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Kinase Fusion Gene:ROS1_CD74 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: ROS1_CD74 | KinaseFusionDB ID: KFG5488 | FusionGDB2.0 ID: KFG5488 | Hgene | Tgene | Gene symbol | ROS1 | CD74 | Gene ID | 6098 | 972 | |
| Gene name | ROS proto-oncogene 1, receptor tyrosine kinase | CD74 molecule | ||||||||||
| Synonyms | MCF3|ROS|c-ros-1 | CLIP|DHLAG|HLADG|II|Ia-GAMMA|p33 | ||||||||||
| Cytomap | 6q22.1 | 5q33.1 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | proto-oncogene tyrosine-protein kinase ROSROS proto-oncogene 1 , receptor tyrosine kinasec-ros oncogene 1 , receptor tyrosine kinaseproto-oncogene c-Ros-1transmembrane tyrosine-specific protein kinasev-ros avian UR2 sarcoma virus oncogene homolog 1 | HLA class II histocompatibility antigen gamma chainCD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated)CD74 molecule, major histocompatibility complex, class II invariant chainHLA-DR antigens-associated | ||||||||||
| Modification date | 20240411 | 20240317 | ||||||||||
| UniProtAcc | P08922 | P04233 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000368507, ENST00000368508, | ENST00000009530, ENST00000353334, ENST00000377795, ENST00000524315, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: ROS1 [Title/Abstract] AND CD74 [Title/Abstract] AND fusion [Title/Abstract] CD74-ROS1 fusion transcripts in resected non-small cell lung carcinoma (pmid: 23877438) | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | CD74(149784243)-ROS1(117645578), # samples:6 CD74(149784243)-ROS1(117645580), # samples:6 ROS1(117700222)-CD74(149782188), # 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 | ROS1 | GO:0001558 | regulation of cell growth | 16885344 |
| Hgene | ROS1 | GO:0006468 | protein phosphorylation | 16885344 |
| Hgene | ROS1 | GO:0032006 | regulation of TOR signaling | 16885344 |
| Tgene | CD74 | GO:0001516 | prostaglandin biosynthetic process | 12782713 |
| Tgene | CD74 | GO:0001934 | positive regulation of protein phosphorylation | 24942581 |
| Tgene | CD74 | GO:0002792 | negative regulation of peptide secretion | 19849849 |
| Tgene | CD74 | GO:0033674 | positive regulation of kinase activity | 24942581 |
| Tgene | CD74 | GO:0034341 | response to type II interferon | 32855215 |
| Tgene | CD74 | GO:0043066 | negative regulation of apoptotic process | 12782713 |
| Tgene | CD74 | GO:0043123 | positive regulation of canonical NF-kappaB signal transduction | 24942581 |
| Tgene | CD74 | GO:0043410 | positive regulation of MAPK cascade | 24942581 |
| Tgene | CD74 | GO:0043518 | negative regulation of DNA damage response, signal transduction by p53 class mediator | 17045821 |
| Tgene | CD74 | GO:0045657 | positive regulation of monocyte differentiation | 24942581 |
| Tgene | CD74 | GO:0045893 | positive regulation of DNA-templated transcription | 24942581 |
| Tgene | CD74 | GO:0046598 | positive regulation of viral entry into host cell | 24942581 |
| Tgene | CD74 | GO:0050731 | positive regulation of peptidyl-tyrosine phosphorylation | 17045821 |
| Tgene | CD74 | GO:0070374 | positive regulation of ERK1 and ERK2 cascade | 17045821|24942581 |
| Kinase Fusion gene breakpoints across ROS1 (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 CD74 (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-86-8278-01A | ROS1 | chr6 | 117700221 | CD74 | chr5 | 149782187 |
| ChimerDB4 | TCGA-86-8278-01A | ROS1 | chr6 | 117700221 | CD74 | chr5 | 149782874 |
| ChimerDB4 | TCGA-86-8278-01A | ROS1 | chr6 | 117700222 | CD74 | chr5 | 149782188 |
| ChimerDB4 | TCGA-86-8278-01A | ROS1 | chr6 | 117700222 | CD74 | chr5 | 149782875 |
