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Kinase Fusion Gene:RPL13_MAPKAPK3 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: RPL13_MAPKAPK3 | KinaseFusionDB ID: KFG5492 | FusionGDB2.0 ID: KFG5492 | Hgene | Tgene | Gene symbol | RPL13 | MAPKAPK3 | Gene ID | 28998 | 7867 | |
| Gene name | MAPK activated protein kinase 3 | |||||||||||
| Synonyms | 3PK|MAPKAP-K3|MAPKAP3|MAPKAPK-3|MDPT3|MK-3|MK3 | |||||||||||
| Cytomap | 3p21.2 | |||||||||||
| Type of gene | protein-coding | |||||||||||
| Description | MAP kinase-activated protein kinase 3MAPKAP kinase 3chromosome 3p kinasemitogen-activated protein kinase-activated protein kinase 3 | |||||||||||
| Modification date | 20240403 | |||||||||||
| UniProtAcc | P26373 | Q16644 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000311528, ENST00000393099, ENST00000452368, ENST00000567815, | ENST00000357955, ENST00000497283, ENST00000446044, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: RPL13 [Title/Abstract] AND MAPKAPK3 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | RPL13(89629431)-MAPKAPK3(50683209), # samples:1 | |||||||||||
| 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 |
| Tgene | MAPKAPK3 | GO:0018105 | peptidyl-serine phosphorylation | 15850461 |
| Tgene | MAPKAPK3 | GO:0034097 | response to cytokine | 8774846 |
| Kinase Fusion gene breakpoints across RPL13 (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 MAPKAPK3 (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 |
| ChiTaRS5.0 | AA524181 | RPL13 | chr16 | 89629431 | MAPKAPK3 | chr3 | 50683209 |
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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) |
| ENST00000452368 | ENST00000446044 | RPL13 | chr16 | 89629431 | MAPKAPK3 | chr3 | 50683209 | 3010 | 174 |
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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 >ENST00000452368_ENST00000446044_RPL13_chr16_89629431_MAPKAPK3_chr3_50683209_length(amino acids)=174 MRWPCQVSASPVKQKHSKAIVLASYILLCGFPPFYSNTGQAISPGMKRRIRLGQYGFPNPEWSEVSEDAKQLIRLLLKTDPTERLTITQF -------------------------------------------------------------- |
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/chr16:89629431/chr3:50683209) - 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 |
| RPL13 | MAPKAPK3 |
| FUNCTION: Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:31630789, PubMed:23636399, PubMed:32669547). The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules (Probable). The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain (Probable). The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (Probable). As part of the LSU, it is probably required for its formation and the maturation of rRNAs (PubMed:31630789). Plays a role in bone development (PubMed:31630789). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:31630789, ECO:0000269|PubMed:32669547}. | FUNCTION: Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins, such as TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:15563468, ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20599781, ECO:0000269|PubMed:8626550, ECO:0000269|PubMed:8774846}. |
| 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 | RPL13 | 89629431 | MAPKAPK3 | 50683209 | ENST00000452368 | 0 | 11 | 44_304 | 0 | 383 | Domain | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Tgene | RPL13 | 89629431 | MAPKAPK3 | 50683209 | ENST00000452368 | 0 | 13 | 44_304 | 0 | 383 | 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 >>>425_RPL13_MAPKAPK3 | ENST00000452368 | ENST00000446044 | RPL13 | chr16 | 89629431 | MAPKAPK3 | chr3 | 50683209 | MRWPCQVSASPVKQKHSKAIVLASYILLCGFPPFYSNTGQAISPGMKRRIRLGQYGFPNPEWSEVSEDAKQLIRLLLKTDPTERLTITQF | 174 |
| 3D view using mol* of 425_RPL13_MAPKAPK3 | ||||||||||
| PDB file >>>TKFP_711_RPL13_MAPKAPK3 | ENST00000452368 | ENST00000446044 | RPL13 | chr16 | 89629431 | MAPKAPK3 | chr3 | 50683209 | MRWPCQVSASPVKQKHSKAIVLASYILLCGFPPFYSNTGQAISPGMKRRIRLGQYGFPNPEWSEVSEDAKQLIRLLLKTDPTERLTITQF | 174_RPL13_MAPKAPK3 |
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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. |
| 425_RPL13_MAPKAPK3.png |
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| 425_RPL13_MAPKAPK3.png |
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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. |
| 425_RPL13_MAPKAPK3_ramachandran.png |
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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 RPL13_MAPKAPK3 |
| 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 |
