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Kinase Fusion Gene:RAD51D_MAP2K4 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: RAD51D_MAP2K4 | KinaseFusionDB ID: KFG5241 | FusionGDB2.0 ID: KFG5241 | 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 1c-Jun NH2-terminal kinase kinase 1stress-acti | ||||||||||
| Modification date | 20240407 | 20240403 | ||||||||||
| UniProtAcc | O75771 | P45985 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000335858, ENST00000345365, ENST00000360276, ENST00000394589, ENST00000460118, ENST00000590016, ENST00000590380, ENST00000357906, | ENST00000581941, ENST00000353533, ENST00000415385, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | 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 | |||||||||||
| 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 | DNA strand invasion | 11834724 |
| Kinase 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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| Kinase 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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Kinase Fusion Gene Sample Information |
| Kinase Fusion gene information. |
| Kinase Fusion gene information from four resources (ChiTars 5.0, ChimerDB 4.0, COSMIC, and CCLE) * 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 | Sample | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp |
| ChimerDB4 | TCGA-3U-A98I-01A | RAD51D | chr17 | 33428220 | MAP2K4 | chr17 | 11984673 |
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Kinase Fusion ORF Analysis |
| Kinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB. |
| Henst | Tenst | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Seq length (transcript) | Seq length (amino acids) |
| ENST00000394589 | ENST00000353533 | RAD51D | chr17 | 33428220 | MAP2K4 | chr17 | 11984673 | 4587 | 366 |
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Kinase Fusion Amino Acid Sequences |
| For individual full-length fusion transcript sequence from KinaseFusionDB, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
| >Henst_Tenst_Hgene_Hchr_Hbp_Tgene_Tchr_Tbp_length(fusion AA)_AAseq >ENST00000394589_ENST00000353533_RAD51D_chr17_33428220_MAP2K4_chr17_11984673_length(amino acids)=366 MPSDAPGALCPALGFSWTPSREQEHQAAGAWRVWPNLPDRERLRTHSIESSGKLKISPEQHWDFTAEDLKDLGEIGRGAYGSVNKMVHKP SGQIMAVKRIRSTVDEKEQKQLLMDLDVVMRSSDCPYIVQFYGALFREGDCWICMELMSTSFDKFYKYVYSVLDDVIPEEILGKITLATV KALNHLKENLKIIHRDIKPSNILLDRSGNIKLCDFGISGQLVDSIAKTRDAGCRPYMAPERIDPSASRQGYDVRSDVWSLGITLYELATG RFPYPKWNSVFDQLTQVVKGDPPQLSNSEEREFSPSFINFVNLCLTKDESKRPKYKELLKHPFILMYEERAVEVACYVCKILDQMPATPS -------------------------------------------------------------- |
Multiple Sequence Alignment of All Fusion Protein Isoforms |
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Kinase 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 |
| RAD51D | MAP2K4 |
| FUNCTION: Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. Bind to single-stranded DNA (ssDNA) and has DNA-dependent ATPase activity. Part of the RAD51 paralog protein complex BCDX2 which acts in the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 acts downstream of BRCA2 recruitment and upstream of RAD51 recruitment. BCDX2 binds predominantly to the intersection of the four duplex arms of the Holliday junction and to junction of replication forks. The BCDX2 complex was originally reported to bind single-stranded DNA, single-stranded gaps in duplex DNA and specifically to nicks in duplex DNA. Involved in telomere maintenance. The BCDX2 subcomplex XRCC2:RAD51D can stimulate Holliday junction resolution by BLM. {ECO:0000269|PubMed:10871607, ECO:0000269|PubMed:11751635, ECO:0000269|PubMed:11834724, ECO:0000269|PubMed:11842113, ECO:0000269|PubMed:12975363, ECO:0000269|PubMed:15109494, ECO:0000269|PubMed:23149936}. | 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 pro-inflammatory 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 domain in the 5'-partner of fusion protein (protein functional feature from UniProt). |
