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Fusion Protein:NRBF2-CYP26A1 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: NRBF2-CYP26A1 | FusionPDB ID: 60196 | FusionGDB2.0 ID: 60196 | Hgene | Tgene | Gene symbol | NRBF2 | CYP26A1 | Gene ID | 29982 | 1592 |
| Gene name | nuclear receptor binding factor 2 | cytochrome P450 family 26 subfamily A member 1 | |
| Synonyms | COPR|COPR1|COPR2|NRBF-2 | CP26|CYP26|P450RAI|P450RAI1 | |
| Cytomap | 10q21.3 | 10q23.33 | |
| Type of gene | protein-coding | protein-coding | |
| Description | nuclear receptor-binding factor 2comodulator of PPAR and RXR 1comodulator of PPAR and RXR 2 | cytochrome P450 26A1P450, retinoic acid-inactivating, 1cytochrome P450 retinoic acid-inactivating 1cytochrome P450, family 26, subfamily A, polypeptide 1cytochrome P450, subfamily XXVIA, polypeptide 1cytochrome P450RAIhP450RAIretinoic acid 4-hydrox | |
| Modification date | 20200313 | 20200329 | |
| UniProtAcc | Q96F24 | O43174 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000435510, ENST00000277746, | ENST00000224356, ENST00000371531, ENST00000394139, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 9 X 6 X 5=270 | 3 X 3 X 3=27 |
| # samples | 10 | 4 | |
| ** MAII score | log2(10/270*10)=-1.43295940727611 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(4/27*10)=0.567040592723894 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: NRBF2 [Title/Abstract] AND CYP26A1 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | NRBF2(64893260)-CYP26A1(94835583), # samples:3 | ||
| Anticipated loss of major functional domain due to fusion event. | NRBF2-CYP26A1 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. NRBF2-CYP26A1 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. NRBF2-CYP26A1 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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 |
| Tgene | CYP26A1 | GO:0006805 | xenobiotic metabolic process | 26937021 |
| Tgene | CYP26A1 | GO:0034653 | retinoic acid catabolic process | 10823918 |
| Tgene | CYP26A1 | GO:0042573 | retinoic acid metabolic process | 9716180|22020119 |
| Fusion gene breakpoints across NRBF2 (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 CYP26A1 (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 | BRCA | TCGA-E2-A576-01A | NRBF2 | chr10 | 64893260 | - | CYP26A1 | chr10 | 94835583 | + |
| ChimerDB4 | BRCA | TCGA-E2-A576-01A | NRBF2 | chr10 | 64893260 | + | CYP26A1 | chr10 | 94835583 | + |
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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) |
| ENST00000277746 | NRBF2 | chr10 | 64893260 | + | ENST00000371531 | CYP26A1 | chr10 | 94835583 | + | 1421 | 211 | 64 | 840 | 258 |
| ENST00000277746 | NRBF2 | chr10 | 64893260 | + | ENST00000224356 | CYP26A1 | chr10 | 94835583 | + | 1427 | 211 | 64 | 840 | 258 |
| ENST00000277746 | NRBF2 | chr10 | 64893260 | + | ENST00000394139 | CYP26A1 | chr10 | 94835583 | + | 1427 | 211 | 64 | 840 | 258 |
| 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 |
| ENST00000277746 | ENST00000371531 | NRBF2 | chr10 | 64893260 | + | CYP26A1 | chr10 | 94835583 | + | 0.000805217 | 0.9991948 |
| ENST00000277746 | ENST00000224356 | NRBF2 | chr10 | 64893260 | + | CYP26A1 | chr10 | 94835583 | + | 0.000818856 | 0.9991811 |
| ENST00000277746 | ENST00000394139 | NRBF2 | chr10 | 64893260 | + | CYP26A1 | chr10 | 94835583 | + | 0.000818856 | 0.9991811 |
