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Fusion Protein:NR1D2-UBE2E2 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: NR1D2-UBE2E2 | FusionPDB ID: 60075 | FusionGDB2.0 ID: 60075 | Hgene | Tgene | Gene symbol | NR1D2 | UBE2E2 | Gene ID | 9975 | 7325 |
| Gene name | nuclear receptor subfamily 1 group D member 2 | ubiquitin conjugating enzyme E2 E2 | |
| Synonyms | BD73|EAR-1R|REVERBB|REVERBbeta|RVR | UBCH8 | |
| Cytomap | 3p24.2 | 3p24.3 | |
| Type of gene | protein-coding | protein-coding | |
| Description | nuclear receptor subfamily 1 group D member 2V-erbA-related protein 1-relatednuclear receptor Rev-ErbA beta variant 1nuclear receptor Rev-ErbA beta variant 2orphan nuclear hormone receptor BD73rev-erb alpha-related receptorrev-erb-betarev-erba-alph | ubiquitin-conjugating enzyme E2 E2E2 ubiquitin-conjugating enzyme E2ubiquitin carrier protein E2ubiquitin conjugating enzyme E2E 2ubiquitin-conjugating enzyme E2E 2 (UBC4/5 homolog, yeast)ubiquitin-conjugating enzyme E2E 2 (homologous to yeast UBC4/5 | |
| Modification date | 20200313 | 20200327 | |
| UniProtAcc | Q14995 | . | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000492552, ENST00000312521, | ENST00000396703, ENST00000425792, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 3 X 3 X 3=27 | 15 X 12 X 6=1080 |
| # samples | 3 | 15 | |
| ** MAII score | log2(3/27*10)=0.15200309344505 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0 | log2(15/1080*10)=-2.84799690655495 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: NR1D2 [Title/Abstract] AND UBE2E2 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | NR1D2(24004096)-UBE2E2(23574045), # samples:3 | ||
| Anticipated loss of major functional domain due to fusion event. | NR1D2-UBE2E2 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. NR1D2-UBE2E2 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. NR1D2-UBE2E2 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. NR1D2-UBE2E2 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 | NR1D2 | GO:0045892 | negative regulation of transcription, DNA-templated | 17892483|17996965 |
| Tgene | UBE2E2 | GO:0032020 | ISG15-protein conjugation | 16428300 |
| Tgene | UBE2E2 | GO:0070534 | protein K63-linked ubiquitination | 20061386 |
| Tgene | UBE2E2 | GO:0070936 | protein K48-linked ubiquitination | 20061386 |
| Tgene | UBE2E2 | GO:0070979 | protein K11-linked ubiquitination | 20061386 |
| Fusion gene breakpoints across NR1D2 (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 UBE2E2 (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 | LUAD | TCGA-55-A57B-01A | NR1D2 | chr3 | 24004096 | - | UBE2E2 | chr3 | 23574045 | + |
| ChimerDB4 | LUAD | TCGA-55-A57B-01A | NR1D2 | chr3 | 24004096 | + | UBE2E2 | chr3 | 23574045 | + |
| ChimerDB4 | LUAD | TCGA-55-A57B | NR1D2 | chr3 | 24004096 | + | UBE2E2 | chr3 | 23574045 | + |
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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) |
| ENST00000312521 | NR1D2 | chr3 | 24004096 | + | ENST00000425792 | UBE2E2 | chr3 | 23574045 | + | 2102 | 1465 | 268 | 1710 | 480 |
| ENST00000312521 | NR1D2 | chr3 | 24004096 | + | ENST00000396703 | UBE2E2 | chr3 | 23574045 | + | 3673 | 1465 | 268 | 1710 | 480 |
| 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 |
| ENST00000312521 | ENST00000425792 | NR1D2 | chr3 | 24004096 | + | UBE2E2 | chr3 | 23574045 | + | 0.002537863 | 0.99746215 |
