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Fusion Protein:RAD51D-MAP2K4 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: RAD51D-MAP2K4 | FusionPDB ID: 71769 | FusionGDB2.0 ID: 71773 | Hgene | Tgene | Gene symbol | RAD51D | MAP2K4 | Gene ID | 5892 | 6416 |
| Gene name | RAD51 paralog D | mitogen-activated protein kinase kinase 4 | |
| Synonyms | BROVCA4|R51H3|RAD51L3|TRAD | JNKK|JNKK1|MAPKK4|MEK4|MKK4|PRKMK4|SAPKK-1|SAPKK1|SEK1|SERK1|SKK1 | |
| Cytomap | 17q12 | 17p12 | |
| Type of gene | protein-coding | protein-coding | |
| Description | DNA repair protein RAD51 homolog 4RAD51 homolog DRAD51-like protein 3recombination repair protein | dual specificity mitogen-activated protein kinase kinase 4JNK-activated kinase 1JNK-activating kinase 1MAP kinase kinase 4MAPK/ERK kinase 4MAPKK 4MEK 4SAPK/ERK kinase 1c-Jun N-terminal kinase kinase 1stress-activated protein kinase kinase 1 | |
| Modification date | 20200313 | 20200329 | |
| UniProtAcc | . | P45985 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000335858, ENST00000345365, ENST00000360276, ENST00000394589, ENST00000460118, ENST00000590016, ENST00000590380, ENST00000357906, | ENST00000581941, ENST00000353533, ENST00000415385, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 4 X 3 X 4=48 | 8 X 10 X 6=480 |
| # samples | 4 | 10 | |
| ** MAII score | log2(4/48*10)=-0.263034405833794 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(10/480*10)=-2.26303440583379 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: RAD51D [Title/Abstract] AND MAP2K4 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | RAD51D(33428220)-MAP2K4(11984673), # samples:2 | ||
| Anticipated loss of major functional domain due to fusion event. | RAD51D-MAP2K4 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. RAD51D-MAP2K4 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. RAD51D-MAP2K4 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. RAD51D-MAP2K4 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. RAD51D-MAP2K4 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. RAD51D-MAP2K4 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF. RAD51D-MAP2K4 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. RAD51D-MAP2K4 seems lost the major protein functional domain in Tgene partner, which is a kinase due to the frame-shifted ORF. RAD51D-MAP2K4 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 | RAD51D | GO:0042148 | strand invasion | 11834724 |
| Fusion gene breakpoints across RAD51D (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 MAP2K4 (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 | MESO | TCGA-3U-A98I-01A | RAD51D | chr17 | 33428220 | - | MAP2K4 | chr17 | 11984673 | + |
| ChimerDB4 | MESO | TCGA-3U-A98I | RAD51D | chr17 | 33428220 | - | MAP2K4 | chr17 | 11984673 | + |
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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) |
| ENST00000394589 | RAD51D | chr17 | 33428220 | - | ENST00000353533 | MAP2K4 | chr17 | 11984673 | + | 4587 | 1042 | 923 | 2023 | 366 |
| ENST00000394589 | RAD51D | chr17 | 33428220 | - | ENST00000415385 | MAP2K4 | chr17 | 11984673 | + | 4594 | 1042 | 923 | 2023 | 366 |
| 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 |
| ENST00000394589 | ENST00000353533 | RAD51D | chr17 | 33428220 | - | MAP2K4 | chr17 | 11984673 | + | 0.001369176 | 0.9986308 |
| ENST00000394589 | ENST00000415385 | RAD51D | chr17 | 33428220 | - | MAP2K4 | chr17 | 11984673 | + | 0.001360903 | 0.99863905 |
