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Fusion Protein:PDE4D-NLK |
Fusion Gene and Fusion Protein Summary |
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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) |
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Partner | Gene | GO ID | GO term | PubMed ID |
Tgene | NLK | GO:0050821 | protein stabilization | 25512613 |
![]() 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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![]() * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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![]() * 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 |
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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 |
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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 |
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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 |
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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 |
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PDE4D-NLK_59284315_26449629.msa |
![]() * 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 |
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PDE4D-NLK_59284315_26449629.msa |
![]() * 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 |
![]() * 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 |
![]() * 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 |
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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 |
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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 |
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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 |
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![]() * 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 |
![]() * 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 |
![]() (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
Hgene | Tgene | Drug | Source | PMID |
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Related Diseases to PDE4D-NLK |
![]() (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
Hgene | Tgene | Disease | Source | PMID |
![]() (DisGeNet 4.0) |
Partner | Gene | Disease ID | Disease name | # pubmeds | Source |