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Fusion Protein:CUL4B-DAPK2 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: CUL4B-DAPK2 | FusionPDB ID: 20689 | FusionGDB2.0 ID: 20689 | Hgene | Tgene | Gene symbol | CUL4B | DAPK2 | Gene ID | 8450 | 23604 |
| Gene name | cullin 4B | death associated protein kinase 2 | |
| Synonyms | CUL-4B|MRXHF2|MRXS15|MRXSC|SFM2 | DRP-1|DRP1 | |
| Cytomap | Xq24 | 15q22.31 | |
| Type of gene | protein-coding | protein-coding | |
| Description | cullin-4B | death-associated protein kinase 2DAP kinase 2DAP-kinase-related protein 1 beta isoform | |
| Modification date | 20200327 | 20200313 | |
| UniProtAcc | Q13620 | Q9UIK4 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000336592, ENST00000371322, ENST00000404115, ENST00000486604, | ENST00000558482, ENST00000261891, ENST00000457488, ENST00000558069, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 5 X 6 X 4=120 | 8 X 9 X 8=576 |
| # samples | 6 | 13 | |
| ** MAII score | log2(6/120*10)=-1 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(13/576*10)=-2.14755718841386 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: CUL4B [Title/Abstract] AND DAPK2 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | CUL4B(119691779)-DAPK2(64275953), # samples:3 | ||
| Anticipated loss of major functional domain due to fusion event. | CUL4B-DAPK2 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. CUL4B-DAPK2 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. CUL4B-DAPK2 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. CUL4B-DAPK2 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. CUL4B-DAPK2 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF. CUL4B-DAPK2 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. CUL4B-DAPK2 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. CUL4B-DAPK2 seems lost the major protein functional domain in Tgene partner, which is a kinase due to the frame-shifted ORF. CUL4B-DAPK2 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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 |
| Hgene | CUL4B | GO:0010498 | proteasomal protein catabolic process | 25970626 |
| Hgene | CUL4B | GO:0035518 | histone H2A monoubiquitination | 22334663 |
| Hgene | CUL4B | GO:0070914 | UV-damage excision repair | 22334663 |
| Tgene | DAPK2 | GO:0006468 | protein phosphorylation | 10376525 |
| Tgene | DAPK2 | GO:0035556 | intracellular signal transduction | 10376525 |
| Fusion gene breakpoints across CUL4B (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 DAPK2 (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 | LIHC | TCGA-DD-A11C-01A | CUL4B | chrX | 119691779 | - | DAPK2 | chr15 | 64275953 | - |
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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) |
| ENST00000404115 | CUL4B | chrX | 119691779 | - | ENST00000261891 | DAPK2 | chr15 | 64275953 | - | 3633 | 1128 | 1267 | 2148 | 293 |
| ENST00000404115 | CUL4B | chrX | 119691779 | - | ENST00000457488 | DAPK2 | chr15 | 64275953 | - | 2746 | 1128 | 1267 | 2148 | 293 |
| ENST00000404115 | CUL4B | chrX | 119691779 | - | ENST00000558069 | DAPK2 | chr15 | 64275953 | - | 2503 | 1128 | 1267 | 2502 | 412 |
| 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 |
| ENST00000404115 | ENST00000261891 | CUL4B | chrX | 119691779 | - | DAPK2 | chr15 | 64275953 | - | 0.0118952 | 0.9881048 |
| ENST00000404115 | ENST00000457488 | CUL4B | chrX | 119691779 | - | DAPK2 | chr15 | 64275953 | - | 0.013315667 | 0.9866844 |
| ENST00000404115 | ENST00000558069 | CUL4B | chrX | 119691779 | - | DAPK2 | chr15 | 64275953 | - | 0.004364174 | 0.9956358 |
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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 >20689_20689_1_CUL4B-DAPK2_CUL4B_chrX_119691779_ENST00000404115_DAPK2_chr15_64275953_ENST00000261891_length(amino acids)=293AA_BP= MRQVLHHNVITLHDVYENRTDVVLILELVSGGELFDFLAQKESLSEEEATSFIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNIPIPHI KLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVSYDFDEEFFSQTSEL AKDFIRKLLVKETRKRLTIQEALRHPWITPVDNQQAMVRRESVVNLENFRKQYVRRRWKLSFSIVSLCNHLTRSLMKKVHLRPDEDLRNC -------------------------------------------------------------- >20689_20689_2_CUL4B-DAPK2_CUL4B_chrX_119691779_ENST00000404115_DAPK2_chr15_64275953_ENST00000457488_length(amino acids)=293AA_BP= MRQVLHHNVITLHDVYENRTDVVLILELVSGGELFDFLAQKESLSEEEATSFIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNIPIPHI KLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVSYDFDEEFFSQTSEL AKDFIRKLLVKETRKRLTIQEALRHPWITPVDNQQAMVRRESVVNLENFRKQYVRRRWKLSFSIVSLCNHLTRSLMKKVHLRPDEDLRNC -------------------------------------------------------------- >20689_20689_3_CUL4B-DAPK2_CUL4B_chrX_119691779_ENST00000404115_DAPK2_chr15_64275953_ENST00000558069_length(amino acids)=412AA_BP= MRQVLHHNVITLHDVYENRTDVVLILELVSGGELFDFLAQKESLSEEEATSFIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNIPIPHI KLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVSYDFDEEFFSQTSEL AKDFIRKLLVKETRKRLTIQEALRHPWITSKGEGRAPEQRKTEPTQLKTKHLREYTLKCHSSMPPNNSYVNFERFACVVEDVARVDLGCR ALVEAHDTIQDDVEALVSIFNEKEAWYREENESARHDLSQLRYEFRKVESLKKLLREDIQATGCSLGSMARKLDHLQAQFEILRQELSAD -------------------------------------------------------------- |
