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Fusion Protein:HSP90B1-MDM2 |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: HSP90B1-MDM2 | FusionPDB ID: 37826 | FusionGDB2.0 ID: 37826 | Hgene | Tgene | Gene symbol | HSP90B1 | MDM2 | Gene ID | 7184 | 4193 |
| Gene name | heat shock protein 90 beta family member 1 | MDM2 proto-oncogene | |
| Synonyms | ECGP|GP96|GRP94|HEL-S-125m|HEL35|TRA1 | ACTFS|HDMX|LSKB|hdm2 | |
| Cytomap | 12q23.3 | 12q15 | |
| Type of gene | protein-coding | protein-coding | |
| Description | endoplasmin94 kDa glucose-regulated proteinendothelial cell (HBMEC) glycoproteinepididymis luminal protein 35epididymis secretory sperm binding protein Li 125mheat shock protein 90 kDa beta member 1heat shock protein 90kDa beta (Grp94), member 1hea | E3 ubiquitin-protein ligase Mdm2MDM2 oncogene, E3 ubiquitin protein ligaseMDM2 proto-oncogene, E3 ubiquitin protein ligaseMdm2, p53 E3 ubiquitin protein ligase homologMdm2, transformed 3T3 cell double minute 2, p53 binding proteindouble minute 2, hum | |
| Modification date | 20200320 | 20200329 | |
| UniProtAcc | P14625 Main function of 5'-partner protein: FUNCTION: Molecular chaperone that functions in the processing and transport of secreted proteins (By similarity). When associated with CNPY3, required for proper folding of Toll-like receptors (By similarity). Functions in endoplasmic reticulum associated degradation (ERAD) (PubMed:18264092). Has ATPase activity (By similarity). May participate in the unfolding of cytosolic leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1 to facilitate their translocation into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and secretion; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000250|UniProtKB:P08113, ECO:0000269|PubMed:18264092, ECO:0000269|PubMed:32272059}. | Q00987 Main function of 5'-partner protein: FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal degradation (PubMed:12821780, PubMed:15053880, PubMed:15195100, PubMed:15632057, PubMed:16337594, PubMed:17290220, PubMed:19098711, PubMed:19219073, PubMed:19837670, PubMed:19965871, PubMed:20173098, PubMed:20385133, PubMed:20858735, PubMed:22128911). Ubiquitinates DCX, leading to DCX degradation and reduction of the dendritic spine density of olfactory bulb granule cells (By similarity). Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor endocytosis (By similarity). Negatively regulates NDUFS1, leading to decreased mitochondrial respiration, marked oxidative stress, and commitment to the mitochondrial pathway of apoptosis (PubMed:30879903). Binds NDUFS1 leading to its cytosolic retention rather than mitochondrial localization resulting in decreased supercomplex assembly (interactions between complex I and complex III), decreased complex I activity, ROS production, and apoptosis (PubMed:30879903). {ECO:0000250|UniProtKB:P23804, ECO:0000269|PubMed:12821780, ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:15195100, ECO:0000269|PubMed:15632057, ECO:0000269|PubMed:16337594, ECO:0000269|PubMed:17290220, ECO:0000269|PubMed:19098711, ECO:0000269|PubMed:19219073, ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:19965871, ECO:0000269|PubMed:20173098, ECO:0000269|PubMed:20385133, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:22128911, ECO:0000269|PubMed:30879903}. | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000299767, | ENST00000258148, ENST00000299252, ENST00000348801, ENST00000350057, ENST00000360430, ENST00000393410, ENST00000393412, ENST00000393413, ENST00000478070, ENST00000517852, ENST00000544125, ENST00000544561, ENST00000545204, ENST00000258149, ENST00000356290, ENST00000428863, ENST00000462284, ENST00000540827, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 19 X 19 X 10=3610 | 12 X 10 X 6=720 |
| # samples | 25 | 12 | |
