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Fusion Protein:PDE4D-NLK |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: PDE4D-NLK | FusionPDB ID: 63749 | FusionGDB2.0 ID: 63749 | Hgene | Tgene | Gene symbol | PDE4D | NLK | Gene ID | 5144 | 51701 |
| Gene name | phosphodiesterase 4D | nemo like kinase | |
| Synonyms | ACRDYS2|DPDE3|HSPDE4D|PDE43|PDE4DN2|STRK1 | - | |
| Cytomap | 5q11.2-q12.1 | 17q11.2 | |
| Type of gene | protein-coding | protein-coding | |
| Description | cAMP-specific 3',5'-cyclic phosphodiesterase 4DcAMP-specific phosphodiesterase PDE4D6phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, Drosophila)testicular tissue protein Li 136 | serine/threonine-protein kinase NLK | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | . | Q9UBE8 Main function of 5'-partner protein: FUNCTION: Serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination. Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2. Negative regulator of the canonical Wnt/beta-catenin signaling pathway. Binds to and phosphorylates TCF7L2/TCF4 and LEF1, promoting the dissociation of the TCF7L2/LEF1/beta-catenin complex from DNA, as well as the ubiquitination and subsequent proteolysis of LEF1. Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes. Negative regulator of the Notch signaling pathway. Binds to and phosphorylates NOTCH1, thereby preventing the formation of a transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1. Negative regulator of the MYB family of transcription factors. Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP. Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself. Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1. Upon IL1B stimulus, cooperates with ATF5 to activate the transactivation activity of C/EBP subfamily members. Phosphorylates ATF5 but also stabilizes ATF5 protein levels in a kinase-independent manner (PubMed:25512613). {ECO:0000250|UniProtKB:O54949, ECO:0000269|PubMed:12482967, ECO:0000269|PubMed:14960582, ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:15764709, ECO:0000269|PubMed:20061393, ECO:0000269|PubMed:20118921, ECO:0000269|PubMed:20874444, ECO:0000269|PubMed:21454679, ECO:0000269|PubMed:25512613}. | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000502484, ENST00000546160, ENST00000317118, ENST00000340635, ENST00000358923, ENST00000360047, ENST00000405755, ENST00000502575, ENST00000503258, ENST00000503947, ENST00000507116, | ENST00000582037, ENST00000583517, ENST00000407008, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 40 X 32 X 12=15360 | 10 X 10 X 5=500 |
| # samples | 56 | 15 | |
| ** MAII score | log2(56/15360*10)=-4.77760757866355 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(15/500*10)=-1.73696559416621 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Fusion gene context | PubMed: PDE4D [Title/Abstract] AND NLK [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: PDE4D [Title/Abstract] AND NLK [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | PDE4D(59284315)-NLK(26449629), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | PDE4D-NLK 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. PDE4D-NLK 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. PDE4D-NLK 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. PDE4D-NLK 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. PDE4D-NLK seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF. PDE4D-NLK seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. PDE4D-NLK seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. PDE4D-NLK seems lost the major protein functional domain in Tgene partner, which is a kinase 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 | NLK | GO:0050821 | protein stabilization | 25512613 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr5:59284315/chr17:26449629) - 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 PDE4D (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 NLK (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) |
| ENST00000546160 | PDE4D | chr5 | 59284315 | - | ENST00000407008 | NLK | chr17 | 26449629 | + | 3143 | 272 | 0 | 1397 | 465 |
| 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 |
| ENST00000546160 | ENST00000407008 | PDE4D | chr5 | 59284315 | - | NLK | chr17 | 26449629 | + | 0.000355982 | 0.99964404 |
| 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 PDE4D-NLK |
| +/-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 |