| MAPKAPK3 | Q16644 | human | TAB3 | Q8N5C8 | S506 | HKYQRsSsSGSDDyA | |
| MAPKAPK3 | Q16644 | human | BECN1 | Q14457 | S90 | IPPARMMstEsANsF | |
| MAPKAPK3 | Q16644 | human | HSPB1 | P04792 | S82 | RALsRQLssGVsEIr |
| 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 |
| MAPKAPK3 | ID | Description | 0.00e+00 |
| MAPKAPK3 | GO:0010506 | regulation of autophagy | 1.63e-03 |
| MAPKAPK3 | GO:0010507 | negative regulation of autophagy | 8.31e-03 |
| MAPKAPK3 | GO:2001242 | regulation of intrinsic apoptotic signaling pathway | 2.22e-02 |
| MAPKAPK3 | GO:0031330 | negative regulation of cellular catabolic process | 2.22e-02 |
| MAPKAPK3 | GO:0043122 | regulation of canonical NF-kappaB signal transduction | 2.80e-02 |
| MAPKAPK3 | GO:0007249 | canonical NF-kappaB signal transduction | 2.80e-02 |
| MAPKAPK3 | GO:0097193 | intrinsic apoptotic signaling pathway | 2.80e-02 |
| MAPKAPK3 | GO:0009895 | negative regulation of catabolic process | 2.80e-02 |
| MAPKAPK3 | GO:2001233 | regulation of apoptotic signaling pathway | 2.80e-02 |
| MAPKAPK3 | GO:0009615 | response to virus | 2.80e-02 |
| MAPKAPK3 | GO:0051987 | positive regulation of attachment of spindle microtubules to kinetochore | 2.80e-02 |
| MAPKAPK3 | GO:1905383 | protein localization to presynapse | 2.80e-02 |
| MAPKAPK3 | GO:0006995 | cellular response to nitrogen starvation | 2.80e-02 |
| MAPKAPK3 | GO:0043562 | cellular response to nitrogen levels | 2.80e-02 |
| MAPKAPK3 | GO:1905671 | regulation of lysosome organization | 2.80e-02 |
| MAPKAPK3 | GO:0090235 | regulation of metaphase plate congression | 2.80e-02 |
| MAPKAPK3 | GO:1902902 | negative regulation of autophagosome assembly | 2.80e-02 |
| MAPKAPK3 | GO:0098840 | protein transport along microtubule | 2.80e-02 |
| MAPKAPK3 | GO:0099118 | microtubule-based protein transport | 2.80e-02 |
| MAPKAPK3 | GO:0043652 | engulfment of apoptotic cell | 2.80e-02 |
| MAPKAPK3 | GO:2001028 | positive regulation of endothelial cell chemotaxis | 2.80e-02 |
| MAPKAPK3 | GO:0035821 | modulation of process of another organism | 3.05e-02 |
| MAPKAPK3 | GO:2000786 | positive regulation of autophagosome assembly | 3.05e-02 |
| MAPKAPK3 | GO:0010288 | response to lead ion | 3.05e-02 |
| MAPKAPK3 | GO:0051315 | attachment of mitotic spindle microtubules to kinetochore | 3.05e-02 |
| MAPKAPK3 | GO:0051988 | regulation of attachment of spindle microtubules to kinetochore | 3.05e-02 |
| MAPKAPK3 | GO:0098780 | response to mitochondrial depolarisation | 3.05e-02 |
| MAPKAPK3 | GO:0036092 | phosphatidylinositol-3-phosphate biosynthetic process | 3.08e-02 |
| MAPKAPK3 | GO:0044090 | positive regulation of vacuole organization | 3.14e-02 |
| MAPKAPK3 | GO:2001026 | regulation of endothelial cell chemotaxis | 3.14e-02 |
| MAPKAPK3 | GO:0071280 | cellular response to copper ion | 3.21e-02 |
| MAPKAPK3 | GO:0042026 | protein refolding | 3.21e-02 |
| MAPKAPK3 | GO:0051984 | positive regulation of chromosome segregation | 3.21e-02 |
| MAPKAPK3 | GO:0032801 | receptor catabolic process | 3.23e-02 |
| MAPKAPK3 | GO:0010039 | response to iron ion | 3.32e-02 |
| MAPKAPK3 | GO:0035767 | endothelial cell chemotaxis | 3.32e-02 |
| MAPKAPK3 | GO:0016242 | negative regulation of macroautophagy | 3.32e-02 |
| MAPKAPK3 | GO:0006622 | protein targeting to lysosome | 3.32e-02 |
| MAPKAPK3 | GO:1902176 | negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway | 3.32e-02 |
| MAPKAPK3 | GO:0010613 | positive regulation of cardiac muscle hypertrophy | 3.32e-02 |
| MAPKAPK3 | GO:0014742 | positive regulation of muscle hypertrophy | 3.32e-02 |
| MAPKAPK3 | GO:0045324 | late endosome to vacuole transport | 3.32e-02 |
| MAPKAPK3 | GO:0046688 | response to copper ion | 3.32e-02 |
| MAPKAPK3 | GO:0000423 | mitophagy | 3.32e-02 |
| MAPKAPK3 | GO:0071364 | cellular response to epidermal growth factor stimulus | 3.32e-02 |
| MAPKAPK3 | GO:0045022 | early endosome to late endosome transport | 3.32e-02 |
| MAPKAPK3 | GO:0070849 | response to epidermal growth factor | 3.32e-02 |
| MAPKAPK3 | GO:1902116 | negative regulation of organelle assembly | 3.32e-02 |
| MAPKAPK3 | GO:1902175 | regulation of oxidative stress-induced intrinsic apoptotic signaling pathway | 3.32e-02 |
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Related Drugs to RPL13_MAPKAPK3 |
| 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 RPL13-MAPKAPK3 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 RPL13_MAPKAPK3 |
| 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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