| ** MAII score | log2(25/3610*10)=-3.85199883711245 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(12/720*10)=-2.58496250072116 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Fusion gene context | PubMed: HSP90B1 [Title/Abstract] AND MDM2 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: HSP90B1 [Title/Abstract] AND MDM2 [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | HSP90B1(104341208)-MDM2(69229609), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | HSP90B1-MDM2 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. HSP90B1-MDM2 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. HSP90B1-MDM2 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. HSP90B1-MDM2 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 | HSP90B1 | GO:0001666 | response to hypoxia | 15620698 |
| Hgene | HSP90B1 | GO:0031247 | actin rod assembly | 19000834 |
| Hgene | HSP90B1 | GO:0043666 | regulation of phosphoprotein phosphatase activity | 19000834 |
| Hgene | HSP90B1 | GO:0071318 | cellular response to ATP | 19000834 |
| Tgene | MDM2 | GO:0000122 | negative regulation of transcription by RNA polymerase II | 9271120|17310983 |
| Tgene | MDM2 | GO:0006511 | ubiquitin-dependent protein catabolic process | 11278372|15314173|16173922|17310983 |
| Tgene | MDM2 | GO:0016567 | protein ubiquitination | 9450543|15878855|19656744|20153724 |
| Tgene | MDM2 | GO:0031648 | protein destabilization | 9529249|10360174|15314173 |
| Tgene | MDM2 | GO:0032436 | positive regulation of proteasomal ubiquitin-dependent protein catabolic process | 11278372 |
| Tgene | MDM2 | GO:0034504 | protein localization to nucleus | 10360174 |
| Tgene | MDM2 | GO:0042176 | regulation of protein catabolic process | 9153395 |
| Tgene | MDM2 | GO:0043518 | negative regulation of DNA damage response, signal transduction by p53 class mediator | 9529249|10360174 |
| Tgene | MDM2 | GO:0045184 | establishment of protein localization | 10360174 |
| Tgene | MDM2 | GO:0045892 | negative regulation of transcription, DNA-templated | 9271120 |
| Tgene | MDM2 | GO:0065003 | protein-containing complex assembly | 10608892|12915590 |
| Tgene | MDM2 | GO:0071157 | negative regulation of cell cycle arrest | 9529249 |
| Tgene | MDM2 | GO:0071480 | cellular response to gamma radiation | 16213212 |
| Tgene | MDM2 | GO:0072717 | cellular response to actinomycin D | 15314173 |
| Tgene | MDM2 | GO:1901797 | negative regulation of signal transduction by p53 class mediator | 16173922 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr12:104341208/chr12:69229609) - 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 HSP90B1 (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 MDM2 (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) |
| ENST00000299767 | HSP90B1 | chr12 | 104341208 | + | ENST00000462284 | MDM2 | chr12 | 69229609 | + | 8959 | 2564 | 182 | 3373 | 1063 |
| ENST00000299767 | HSP90B1 | chr12 | 104341208 | + | ENST00000356290 | MDM2 | chr12 | 69229609 | + | 8956 | 2564 | 182 | 3373 | 1063 |
| ENST00000299767 | HSP90B1 | chr12 | 104341208 | + | ENST00000540827 | MDM2 | chr12 | 69229609 | + | 8956 | 2564 | 182 | 3373 | 1063 |
| ENST00000299767 | HSP90B1 | chr12 | 104341208 | + | ENST00000258149 | MDM2 | chr12 | 69229609 | + | 8956 | 2564 | 182 | 3373 | 1063 |
| ENST00000299767 | HSP90B1 | chr12 | 104341208 | + | ENST00000428863 | MDM2 | chr12 | 69229609 | + | 8878 | 2564 | 182 | 3295 | 1037 |
| 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 |
| ENST00000299767 | ENST00000462284 | HSP90B1 | chr12 | 104341208 | + | MDM2 | chr12 | 69229609 | + | 8.97E-05 | 0.99991024 |
| ENST00000299767 | ENST00000356290 | HSP90B1 | chr12 | 104341208 | + | MDM2 | chr12 | 69229609 | + | 8.93E-05 | 0.9999106 |
| ENST00000299767 | ENST00000540827 | HSP90B1 | chr12 | 104341208 | + | MDM2 | chr12 | 69229609 | + | 8.93E-05 | 0.9999106 |
| ENST00000299767 | ENST00000258149 | HSP90B1 | chr12 | 104341208 | + | MDM2 | chr12 | 69229609 | + | 8.93E-05 | 0.9999106 |
