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Fusion Protein:ISG15-IFITM1 |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: ISG15-IFITM1 | FusionPDB ID: 40301 | FusionGDB2.0 ID: 40301 | Hgene | Tgene | Gene symbol | ISG15 | IFITM1 | Gene ID | 9636 | 8519 |
| Gene name | ISG15 ubiquitin like modifier | interferon induced transmembrane protein 1 | |
| Synonyms | G1P2|IFI15|IMD38|IP17|UCRP|hUCRP | 9-27|CD225|DSPA2a|IFI17|LEU13 | |
| Cytomap | 1p36.33 | 11p15.5 | |
| Type of gene | protein-coding | protein-coding | |
| Description | ubiquitin-like protein ISG15interferon, alpha-inducible protein (clone IFI-15K)interferon-induced 17-kDa/15-kDa proteininterferon-stimulated protein, 15 kDaubiquitin cross-reactive protein | interferon-induced transmembrane protein 1dispanin subfamily A member 2ainterferon-induced protein 17interferon-inducible protein 9-27leu-13 antigen | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | P05161 Main function of 5'-partner protein: FUNCTION: Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated protein. ISGylation involves a cascade of enzymatic reactions involving E1, E2, and E3 enzymes which catalyze the conjugation of ISG15 to a lysine residue in the target protein. Its target proteins include IFIT1, MX1/MxA, PPM1B, UBE2L6, UBA7, CHMP5, CHMP2A, CHMP4B and CHMP6. Can also isgylate: EIF2AK2/PKR which results in its activation, DDX58/RIG-I which inhibits its function in antiviral signaling response, EIF4E2 which enhances its cap structure-binding activity and translation-inhibition activity, UBE2N and UBE2E1 which negatively regulates their activity, IRF3 which inhibits its ubiquitination and degradation and FLNB which prevents its ability to interact with the upstream activators of the JNK cascade thereby inhibiting IFNA-induced JNK signaling. Exhibits antiviral activity towards both DNA and RNA viruses, including influenza A, HIV-1 and Ebola virus. Restricts HIV-1 and ebola virus via disruption of viral budding. Inhibits the ubiquitination of HIV-1 Gag and host TSG101 and disrupts their interaction, thereby preventing assembly and release of virions from infected cells. Inhibits Ebola virus budding mediated by the VP40 protein by disrupting ubiquitin ligase activity of NEDD4 and its ability to ubiquitinate VP40. ISGylates influenza A virus NS1 protein which causes a loss of function of the protein and the inhibition of virus replication. The secreted form of ISG15 can: induce natural killer cell proliferation, act as a chemotactic factor for neutrophils and act as a IFN-gamma-inducing cytokine playing an essential role in antimycobacterial immunity. The secreted form acts through the integrin ITGAL/ITGB2 receptor to initiate activation of SRC family tyrosine kinases including LYN, HCK and FGR which leads to secretion of IFNG and IL10; the interaction is mediated by ITGAL (PubMed:29100055). {ECO:0000269|PubMed:1373138, ECO:0000269|PubMed:16009940, ECO:0000269|PubMed:16112642, ECO:0000269|PubMed:16428300, ECO:0000269|PubMed:16434471, ECO:0000269|PubMed:16872604, ECO:0000269|PubMed:18305167, ECO:0000269|PubMed:19270716, ECO:0000269|PubMed:19357168, ECO:0000269|PubMed:2005397, ECO:0000269|PubMed:20133869, ECO:0000269|PubMed:20308324, ECO:0000269|PubMed:20639253, ECO:0000269|PubMed:21543490, ECO:0000269|PubMed:22693631, ECO:0000269|PubMed:22859821, ECO:0000269|PubMed:23229543, ECO:0000269|PubMed:29100055, ECO:0000269|PubMed:7526157, ECO:0000269|PubMed:8550581}. | A6NMD0 Main function of 5'-partner protein: | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000379389, | ENST00000525554, ENST00000408968, ENST00000528780, ENST00000328221, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 2 X 1 X 1=2 | 7 X 8 X 5=280 |
| # samples | 1 | 8 | |
| ** MAII score | log2(1/2*10)=2.32192809488736 | log2(8/280*10)=-1.8073549220576 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Fusion gene context | PubMed: ISG15 [Title/Abstract] AND IFITM1 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: ISG15 [Title/Abstract] AND IFITM1 [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | ISG15(949543)-IFITM1(314961), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | ISG15-IFITM1 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. ISG15-IFITM1 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. ISG15-IFITM1 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. ISG15-IFITM1 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. ISG15-IFITM1 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor 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 | ISG15 | GO:0007229 | integrin-mediated signaling pathway | 29100055 |
| Hgene | ISG15 | GO:0031397 | negative regulation of protein ubiquitination | 18305167 |
| Hgene | ISG15 | GO:0032020 | ISG15-protein conjugation | 16122702|21543490 |
| Hgene | ISG15 | GO:0034340 | response to type I interferon | 22859821 |
| Hgene | ISG15 | GO:0072608 | interleukin-10 secretion | 29100055 |
| Hgene | ISG15 | GO:0072643 | interferon-gamma secretion | 29100055 |
| Tgene | IFITM1 | GO:0009615 | response to virus | 21253575|22479637 |
| Tgene | IFITM1 | GO:0034341 | response to interferon-gamma | 21253575 |
| Tgene | IFITM1 | GO:0035455 | response to interferon-alpha | 22479637 |
| Tgene | IFITM1 | GO:0035456 | response to interferon-beta | 21253575 |