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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/chrX:119691779/chr15:64275953) - 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 |
| CUL4B | DAPK2 |
| FUNCTION: Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition subunit. CUL4B may act within the complex as a scaffold protein, contributing to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. Plays a role as part of the E3 ubiquitin-protein ligase complex in polyubiquitination of CDT1, histone H2A, histone H3 and histone H4 in response to radiation-induced DNA damage. Targeted to UV damaged chromatin by DDB2 and may be important for DNA repair and DNA replication. Required for ubiquitination of cyclin E, and consequently, normal G1 cell cycle progression. Regulates the mammalian target-of-rapamycin (mTOR) pathway involved in control of cell growth, size and metabolism. Specific CUL4B regulation of the mTORC1-mediated pathway is dependent upon 26S proteasome function and requires interaction between CUL4B and MLST8. With CUL4A, contributes to ribosome biogenesis (PubMed:26711351). {ECO:0000269|PubMed:14578910, ECO:0000269|PubMed:16322693, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:18235224, ECO:0000269|PubMed:18593899, ECO:0000269|PubMed:19801544, ECO:0000269|PubMed:22118460, ECO:0000269|PubMed:26711351}. | FUNCTION: Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell death signals, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Acts as a mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation (PubMed:17347302). Regulates granulocytic motility by controlling cell spreading and polarization (PubMed:24163421). {ECO:0000269|PubMed:17347302, ECO:0000269|PubMed:24163421, ECO:0000269|PubMed:26047703}.; FUNCTION: Isoform 2 is not regulated by calmodulin. It can phosphorylate MYL9. It can induce membrane blebbing and autophagic cell death. |
| 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 | CUL4B | chrX:119691779 | chr15:64275953 | ENST00000371322 | - | 2 | 20 | 3_193 | 224.0 | 896.0 | Compositional bias | Note=Ser-rich |
| Hgene | CUL4B | chrX:119691779 | chr15:64275953 | ENST00000404115 | - | 4 | 22 | 3_193 | 242.0 | 914.0 | Compositional bias | Note=Ser-rich |
| Tgene | DAPK2 | chrX:119691779 | chr15:64275953 | ENST00000261891 | 0 | 11 | 29_37 | 30.666666666666668 | 371.0 | Nucleotide binding | ATP | |
| Tgene | DAPK2 | chrX:119691779 | chr15:64275953 | ENST00000457488 | 1 | 12 | 29_37 | 30.666666666666668 | 371.0 | Nucleotide binding | ATP | |
| Tgene | DAPK2 | chrX:119691779 | chr15:64275953 | ENST00000558069 | 1 | 10 | 29_37 | 30.666666666666668 | 489.0 | Nucleotide binding | ATP | |
| Tgene | DAPK2 | chrX:119691779 | chr15:64275953 | ENST00000261891 | 0 | 11 | 277_344 | 30.666666666666668 | 371.0 | Region | Note=Calmodulin-binding | |
| Tgene | DAPK2 | chrX:119691779 | chr15:64275953 | ENST00000261891 | 0 | 11 | 292_301 | 30.666666666666668 | 371.0 | Region | Autoinhibitory domain | |
| Tgene | DAPK2 | chrX:119691779 | chr15:64275953 | ENST00000457488 | 1 | 12 | 277_344 | 30.666666666666668 | 371.0 | Region | Note=Calmodulin-binding | |
| Tgene | DAPK2 | chrX:119691779 | chr15:64275953 | ENST00000457488 | 1 | 12 | 292_301 | 30.666666666666668 | 371.0 | Region | Autoinhibitory domain | |
| Tgene | DAPK2 | chrX:119691779 | chr15:64275953 | ENST00000558069 | 1 | 10 | 277_344 | 30.666666666666668 | 489.0 | Region | Note=Calmodulin-binding | |
| Tgene | DAPK2 | chrX:119691779 | chr15:64275953 | ENST00000558069 | 1 | 10 | 292_301 | 30.666666666666668 | 489.0 | Region | Autoinhibitory domain |
| - 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 |
| Tgene | DAPK2 | chrX:119691779 | chr15:64275953 | ENST00000261891 | 0 | 11 | 23_285 | 30.666666666666668 | 371.0 | Domain | Protein kinase | |
| Tgene | DAPK2 | chrX:119691779 | chr15:64275953 | ENST00000457488 | 1 | 12 | 23_285 | 30.666666666666668 | 371.0 | Domain | Protein kinase | |
| Tgene | DAPK2 | chrX:119691779 | chr15:64275953 | ENST00000558069 | 1 | 10 | 23_285 | 30.666666666666668 | 489.0 | Domain | Protein kinase |
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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 |
| CUL4B | |
| DAPK2 |
| - 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 CUL4B-DAPK2 |
| 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 CUL4B-DAPK2 |
| 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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