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Fusion Protein:ITGA4-UBE2E3 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: ITGA4-UBE2E3 | FusionPDB ID: 40432 | FusionGDB2.0 ID: 40432 | Hgene | Tgene | Gene symbol | ITGA4 | UBE2E3 | Gene ID | 3676 | 10477 |
| Gene name | integrin subunit alpha 4 | ubiquitin conjugating enzyme E2 E3 | |
| Synonyms | CD49D|IA4 | UBCH9|UbcM2 | |
| Cytomap | 2q31.3 | 2q31.3 | |
| Type of gene | protein-coding | protein-coding | |
| Description | integrin alpha-4269C wild typeCD49 antigen-like family member DVLA-4 subunit alphaalpha 4 subunit of VLA-4 receptorantigen CD49D, alpha-4 subunit of VLA-4 receptorintegrin alpha-IVvery late activation protein 4 receptor, alpha 4 subunit | ubiquitin-conjugating enzyme E2 E3E2 ubiquitin-conjugating enzyme E3ubiquitin carrier protein E3ubiquitin conjugating enzyme E2E 3ubiquitin-conjugating enzyme E2-23 kDaubiquitin-conjugating enzyme E2E 3 (UBC4/5 homolog, yeast)ubiquitin-conjugating e | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | P13612 | . | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000397033, ENST00000339307, ENST00000478440, | ENST00000602837, ENST00000602959, ENST00000602475, ENST00000602632, ENST00000392415, ENST00000410062, ENST00000602710, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 6 X 5 X 4=120 | 12 X 11 X 6=792 |
| # samples | 6 | 13 | |
| ** MAII score | log2(6/120*10)=-1 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(13/792*10)=-2.60698880705116 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: ITGA4 [Title/Abstract] AND UBE2E3 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | ITGA4(182347378)-UBE2E3(181925392), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | ITGA4-UBE2E3 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. ITGA4-UBE2E3 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 | ITGA4 | GO:0007159 | leukocyte cell-cell adhesion | 1715889 |
| Hgene | ITGA4 | GO:0090074 | negative regulation of protein homodimerization activity | 12869515 |
| Tgene | UBE2E3 | GO:0070534 | protein K63-linked ubiquitination | 20061386 |
| Tgene | UBE2E3 | GO:0070936 | protein K48-linked ubiquitination | 20061386 |
| Tgene | UBE2E3 | GO:0070979 | protein K11-linked ubiquitination | 20061386 |
| Fusion gene breakpoints across ITGA4 (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 UBE2E3 (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 Gene Sample Information |
| Fusion gene information from FusionGDB2.0. |
| Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0) * All genome coordinats were lifted-over on hg19. * Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser. |
| Source | Disease | Sample | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| ChimerDB4 | SARC | TCGA-X6-A8C3-01A | ITGA4 | chr2 | 182347378 | + | UBE2E3 | chr2 | 181925392 | + |
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Fusion ORF Analysis |
| 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) |
| ENST00000397033 | ITGA4 | chr2 | 182347378 | + | ENST00000392415 | UBE2E3 | chr2 | 181925392 | + | 2252 | 1471 | 13 | 1716 | 567 |
| ENST00000397033 | ITGA4 | chr2 | 182347378 | + | ENST00000410062 | UBE2E3 | chr2 | 181925392 | + | 2270 | 1471 | 13 | 1716 | 567 |
| ENST00000397033 | ITGA4 | chr2 | 182347378 | + | ENST00000602710 | UBE2E3 | chr2 | 181925392 | + | 2270 | 1471 | 13 | 1716 | 567 |
| 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 |
| ENST00000397033 | ENST00000392415 | ITGA4 | chr2 | 182347378 | + | UBE2E3 | chr2 | 181925392 | + | 0.000696846 | 0.9993031 |
| ENST00000397033 | ENST00000410062 | ITGA4 | chr2 | 182347378 | + | UBE2E3 | chr2 | 181925392 | + | 0.0006679 | 0.99933213 |