| ENST00000312521 | ENST00000396703 | NR1D2 | chr3 | 24004096 | + | UBE2E2 | chr3 | 23574045 | + | 0.000323617 | 0.99967635 |
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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 >60075_60075_1_NR1D2-UBE2E2_NR1D2_chr3_24004096_ENST00000312521_UBE2E2_chr3_23574045_ENST00000396703_length(amino acids)=480AA_BP=399 MPPLREAGGPGRLREGTMEVNAGGVIAYISSSSSASSPASCHSEGSENSFQSSSSSVPSSPNSSNSDTNGNPKNGDLANIEGILKNDRID CSMKTSKSSAPGMTKSHSGVTKFSGMVLLCKVCGDVASGFHYGVHACEGCKGFFRRSIQQNIQYKKCLKNENCSIMRMNRNRCQQCRFKK CLSVGMSRDAVRFGRIPKREKQRMLIEMQSAMKTMMNSQFSGHLQNDTLVEHHEQTALPAQEQLRPKPQLEQENIKSSSPPSSDFAKEEV IGMVTRAHKDTFMYNQEQQENSAESMQPQRGERIPKNMEQYNLNHDHCGNGLSSHFPCSESQQHLNGQFKGRNIMHYPNGHAICIANGHC MNFSNAYTQRVCDRVPIDGFSQNENKNSYLCNTGGRMHLVTFRTRIYHCNINSQGVICLDILKDNWSPALTISKVLLSICSLLTDCNPAD -------------------------------------------------------------- >60075_60075_2_NR1D2-UBE2E2_NR1D2_chr3_24004096_ENST00000312521_UBE2E2_chr3_23574045_ENST00000425792_length(amino acids)=480AA_BP=399 MPPLREAGGPGRLREGTMEVNAGGVIAYISSSSSASSPASCHSEGSENSFQSSSSSVPSSPNSSNSDTNGNPKNGDLANIEGILKNDRID CSMKTSKSSAPGMTKSHSGVTKFSGMVLLCKVCGDVASGFHYGVHACEGCKGFFRRSIQQNIQYKKCLKNENCSIMRMNRNRCQQCRFKK CLSVGMSRDAVRFGRIPKREKQRMLIEMQSAMKTMMNSQFSGHLQNDTLVEHHEQTALPAQEQLRPKPQLEQENIKSSSPPSSDFAKEEV IGMVTRAHKDTFMYNQEQQENSAESMQPQRGERIPKNMEQYNLNHDHCGNGLSSHFPCSESQQHLNGQFKGRNIMHYPNGHAICIANGHC MNFSNAYTQRVCDRVPIDGFSQNENKNSYLCNTGGRMHLVTFRTRIYHCNINSQGVICLDILKDNWSPALTISKVLLSICSLLTDCNPAD -------------------------------------------------------------- |
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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/chr3:24004096/chr3:23574045) - 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 |
| NR1D2 | . |
| FUNCTION: Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components ARNTL/BMAL1 and CLOCK. Also regulates genes involved in metabolic functions, including lipid metabolism and the inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression. Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response element composed of the consensus half-site motif 5'-[A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a direct repeat of the core motif spaced by two nuclegotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and also negatively regulates the expression of NR1D1. Regulates lipid and energy homeostasis in the skeletal muscle via repression of genes involved in lipid metabolism and myogenesis including: CD36, FABP3, FABP4, UCP3, SCD1 and MSTN. Regulates hepatic lipid metabolism via the repression of APOC3. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). In addition to its activity as a repressor, can also act as a transcriptional activator. Acts as a transcriptional activator of the sterol regulatory element-binding protein 1 (SREBF1) and the inflammatory mediator interleukin-6 (IL6) in the skeletal muscle (By similarity). Plays a role in the regulation of circadian sleep/wake cycle; essential for maintaining wakefulness during the dark phase or active period (By similarity). Key regulator of skeletal muscle mitochondrial function; negatively regulates the skeletal muscle expression of core clock genes and genes involved in mitochondrial biogenesis, fatty acid beta-oxidation and lipid metabolism (By similarity). May play a role in the circadian control of neutrophilic inflammation in the lung (By similarity). {ECO:0000250|UniProtKB:Q60674, ECO:0000269|PubMed:17892483, ECO:0000269|PubMed:17996965}. | 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 | NR1D2 | chr3:24004096 | chr3:23574045 | ENST00000312521 | + | 5 | 8 | 13_20 | 382.0 | 580.0 | Compositional bias | Note=Poly-Ser |