| ENST00000299767 | ENST00000428863 | HSP90B1 | chr12 | 104341208 | + | MDM2 | chr12 | 69229609 | + | 0.000101205 | 0.9998988 |
| 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 HSP90B1-MDM2 |
| +/-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 |
| HSP90B1 | chr12 | 104341208 | MDM2 | chr12 | 69229609 | 2564 | 794 | MDVGTDEEEETAKDLDAGVSEHSGDW |
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Potential FusionNeoAntigen Information of HSP90B1-MDM2 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. |
| HSP90B1-MDM2_104341208_69229609.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) |
| HSP90B1-MDM2 | chr12 | 104341208 | chr12 | 69229609 | 2564 | HLA-B44:03 | EEEETAKDL | 0.9083 | 0.9663 | 6 | 15 |
| HSP90B1-MDM2 | chr12 | 104341208 | chr12 | 69229609 | 2564 | HLA-B45:01 | EETAKDLDA | 0.8725 | 0.7384 | 8 | 17 |
| HSP90B1-MDM2 | chr12 | 104341208 | chr12 | 69229609 | 2564 | HLA-B44:13 | EEEETAKDL | 0.9083 | 0.9663 | 6 | 15 |
| HSP90B1-MDM2 | chr12 | 104341208 | chr12 | 69229609 | 2564 | HLA-B44:26 | EEEETAKDL | 0.9083 | 0.9663 | 6 | 15 |
| HSP90B1-MDM2 | chr12 | 104341208 | chr12 | 69229609 | 2564 | HLA-B44:07 | EEEETAKDL | 0.9083 | 0.9663 | 6 | 15 |
| HSP90B1-MDM2 | chr12 | 104341208 | chr12 | 69229609 | 2564 | HLA-B41:03 | EEEETAKDL | 0.4228 | 0.5625 | 6 | 15 |
| HSP90B1-MDM2 | chr12 | 104341208 | chr12 | 69229609 | 2564 | HLA-A68:02 | ETAKDLDAGV | 0.9955 | 0.6101 | 9 | 19 |
| HSP90B1-MDM2 | chr12 | 104341208 | chr12 | 69229609 | 2564 | HLA-A69:01 | ETAKDLDAGV | 0.9862 | 0.6687 | 9 | 19 |
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Potential FusionNeoAntigen Information of HSP90B1-MDM2 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 HSP90B1-MDM2 |
| 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 |
| 1644 | EEEETAKDLDAGVS | HSP90B1 | MDM2 | chr12 | 104341208 | chr12 | 69229609 | 2564 |
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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of HSP90B1-MDM2 |
| 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 | 1644 | EEEETAKDLDAGVS | -7.07721 | -7.27171 |
| HLA-B14:02 | 3BVN | 1644 | EEEETAKDLDAGVS | -6.02599 | -6.78049 |
| HLA-B52:01 | 3W39 | 1644 | EEEETAKDLDAGVS | -7.19743 | -7.39193 |
| HLA-B52:01 | 3W39 | 1644 | EEEETAKDLDAGVS | -4.19003 | -4.94453 |
| HLA-A11:01 | 4UQ2 | 1644 | EEEETAKDLDAGVS | -8.33023 | -9.08473 |
| HLA-A11:01 | 4UQ2 | 1644 | EEEETAKDLDAGVS | -6.32448 | -6.51898 |
| HLA-A24:02 | 5HGA | 1644 | EEEETAKDLDAGVS | -8.75651 | -8.95101 |
| HLA-A24:02 | 5HGA | 1644 | EEEETAKDLDAGVS | -6.08094 | -6.83544 |
| HLA-B44:05 | 3DX8 | 1644 | EEEETAKDLDAGVS | -5.59245 | -5.78695 |
| HLA-B44:05 | 3DX8 | 1644 | EEEETAKDLDAGVS | -4.19666 | -4.95116 |
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Vaccine Design for the FusionNeoAntigens of HSP90B1-MDM2 |
| 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 |
| HSP90B1-MDM2 | chr12 | 104341208 | chr12 | 69229609 | 6 | 15 | EEEETAKDL | GAAGAAGAAGAAACAGCAAAGGATCTT |
| HSP90B1-MDM2 | chr12 | 104341208 | chr12 | 69229609 | 8 | 17 | EETAKDLDA | GAAGAAACAGCAAAGGATCTTGATGCT |
| HSP90B1-MDM2 | chr12 | 104341208 | chr12 | 69229609 | 9 | 19 | ETAKDLDAGV | GAAACAGCAAAGGATCTTGATGCTGGTGTA |
| 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 HSP90B1-MDM2 |
| 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 |
| SARC | HSP90B1-MDM2 | chr12 | 104341208 | ENST00000299767 | chr12 | 69229609 | ENST00000258149 | TCGA-PC-A5DN-01A |
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Potential target of CAR-T therapy development for HSP90B1-MDM2 |
| 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 HSP90B1-MDM2 |
| 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 HSP90B1-MDM2 |
| 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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