| ENST00000397033 | ENST00000602710 | ITGA4 | chr2 | 182347378 | + | UBE2E3 | chr2 | 181925392 | + | 0.0006679 | 0.99933213 |
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Fusion Amino Acid Sequences |
| For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
| >FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP >40432_40432_1_ITGA4-UBE2E3_ITGA4_chr2_182347378_ENST00000397033_UBE2E3_chr2_181925392_ENST00000392415_length(amino acids)=567AA_BP=486 MRAGRPGPGRESCAAEVPQRPLQPRVGRDGARPCASAPRPGPHPAARTRRSSASTRSSRLAAETGSGAGRVRGIPGRPERSARGGPTSPP LPSLLPLARWRRTRCASSLGAFFPVGQPSHPVQLWGSGRLVLNVPHRERMAWEARREPGPRRAAVRETVMLLLCLGVPTGRPYNVDTESA LLYQGPHNTLFGYSVVLHSHGANRWLLVGAPTANWLANASVINPGAIYRCRIGKNPGQTCEQLQLGSPNGEPCGKTCLEERDNQWLGVTL SRQPGENGSIVTCGHRWKNIFYIKNENKLPTGGCYGVPPDLRTELSKRIAPCYQDYVKKFGENFASCQAGISSFYTKDLIVMGAPGSSYW TGSLFVYNITTNKYKAFLDKQNQVKFGSYLGYSVGAGHFRSQHTTEVVGGAPQHEQIGKAYIFSIDEKELNILHEMKGKKLGSYFGASVC AVDLNADGFSDLLVGAPMQSTIREEGRVFVYINSGSVTFRTRIYHCNINSQGVICLDILKDNWSPALTISKVLLSICSLLTDCNPADPLV -------------------------------------------------------------- >40432_40432_2_ITGA4-UBE2E3_ITGA4_chr2_182347378_ENST00000397033_UBE2E3_chr2_181925392_ENST00000410062_length(amino acids)=567AA_BP=486 MRAGRPGPGRESCAAEVPQRPLQPRVGRDGARPCASAPRPGPHPAARTRRSSASTRSSRLAAETGSGAGRVRGIPGRPERSARGGPTSPP LPSLLPLARWRRTRCASSLGAFFPVGQPSHPVQLWGSGRLVLNVPHRERMAWEARREPGPRRAAVRETVMLLLCLGVPTGRPYNVDTESA LLYQGPHNTLFGYSVVLHSHGANRWLLVGAPTANWLANASVINPGAIYRCRIGKNPGQTCEQLQLGSPNGEPCGKTCLEERDNQWLGVTL SRQPGENGSIVTCGHRWKNIFYIKNENKLPTGGCYGVPPDLRTELSKRIAPCYQDYVKKFGENFASCQAGISSFYTKDLIVMGAPGSSYW TGSLFVYNITTNKYKAFLDKQNQVKFGSYLGYSVGAGHFRSQHTTEVVGGAPQHEQIGKAYIFSIDEKELNILHEMKGKKLGSYFGASVC AVDLNADGFSDLLVGAPMQSTIREEGRVFVYINSGSVTFRTRIYHCNINSQGVICLDILKDNWSPALTISKVLLSICSLLTDCNPADPLV -------------------------------------------------------------- >40432_40432_3_ITGA4-UBE2E3_ITGA4_chr2_182347378_ENST00000397033_UBE2E3_chr2_181925392_ENST00000602710_length(amino acids)=567AA_BP=486 MRAGRPGPGRESCAAEVPQRPLQPRVGRDGARPCASAPRPGPHPAARTRRSSASTRSSRLAAETGSGAGRVRGIPGRPERSARGGPTSPP LPSLLPLARWRRTRCASSLGAFFPVGQPSHPVQLWGSGRLVLNVPHRERMAWEARREPGPRRAAVRETVMLLLCLGVPTGRPYNVDTESA LLYQGPHNTLFGYSVVLHSHGANRWLLVGAPTANWLANASVINPGAIYRCRIGKNPGQTCEQLQLGSPNGEPCGKTCLEERDNQWLGVTL SRQPGENGSIVTCGHRWKNIFYIKNENKLPTGGCYGVPPDLRTELSKRIAPCYQDYVKKFGENFASCQAGISSFYTKDLIVMGAPGSSYW TGSLFVYNITTNKYKAFLDKQNQVKFGSYLGYSVGAGHFRSQHTTEVVGGAPQHEQIGKAYIFSIDEKELNILHEMKGKKLGSYFGASVC AVDLNADGFSDLLVGAPMQSTIREEGRVFVYINSGSVTFRTRIYHCNINSQGVICLDILKDNWSPALTISKVLLSICSLLTDCNPADPLV -------------------------------------------------------------- |
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Fusion Protein Functional Features |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr2:182347378/chr2:181925392) - 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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| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| ITGA4 | . |
| FUNCTION: Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are also receptors for VCAM1. Integrin alpha-4/beta-1 recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-4/beta-7 is also a receptor for MADCAM1. It recognizes the sequence L-D-T in MADCAM1. On activated endothelial cells integrin VLA-4 triggers homotypic aggregation for most VLA-4-positive leukocyte cell lines. It may also participate in cytolytic T-cell interactions with target cells. ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415). ITGA4:ITGB1 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877). {ECO:0000269|PubMed:18635536, ECO:0000269|PubMed:19064666, ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:25398877}. | FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes. |
