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Fusion Protein:DAB2-ARSB |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: DAB2-ARSB | FusionPDB ID: 21224 | FusionGDB2.0 ID: 21224 | Hgene | Tgene | Gene symbol | DAB2 | ARSB | Gene ID | 1601 | 411 |
| Gene name | DAB adaptor protein 2 | arylsulfatase B | |
| Synonyms | DOC-2|DOC2 | ASB|G4S|MPS6 | |
| Cytomap | 5p13.1 | 5q14.1 | |
| Type of gene | protein-coding | protein-coding | |
| Description | disabled homolog 2DAB2, clathrin adaptor proteinDab, mitogen-responsive phosphoprotein, homolog 2adaptor molecule disabled-2differentially expressed in ovarian carcinoma 2differentially-expressed protein 2disabled homolog 2, mitogen-responsive phosp | arylsulfatase BN-acetylgalactosamine-4-sulfatase | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | Q5VWQ8 Main function of 5'-partner protein: FUNCTION: Functions as a scaffold protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Involved in several processes such as innate immune response, inflammation and cell growth inhibition, apoptosis, cell survival, angiogenesis, cell migration and maturation. Plays also a role in cell cycle checkpoint control; reduces G1 phase cyclin levels resulting in G0/G1 cell cycle arrest. Mediates signal transduction by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF), interferon (IFN) or lipopolysaccharide (LPS). Modulates the balance between phosphatidylinositol 3-kinase (PI3K)-AKT-mediated cell survival and apoptosis stimulated kinase (MAP3K5)-JNK signaling pathways; sequesters both AKT1 and MAP3K5 and counterbalances the activity of each kinase by modulating their phosphorylation status in response to proinflammatory stimuli. Acts as a regulator of the endoplasmic reticulum (ER) unfolded protein response (UPR) pathway; specifically involved in transduction of the ER stress-response to the JNK cascade through ERN1. Mediates TNF-alpha-induced apoptosis activation by facilitating dissociation of inhibitor 14-3-3 from MAP3K5; recruits the PP2A phosphatase complex which dephosphorylates MAP3K5 on 'Ser-966', leading to the dissociation of 13-3-3 proteins and activation of the MAP3K5-JNK signaling pathway in endothelial cells. Mediates also TNF/TRAF2-induced MAP3K5-JNK activation, while it inhibits CHUK-NF-kappa-B signaling. Acts a negative regulator in the IFN-gamma-mediated JAK-STAT signaling cascade by inhibiting smooth muscle cell (VSMCs) proliferation and intimal expansion, and thus, prevents graft arteriosclerosis (GA). Acts as a GTPase-activating protein (GAP) for the ADP ribosylation factor 6 (ARF6) and Ras. Promotes hydrolysis of the ARF6-bound GTP and thus, negatively regulates phosphatidylinositol 4,5-bisphosphate (PIP2)-dependent TLR4-TIRAP-MyD88 and NF-kappa-B signaling pathways in endothelial cells in response to lipopolysaccharides (LPS). Binds specifically to phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 3-phosphate (PtdIns3P). In response to vascular endothelial growth factor (VEGFA), acts as a negative regulator of the VEGFR2-PI3K-mediated angiogenic signaling pathway by inhibiting endothelial cell migration and tube formation. In the developing brain, promotes both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex in a glial-dependent locomotion process. Probable downstream effector of the Reelin signaling pathway; promotes Purkinje cell (PC) dendrites development and formation of cerebellar synapses. Functions also as a tumor suppressor protein in prostate cancer progression; prevents cell proliferation and epithelial-to-mesenchymal transition (EMT) through activation of the glycogen synthase kinase-3 beta (GSK3B)-induced beta-catenin and inhibition of PI3K-AKT and Ras-MAPK survival downstream signaling cascades, respectively. {ECO:0000269|PubMed:12813029, ECO:0000269|PubMed:17389591, ECO:0000269|PubMed:18292600, ECO:0000269|PubMed:19033661, ECO:0000269|PubMed:19903888, ECO:0000269|PubMed:19948740, ECO:0000269|PubMed:20080667, ECO:0000269|PubMed:20154697, ECO:0000269|PubMed:21700930, ECO:0000269|PubMed:22696229}. | P15848 Main function of 5'-partner protein: FUNCTION: Removes sulfate groups from chondroitin-4-sulfate (C4S) and regulates its degradation (PubMed:19306108). Involved in the regulation of cell adhesion, cell migration and invasion in colonic epithelium (PubMed:19306108). In the central nervous system, is a regulator of neurite outgrowth and neuronal plasticity, acting through the control of sulfate glycosaminoglycans and neurocan levels (By similarity). {ECO:0000250|UniProtKB:P50430, ECO:0000269|PubMed:19306108}. | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000320816, ENST00000339788, ENST00000509337, ENST00000545653, ENST00000512525, | ENST00000521800, ENST00000264914, ENST00000396151, ENST00000565165, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 10 X 9 X 5=450 | 10 X 8 X 5=400 |