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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 >71769_71769_1_RAD51D-MAP2K4_RAD51D_chr17_33428220_ENST00000394589_MAP2K4_chr17_11984673_ENST00000353533_length(amino acids)=366AA_BP=39 MPSDAPGALCPALGFSWTPSREQEHQAAGAWRVWPNLPDRERLRTHSIESSGKLKISPEQHWDFTAEDLKDLGEIGRGAYGSVNKMVHKP SGQIMAVKRIRSTVDEKEQKQLLMDLDVVMRSSDCPYIVQFYGALFREGDCWICMELMSTSFDKFYKYVYSVLDDVIPEEILGKITLATV KALNHLKENLKIIHRDIKPSNILLDRSGNIKLCDFGISGQLVDSIAKTRDAGCRPYMAPERIDPSASRQGYDVRSDVWSLGITLYELATG RFPYPKWNSVFDQLTQVVKGDPPQLSNSEEREFSPSFINFVNLCLTKDESKRPKYKELLKHPFILMYEERAVEVACYVCKILDQMPATPS -------------------------------------------------------------- >71769_71769_2_RAD51D-MAP2K4_RAD51D_chr17_33428220_ENST00000394589_MAP2K4_chr17_11984673_ENST00000415385_length(amino acids)=366AA_BP=39 MPSDAPGALCPALGFSWTPSREQEHQAAGAWRVWPNLPDRERLRTHSIESSGKLKISPEQHWDFTAEDLKDLGEIGRGAYGSVNKMVHKP SGQIMAVKRIRSTVDEKEQKQLLMDLDVVMRSSDCPYIVQFYGALFREGDCWICMELMSTSFDKFYKYVYSVLDDVIPEEILGKITLATV KALNHLKENLKIIHRDIKPSNILLDRSGNIKLCDFGISGQLVDSIAKTRDAGCRPYMAPERIDPSASRQGYDVRSDVWSLGITLYELATG RFPYPKWNSVFDQLTQVVKGDPPQLSNSEEREFSPSFINFVNLCLTKDESKRPKYKELLKHPFILMYEERAVEVACYVCKILDQMPATPS -------------------------------------------------------------- |
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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/chr17:33428220/chr17:11984673) - 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 |
| . | MAP2K4 |
| 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. | FUNCTION: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14. {ECO:0000269|PubMed:7716521}. |
| 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 | RAD51D | chr17:33428220 | chr17:11984673 | ENST00000345365 | - | 9 | 10 | 200_205 | 301.0 | 329.0 | Compositional bias | Note=Poly-Val |
| Hgene | RAD51D | chr17:33428220 | chr17:11984673 | ENST00000360276 | - | 8 | 9 | 200_205 | 256.0 | 284.0 | Compositional bias | Note=Poly-Val |
| Hgene | RAD51D | chr17:33428220 | chr17:11984673 | ENST00000394589 | - | 10 | 11 | 200_205 | 301.0 | 329.0 | Compositional bias | Note=Poly-Val |
| Hgene | RAD51D | chr17:33428220 | chr17:11984673 | ENST00000590016 | - | 9 | 10 | 200_205 | 321.0 | 349.0 | Compositional bias | Note=Poly-Val |
| Hgene | RAD51D | chr17:33428220 | chr17:11984673 | ENST00000335858 | - | 6 | 7 | 107_114 | 189.0 | 217.0 | Nucleotide binding | ATP |
| Hgene | RAD51D | chr17:33428220 | chr17:11984673 | ENST00000345365 | - | 9 | 10 | 107_114 | 301.0 | 329.0 | Nucleotide binding | ATP |
| Hgene | RAD51D | chr17:33428220 | chr17:11984673 | ENST00000360276 | - | 8 | 9 | 107_114 | 256.0 | 284.0 | Nucleotide binding | ATP |
| Hgene | RAD51D | chr17:33428220 | chr17:11984673 | ENST00000394589 | - | 10 | 11 | 107_114 | 301.0 | 329.0 | Nucleotide binding | ATP |
| Hgene | RAD51D | chr17:33428220 | chr17:11984673 | ENST00000590016 | - | 9 | 10 | 107_114 | 321.0 | 349.0 | Nucleotide binding | ATP |
| Hgene | RAD51D | chr17:33428220 | chr17:11984673 | ENST00000335858 | - | 6 | 7 | 1_83 | 189.0 | 217.0 | Region | Note=preferentially binds ssDNA |
| Hgene | RAD51D | chr17:33428220 | chr17:11984673 | ENST00000345365 | - | 9 | 10 | 1_83 | 301.0 | 329.0 | Region | Note=preferentially binds ssDNA |
| Hgene | RAD51D | chr17:33428220 | chr17:11984673 | ENST00000360276 | - | 8 | 9 | 1_83 | 256.0 | 284.0 | Region | Note=preferentially binds ssDNA |