| Partner | Hgeneene | Hbp | Tgeneene | Tbp | ENST | BPexon | TotalExon | Protein feature loci | BPloci | TotalLen | Feature | Note |
| - Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt). |
| Partner | Hgeneene | Hbp | Tgeneene | Tbp | ENST | BPexon | TotalExon | Protein feature loci | BPloci | TotalLen | Feature | Note |
| Tgene | RAD51D | 33428220 | MAP2K4 | 11984673 | ENST00000394589 | 1 | 11 | 102_367 | 72 | 400 | Domain | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Tgene | RAD51D | 33428220 | MAP2K4 | 11984673 | ENST00000394589 | 2 | 12 | 102_367 | 83 | 411 | Domain | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
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Kinase Fusion Protein Structures |
| CIF files of the predicted kinase 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. |
| Kinase Fusion protein CIF link (fusion AA seq ID in KinaseFusionDB) | Henst | Tenst | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | AA seq | Len(AA seq) |
| PDB file >>>406_RAD51D_MAP2K4 | ENST00000394589 | ENST00000353533 | RAD51D | chr17 | 33428220 | MAP2K4 | chr17 | 11984673 | MPSDAPGALCPALGFSWTPSREQEHQAAGAWRVWPNLPDRERLRTHSIESSGKLKISPEQHWDFTAEDLKDLGEIGRGAYGSVNKMVHKP SGQIMAVKRIRSTVDEKEQKQLLMDLDVVMRSSDCPYIVQFYGALFREGDCWICMELMSTSFDKFYKYVYSVLDDVIPEEILGKITLATV KALNHLKENLKIIHRDIKPSNILLDRSGNIKLCDFGISGQLVDSIAKTRDAGCRPYMAPERIDPSASRQGYDVRSDVWSLGITLYELATG RFPYPKWNSVFDQLTQVVKGDPPQLSNSEEREFSPSFINFVNLCLTKDESKRPKYKELLKHPFILMYEERAVEVACYVCKILDQMPATPS | 366 |
| 3D view using mol* of 406_RAD51D_MAP2K4 | ||||||||||
| PDB file >>>TKFP_686_RAD51D_MAP2K4 | ENST00000394589 | ENST00000353533 | RAD51D | chr17 | 33428220 | MAP2K4 | chr17 | 11984673 | MPSDAPGALCPALGFSWTPSREQEHQAAGAWRVWPNLPDRERLRTHSIESSGKLKISPEQHWDFTAEDLKDLGEIGRGAYGSVNKMVHKP SGQIMAVKRIRSTVDEKEQKQLLMDLDVVMRSSDCPYIVQFYGALFREGDCWICMELMSTSFDKFYKYVYSVLDDVIPEEILGKITLATV KALNHLKENLKIIHRDIKPSNILLDRSGNIKLCDFGISGQLVDSIAKTRDAGCRPYMAPERIDPSASRQGYDVRSDVWSLGITLYELATG RFPYPKWNSVFDQLTQVVKGDPPQLSNSEEREFSPSFINFVNLCLTKDESKRPKYKELLKHPFILMYEERAVEVACYVCKILDQMPATPS | 366_RAD51D_MAP2K4 |
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Comparison of Fusion Protein Isoforms |
| Superimpose the 3D Structures Among All Fusion Protein Isoforms * Download the pdb file and open it from the molstar online viewer. |
| Comparison of the Secondary Structures of Fusion Protein Isoforms |
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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB |
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pLDDT score distribution |
| pLDDT score distribution of the predicted fusion protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. * The blue color at the bottom marks the best active site residues. |
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Potential Active Site Information |
| The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite. |
| Kinase Fusion AA seq ID in KinaseFusionDB | Site score | Size | Dscore | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
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Ramachandran Plot of Kinase 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. |