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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 >60196_60196_1_NRBF2-CYP26A1_NRBF2_chr10_64893260_ENST00000277746_CYP26A1_chr10_94835583_ENST00000224356_length(amino acids)=258AA_BP=49 MGRREGPQSPRLRRAPLQSPPCSPAPLLPFLRPPLTPGSMEVMEGPLNLALKQSSTELLFGGHETTASAATSLITYLGLYPHVLQKVREE LKSKGLLCKSNQDNKLDMEILEQLKYIGCVIKETLRLNPPVPGGFRVALKTFELNGYQIPKGWNVIYSICDTHDVAEIFTNKEEFNPDRF -------------------------------------------------------------- >60196_60196_2_NRBF2-CYP26A1_NRBF2_chr10_64893260_ENST00000277746_CYP26A1_chr10_94835583_ENST00000371531_length(amino acids)=258AA_BP=49 MGRREGPQSPRLRRAPLQSPPCSPAPLLPFLRPPLTPGSMEVMEGPLNLALKQSSTELLFGGHETTASAATSLITYLGLYPHVLQKVREE LKSKGLLCKSNQDNKLDMEILEQLKYIGCVIKETLRLNPPVPGGFRVALKTFELNGYQIPKGWNVIYSICDTHDVAEIFTNKEEFNPDRF -------------------------------------------------------------- >60196_60196_3_NRBF2-CYP26A1_NRBF2_chr10_64893260_ENST00000277746_CYP26A1_chr10_94835583_ENST00000394139_length(amino acids)=258AA_BP=49 MGRREGPQSPRLRRAPLQSPPCSPAPLLPFLRPPLTPGSMEVMEGPLNLALKQSSTELLFGGHETTASAATSLITYLGLYPHVLQKVREE LKSKGLLCKSNQDNKLDMEILEQLKYIGCVIKETLRLNPPVPGGFRVALKTFELNGYQIPKGWNVIYSICDTHDVAEIFTNKEEFNPDRF -------------------------------------------------------------- |
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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/chr10:64893260/chr10:94835583) - 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 |
| NRBF2 | CYP26A1 |
| FUNCTION: May modulate transcriptional activation by target nuclear receptors. Can act as transcriptional activator (in vitro). {ECO:0000269|PubMed:15610520}.; FUNCTION: Involved in starvation-induced autophagy probably by its association with PI3K complex I (PI3KC3-C1). However, effects has been described variably. Involved in the induction of starvation-induced autophagy (PubMed:24785657). Stabilzes PI3KC3-C1 assembly and enhances ATG14-linked lipid kinase activity of PIK3C3 (By similarity). Proposed to negatively regulate basal and starvation-induced autophagy and to inhibit PIK3C3 activity by modulating interactions in PI3KC3-C1 (PubMed:25086043). May be involved in autophagosome biogenesis (PubMed:25086043). May play a role in neural progenitor cell survival during differentiation (By similarity). {ECO:0000250|UniProtKB:Q8VCQ3, ECO:0000269|PubMed:24785657, ECO:0000269|PubMed:25086043}. | FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of all-trans retinoic acid (atRA), a signaling molecule that binds to retinoic acid receptors and regulates gene transcription. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase). Catalyzes the hydroxylation of carbon hydrogen bonds of atRA primarily at C-4 and C-18. Has no activity toward 9-cis and 13-cis retinoic acid stereoisomers (PubMed:22020119, PubMed:9228017, PubMed:9716180). May play a role in the oxidative metabolism of xenobiotics such as tazarotenic acid (PubMed:26937021). {ECO:0000269|PubMed:22020119, ECO:0000269|PubMed:26937021, ECO:0000269|PubMed:9228017, ECO:0000269|PubMed:9716180}. |
| 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 |
| - 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 | NRBF2 | chr10:64893260 | chr10:94835583 | ENST00000277746 | + | 1 | 4 | 168_209 | 10.0 | 288.0 | Coiled coil | Ontology_term=ECO:0000255 |
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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 |
| NRBF2 | |
| CYP26A1 |
| - 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 NRBF2-CYP26A1 |
| 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 NRBF2-CYP26A1 |
| 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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