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Fusion Protein:STK4-WISP2 |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: STK4-WISP2 | FusionPDB ID: 87606 | FusionGDB2.0 ID: 87606 | Hgene | Tgene | Gene symbol | STK4 | WISP2 | Gene ID | 6789 | 8839 |
| Gene name | serine/threonine kinase 4 | cellular communication network factor 5 | |
| Synonyms | KRS2|MST1|YSK3 | CT58|CTGF-L|WISP2 | |
| Cytomap | 20q13.12 | 20q13.12 | |
| Type of gene | protein-coding | protein-coding | |
| Description | serine/threonine-protein kinase 4STE20-like kinase MST1kinase responsive to stress 2mammalian STE20-like protein kinase 1mammalian sterile 20-like 1serine/threonine-protein kinase Krs-2 | WNT1-inducible-signaling pathway protein 2CCN family member 5WNT1 inducible signaling pathway protein 2connective tissue growth factor-like proteinconnective tissue growth factor-related protein 58 | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | Q13043 Main function of 5'-partner protein: FUNCTION: Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes. {ECO:0000250|UniProtKB:Q9JI11, ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:11517310, ECO:0000269|PubMed:12757711, ECO:0000269|PubMed:15109305, ECO:0000269|PubMed:16510573, ECO:0000269|PubMed:16751106, ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:17932490, ECO:0000269|PubMed:18328708, ECO:0000269|PubMed:18986304, ECO:0000269|PubMed:19525978, ECO:0000269|PubMed:21212262, ECO:0000269|PubMed:21245099, ECO:0000269|PubMed:21512132, ECO:0000269|PubMed:8702870, ECO:0000269|PubMed:8816758}. | . | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000372801, ENST00000372806, ENST00000396731, ENST00000499879, ENST00000487587, | ENST00000471629, ENST00000190983, ENST00000372865, ENST00000372868, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 9 X 6 X 7=378 | 3 X 3 X 3=27 |
| # samples | 9 | 3 | |
| ** MAII score | log2(9/378*10)=-2.0703893278914 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(3/27*10)=0.15200309344505 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0 | |
| Fusion gene context | PubMed: STK4 [Title/Abstract] AND WISP2 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: STK4 [Title/Abstract] AND WISP2 [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | STK4(43629994)-WISP2(43353379), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | STK4-WISP2 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. STK4-WISP2 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. STK4-WISP2 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. STK4-WISP2 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 | STK4 | GO:0000902 | cell morphogenesis | 11805089 |
| Hgene | STK4 | GO:0001934 | positive regulation of protein phosphorylation | 19962960 |
| Hgene | STK4 | GO:0006468 | protein phosphorylation | 8566796|11805089 |
| Hgene | STK4 | GO:0006915 | apoptotic process | 21212262 |
| Hgene | STK4 | GO:0018105 | peptidyl-serine phosphorylation | 16751106 |
| Hgene | STK4 | GO:0032092 | positive regulation of protein binding | 22292086 |
| Hgene | STK4 | GO:0033138 | positive regulation of peptidyl-serine phosphorylation | 19962960 |
| Hgene | STK4 | GO:0035329 | hippo signaling | 20412773 |
| Hgene | STK4 | GO:0035556 | intracellular signal transduction | 8566796 |
| Hgene | STK4 | GO:0043065 | positive regulation of apoptotic process | 15109305 |
| Hgene | STK4 | GO:0046777 | protein autophosphorylation | 11805089 |
| Hgene | STK4 | GO:0050821 | protein stabilization | 19962960 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr20:43629994/chr20:43353379) - 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 STK4 (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 WISP2 (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) |
| ENST00000372806 | STK4 | chr20 | 43629994 | + | ENST00000372868 | WISP2 | chr20 | 43353379 | + | 2222 | 1242 | 23 | 1717 | 564 |
| ENST00000396731 | STK4 | chr20 | 43629994 | + | ENST00000372868 | WISP2 | chr20 | 43353379 | + | 2195 | 1215 | 68 | 1690 | 540 |
| ENST00000372801 | STK4 | chr20 | 43629994 | + | ENST00000372868 | WISP2 | chr20 | 43353379 | + | 2174 | 1194 | 47 | 1669 | 540 |
