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Fusion Protein:NOTCH2-MACF1 |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: NOTCH2-MACF1 | FusionPDB ID: 59734 | FusionGDB2.0 ID: 59734 | Hgene | Tgene | Gene symbol | NOTCH2 | MACF1 | Gene ID | 4853 | 23499 |
| Gene name | notch receptor 2 | microtubule actin crosslinking factor 1 | |
| Synonyms | AGS2|HJCYS|hN2 | ABP620|ACF7|LIS9|MACF|OFC4 | |
| Cytomap | 1p12 | 1p34.3 | |
| Type of gene | protein-coding | protein-coding | |
| Description | neurogenic locus notch homolog protein 2Notch homolog 2notch 2 | microtubule-actin cross-linking factor 1620 kDa actin binding proteinactin cross-linking family protein 7macrophin 1 isoformtrabeculin-alpha | |
| Modification date | 20200329 | 20200313 | |
| UniProtAcc | P0DPK3 Main function of 5'-partner protein: FUNCTION: Human-specific protein that promotes neural progenitor proliferation and evolutionary expansion of the brain neocortex by regulating the Notch signaling pathway (PubMed:29856954, PubMed:29856955, PubMed:29561261). Able to promote neural progenitor self-renewal, possibly by down-regulating neuronal differentiation genes, thereby delaying the differentiation of neuronal progenitors and leading to an overall final increase in neuronal production (PubMed:29856954, PubMed:29856955). Acts by enhancing the Notch signaling pathway via two different mechanisms that probably work in parallel to reach the same effect (PubMed:29856954, PubMed:29856955). Enhances Notch signaling pathway in a non-cell-autonomous manner via direct interaction with NOTCH2 (PubMed:29856954). Also promotes Notch signaling pathway in a cell-autonomous manner through inhibition of cis DLL1-NOTCH2 interactions, which promotes neuronal differentiation (PubMed:29856955). {ECO:0000269|PubMed:29561261, ECO:0000269|PubMed:29856954, ECO:0000269|PubMed:29856955}. | Q9UPN3 Main function of 5'-partner protein: FUNCTION: [Isoform 2]: F-actin-binding protein which plays a role in cross-linking actin to other cytoskeletal proteins and also binds to microtubules (PubMed:15265687, PubMed:20937854). Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854). Acts as a positive regulator of Wnt receptor signaling pathway and is involved in the translocation of AXIN1 and its associated complex (composed of APC, CTNNB1 and GSK3B) from the cytoplasm to the cell membrane (By similarity). Has actin-regulated ATPase activity and is essential for controlling focal adhesions (FAs) assembly and dynamics (By similarity). Interaction with CAMSAP3 at the minus ends of non-centrosomal microtubules tethers microtubules minus-ends to actin filaments, regulating focal adhesion size and cell migration (PubMed:27693509). May play role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with GOLGA4 (PubMed:15265687). Plays a key role in wound healing and epidermal cell migration (By similarity). Required for efficient upward migration of bulge cells in response to wounding and this function is primarily rooted in its ability to coordinate microtubule dynamics and polarize hair follicle stem cells (By similarity). As a regulator of actin and microtubule arrangement and stabilization, it plays an essential role in neurite outgrowth, branching and spine formation during brain development (By similarity). {ECO:0000250|UniProtKB:Q9QXZ0, ECO:0000269|PubMed:15265687, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:27693509}. | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000256646, ENST00000602566, ENST00000493703, | ENST00000476350, ENST00000289893, ENST00000484793, ENST00000536367, ENST00000602421, ENST00000317713, ENST00000361689, ENST00000372915, ENST00000539005, ENST00000545844, ENST00000564288, ENST00000567887, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 26 X 22 X 14=8008 | 24 X 23 X 9=4968 |
| # samples | 35 | 24 | |