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Virtual Screening Results |
| Distribution of the average docking score across all approved kinase inhibitors. Distribution of the number of occurrence across all approved kinase inhibitors. |
| 5'-kinase fusion protein case |
| 3'-kinase fusion protein case |
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| Drug information from DrugBank of the top 20 interacting small molecules. * The detailed information of individual kinase inhibitors are available in the download page. |
| Fusion gene name info | Drug | Docking score | Glide g score | Glide energy |
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Kinase-Substrate Information of RAD51D_MAP2K4 |
| Phosphorylation target of the kinase (phosphosite, 03-17-2024) |
| Kinase | Kinase UniProt Acc | Kinase species | Substrate | Substrate UniProt Acc | Substrate phosphorylated residues | Substrate phosphorylated sites (+/-7AA) | Domain |
| MAP2K4 | P45985 | human | MAPK8 | P45983-2 | Y185 | TSFMMtPyVVTRYYR | Pkinase |
| MAP2K4 | P45985 | human | MAPK9 | P45984 | Y185 | tNFMMtPyVVtRYYR | Pkinase |
| MAP2K4 | P45985 | human | MAPK8 | P45983 | Y185 | tsFMMtPyVVtRYYR | Pkinase |
| MAP2K4 | P45985 | human | RXRA | P19793 | Y249 | VEPKTETyVEANMGL | |
| MAP2K4 | P45985 | human | MAPK10 | P53779 | Y223 | tsFMMtPyVVtRYYR | Pkinase |
| MAP2K4 | P45985 | human | MAP2K4 | P45985 | S257 | ISGQLVDsIAKtRDA | Pkinase |
| MAP2K4 | P45985 | human | MAPK8 | P45983-3 | T228 | GGVLFPGtDHIDQWN | Pkinase |
| MAP2K4 | P45985 | human | MAPK8 | P45983-3 | S377 | GVIRGQPsPLAQVQQ | |
| MAP2K4 | P45985 | human | MAPK10 | P53779-2 | Y223 | TSFMMtPyVVTRYYR | Pkinase |
| MAP2K4 | P45985 | human | MAPK8 | P45983 | T183 | AGtsFMMtPyVVtRY | Pkinase |
| MAP2K4 | P45985 | human | MAPK8 | P45983-3 | T183 | AGTSFMMtPyVVTRY | Pkinase |
| MAP2K4 | P45985 | human | MAPK14 | Q16539 | T180 | RHtDDEMtGyVAtRW | Pkinase |
| MAP2K4 | P45985 | human | MAPK8 | P45983-3 | S284 | DVLFPADsEHNKLKA | Pkinase |
| MAP2K4 | P45985 | human | MAPK8 | P45983-3 | Y185 | TSFMMtPyVVTRYYR | Pkinase |
| MAP2K4 | P45985 | human | MAP2K4 | P45985 | T261 | LVDsIAKtRDAGCRP | Pkinase |
| MAP2K4 | P45985 | human | MAPK14 | Q16539 | Y182 | tDDEMtGyVAtRWYR | Pkinase |
| Biological Network Integration of This Kinase and Substrates (GeneMANIA website) |
| Enriched GO biological processes of the phosphorylation target genes of the kinase |
| Kinase | GOID | GO term | P.adjust |
| MAP2K4 | ID | Description | 0.00e+00 |
| MAP2K4 | GO:0038095 | Fc-epsilon receptor signaling pathway | 7.81e-09 |
| MAP2K4 | GO:0090398 | cellular senescence | 7.81e-09 |
| MAP2K4 | GO:0038093 | Fc receptor signaling pathway | 1.47e-07 |
| MAP2K4 | GO:0051403 | stress-activated MAPK cascade | 1.55e-07 |
| MAP2K4 | GO:0031098 | stress-activated protein kinase signaling cascade | 1.55e-07 |
| MAP2K4 | GO:0007254 | JNK cascade | 5.64e-06 |
| MAP2K4 | GO:0002768 | immune response-regulating cell surface receptor signaling pathway | 9.85e-05 |
| MAP2K4 | GO:0042752 | regulation of circadian rhythm | 2.26e-04 |
| MAP2K4 | GO:0002764 | immune response-regulating signaling pathway | 3.32e-04 |
| MAP2K4 | GO:0034614 | cellular response to reactive oxygen species | 4.46e-04 |
| MAP2K4 | GO:0007623 | circadian rhythm | 8.76e-04 |
| MAP2K4 | GO:0000302 | response to reactive oxygen species | 8.76e-04 |
| MAP2K4 | GO:0009612 | response to mechanical stimulus | 9.06e-04 |
| MAP2K4 | GO:0034599 | cellular response to oxidative stress | 1.44e-03 |