| # samples | 11 | 11 | |
| ** MAII score | log2(11/450*10)=-2.03242147769238 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(11/400*10)=-1.86249647625006 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Fusion gene context | PubMed: DAB2 [Title/Abstract] AND ARSB [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: DAB2 [Title/Abstract] AND ARSB [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | DAB2(39392467)-ARSB(78265015), # samples:3 | ||
| Anticipated loss of major functional domain due to fusion event. | DAB2-ARSB 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. DAB2-ARSB 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. DAB2-ARSB seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF. DAB2-ARSB 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 | DAB2 | GO:0010718 | positive regulation of epithelial to mesenchymal transition | 15734730 |
| Hgene | DAB2 | GO:0010862 | positive regulation of pathway-restricted SMAD protein phosphorylation | 11387212 |
| Hgene | DAB2 | GO:0030511 | positive regulation of transforming growth factor beta receptor signaling pathway | 11387212 |
| Hgene | DAB2 | GO:0043066 | negative regulation of apoptotic process | 15734730 |
| Hgene | DAB2 | GO:0060391 | positive regulation of SMAD protein signal transduction | 11387212 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr5:39392467/chr5:78265015) - 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 DAB2 (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 ARSB (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) |
| ENST00000509337 | DAB2 | chr5 | 39392467 | - | ENST00000264914 | ARSB | chr5 | 78265015 | - | 4888 | 410 | 47 | 1699 | 550 |
| ENST00000509337 | DAB2 | chr5 | 39392467 | - | ENST00000396151 | ARSB | chr5 | 78265015 | - | 1915 | 410 | 47 | 1339 | 430 |
| ENST00000509337 | DAB2 | chr5 | 39392467 | - | ENST00000565165 | ARSB | chr5 | 78265015 | - | 1371 | 410 | 47 | 1339 | 430 |
| ENST00000509337 | DAB2 | chr5 | 39392466 | - | ENST00000264914 | ARSB | chr5 | 78265015 | - | 4888 | 410 | 47 | 1699 | 550 |
| ENST00000509337 | DAB2 | chr5 | 39392466 | - | ENST00000396151 | ARSB | chr5 | 78265015 | - | 1915 | 410 | 47 | 1339 | 430 |
| ENST00000509337 | DAB2 | chr5 | 39392466 | - | ENST00000565165 | ARSB | chr5 | 78265015 | - | 1371 | 410 | 47 | 1339 | 430 |
| 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 |
| ENST00000509337 | ENST00000264914 | DAB2 | chr5 | 39392467 | - | ARSB | chr5 | 78265015 | - | 0.000457634 | 0.99954236 |
| ENST00000509337 | ENST00000396151 | DAB2 | chr5 | 39392467 | - | ARSB | chr5 | 78265015 | - | 0.00118801 | 0.99881196 |
| ENST00000509337 | ENST00000565165 | DAB2 | chr5 | 39392467 | - | ARSB | chr5 | 78265015 | - | 0.002189327 | 0.99781066 |
| ENST00000509337 | ENST00000264914 | DAB2 | chr5 | 39392466 | - | ARSB | chr5 | 78265015 | - | 0.000457634 | 0.99954236 |
| ENST00000509337 | ENST00000396151 | DAB2 | chr5 | 39392466 | - | ARSB | chr5 | 78265015 | - | 0.00118801 | 0.99881196 |
| ENST00000509337 | ENST00000565165 | DAB2 | chr5 | 39392466 | - | ARSB | chr5 | 78265015 | - | 0.002189327 | 0.99781066 |
| 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 DAB2-ARSB |
| +/-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 |
| DAB2 | chr5 | 39392466 | ARSB | chr5 | 78265015 | 410 | 121 | SLSGIKIIDEKTGIRTGLQHQIIWPC |
| DAB2 | chr5 | 39392467 | ARSB | chr5 | 78265015 | 410 | 121 | SLSGIKIIDEKTGIRTGLQHQIIWPC |
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Potential FusionNeoAntigen Information of DAB2-ARSB 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. |