| Hgene | NR1D2 | chr3:24004096 | chr3:23574045 | ENST00000312521 | + | 5 | 8 | 35_39 | 382.0 | 580.0 | Compositional bias | Note=Poly-Ser |
| Hgene | NR1D2 | chr3:24004096 | chr3:23574045 | ENST00000312521 | + | 5 | 8 | 100_176 | 382.0 | 580.0 | DNA binding | Nuclear receptor |
| Hgene | NR1D2 | chr3:24004096 | chr3:23574045 | ENST00000312521 | + | 5 | 8 | 1_60 | 382.0 | 580.0 | Region | Required for phosphorylation by CSNK1E and cytoplasmic localization |
| Hgene | NR1D2 | chr3:24004096 | chr3:23574045 | ENST00000312521 | + | 5 | 8 | 1_99 | 382.0 | 580.0 | Region | Note=Modulating |
| Hgene | NR1D2 | chr3:24004096 | chr3:23574045 | ENST00000312521 | + | 5 | 8 | 103_123 | 382.0 | 580.0 | Zinc finger | NR C4-type |
| Hgene | NR1D2 | chr3:24004096 | chr3:23574045 | ENST00000312521 | + | 5 | 8 | 140_164 | 382.0 | 580.0 | Zinc finger | NR C4-type |
| - 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 | NR1D2 | chr3:24004096 | chr3:23574045 | ENST00000312521 | + | 5 | 8 | 369_579 | 382.0 | 580.0 | Domain | NR LBD |
| Tgene | UBE2E2 | chr3:24004096 | chr3:23574045 | ENST00000396703 | 3 | 6 | 55_201 | 120.0 | 202.0 | Domain | UBC core | |
| Tgene | UBE2E2 | chr3:24004096 | chr3:23574045 | ENST00000425792 | 3 | 6 | 55_201 | 120.0 | 202.0 | Domain | UBC core |
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Fusion Protein Structures |
| PDB and CIF files of the predicted fusion proteins * Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| Fusion protein PDB link (fusion AA seq ID in FusionPDB) | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | AA seq | Len(AA seq) |
| PDB file >>>1007_NR1D2_24004096_UBE2E2_23574045_1007_NR1D2_24004096_UBE2E2_23574045_ranked_0.pdb | NR1D2 | 24004096 | 24004096 | ENST00000396703 | UBE2E2 | chr3 | 23574045 | + | MPPLREAGGPGRLREGTMEVNAGGVIAYISSSSSASSPASCHSEGSENSFQSSSSSVPSSPNSSNSDTNGNPKNGDLANIEGILKNDRID CSMKTSKSSAPGMTKSHSGVTKFSGMVLLCKVCGDVASGFHYGVHACEGCKGFFRRSIQQNIQYKKCLKNENCSIMRMNRNRCQQCRFKK CLSVGMSRDAVRFGRIPKREKQRMLIEMQSAMKTMMNSQFSGHLQNDTLVEHHEQTALPAQEQLRPKPQLEQENIKSSSPPSSDFAKEEV IGMVTRAHKDTFMYNQEQQENSAESMQPQRGERIPKNMEQYNLNHDHCGNGLSSHFPCSESQQHLNGQFKGRNIMHYPNGHAICIANGHC MNFSNAYTQRVCDRVPIDGFSQNENKNSYLCNTGGRMHLVTFRTRIYHCNINSQGVICLDILKDNWSPALTISKVLLSICSLLTDCNPAD | 480 |
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pLDDT score distribution |
| pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
NR1D2_pLDDT.png  |
UBE2E2_pLDDT.png  |
| pLDDT score distribution of the predicted fusion protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
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Ramachandran Plot of Fusion Protein Structure |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide. |
| Fusion AA seq ID in FusionPDB and their Ramachandran plots |
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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 |
| NR1D2 | |
| UBE2E2 |
| - 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 |
| Hgene | NR1D2 | chr3:24004096 | chr3:23574045 | ENST00000312521 | + | 5 | 8 | 397_579 | 382.0 | 580.0 | ZNHIT1 |
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Related Drugs to NR1D2-UBE2E2 |
| 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 NR1D2-UBE2E2 |
| 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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