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Fusion Protein:NLK-DOK5 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: NLK-DOK5 | FusionPDB ID: 59343 | FusionGDB2.0 ID: 59343 | Hgene | Tgene | Gene symbol | NLK | DOK5 | Gene ID | 51701 | 55816 |
| Gene name | nemo like kinase | docking protein 5 | |
| Synonyms | - | C20orf180|IRS-6|IRS6 | |
| Cytomap | 17q11.2 | 20q13.2 | |
| Type of gene | protein-coding | protein-coding | |
| Description | serine/threonine-protein kinase NLK | docking protein 5downstream of tyrosine kinase 5insulin receptor substrate 6 | |
| Modification date | 20200313 | 20200320 | |
| UniProtAcc | Q9UBE8 | Q9P104 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000407008, ENST00000582037, ENST00000583517, | ENST00000395939, ENST00000491469, ENST00000262593, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 18 X 10 X 9=1620 | 11 X 9 X 8=792 |
| # samples | 20 | 12 | |
| ** MAII score | log2(20/1620*10)=-3.01792190799726 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(12/792*10)=-2.72246602447109 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: NLK [Title/Abstract] AND DOK5 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | NLK(26495683)-DOK5(53171472), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | NLK-DOK5 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. NLK-DOK5 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. NLK-DOK5 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. NLK-DOK5 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 | NLK | GO:0050821 | protein stabilization | 25512613 |
| Fusion gene breakpoints across NLK (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 DOK5 (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-3C-AALJ-01A | NLK | chr17 | 26495683 | - | DOK5 | chr20 | 53171472 | + |
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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) |
| ENST00000407008 | NLK | chr17 | 26495683 | - | ENST00000262593 | DOK5 | chr20 | 53171472 | + | 3312 | 1765 | 718 | 2619 | 633 |
| 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 |
| ENST00000407008 | ENST00000262593 | NLK | chr17 | 26495683 | - | DOK5 | chr20 | 53171472 | + | 0.004948655 | 0.9950513 |
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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 >59343_59343_1_NLK-DOK5_NLK_chr17_26495683_ENST00000407008_DOK5_chr20_53171472_ENST00000262593_length(amino acids)=633AA_BP=67 MSLCGARANAKMMAAYNGGTSAAAAGHHHHHHHHLPHLPPPHLHHHHHPQHHLHPGSAAAVHPVQQHTSSAAAAAAAAAAAAAMLNPGQQ QPYFPSPAPGQAPGPAAAAPAQVQAAAAATVKAHHHQHSHHPQQQLDIEPDRPIGYGAFGVVWSVTDPRDGKRVALKKMPNVFQNLVSCK RVFRELKMLCFFKHDNVLSALDILQPPHIDYFEEIYVVTELMQSDLHKIIVSPQPLSSDHVKVFLYQILRGLKYLHSAGILHRDIKPGNL LVNSNCVLKICDFGLARVEELDESRHMTQEVVTQYYRAPEILMGSRHYSNAIDIWSVGCIFAELLGRRILFQAQSPIQQIYQRCWLVFKK ASSKGPKRLEKFSDERAAYFRCYHKVTELNNVKNVARLPKSTKKHAIGIYFNDDTSKTFACESDLEADEWCKVLQMECVGTRINDISLGE PDLLATGVEREQSERFNVYLMPSPNLDVHGECALQITYEYICLWDVQNPRVKLISWPLSALRRYGRDTTWFTFEAGRMCETGEGLFIFQT RDGEAIYQKVHSAALAIAEQHERLLQSVKNSMLQMKMSERAASLSTMVPLPRSAYWQHITRQHSTGQLYRLQDVSSPLKLHRTETFPAYR -------------------------------------------------------------- |
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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/chr17:26495683/chr20:53171472) - 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 |
| NLK | DOK5 |
| 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}. | FUNCTION: DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK5 functions in RET-mediated neurite outgrowth and plays a positive role in activation of the MAP kinase pathway. Putative link with downstream effectors of RET in neuronal differentiation. |
| 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 | NLK | chr17:26495683 | chr20:53171472 | ENST00000407008 | - | 6 | 11 | 106_111 | 349.0 | 528.0 | Compositional bias | Note=Poly-Ala |
| Hgene | NLK | chr17:26495683 | chr20:53171472 | ENST00000407008 | - | 6 | 11 | 115_119 | 349.0 | 528.0 | Compositional bias | Note=Poly-Ala |
| Hgene | NLK | chr17:26495683 | chr20:53171472 | ENST00000407008 | - | 6 | 11 | 22_25 | 349.0 | 528.0 | Compositional bias | Note=Poly-Ala |
| Hgene | NLK | chr17:26495683 | chr20:53171472 | ENST00000407008 | - | 6 | 11 | 27_34 | 349.0 | 528.0 | Compositional bias | Note=Poly-His |
| Hgene | NLK | chr17:26495683 | chr20:53171472 | ENST00000407008 | - | 6 | 11 | 42_48 | 349.0 | 528.0 | Compositional bias | Note=Poly-His |
| Hgene | NLK | chr17:26495683 | chr20:53171472 | ENST00000407008 | - | 6 | 11 | 71_83 | 349.0 | 528.0 | Compositional bias | Note=Poly-Ala |
| Hgene | NLK | chr17:26495683 | chr20:53171472 | ENST00000407008 | - | 6 | 11 | 298_300 | 349.0 | 528.0 | Motif | Note=TQE |
| Hgene | NLK | chr17:26495683 | chr20:53171472 | ENST00000407008 | - | 6 | 11 | 144_152 | 349.0 | 528.0 | Nucleotide binding | ATP |
| Tgene | DOK5 | chr17:26495683 | chr20:53171472 | ENST00000262593 | 0 | 8 | 132_237 | 22.0 | 307.0 | Domain | IRS-type PTB | |
| Tgene | DOK5 | chr17:26495683 | chr20:53171472 | ENST00000395939 | 0 | 8 | 132_237 | 0 | 199.0 | Domain | IRS-type PTB | |
| Tgene | DOK5 | chr17:26495683 | chr20:53171472 | ENST00000395939 | 0 | 8 | 8_112 | 0 | 199.0 | Domain | Note=PH | |
| Tgene | DOK5 | chr17:26495683 | chr20:53171472 | ENST00000262593 | 0 | 8 | 263_273 | 22.0 | 307.0 | Motif | Note=DKFBH motif | |
| Tgene | DOK5 | chr17:26495683 | chr20:53171472 | ENST00000395939 | 0 | 8 | 263_273 | 0 | 199.0 | Motif | Note=DKFBH motif |
| - 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 | NLK | chr17:26495683 | chr20:53171472 | ENST00000407008 | - | 6 | 11 | 138_427 | 349.0 | 528.0 | Domain | Protein kinase |
| Hgene | NLK | chr17:26495683 | chr20:53171472 | ENST00000407008 | - | 6 | 11 | 428_527 | 349.0 | 528.0 | Region | Required for homodimerization and kinase activation and localization to the nucleus |
| Tgene | DOK5 | chr17:26495683 | chr20:53171472 | ENST00000262593 | 0 | 8 | 8_112 | 22.0 | 307.0 | Domain | Note=PH |
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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 |
| NLK | |
| DOK5 |
| - 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 NLK-DOK5 |
| 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 NLK-DOK5 |
| 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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