, leading to the release of secreted forms of IL6R and IL11RA (PubMed:26876177). Enhances the cleavage of CHL1 by BACE1 (By similarity). Cleaves NRCAM (By similarity). Cleaves TREM2, resulting in shedding of the TREM2 ectodomain (PubMed:24990881). Involved in the development and maturation of glomerular and coronary vasculature (By similarity). During development of the cochlear organ of Corti, promotes pillar cell separation by forming a ternary complex with CADH1 and EPHA4 and cleaving CADH1 at adherens junctions (By similarity). May regulate the EFNA5-EPHA3 signaling (PubMed:16239146). {ECO:0000250|UniProtKB:O35598, ECO:0000269|PubMed:11477090, ECO:0000269|PubMed:11786905, ECO:0000269|PubMed:12475894, ECO:0000269|PubMed:16239146, ECO:0000269|PubMed:17557115, ECO:0000269|PubMed:19114711, ECO:0000269|PubMed:20592283, ECO:0000269|PubMed:21288900, ECO:0000269|PubMed:24990881, ECO:0000269|PubMed:26686862, ECO:0000269|PubMed:26876177, ECO:0000269|PubMed:29224781}.; FUNCTION: (Microbial infection) Promotes the cytotoxic activity of S.aureus hly by binding to the toxin at zonula adherens and promoting formation of toxin pores. {ECO:0000269|PubMed:20624979, ECO:0000269|PubMed:30463011}. |
| 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 | THSD4 | chr15:71549054 | chr15:58957396 | ENST00000261862 | - | 5 | 17 | 53_307 | 338.3333333333333 | 1019.0 | Domain | TSP type-1 1 |
| Hgene | THSD4 | chr15:71549054 | chr15:58957396 | ENST00000355327 | - | 6 | 18 | 53_307 | 338.3333333333333 | 1019.0 | Domain | TSP type-1 1 |
| Tgene | ADAM10 | chr15:71549054 | chr15:58957396 | ENST00000260408 | 3 | 16 | 555_673 | 161.33333333333334 | 749.0 | Compositional bias | Cys-rich | |
| Tgene | ADAM10 | chr15:71549054 | chr15:58957396 | ENST00000260408 | 3 | 16 | 220_456 | 161.33333333333334 | 749.0 | Domain | Peptidase M12B | |
| Tgene | ADAM10 | chr15:71549054 | chr15:58957396 | ENST00000260408 | 3 | 16 | 457_551 | 161.33333333333334 | 749.0 | Domain | Disintegrin | |
| Tgene | ADAM10 | chr15:71549054 | chr15:58957396 | ENST00000260408 | 3 | 16 | 171_178 | 161.33333333333334 | 749.0 | Motif | Cysteine switch | |
| Tgene | ADAM10 | chr15:71549054 | chr15:58957396 | ENST00000260408 | 3 | 16 | 708_715 | 161.33333333333334 | 749.0 | Motif | SH3-binding | |
| Tgene | ADAM10 | chr15:71549054 | chr15:58957396 | ENST00000260408 | 3 | 16 | 722_728 | 161.33333333333334 | 749.0 | Motif | SH3-binding | |
| Tgene | ADAM10 | chr15:71549054 | chr15:58957396 | ENST00000260408 | 3 | 16 | 694_748 | 161.33333333333334 | 749.0 | Topological domain | Cytoplasmic | |
| Tgene | ADAM10 | chr15:71549054 | chr15:58957396 | ENST00000260408 | 3 | 16 | 673_693 | 161.33333333333334 | 749.0 | Transmembrane | Helical |
| - 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 | THSD4 | chr15:71549054 | chr15:58957396 | ENST00000261862 | - | 5 | 17 | 676_737 | 338.3333333333333 | 1019.0 | Domain | TSP type-1 2 |
| Hgene | THSD4 | chr15:71549054 | chr15:58957396 | ENST00000261862 | - | 5 | 17 | 739_792 | 338.3333333333333 | 1019.0 | Domain | TSP type-1 3 |
| Hgene | THSD4 | chr15:71549054 | chr15:58957396 | ENST00000261862 | - | 5 | 17 | 793_851 | 338.3333333333333 | 1019.0 | Domain | TSP type-1 4 |
| Hgene | THSD4 | chr15:71549054 | chr15:58957396 | ENST00000261862 | - | 5 | 17 | 852_911 | 338.3333333333333 | 1019.0 | Domain | TSP type-1 5 |
| Hgene | THSD4 | chr15:71549054 | chr15:58957396 | ENST00000261862 | - | 5 | 17 | 912_968 | 338.3333333333333 | 1019.0 | Domain | TSP type-1 6 |
| Hgene | THSD4 | chr15:71549054 | chr15:58957396 | ENST00000261862 | - | 5 | 17 | 971_1008 | 338.3333333333333 | 1019.0 | Domain | PLAC |
| Hgene | THSD4 | chr15:71549054 | chr15:58957396 | ENST00000355327 | - | 6 | 18 | 676_737 | 338.3333333333333 | 1019.0 | Domain | TSP type-1 2 |
| Hgene | THSD4 | chr15:71549054 | chr15:58957396 | ENST00000355327 | - | 6 | 18 | 739_792 | 338.3333333333333 | 1019.0 | Domain | TSP type-1 3 |
| Hgene | THSD4 | chr15:71549054 | chr15:58957396 | ENST00000355327 | - | 6 | 18 | 793_851 | 338.3333333333333 | 1019.0 | Domain | TSP type-1 4 |
| Hgene | THSD4 | chr15:71549054 | chr15:58957396 | ENST00000355327 | - | 6 | 18 | 852_911 | 338.3333333333333 | 1019.0 | Domain | TSP type-1 5 |
| Hgene | THSD4 | chr15:71549054 | chr15:58957396 | ENST00000355327 | - | 6 | 18 | 912_968 | 338.3333333333333 | 1019.0 | Domain | TSP type-1 6 |
| Hgene | THSD4 | chr15:71549054 | chr15:58957396 | ENST00000355327 | - | 6 | 18 | 971_1008 | 338.3333333333333 | 1019.0 | Domain | PLAC |
| Tgene | ADAM10 | chr15:71549054 | chr15:58957396 | ENST00000260408 | 3 | 16 | 20_672 | 161.33333333333334 | 749.0 | Topological domain | Extracellular |
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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 |
| THSD4 | |
| ADAM10 |
| - 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 THSD4-ADAM10 |
| 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 THSD4-ADAM10 |
| 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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