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Fusion Protein:KARS-PLGRKT |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: KARS-PLGRKT | FusionPDB ID: 41175 | FusionGDB2.0 ID: 41175 | Hgene | Tgene | Gene symbol | KARS | PLGRKT | Gene ID | 3735 | 55848 |
| Gene name | lysyl-tRNA synthetase 1 | plasminogen receptor with a C-terminal lysine | |
| Synonyms | CMTRIB|DFNB89|KARS|KARS2|KRS | AD025|C9orf46|MDS030|PLG-RKT|Plg-R(KT) | |
| Cytomap | 16q23.1 | 9p24.1 | |
| Type of gene | protein-coding | protein-coding | |
| Description | lysine--tRNA ligaselysRSlysine tRNA ligase | plasminogen receptor (KT)5033414D02Rikplasminogen receptor, C-terminal lysine transmembrane proteintransmembrane protein C9orf46 | |
| Modification date | 20200318 | 20200313 | |
| UniProtAcc | Q15046 | Q9HBL7 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000302445, ENST00000319410, ENST00000568378, | ENST00000482696, ENST00000223864, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 5 X 7 X 4=140 | 12 X 5 X 9=540 |
| # samples | 6 | 13 | |
| ** MAII score | log2(6/140*10)=-1.22239242133645 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(13/540*10)=-2.05444778402238 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: KARS [Title/Abstract] AND PLGRKT [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | KARS(75674082)-PLGRKT(5361888), # samples:2 | ||
| Anticipated loss of major functional domain due to fusion event. | KARS-PLGRKT seems lost the major protein functional domain in Hgene partner, which is a essential gene 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 | KARS | GO:0000187 | activation of MAPK activity | 15851690 |
| Hgene | KARS | GO:0002741 | positive regulation of cytokine secretion involved in immune response | 15851690 |
| Hgene | KARS | GO:0006430 | lysyl-tRNA aminoacylation | 9278442|10952987|23159739 |
| Hgene | KARS | GO:0008285 | negative regulation of cell proliferation | 15851690 |
| Hgene | KARS | GO:0010759 | positive regulation of macrophage chemotaxis | 15851690 |
| Hgene | KARS | GO:0015966 | diadenosine tetraphosphate biosynthetic process | 23159739 |
| Hgene | KARS | GO:0033209 | tumor necrosis factor-mediated signaling pathway | 15851690 |
| Hgene | KARS | GO:0043032 | positive regulation of macrophage activation | 15851690 |
| Hgene | KARS | GO:0070374 | positive regulation of ERK1 and ERK2 cascade | 15851690 |
| Hgene | KARS | GO:1900017 | positive regulation of cytokine production involved in inflammatory response | 15851690 |
| Hgene | KARS | GO:1900745 | positive regulation of p38MAPK cascade | 15851690 |
| Hgene | KARS | GO:1905050 | positive regulation of metallopeptidase activity | 15851690 |
| Fusion gene breakpoints across KARS (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 PLGRKT (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 | UCS | TCGA-N5-A4RV-01A | KARS | chr16 | 75674082 | - | PLGRKT | chr9 | 5361888 | - |
| ChimerDB4 | UCS | TCGA-N5-A4RV | KARS | chr16 | 75674082 | - | PLGRKT | chr9 | 5361888 | - |
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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) |
| ENST00000319410 | KARS | chr16 | 75674082 | - | ENST00000223864 | PLGRKT | chr9 | 5361888 | - | 1223 | 594 | 122 | 622 | 166 |
| 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 |
| ENST00000319410 | ENST00000223864 | KARS | chr16 | 75674082 | - | PLGRKT | chr9 | 5361888 | - | 0.002998354 | 0.9970016 |
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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 >41175_41175_1_KARS-PLGRKT_KARS_chr16_75674082_ENST00000319410_PLGRKT_chr9_5361888_ENST00000223864_length(amino acids)=166AA_BP= MLTQAAVRLVRGSLRKTSWAEWGHRELRLGQLAPFTAPHKDKSFSDQRSELKRRLKAEKKVAEKEAKQKELSEKQLSQATAAATNHTTDN -------------------------------------------------------------- |
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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/chr16:75674082/chr9:5361888) - 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 |
| KARS | PLGRKT |