| PDE4D | chr5 | 59284315 | NLK | chr17 | 26449629 | 272 | 91 | LPLIAITSAESSGSVTDPRDGKRVAL |
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Potential FusionNeoAntigen Information of PDE4D-NLK 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. |
| PDE4D-NLK_59284315_26449629.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) |
| PDE4D-NLK | chr5 | 59284315 | chr17 | 26449629 | 272 | HLA-A66:01 | ESSGSVTDPR | 0.9886 | 0.514 | 9 | 19 |
| PDE4D-NLK | chr5 | 59284315 | chr17 | 26449629 | 272 | HLA-B45:01 | AESSGSVTDP | 0.9283 | 0.9226 | 8 | 18 |
| PDE4D-NLK | chr5 | 59284315 | chr17 | 26449629 | 272 | HLA-B50:02 | AESSGSVTDP | 0.8631 | 0.7243 | 8 | 18 |
| PDE4D-NLK | chr5 | 59284315 | chr17 | 26449629 | 272 | HLA-B50:01 | AESSGSVTDP | 0.8395 | 0.7739 | 8 | 18 |
| PDE4D-NLK | chr5 | 59284315 | chr17 | 26449629 | 272 | HLA-B41:01 | AESSGSVTDP | 0.6512 | 0.8886 | 8 | 18 |
| PDE4D-NLK | chr5 | 59284315 | chr17 | 26449629 | 272 | HLA-A69:01 | TSAESSGSV | 0.9022 | 0.7735 | 6 | 15 |
| PDE4D-NLK | chr5 | 59284315 | chr17 | 26449629 | 272 | HLA-B50:04 | AESSGSVTDP | 0.8395 | 0.7739 | 8 | 18 |
| PDE4D-NLK | chr5 | 59284315 | chr17 | 26449629 | 272 | HLA-B50:05 | AESSGSVTDP | 0.8395 | 0.7739 | 8 | 18 |
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Potential FusionNeoAntigen Information of PDE4D-NLK 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. |
| PDE4D-NLK_59284315_26449629.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) |
| PDE4D-NLK | chr5 | 59284315 | chr17 | 26449629 | 272 | DRB1-0455 | LPLIAITSAESSGSV | 0 | 15 |
| PDE4D-NLK | chr5 | 59284315 | chr17 | 26449629 | 272 | DRB1-0458 | LPLIAITSAESSGSV | 0 | 15 |
| PDE4D-NLK | chr5 | 59284315 | chr17 | 26449629 | 272 | DRB1-0478 | LPLIAITSAESSGSV | 0 | 15 |
| PDE4D-NLK | chr5 | 59284315 | chr17 | 26449629 | 272 | DRB1-0479 | LPLIAITSAESSGSV | 0 | 15 |
| PDE4D-NLK | chr5 | 59284315 | chr17 | 26449629 | 272 | DRB1-1002 | LPLIAITSAESSGSV | 0 | 15 |
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Fusion breakpoint peptide structures of PDE4D-NLK |
| 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 |
| 9621 | TSAESSGSVTDPRD | PDE4D | NLK | chr5 | 59284315 | chr17 | 26449629 | 272 |
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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PDE4D-NLK |
| 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 | 9621 | TSAESSGSVTDPRD | -7.15543 | -7.26883 |
| HLA-B14:02 | 3BVN | 9621 | TSAESSGSVTDPRD | -4.77435 | -5.80965 |
| HLA-B52:01 | 3W39 | 9621 | TSAESSGSVTDPRD | -6.80875 | -6.92215 |
| HLA-B52:01 | 3W39 | 9621 | TSAESSGSVTDPRD | -4.20386 | -5.23916 |
| HLA-A11:01 | 4UQ2 | 9621 | TSAESSGSVTDPRD | -7.5194 | -8.5547 |
| HLA-A11:01 | 4UQ2 | 9621 | TSAESSGSVTDPRD | -6.9601 | -7.0735 |
| HLA-A24:02 | 5HGA | 9621 | TSAESSGSVTDPRD | -7.52403 | -7.63743 |
| HLA-A24:02 | 5HGA | 9621 | TSAESSGSVTDPRD | -5.82433 | -6.85963 |
| HLA-B27:05 | 6PYJ | 9621 | TSAESSGSVTDPRD | -3.28285 | -4.31815 |
| HLA-B44:05 | 3DX8 | 9621 | TSAESSGSVTDPRD | -5.91172 | -6.94702 |
| HLA-B44:05 | 3DX8 | 9621 | TSAESSGSVTDPRD | -4.24346 | -4.35686 |
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Vaccine Design for the FusionNeoAntigens of PDE4D-NLK |
| 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 |
| PDE4D-NLK | chr5 | 59284315 | chr17 | 26449629 | 6 | 15 | TSAESSGSV | CACTTCTGCAGAATCCAGTGGGTCAGT |
| PDE4D-NLK | chr5 | 59284315 | chr17 | 26449629 | 8 | 18 | AESSGSVTDP | TGCAGAATCCAGTGGGTCAGTAACAGATCC |
| PDE4D-NLK | chr5 | 59284315 | chr17 | 26449629 | 9 | 19 | ESSGSVTDPR | AGAATCCAGTGGGTCAGTAACAGATCCAAG |
| 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 |
| PDE4D-NLK | chr5 | 59284315 | chr17 | 26449629 | 0 | 15 | LPLIAITSAESSGSV | TCTGCCGCTGATTGCTATCACTTCTGCAGAATCCAGTGGGTCAGT |
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Information of the samples that have these potential fusion neoantigens of PDE4D-NLK |
| 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 |
| PRAD | PDE4D-NLK | chr5 | 59284315 | ENST00000546160 | chr17 | 26449629 | ENST00000407008 | TCGA-G9-6499 |
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Potential target of CAR-T therapy development for PDE4D-NLK |
| 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 PDE4D-NLK |
| 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 PDE4D-NLK |
| 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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