| ** MAII score | log2(35/8008*10)=-4.51601514700366 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(24/4968*10)=-4.37155886261196 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Fusion gene context | PubMed: NOTCH2 [Title/Abstract] AND MACF1 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: NOTCH2 [Title/Abstract] AND MACF1 [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | NOTCH2(120572529)-MACF1(39775242), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | NOTCH2-MACF1 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. NOTCH2-MACF1 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. NOTCH2-MACF1 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. NOTCH2-MACF1 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. NOTCH2-MACF1 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF. NOTCH2-MACF1 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. NOTCH2-MACF1 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 | NOTCH2 | GO:0007050 | cell cycle arrest | 11306509 |
| Hgene | NOTCH2 | GO:0007219 | Notch signaling pathway | 11306509|25985737 |
| Hgene | NOTCH2 | GO:0010629 | negative regulation of gene expression | 11306509 |
| Hgene | NOTCH2 | GO:0010838 | positive regulation of keratinocyte proliferation | 18469519 |
| Hgene | NOTCH2 | GO:0045967 | negative regulation of growth rate | 11306509 |
| Hgene | NOTCH2 | GO:0046579 | positive regulation of Ras protein signal transduction | 11306509 |
| Hgene | NOTCH2 | GO:0070374 | positive regulation of ERK1 and ERK2 cascade | 11306509 |
| Hgene | NOTCH2 | GO:2000249 | regulation of actin cytoskeleton reorganization | 18469519 |
| Tgene | MACF1 | GO:0030334 | regulation of cell migration | 27693509 |
| Tgene | MACF1 | GO:0043001 | Golgi to plasma membrane protein transport | 15265687 |
| Tgene | MACF1 | GO:0045773 | positive regulation of axon extension | 22705394 |
| Tgene | MACF1 | GO:0051893 | regulation of focal adhesion assembly | 27693509 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr1:120572529/chr1:39775242) - 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 NOTCH2 (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 MACF1 (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) |
| ENST00000256646 | NOTCH2 | chr1 | 120572529 | - | ENST00000545844 | MACF1 | chr1 | 39775242 | + | 15187 | 375 | 16 | 13863 | 4615 |
| ENST00000256646 | NOTCH2 | chr1 | 120572529 | - | ENST00000567887 | MACF1 | chr1 | 39775242 | + | 21637 | 375 | 16 | 20253 | 6745 |
| ENST00000256646 | NOTCH2 | chr1 | 120572529 | - | ENST00000372915 | MACF1 | chr1 | 39775242 | + | 20924 | 375 | 16 | 19737 | 6573 |
| ENST00000256646 | NOTCH2 | chr1 | 120572529 | - | ENST00000361689 | MACF1 | chr1 | 39775242 | + | 15057 | 375 | 16 | 13863 | 4615 |
| ENST00000256646 | NOTCH2 | chr1 | 120572529 | - | ENST00000539005 | MACF1 | chr1 | 39775242 | + | 14797 | 375 | 16 | 13473 | 4485 |
| ENST00000256646 | NOTCH2 | chr1 | 120572529 | - | ENST00000317713 | MACF1 | chr1 | 39775242 | + | 15187 | 375 | 16 | 13863 | 4615 |
| ENST00000256646 | NOTCH2 | chr1 | 120572529 | - | ENST00000564288 | MACF1 | chr1 | 39775242 | + | 21637 | 375 | 16 | 20253 | 6745 |
| 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 |
| ENST00000256646 | ENST00000545844 | NOTCH2 | chr1 | 120572529 | - | MACF1 | chr1 | 39775242 | + | 0.006554564 | 0.9934455 |
| ENST00000256646 | ENST00000567887 | NOTCH2 | chr1 | 120572529 | - | MACF1 | chr1 | 39775242 | + | 0.004203092 | 0.9957969 |
| ENST00000256646 | ENST00000372915 | NOTCH2 | chr1 | 120572529 | - | MACF1 | chr1 | 39775242 | + | 0.004229667 | 0.9957703 |
| ENST00000256646 | ENST00000361689 | NOTCH2 | chr1 | 120572529 | - | MACF1 | chr1 | 39775242 | + | 0.00693754 | 0.99306244 |
| ENST00000256646 | ENST00000539005 | NOTCH2 | chr1 | 120572529 | - | MACF1 | chr1 | 39775242 | + | 0.006489898 | 0.99351007 |