| Tgene | IFITM1 | GO:0045071 | negative regulation of viral genome replication | 21253575 |
| Tgene | IFITM1 | GO:0046597 | negative regulation of viral entry into host cell | 21253575|23358889 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr1:949543/chr11:314961) - 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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| Retention analysis results 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, are available here. |
| Fusion gene breakpoints across ISG15 (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 IFITM1 (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 Amino Acid Sequences |
| 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) |
| ENST00000379389 | ISG15 | chr1 | 949543 | + | ENST00000328221 | IFITM1 | chr11 | 314961 | + | 810 | 531 | 22 | 468 | 148 |
| 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 |
| ENST00000379389 | ENST00000328221 | ISG15 | chr1 | 949543 | + | IFITM1 | chr11 | 314961 | + | 0.19841786 | 0.80158216 |
| Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones. |
Get the fusion protein sequences from here. |
| Fusion protein sequence information is available in the fasta format. >FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP |
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Fusion Protein Breakpoint Sequences for ISG15-IFITM1 |
| +/-13 AA sequence from the breakpoints of the fusion protein sequences. |
| Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Length(fusion protein) | BP in fusion protein | Peptide |
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Potential FusionNeoAntigen Information of ISG15-IFITM1 in HLA I |
| Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific. |
| Potential FusionNeoAntigen Information * We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5) |
| Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA I | FusionNeoAntigen peptide | Binding score | Immunogenic score | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
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Potential FusionNeoAntigen Information of ISG15-IFITM1 in HLA II |
| Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific. |
| Potential FusionNeoAntigen Information * We used NetMHCIIpan v4.1 (%rank<0.5). |
| Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA II | FusionNeoAntigen peptide | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
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Fusion breakpoint peptide structures of ISG15-IFITM1 |
| 3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens * The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA. |
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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ISG15-IFITM1 |
| Virtual screening between 25 HLAs (from PDB) and FusionNeoAntigens * We used Glide to predict the interaction between HLAs and neoantigens. |
| HLA allele | PDB ID | File name | BPseq | Docking score | Glide score |
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Vaccine Design for the FusionNeoAntigens of ISG15-IFITM1 |
| mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is. |
| Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide sequence | FusionNeoAntigen RNA sequence |
| mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs. |
| Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide | FusionNEoAntigen RNA sequence |
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Information of the samples that have these potential fusion neoantigens of ISG15-IFITM1 |
| These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens. |
| Cancer type | Fusion gene | Hchr | Hbp | Henst | Tchr | Tbp | Tenst | Sample |
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Potential target of CAR-T therapy development for ISG15-IFITM1 |
| Predicted 3D structure. We used RoseTTAFold. |
| 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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features * Minus value of BPloci means that the break point is located before the CDS. |
| - In-frame and retained 'Transmembrane'. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Tgene | IFITM1 | chr1:949543 | chr11:314961 | ENST00000328221 | 0 | 3 | 37_57 | 0 | 126.0 | Intramembrane | Helical | |
| Tgene | IFITM1 | chr1:949543 | chr11:314961 | ENST00000408968 | 0 | 2 | 37_57 | 0 | 126.0 | Intramembrane | Helical | |
| Tgene | IFITM1 | chr1:949543 | chr11:314961 | ENST00000528780 | 0 | 3 | 37_57 | 0 | 126.0 | Intramembrane | Helical | |
| Tgene | IFITM1 | chr1:949543 | chr11:314961 | ENST00000328221 | 0 | 3 | 87_107 | 0 | 126.0 | Transmembrane | Helical | |
| Tgene | IFITM1 | chr1:949543 | chr11:314961 | ENST00000408968 | 0 | 2 | 87_107 | 0 | 126.0 | Transmembrane | Helical | |
| Tgene | IFITM1 | chr1:949543 | chr11:314961 | ENST00000528780 | 0 | 3 | 87_107 | 0 | 126.0 | Transmembrane | Helical |
| Subcellular localization prediction of the transmembrane domain retained fusion proteins * We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image. |
| Hgene | Hchr | Hbp | Henst | Tgene | Tchr | Tbp | Tenst | DeepLoc result |
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Related Drugs to ISG15-IFITM1 |
| 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 ISG15-IFITM1 |
| 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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