| Hgene | RAD51D | chr17:33428220 | chr17:11984673 | ENST00000394589 | - | 10 | 11 | 1_83 | 301.0 | 329.0 | Region | Note=preferentially binds ssDNA |
| Hgene | RAD51D | chr17:33428220 | chr17:11984673 | ENST00000590016 | - | 9 | 10 | 1_83 | 321.0 | 349.0 | Region | Note=preferentially binds ssDNA |
| Tgene | MAP2K4 | chr17:33428220 | chr17:11984673 | ENST00000353533 | 1 | 11 | 102_367 | 72.66666666666667 | 400.0 | Domain | Protein kinase | |
| Tgene | MAP2K4 | chr17:33428220 | chr17:11984673 | ENST00000415385 | 2 | 12 | 102_367 | 83.66666666666667 | 411.0 | Domain | Protein kinase | |
| Tgene | MAP2K4 | chr17:33428220 | chr17:11984673 | ENST00000353533 | 1 | 11 | 108_116 | 72.66666666666667 | 400.0 | Nucleotide binding | ATP | |
| Tgene | MAP2K4 | chr17:33428220 | chr17:11984673 | ENST00000415385 | 2 | 12 | 108_116 | 83.66666666666667 | 411.0 | Nucleotide binding | ATP | |
| Tgene | MAP2K4 | chr17:33428220 | chr17:11984673 | ENST00000353533 | 1 | 11 | 364_387 | 72.66666666666667 | 400.0 | Region | Note=DVD domain | |
| Tgene | MAP2K4 | chr17:33428220 | chr17:11984673 | ENST00000415385 | 2 | 12 | 364_387 | 83.66666666666667 | 411.0 | Region | Note=DVD 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 |
| Hgene | RAD51D | chr17:33428220 | chr17:11984673 | ENST00000335858 | - | 6 | 7 | 200_205 | 189.0 | 217.0 | Compositional bias | Note=Poly-Val |
| Hgene | RAD51D | chr17:33428220 | chr17:11984673 | ENST00000357906 | - | 1 | 4 | 200_205 | 0 | 119.0 | Compositional bias | Note=Poly-Val |
| Hgene | RAD51D | chr17:33428220 | chr17:11984673 | ENST00000357906 | - | 1 | 4 | 107_114 | 0 | 119.0 | Nucleotide binding | ATP |
| Hgene | RAD51D | chr17:33428220 | chr17:11984673 | ENST00000357906 | - | 1 | 4 | 1_83 | 0 | 119.0 | Region | Note=preferentially binds ssDNA |
| Tgene | MAP2K4 | chr17:33428220 | chr17:11984673 | ENST00000353533 | 1 | 11 | 5_19 | 72.66666666666667 | 400.0 | Compositional bias | Note=Gly/Ser-rich | |
| Tgene | MAP2K4 | chr17:33428220 | chr17:11984673 | ENST00000415385 | 2 | 12 | 5_19 | 83.66666666666667 | 411.0 | Compositional bias | Note=Gly/Ser-rich | |
| Tgene | MAP2K4 | chr17:33428220 | chr17:11984673 | ENST00000353533 | 1 | 11 | 37_52 | 72.66666666666667 | 400.0 | Region | Note=D domain | |
| Tgene | MAP2K4 | chr17:33428220 | chr17:11984673 | ENST00000415385 | 2 | 12 | 37_52 | 83.66666666666667 | 411.0 | Region | Note=D domain |
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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 >>>724_RAD51D_33428220_MAP2K4_11984673_ranked_0.pdb | RAD51D | 33428220 | 33428220 | ENST00000415385 | MAP2K4 | chr17 | 11984673 | + | MPSDAPGALCPALGFSWTPSREQEHQAAGAWRVWPNLPDRERLRTHSIESSGKLKISPEQHWDFTAEDLKDLGEIGRGAYGSVNKMVHKP SGQIMAVKRIRSTVDEKEQKQLLMDLDVVMRSSDCPYIVQFYGALFREGDCWICMELMSTSFDKFYKYVYSVLDDVIPEEILGKITLATV KALNHLKENLKIIHRDIKPSNILLDRSGNIKLCDFGISGQLVDSIAKTRDAGCRPYMAPERIDPSASRQGYDVRSDVWSLGITLYELATG RFPYPKWNSVFDQLTQVVKGDPPQLSNSEEREFSPSFINFVNLCLTKDESKRPKYKELLKHPFILMYEERAVEVACYVCKILDQMPATPS | 366 |
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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. |
RAD51D_pLDDT.png  |
MAP2K4_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 |
| RAD51D | |
| MAP2K4 |
| - 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 RAD51D-MAP2K4 |
| 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 RAD51D-MAP2K4 |
| 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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