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Fusion Protein:MAP3K5-ATG5 |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: MAP3K5-ATG5 | FusionPDB ID: 51324 | FusionGDB2.0 ID: 51324 | Hgene | Tgene | Gene symbol | MAP3K5 | ATG5 | Gene ID | 4217 | 9474 |
| Gene name | mitogen-activated protein kinase kinase kinase 5 | autophagy related 5 | |
| Synonyms | ASK1|MAPKKK5|MEKK5 | APG5|APG5-LIKE|APG5L|ASP|SCAR25|hAPG5 | |
| Cytomap | 6q23.3 | 6q21 | |
| Type of gene | protein-coding | protein-coding | |
| Description | mitogen-activated protein kinase kinase kinase 5ASK-1MAP/ERK kinase kinase 5MAPK/ERK kinase kinase 5MEK kinase 5MEKK 5apoptosis signal-regulating kinase 1 | autophagy protein 5APG5 autophagy 5-likeATG5 autophagy related 5 homologapoptosis-specific protein | |
| Modification date | 20200327 | 20200313 | |
| UniProtAcc | Q99683 Main function of 5'-partner protein: FUNCTION: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1). {ECO:0000269|PubMed:10411906, ECO:0000269|PubMed:10688666, ECO:0000269|PubMed:10849426, ECO:0000269|PubMed:11029458, ECO:0000269|PubMed:11154276, ECO:0000269|PubMed:11689443, ECO:0000269|PubMed:11920685, ECO:0000269|PubMed:12697749, ECO:0000269|PubMed:14688258, ECO:0000269|PubMed:14749717, ECO:0000269|PubMed:15023544, ECO:0000269|PubMed:16129676, ECO:0000269|PubMed:17220297, ECO:0000269|PubMed:23102700, ECO:0000269|PubMed:26095851, ECO:0000269|PubMed:8940179, ECO:0000269|PubMed:8974401, ECO:0000269|PubMed:9564042, ECO:0000269|PubMed:9774977}. | Q9H1Y0 Main function of 5'-partner protein: FUNCTION: Involved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for MHC II. Involved in the maintenance of axon morphology and membrane structures, as well as in normal adipocyte differentiation. Promotes primary ciliogenesis through removal of OFD1 from centriolar satellites and degradation of IFT20 via the autophagic pathway. {ECO:0000250|UniProtKB:Q99J83, ECO:0000269|PubMed:12207896, ECO:0000269|PubMed:20580051, ECO:0000269|PubMed:22170153, ECO:0000269|PubMed:26812546}.; FUNCTION: May play an important role in the apoptotic process, possibly within the modified cytoskeleton. Its expression is a relatively late event in the apoptotic process, occurring downstream of caspase activity. Plays a crucial role in IFN-gamma-induced autophagic cell death by interacting with FADD. {ECO:0000269|PubMed:15778222, ECO:0000269|PubMed:7796880}.; FUNCTION: (Microbial infection) May act as a proviral factor. In association with ATG12, negatively regulates the innate antiviral immune response by impairing the type I IFN production pathway upon vesicular stomatitis virus (VSV) infection (PubMed:17709747). Required for the translation of incoming hepatitis C virus (HCV) RNA and, thereby, for initiation of HCV replication, but not required once infection is established (PubMed:19666601). {ECO:0000269|PubMed:17709747, ECO:0000269|PubMed:19666601}. | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000359015, ENST00000355845, ENST00000463140, | ENST00000360666, ENST00000475645, ENST00000343245, ENST00000369070, ENST00000369076, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 14 X 11 X 10=1540 | 15 X 12 X 7=1260 |
| # samples | 16 | 15 | |
| ** MAII score | log2(16/1540*10)=-3.2667865406949 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(15/1260*10)=-3.0703893278914 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Fusion gene context | PubMed: MAP3K5 [Title/Abstract] AND ATG5 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: MAP3K5 [Title/Abstract] AND ATG5 [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | MAP3K5(137112847)-ATG5(106727698), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | MAP3K5-ATG5 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. MAP3K5-ATG5 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 | MAP3K5 | GO:0000165 | MAPK cascade | 17210579|21771788 |
| Hgene | MAP3K5 | GO:0000186 | activation of MAPKK activity | 11959862 |
| Hgene | MAP3K5 | GO:0006468 | protein phosphorylation | 11096076|15983381 |
| Hgene | MAP3K5 | GO:0007254 | JNK cascade | 21771788 |
| Hgene | MAP3K5 | GO:0008631 | intrinsic apoptotic signaling pathway in response to oxidative stress | 21771788 |
| Hgene | MAP3K5 | GO:0034198 | cellular response to amino acid starvation | 11096076 |
| Hgene | MAP3K5 | GO:0043065 | positive regulation of apoptotic process | 21771788 |
| Hgene | MAP3K5 | GO:0043280 | positive regulation of cysteine-type endopeptidase activity involved in apoptotic process | 20674765 |
| Hgene | MAP3K5 | GO:0045893 | positive regulation of transcription, DNA-templated | 11096076 |
| Hgene | MAP3K5 | GO:0051403 | stress-activated MAPK cascade | 11096076 |
| Hgene | MAP3K5 | GO:0070301 | cellular response to hydrogen peroxide | 20674765 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr6:137112847/chr6:106727698) - 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 MAP3K5 (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 ATG5 (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) |
| ENST00000359015 | MAP3K5 | chr6 | 137112847 | - | ENST00000343245 | ATG5 | chr6 | 106727698 | - | 3386 | 809 | 124 | 846 | 240 |
| ENST00000359015 | MAP3K5 | chr6 | 137112847 | - | ENST00000369070 | ATG5 | chr6 | 106727698 | - | 3386 | 809 | 124 | 846 | 240 |
| ENST00000359015 | MAP3K5 | chr6 | 137112847 | - | ENST00000369076 | ATG5 | chr6 | 106727698 | - | 3386 | 809 | 124 | 846 | 240 |
| 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 |
| ENST00000359015 | ENST00000343245 | MAP3K5 | chr6 | 137112847 | - | ATG5 | chr6 | 106727698 | - | 0.0010787 | 0.9989213 |
| ENST00000359015 | ENST00000369070 | MAP3K5 | chr6 | 137112847 | - | ATG5 | chr6 | 106727698 | - | 0.0010787 | 0.9989213 |
| ENST00000359015 | ENST00000369076 | MAP3K5 | chr6 | 137112847 | - | ATG5 | chr6 | 106727698 | - | 0.0010787 | 0.9989213 |
| 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 MAP3K5-ATG5 |
| +/-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 MAP3K5-ATG5 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 MAP3K5-ATG5 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 MAP3K5-ATG5 |
| 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 MAP3K5-ATG5 |
| 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 MAP3K5-ATG5 |
| 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 MAP3K5-ATG5 |
| 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 MAP3K5-ATG5 |
| 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 MAP3K5-ATG5 |
| 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 MAP3K5-ATG5 |
| 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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