| 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, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Hgene | ITGA4 | chr2:182347378 | chr2:181925392 | ENST00000397033 | + | 9 | 28 | 314_322 | 347.0 | 1033.0 | Calcium binding | Ontology_term=ECO:0000255 |
| Hgene | ITGA4 | chr2:182347378 | chr2:181925392 | ENST00000397033 | + | 9 | 28 | 110_177 | 347.0 | 1033.0 | Repeat | FG-GAP 2 |
| Hgene | ITGA4 | chr2:182347378 | chr2:181925392 | ENST00000397033 | + | 9 | 28 | 185_237 | 347.0 | 1033.0 | Repeat | FG-GAP 3 |
| Hgene | ITGA4 | chr2:182347378 | chr2:181925392 | ENST00000397033 | + | 9 | 28 | 238_291 | 347.0 | 1033.0 | Repeat | FG-GAP 4 |
| Hgene | ITGA4 | chr2:182347378 | chr2:181925392 | ENST00000397033 | + | 9 | 28 | 35_100 | 347.0 | 1033.0 | Repeat | FG-GAP 1 |
| - Not-retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Hgene | ITGA4 | chr2:182347378 | chr2:181925392 | ENST00000397033 | + | 9 | 28 | 377_385 | 347.0 | 1033.0 | Calcium binding | Ontology_term=ECO:0000255 |
| Hgene | ITGA4 | chr2:182347378 | chr2:181925392 | ENST00000397033 | + | 9 | 28 | 439_447 | 347.0 | 1033.0 | Calcium binding | Ontology_term=ECO:0000255 |
| Hgene | ITGA4 | chr2:182347378 | chr2:181925392 | ENST00000397033 | + | 9 | 28 | 1003_1007 | 347.0 | 1033.0 | Motif | Note=GFFKR motif |
| Hgene | ITGA4 | chr2:182347378 | chr2:181925392 | ENST00000397033 | + | 9 | 28 | 606_616 | 347.0 | 1033.0 | Motif | Note=SG1 |
| Hgene | ITGA4 | chr2:182347378 | chr2:181925392 | ENST00000397033 | + | 9 | 28 | 292_351 | 347.0 | 1033.0 | Repeat | FG-GAP 5 |
| Hgene | ITGA4 | chr2:182347378 | chr2:181925392 | ENST00000397033 | + | 9 | 28 | 355_412 | 347.0 | 1033.0 | Repeat | FG-GAP 6 |
| Hgene | ITGA4 | chr2:182347378 | chr2:181925392 | ENST00000397033 | + | 9 | 28 | 416_478 | 347.0 | 1033.0 | Repeat | FG-GAP 7 |
| Hgene | ITGA4 | chr2:182347378 | chr2:181925392 | ENST00000397033 | + | 9 | 28 | 1002_1032 | 347.0 | 1033.0 | Topological domain | Cytoplasmic |
| Hgene | ITGA4 | chr2:182347378 | chr2:181925392 | ENST00000397033 | + | 9 | 28 | 35_977 | 347.0 | 1033.0 | Topological domain | Extracellular |
| Hgene | ITGA4 | chr2:182347378 | chr2:181925392 | ENST00000397033 | + | 9 | 28 | 978_1001 | 347.0 | 1033.0 | Transmembrane | Helical |
| Tgene | UBE2E3 | chr2:182347378 | chr2:181925392 | ENST00000392415 | 3 | 6 | 61_207 | 126.0 | 208.0 | Domain | UBC core | |
| Tgene | UBE2E3 | chr2:182347378 | chr2:181925392 | ENST00000410062 | 3 | 6 | 61_207 | 126.0 | 208.0 | Domain | UBC core | |
| Tgene | UBE2E3 | chr2:182347378 | chr2:181925392 | ENST00000602710 | 3 | 6 | 61_207 | 126.0 | 208.0 | Domain | UBC core | |
| Tgene | UBE2E3 | chr2:182347378 | chr2:181925392 | ENST00000602959 | 4 | 7 | 61_207 | 126.0 | 208.0 | Domain | UBC core |
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Fusion Protein-Protein Interaction |
| Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in |
| Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160) |
| Gene | PPI interactors |
| Protein-protein interactors based on sequence similarity (STRING) |
| Gene | STRING network |
| ITGA4 | |
| UBE2E3 |
| - Retained interactions in fusion protein (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
| - Lost interactions due to fusion (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
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Related Drugs to ITGA4-UBE2E3 |
| 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 ITGA4-UBE2E3 |
| 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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