| MAP2K4 | GO:0071276 | cellular response to cadmium ion | 1.59e-03 |
| MAP2K4 | GO:0031281 | positive regulation of cyclase activity | 1.65e-03 |
| MAP2K4 | GO:0018105 | peptidyl-serine phosphorylation | 1.75e-03 |
| MAP2K4 | GO:0048511 | rhythmic process | 1.75e-03 |
| MAP2K4 | GO:0018209 | peptidyl-serine modification | 1.85e-03 |
| MAP2K4 | GO:0062197 | cellular response to chemical stress | 1.85e-03 |
| MAP2K4 | GO:0009416 | response to light stimulus | 1.85e-03 |
| MAP2K4 | GO:0071214 | cellular response to abiotic stimulus | 1.96e-03 |
| MAP2K4 | GO:0104004 | cellular response to environmental stimulus | 1.96e-03 |
| MAP2K4 | GO:0071496 | cellular response to external stimulus | 2.04e-03 |
| MAP2K4 | GO:0031279 | regulation of cyclase activity | 2.04e-03 |
| MAP2K4 | GO:0046686 | response to cadmium ion | 2.34e-03 |
| MAP2K4 | GO:0006979 | response to oxidative stress | 2.84e-03 |
| MAP2K4 | GO:0071260 | cellular response to mechanical stimulus | 3.24e-03 |
| MAP2K4 | GO:0009314 | response to radiation | 3.24e-03 |
| MAP2K4 | GO:0002534 | cytokine production involved in inflammatory response | 3.71e-03 |
| MAP2K4 | GO:1900015 | regulation of cytokine production involved in inflammatory response | 3.71e-03 |
| MAP2K4 | GO:0055017 | cardiac muscle tissue growth | 4.34e-03 |
| MAP2K4 | GO:0031667 | response to nutrient levels | 4.37e-03 |
| MAP2K4 | GO:0060419 | heart growth | 4.85e-03 |
| MAP2K4 | GO:0002532 | production of molecular mediator involved in inflammatory response | 5.62e-03 |
| MAP2K4 | GO:0030278 | regulation of ossification | 7.12e-03 |
| MAP2K4 | GO:0009411 | response to UV | 1.09e-02 |
| MAP2K4 | GO:0090316 | positive regulation of intracellular protein transport | 1.15e-02 |
| MAP2K4 | GO:0035265 | organ growth | 1.40e-02 |
| MAP2K4 | GO:0031334 | positive regulation of protein-containing complex assembly | 1.67e-02 |
| MAP2K4 | GO:0071248 | cellular response to metal ion | 1.67e-02 |
| MAP2K4 | GO:0032388 | positive regulation of intracellular transport | 1.67e-02 |
| MAP2K4 | GO:0033157 | regulation of intracellular protein transport | 2.01e-02 |
| MAP2K4 | GO:0071222 | cellular response to lipopolysaccharide | 2.01e-02 |
| MAP2K4 | GO:0071241 | cellular response to inorganic substance | 2.02e-02 |
| MAP2K4 | GO:0071219 | cellular response to molecule of bacterial origin | 2.15e-02 |
| MAP2K4 | GO:0048738 | cardiac muscle tissue development | 2.24e-02 |
| MAP2K4 | GO:0031669 | cellular response to nutrient levels | 2.26e-02 |
| MAP2K4 | GO:0014706 | striated muscle tissue development | 2.42e-02 |
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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 |
| Distribution of the number of studies mentioning RAD51D-MAP2K4 and kinase inhibitors the PubMed Abstract (04-01-2024) |
| Fusion gene - drug pair 1 | Fusion gene - drug pair 2 | PMID | Publication date | DOI | Study title |
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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 |
| Related diseases from the literature mentioned this fusion gene and drug. (PubMed, 04-01-2024) |
| MeSH ID | MeSH term |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
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Clinical Trials of the Found Drugs/Small Molecules |
| Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024) |
| Clinical Trials from clinicaltrials.gov (06-17-2024) |
| Fusion Gene | Kinase Inhibitor | NCT ID | Study Status | Phases | Disease | # Enrolment | Date |
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