| FUNCTION: Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA (PubMed:9278442, PubMed:18029264, PubMed:18272479). When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages (PubMed:15851690). Catalyzes the synthesis of the signaling molecule diadenosine tetraphosphate (Ap4A), and thereby mediates disruption of the complex between HINT1 and MITF and the concomitant activation of MITF transcriptional activity (PubMed:5338216, PubMed:14975237, PubMed:19524539, PubMed:23159739). {ECO:0000269|PubMed:14975237, ECO:0000269|PubMed:15851690, ECO:0000269|PubMed:18029264, ECO:0000269|PubMed:19524539, ECO:0000269|PubMed:28887846, ECO:0000269|PubMed:5338216, ECO:0000269|PubMed:9278442}.; FUNCTION: (Microbial infection) Interacts with HIV-1 virus GAG protein, facilitating the selective packaging of tRNA(3)(Lys), the primer for reverse transcription initiation. {ECO:0000269|PubMed:15220430}. | FUNCTION: Receptor for plasminogen. Regulates urokinase plasminogen activator-dependent and stimulates tissue-type plasminogen activator-dependent cell surface plasminogen activation. Proposed to be part of a local catecholaminergic cell plasminogen activation system that regulates neuroendocrine prohormone processing. Involved in regulation of inflammatory response; regulates monocyte chemotactic migration and matrix metalloproteinase activation, such as of MMP2 and MMP9. {ECO:0000269|PubMed:21940822}. |
| 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 |
| Tgene | PLGRKT | chr16:75674082 | chr9:5361888 | ENST00000223864 | 2 | 6 | 100_147 | 27.0 | 148.0 | Topological domain | Extracellular | |
| Tgene | PLGRKT | chr16:75674082 | chr9:5361888 | ENST00000223864 | 2 | 6 | 74_78 | 27.0 | 148.0 | Topological domain | Cytoplasmic | |
| Tgene | PLGRKT | chr16:75674082 | chr9:5361888 | ENST00000223864 | 2 | 6 | 53_73 | 27.0 | 148.0 | Transmembrane | Helical | |
| Tgene | PLGRKT | chr16:75674082 | chr9:5361888 | ENST00000223864 | 2 | 6 | 79_99 | 27.0 | 148.0 | Transmembrane | Helical |
| - 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 | KARS | chr16:75674082 | chr9:5361888 | ENST00000302445 | - | 3 | 14 | 323_325 | 129.33333333333334 | 598.0 | Nucleotide binding | ATP |
| Hgene | KARS | chr16:75674082 | chr9:5361888 | ENST00000302445 | - | 3 | 14 | 331_332 | 129.33333333333334 | 598.0 | Nucleotide binding | ATP |
| Hgene | KARS | chr16:75674082 | chr9:5361888 | ENST00000302445 | - | 3 | 14 | 494_495 | 129.33333333333334 | 598.0 | Nucleotide binding | ATP |
| Hgene | KARS | chr16:75674082 | chr9:5361888 | ENST00000302445 | - | 3 | 14 | 550_553 | 129.33333333333334 | 598.0 | Nucleotide binding | ATP |
| Hgene | KARS | chr16:75674082 | chr9:5361888 | ENST00000319410 | - | 4 | 15 | 323_325 | 157.33333333333334 | 626.0 | Nucleotide binding | ATP |
| Hgene | KARS | chr16:75674082 | chr9:5361888 | ENST00000319410 | - | 4 | 15 | 331_332 | 157.33333333333334 | 626.0 | Nucleotide binding | ATP |
| Hgene | KARS | chr16:75674082 | chr9:5361888 | ENST00000319410 | - | 4 | 15 | 494_495 | 157.33333333333334 | 626.0 | Nucleotide binding | ATP |
| Hgene | KARS | chr16:75674082 | chr9:5361888 | ENST00000319410 | - | 4 | 15 | 550_553 | 157.33333333333334 | 626.0 | Nucleotide binding | ATP |
| Tgene | PLGRKT | chr16:75674082 | chr9:5361888 | ENST00000223864 | 2 | 6 | 1_52 | 27.0 | 148.0 | Topological domain | Extracellular |
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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 >>>171_KARS_75674082_PLGRKT_5361888_ranked_0.pdb | KARS | 75674082 | 75674082 | ENST00000223864 | PLGRKT | chr9 | 5361888 | - | MLTQAAVRLVRGSLRKTSWAEWGHRELRLGQLAPFTAPHKDKSFSDQRSELKRRLKAEKKVAEKEAKQKELSEKQLSQATAAATNHTTDN | 166 |
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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. |
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PLGRKT_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 |
| KARS | |
| PLGRKT |
| - 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 KARS-PLGRKT |
| 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 KARS-PLGRKT |
| 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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