| ENST00000256646 | ENST00000317713 | NOTCH2 | chr1 | 120572529 | - | MACF1 | chr1 | 39775242 | + | 0.006614788 | 0.99338526 |
| ENST00000256646 | ENST00000564288 | NOTCH2 | chr1 | 120572529 | - | MACF1 | chr1 | 39775242 | + | 0.004203092 | 0.9957969 |
| 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 NOTCH2-MACF1 |
| +/-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 |
| NOTCH2 | chr1 | 120572529 | MACF1 | chr1 | 39775242 | 375 | 120 | MCVTYHNGTGYCKVEQSYQKVMALWH |
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Potential FusionNeoAntigen Information of NOTCH2-MACF1 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. |
| NOTCH2-MACF1_120572529_39775242.msa |
| 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) |
| NOTCH2-MACF1 | chr1 | 120572529 | chr1 | 39775242 | 375 | HLA-B38:02 | YHNGTGYCKV | 0.9934 | 0.9596 | 4 | 14 |
| NOTCH2-MACF1 | chr1 | 120572529 | chr1 | 39775242 | 375 | HLA-B38:01 | YHNGTGYCKV | 0.9924 | 0.9635 | 4 | 14 |
| NOTCH2-MACF1 | chr1 | 120572529 | chr1 | 39775242 | 375 | HLA-B39:05 | YHNGTGYCKV | 0.9927 | 0.8514 | 4 | 14 |
| NOTCH2-MACF1 | chr1 | 120572529 | chr1 | 39775242 | 375 | HLA-C14:02 | GYCKVEQSY | 0.0022 | 0.8719 | 9 | 18 |
| NOTCH2-MACF1 | chr1 | 120572529 | chr1 | 39775242 | 375 | HLA-C14:03 | GYCKVEQSY | 0.0022 | 0.8719 | 9 | 18 |
| NOTCH2-MACF1 | chr1 | 120572529 | chr1 | 39775242 | 375 | HLA-B38:05 | YHNGTGYCKV | 0.9924 | 0.9635 | 4 | 14 |
| NOTCH2-MACF1 | chr1 | 120572529 | chr1 | 39775242 | 375 | HLA-B15:09 | YHNGTGYCKV | 0.9635 | 0.5899 | 4 | 14 |
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Potential FusionNeoAntigen Information of NOTCH2-MACF1 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 NOTCH2-MACF1 |
| 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. |
| File name | BPseq | Hgene | Tgene | Hchr | Hbp | Tchr | Tbp | AAlen |
| 6170 | NGTGYCKVEQSYQK | NOTCH2 | MACF1 | chr1 | 120572529 | chr1 | 39775242 | 375 |
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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NOTCH2-MACF1 |
| 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 |
| HLA-B14:02 | 3BVN | 6170 | NGTGYCKVEQSYQK | -7.15543 | -7.26883 |
| HLA-B14:02 | 3BVN | 6170 | NGTGYCKVEQSYQK | -4.77435 | -5.80965 |
| HLA-B52:01 | 3W39 | 6170 | NGTGYCKVEQSYQK | -6.80875 | -6.92215 |
| HLA-B52:01 | 3W39 | 6170 | NGTGYCKVEQSYQK | -4.20386 | -5.23916 |
| HLA-A11:01 | 4UQ2 | 6170 | NGTGYCKVEQSYQK | -7.5194 | -8.5547 |
| HLA-A11:01 | 4UQ2 | 6170 | NGTGYCKVEQSYQK | -6.9601 | -7.0735 |
| HLA-A24:02 | 5HGA | 6170 | NGTGYCKVEQSYQK | -7.52403 | -7.63743 |
| HLA-A24:02 | 5HGA | 6170 | NGTGYCKVEQSYQK | -5.82433 | -6.85963 |
| HLA-B27:05 | 6PYJ | 6170 | NGTGYCKVEQSYQK | -3.28285 | -4.31815 |
| HLA-B44:05 | 3DX8 | 6170 | NGTGYCKVEQSYQK | -5.91172 | -6.94702 |
| HLA-B44:05 | 3DX8 | 6170 | NGTGYCKVEQSYQK | -4.24346 | -4.35686 |
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Vaccine Design for the FusionNeoAntigens of NOTCH2-MACF1 |
| 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 |
| NOTCH2-MACF1 | chr1 | 120572529 | chr1 | 39775242 | 4 | 14 | YHNGTGYCKV | CTACCACAATGGCACAGGATACTGCAAGGT |
| NOTCH2-MACF1 | chr1 | 120572529 | chr1 | 39775242 | 9 | 18 | GYCKVEQSY | AGGATACTGCAAGGTCGAACAATCTTA |
| 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 NOTCH2-MACF1 |
| 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 |
| BRCA | NOTCH2-MACF1 | chr1 | 120572529 | ENST00000256646 | chr1 | 39775242 | ENST00000317713 | TCGA-A2-A0YE-01A |
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Potential target of CAR-T therapy development for NOTCH2-MACF1 |
| 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 |
| 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 NOTCH2-MACF1 |
| 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 NOTCH2-MACF1 |
| 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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