| DAB2-ARSB_39392466_78265015.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) |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 410 | HLA-B14:01 | EKTGIRTGL | 0.978 | 0.6342 | 9 | 18 |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 410 | HLA-B14:02 | EKTGIRTGL | 0.978 | 0.6342 | 9 | 18 |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 410 | HLA-B27:07 | GIRTGLQHQI | 0.9184 | 0.6954 | 12 | 22 |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 410 | HLA-C08:15 | IIDEKTGI | 1 | 0.7862 | 6 | 14 |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 410 | HLA-C05:09 | IIDEKTGI | 1 | 0.7455 | 6 | 14 |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 410 | HLA-C05:01 | IIDEKTGI | 1 | 0.7455 | 6 | 14 |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 410 | HLA-C08:02 | IIDEKTGI | 1 | 0.7862 | 6 | 14 |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 410 | HLA-B18:03 | DEKTGIRTGL | 0.3975 | 0.8434 | 8 | 18 |
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Potential FusionNeoAntigen Information of DAB2-ARSB 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. |
| DAB2-ARSB_39392466_78265015.msa |
| 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) |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 410 | DRB1-1452 | SGIKIIDEKTGIRTG | 2 | 17 |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 410 | DRB1-1523 | LSGIKIIDEKTGIRT | 1 | 16 |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 410 | DRB5-0106 | SGIKIIDEKTGIRTG | 2 | 17 |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 410 | DRB5-0106 | GIKIIDEKTGIRTGL | 3 | 18 |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 410 | DRB5-0205 | SGIKIIDEKTGIRTG | 2 | 17 |
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Fusion breakpoint peptide structures of DAB2-ARSB |
| 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 |
| 3726 | IIDEKTGIRTGLQH | DAB2 | ARSB | chr5 | 39392466 | chr5 | 78265015 | 410 |
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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DAB2-ARSB |
| 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 | 3726 | IIDEKTGIRTGLQH | -5.47913 | -5.67113 |
| HLA-B14:02 | 3BVN | 3726 | IIDEKTGIRTGLQH | -3.84443 | -4.60543 |
| HLA-B52:01 | 3W39 | 3726 | IIDEKTGIRTGLQH | -6.76995 | -6.96195 |
| HLA-B52:01 | 3W39 | 3726 | IIDEKTGIRTGLQH | -5.58751 | -6.34851 |
| HLA-A11:01 | 4UQ2 | 3726 | IIDEKTGIRTGLQH | -5.74663 | -6.50763 |
| HLA-A11:01 | 4UQ2 | 3726 | IIDEKTGIRTGLQH | -5.69582 | -5.88782 |
| HLA-A24:02 | 5HGA | 3726 | IIDEKTGIRTGLQH | -8.42283 | -9.18383 |
| HLA-A24:02 | 5HGA | 3726 | IIDEKTGIRTGLQH | -7.2103 | -7.4023 |
| HLA-B27:05 | 6PYJ | 3726 | IIDEKTGIRTGLQH | -7.69112 | -7.88312 |
| HLA-B44:05 | 3DX8 | 3726 | IIDEKTGIRTGLQH | -5.89348 | -6.08548 |
| HLA-B44:05 | 3DX8 | 3726 | IIDEKTGIRTGLQH | -3.81554 | -4.57654 |
| HLA-A02:01 | 6TDR | 3726 | IIDEKTGIRTGLQH | -3.68024 | -4.44124 |
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Vaccine Design for the FusionNeoAntigens of DAB2-ARSB |
| 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 |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 12 | 22 | GIRTGLQHQI | GGGATCCGTACAGGTTTACAGCACCAAATA |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 6 | 14 | IIDEKTGI | ATAATTGATGAGAAAACTGGGATC |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 8 | 18 | DEKTGIRTGL | GATGAGAAAACTGGGATCCGTACAGGTTTA |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 9 | 18 | EKTGIRTGL | GAGAAAACTGGGATCCGTACAGGTTTA |
| 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 |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 1 | 16 | LSGIKIIDEKTGIRT | CTTTCTGGGATAAAAATAATTGATGAGAAAACTGGGATCCGTACA |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 2 | 17 | SGIKIIDEKTGIRTG | TCTGGGATAAAAATAATTGATGAGAAAACTGGGATCCGTACAGGT |
| DAB2-ARSB | chr5 | 39392466 | chr5 | 78265015 | 3 | 18 | GIKIIDEKTGIRTGL | GGGATAAAAATAATTGATGAGAAAACTGGGATCCGTACAGGTTTA |
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Information of the samples that have these potential fusion neoantigens of DAB2-ARSB |
| 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 |
| ACC | DAB2-ARSB | chr5 | 39392466 | ENST00000509337 | chr5 | 78265015 | ENST00000264914 | TCGA-OR-A5J1 |
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Potential target of CAR-T therapy development for DAB2-ARSB |
| 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 DAB2-ARSB |
| 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 DAB2-ARSB |
| 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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