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Fusion Protein:MAPK9-DGKB |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: MAPK9-DGKB | FusionPDB ID: 51579 | FusionGDB2.0 ID: 51579 | Hgene | Tgene | Gene symbol | MAPK9 | DGKB | Gene ID | 5601 | 1607 |
| Gene name | mitogen-activated protein kinase 9 | diacylglycerol kinase beta | |
| Synonyms | JNK-55|JNK2|JNK2A|JNK2ALPHA|JNK2B|JNK2BETA|PRKM9|SAPK|SAPK1a|p54a|p54aSAPK | DAGK2|DGK|DGK-BETA | |
| Cytomap | 5q35.3 | 7p21.2 | |
| Type of gene | protein-coding | protein-coding | |
| Description | mitogen-activated protein kinase 9Jun kinaseMAP kinase 9MAPK 9c-Jun N-terminal kinase 2c-Jun kinase 2stress-activated protein kinase 1astress-activated protein kinase JNK2 | diacylglycerol kinase beta90 kDa diacylglycerol kinaseDAG kinase betadiacylglycerol kinase, beta 90kDadiglyceride kinase beta | |
| Modification date | 20200327 | 20200313 | |
| UniProtAcc | P45984 Main function of 5'-partner protein: FUNCTION: Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation (By similarity). {ECO:0000250|UniProtKB:Q9WTU6, ECO:0000269|PubMed:22441692}.; FUNCTION: MAPK9 isoforms display different binding patterns: alpha-1 and alpha-2 preferentially bind to JUN, whereas beta-1 and beta-2 bind to ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only weakly to it. | Q9Y6T7 Main function of 5'-partner protein: FUNCTION: Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:11719522). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (Probable). Has a higher activity with long-chain diacylglycerols like 1,2-di-(9Z-octadecenoyl)-sn-glycerol compared to 1,2-didecanoyl-sn-glycerol (By similarity). Specifically expressed in brain, it regulates neuron-specific morphological changes including neurite branching and neurite spine formation (By similarity). {ECO:0000250|UniProtKB:P49621, ECO:0000250|UniProtKB:Q6NS52, ECO:0000269|PubMed:11719522, ECO:0000305}.; FUNCTION: [Isoform 2]: Does not associate with membranes but has a diacylglycerol kinase activity. {ECO:0000269|PubMed:11719522}. | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000397072, ENST00000343111, ENST00000347470, ENST00000393360, ENST00000425491, ENST00000452135, ENST00000455781, ENST00000539014, ENST00000524170, | ENST00000258767, ENST00000399322, ENST00000402815, ENST00000403951, ENST00000406247, ENST00000407950, ENST00000444700, ENST00000403963, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 9 X 10 X 6=540 | 19 X 16 X 9=2736 |
| # samples | 10 | 19 | |
| ** MAII score | log2(10/540*10)=-2.43295940727611 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(19/2736*10)=-3.84799690655495 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Fusion gene context | PubMed: MAPK9 [Title/Abstract] AND DGKB [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: MAPK9 [Title/Abstract] AND DGKB [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | MAPK9(179691781)-DGKB(14661119), # samples:2 | ||
| Anticipated loss of major functional domain due to fusion event. | MAPK9-DGKB 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. MAPK9-DGKB 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. MAPK9-DGKB 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. MAPK9-DGKB 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. MAPK9-DGKB seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. MAPK9-DGKB seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF. MAPK9-DGKB seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF. MAPK9-DGKB 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 | MAPK9 | GO:0007254 | JNK cascade | 8654373 |
| Hgene | MAPK9 | GO:0018105 | peptidyl-serine phosphorylation | 21856198 |
| Tgene | DGKB | GO:0046486 | glycerolipid metabolic process | 22627129 |
| Tgene | DGKB | GO:0046834 | lipid phosphorylation | 22627129 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr5:179691781/chr7:14661119) - 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 MAPK9 (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 DGKB (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) |
| ENST00000539014 | MAPK9 | chr5 | 179691781 | - | ENST00000399322 | DGKB | chr7 | 14661119 | - | 5658 | 331 | 403 | 1575 | 390 |
| ENST00000539014 | MAPK9 | chr5 | 179691781 | - | ENST00000258767 | DGKB | chr7 | 14661119 | - | 5658 | 331 | 403 | 1575 | 390 |
| ENST00000539014 | MAPK9 | chr5 | 179691781 | - | ENST00000403951 | DGKB | chr7 | 14661119 | - | 5658 | 331 | 403 | 1575 | 390 |
| ENST00000539014 | MAPK9 | chr5 | 179691781 | - | ENST00000402815 | DGKB | chr7 | 14661119 | - | 4473 | 331 | 403 | 1575 | 390 |
| ENST00000539014 | MAPK9 | chr5 | 179691781 | - | ENST00000407950 | DGKB | chr7 | 14661119 | - | 2398 | 331 | 403 | 1575 | 390 |
| ENST00000539014 | MAPK9 | chr5 | 179691781 | - | ENST00000444700 | DGKB | chr7 | 14661119 | - | 2115 | 331 | 403 | 1575 | 390 |
| ENST00000539014 | MAPK9 | chr5 | 179691781 | - | ENST00000406247 | DGKB | chr7 | 14661119 | - | 2334 | 331 | 403 | 1482 | 359 |
| 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 |
| ENST00000539014 | ENST00000399322 | MAPK9 | chr5 | 179691781 | - | DGKB | chr7 | 14661119 | - | 0.000214189 | 0.99978584 |
| ENST00000539014 | ENST00000258767 | MAPK9 | chr5 | 179691781 | - | DGKB | chr7 | 14661119 | - | 0.000214189 | 0.99978584 |
| ENST00000539014 | ENST00000403951 | MAPK9 | chr5 | 179691781 | - | DGKB | chr7 | 14661119 | - | 0.000214189 | 0.99978584 |
| ENST00000539014 | ENST00000402815 | MAPK9 | chr5 | 179691781 | - | DGKB | chr7 | 14661119 | - | 0.000252901 | 0.9997471 |
| ENST00000539014 | ENST00000407950 | MAPK9 | chr5 | 179691781 | - | DGKB | chr7 | 14661119 | - | 0.000442892 | 0.9995571 |
| ENST00000539014 | ENST00000444700 | MAPK9 | chr5 | 179691781 | - | DGKB | chr7 | 14661119 | - | 0.000604281 | 0.9993957 |
| ENST00000539014 | ENST00000406247 | MAPK9 | chr5 | 179691781 | - | DGKB | chr7 | 14661119 | - | 0.000305666 | 0.99969435 |
| 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 MAPK9-DGKB |
| +/-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 MAPK9-DGKB 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 MAPK9-DGKB 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 MAPK9-DGKB |
| 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 MAPK9-DGKB |
| 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 MAPK9-DGKB |
| 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 MAPK9-DGKB |
| 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 MAPK9-DGKB |
| 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 MAPK9-DGKB |
| 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 MAPK9-DGKB |
| 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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