| ENST00000499879 | STK4 | chr20 | 43629994 | + | ENST00000372868 | WISP2 | chr20 | 43353379 | + | 2005 | 1025 | 43 | 1500 | 485 |
| 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 |
| ENST00000372806 | ENST00000372868 | STK4 | chr20 | 43629994 | + | WISP2 | chr20 | 43353379 | + | 0.0035281 | 0.9964719 |
| ENST00000396731 | ENST00000372868 | STK4 | chr20 | 43629994 | + | WISP2 | chr20 | 43353379 | + | 0.003794849 | 0.99620515 |
| ENST00000372801 | ENST00000372868 | STK4 | chr20 | 43629994 | + | WISP2 | chr20 | 43353379 | + | 0.003682658 | 0.99631727 |
| ENST00000499879 | ENST00000372868 | STK4 | chr20 | 43629994 | + | WISP2 | chr20 | 43353379 | + | 0.00536524 | 0.99463475 |
| 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 STK4-WISP2 |
| +/-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 |
| STK4 | chr20 | 43629994 | WISP2 | chr20 | 43353379 | 1025 | 328 | NAEDEEEEGTMKMAEDDSSCEVNGRL |
| STK4 | chr20 | 43629994 | WISP2 | chr20 | 43353379 | 1194 | 383 | NAEDEEEEGTMKMAEDDSSCEVNGRL |
| STK4 | chr20 | 43629994 | WISP2 | chr20 | 43353379 | 1215 | 383 | NAEDEEEEGTMKMAEDDSSCEVNGRL |
| STK4 | chr20 | 43629994 | WISP2 | chr20 | 43353379 | 1242 | 407 | NAEDEEEEGTMKMAEDDSSCEVNGRL |
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Potential FusionNeoAntigen Information of STK4-WISP2 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. |
| STK4-WISP2_43629994_43353379.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) |
| STK4-WISP2 | chr20 | 43629994 | chr20 | 43353379 | 1194 | HLA-B45:01 | EEEGTMKMA | 0.9829 | 0.9564 | 5 | 14 |
| STK4-WISP2 | chr20 | 43629994 | chr20 | 43353379 | 1194 | HLA-B50:02 | EEEGTMKMA | 0.8878 | 0.593 | 5 | 14 |
| STK4-WISP2 | chr20 | 43629994 | chr20 | 43353379 | 1194 | HLA-B41:01 | EEEGTMKMA | 0.3196 | 0.9343 | 5 | 14 |
| STK4-WISP2 | chr20 | 43629994 | chr20 | 43353379 | 1194 | HLA-B45:01 | EEEEGTMKMA | 0.9865 | 0.9604 | 4 | 14 |
| STK4-WISP2 | chr20 | 43629994 | chr20 | 43353379 | 1194 | HLA-B50:02 | EEEEGTMKMA | 0.9532 | 0.6359 | 4 | 14 |
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Potential FusionNeoAntigen Information of STK4-WISP2 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 STK4-WISP2 |
| 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 |
| 1663 | EEGTMKMAEDDSSC | STK4 | WISP2 | chr20 | 43629994 | chr20 | 43353379 | 1194 |
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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of STK4-WISP2 |
| 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 | 1663 | EEGTMKMAEDDSSC | -6.77781 | -6.89121 |
| HLA-B14:02 | 3BVN | 1663 | EEGTMKMAEDDSSC | -3.08719 | -4.12249 |
| HLA-B52:01 | 3W39 | 1663 | EEGTMKMAEDDSSC | -6.66315 | -6.77655 |
| HLA-B52:01 | 3W39 | 1663 | EEGTMKMAEDDSSC | -2.65785 | -3.69315 |
| HLA-A24:02 | 5HGA | 1663 | EEGTMKMAEDDSSC | -7.20627 | -7.31967 |
| HLA-A24:02 | 5HGA | 1663 | EEGTMKMAEDDSSC | -6.50211 | -7.53741 |
| HLA-B44:05 | 3DX8 | 1663 | EEGTMKMAEDDSSC | -7.75024 | -7.86364 |
| HLA-B44:05 | 3DX8 | 1663 | EEGTMKMAEDDSSC | -6.53073 | -7.56603 |
| HLA-A02:01 | 6TDR | 1663 | EEGTMKMAEDDSSC | -4.4528 | -5.4881 |
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Vaccine Design for the FusionNeoAntigens of STK4-WISP2 |
| 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 |
| STK4-WISP2 | chr20 | 43629994 | chr20 | 43353379 | 4 | 14 | EEEEGTMKMA | ATGAGGAAGAGGAAGGAACTATGAAAATGG |
| STK4-WISP2 | chr20 | 43629994 | chr20 | 43353379 | 5 | 14 | EEEGTMKMA | AGGAAGAGGAAGGAACTATGAAAATGG |
| 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 STK4-WISP2 |
| 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 |
| GBM | STK4-WISP2 | chr20 | 43629994 | ENST00000372801 | chr20 | 43353379 | ENST00000372868 | TCGA-06-5856-01A |
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Potential target of CAR-T therapy development for STK4-WISP2 |
| 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 STK4-WISP2 |
| 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 STK4-WISP2 |
| 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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