| ChimerDB4 | TCGA-86-8278 | ROS1 | chr6 | 117700221 | CD74 | chr5 | 149782188 |
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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) |
| ENST00000368508 | ENST00000377795 | ROS1 | chr6 | 117700222 | CD74 | chr5 | 149782188 | 3473 | 948 |
| ENST00000368508 | ENST00000377795 | ROS1 | chr6 | 117700221 | CD74 | chr5 | 149782188 | 3473 | 948 |
| ENST00000368508 | ENST00000377795 | ROS1 | chr6 | 117700221 | CD74 | chr5 | 149782187 | 3473 | 948 |
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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 >ENST00000368508_ENST00000377795_ROS1_chr6_117700222_CD74_chr5_149782188_length(amino acids)=948 MKNIYCLIPKLVNFATLGCLWISVVQCTVLNSCLKSCVTNLGQQLDLGTPHNLSEPCIQGCHFWNSVDQKNCALKCRESCEVGCSSAEGA YEEEVLENADLPTAPFASSIGSHNMTLRWKSANFSGVKYIIQWKYAQLLGSWTYTKTVSRPSYVVKPLHPFTEYIFRVVWIFTAQLQLYS PPSPSYRTHPHGVPETAPLIRNIESSSPDTVEVSWDPPQFPGGPILGYNLRLISKNQKLDAGTQRTSFQFYSTLPNTIYRFSIAAVNEVG EGPEAESSITTSSSAVQQEEQWLFLSRKTSLRKRSLKHLVDEAHCLRLDAIYHNITGISVDVHQQIVYFSEGTLIWAKKAANMSDVSDLR IFYRGSGLISSISIDWLYQRMYFIMDELVCVCDLENCSNIEEITPPSISAPQKIVADSYNGYVFYLLRDGIYRADLPVPSGRCAEAVRIV ESCTLKDFAIKPQAKRIIYFNDTAQVFMSTFLDGSASHLILPRIPFADVKSFACENNDFLVTDGKVIFQQDALSFNEFIVGCDLSHIEEF GFGNLVIFGSSSQLHPLPGRPQELSVLFGSHQALVQWKPPALAIGANVILISDIIELFELGPSAWQNWTYEVKVSTQDPPEVTHIFLNIS GTMLNVPELQSAMKYKVSVRASSPKRPGPWSEPSVGTTLVPASEPPFIMAVKEDGLWSKPLNSFGPGEFLSSDIGNVSDMDWYNNSLYYS DTKGDVFVWLLNGTDISENYHLPSIAGAGALAFEWLGHFLYWAGKTYVIQRQSVLTGHTDIVTHVKLLVNDMVVDSVGGYLYWTTLYSVE STRLNGESSLVLQTQPWFSGKKVIALTLDLSDGLLYWLVQDSQCIHLYTAVLRGQRVTGTGGPVFWAGCDQAGSGPSPHVRAAEAVFNIL -------------------------------------------------------------- >ENST00000368508_ENST00000377795_ROS1_chr6_117700221_CD74_chr5_149782188_length(amino acids)=948 MKNIYCLIPKLVNFATLGCLWISVVQCTVLNSCLKSCVTNLGQQLDLGTPHNLSEPCIQGCHFWNSVDQKNCALKCRESCEVGCSSAEGA YEEEVLENADLPTAPFASSIGSHNMTLRWKSANFSGVKYIIQWKYAQLLGSWTYTKTVSRPSYVVKPLHPFTEYIFRVVWIFTAQLQLYS PPSPSYRTHPHGVPETAPLIRNIESSSPDTVEVSWDPPQFPGGPILGYNLRLISKNQKLDAGTQRTSFQFYSTLPNTIYRFSIAAVNEVG EGPEAESSITTSSSAVQQEEQWLFLSRKTSLRKRSLKHLVDEAHCLRLDAIYHNITGISVDVHQQIVYFSEGTLIWAKKAANMSDVSDLR IFYRGSGLISSISIDWLYQRMYFIMDELVCVCDLENCSNIEEITPPSISAPQKIVADSYNGYVFYLLRDGIYRADLPVPSGRCAEAVRIV ESCTLKDFAIKPQAKRIIYFNDTAQVFMSTFLDGSASHLILPRIPFADVKSFACENNDFLVTDGKVIFQQDALSFNEFIVGCDLSHIEEF GFGNLVIFGSSSQLHPLPGRPQELSVLFGSHQALVQWKPPALAIGANVILISDIIELFELGPSAWQNWTYEVKVSTQDPPEVTHIFLNIS GTMLNVPELQSAMKYKVSVRASSPKRPGPWSEPSVGTTLVPASEPPFIMAVKEDGLWSKPLNSFGPGEFLSSDIGNVSDMDWYNNSLYYS DTKGDVFVWLLNGTDISENYHLPSIAGAGALAFEWLGHFLYWAGKTYVIQRQSVLTGHTDIVTHVKLLVNDMVVDSVGGYLYWTTLYSVE STRLNGESSLVLQTQPWFSGKKVIALTLDLSDGLLYWLVQDSQCIHLYTAVLRGQRVTGTGGPVFWAGCDQAGSGPSPHVRAAEAVFNIL -------------------------------------------------------------- >ENST00000368508_ENST00000377795_ROS1_chr6_117700221_CD74_chr5_149782187_length(amino acids)=948 MKNIYCLIPKLVNFATLGCLWISVVQCTVLNSCLKSCVTNLGQQLDLGTPHNLSEPCIQGCHFWNSVDQKNCALKCRESCEVGCSSAEGA YEEEVLENADLPTAPFASSIGSHNMTLRWKSANFSGVKYIIQWKYAQLLGSWTYTKTVSRPSYVVKPLHPFTEYIFRVVWIFTAQLQLYS PPSPSYRTHPHGVPETAPLIRNIESSSPDTVEVSWDPPQFPGGPILGYNLRLISKNQKLDAGTQRTSFQFYSTLPNTIYRFSIAAVNEVG EGPEAESSITTSSSAVQQEEQWLFLSRKTSLRKRSLKHLVDEAHCLRLDAIYHNITGISVDVHQQIVYFSEGTLIWAKKAANMSDVSDLR IFYRGSGLISSISIDWLYQRMYFIMDELVCVCDLENCSNIEEITPPSISAPQKIVADSYNGYVFYLLRDGIYRADLPVPSGRCAEAVRIV ESCTLKDFAIKPQAKRIIYFNDTAQVFMSTFLDGSASHLILPRIPFADVKSFACENNDFLVTDGKVIFQQDALSFNEFIVGCDLSHIEEF GFGNLVIFGSSSQLHPLPGRPQELSVLFGSHQALVQWKPPALAIGANVILISDIIELFELGPSAWQNWTYEVKVSTQDPPEVTHIFLNIS GTMLNVPELQSAMKYKVSVRASSPKRPGPWSEPSVGTTLVPASEPPFIMAVKEDGLWSKPLNSFGPGEFLSSDIGNVSDMDWYNNSLYYS DTKGDVFVWLLNGTDISENYHLPSIAGAGALAFEWLGHFLYWAGKTYVIQRQSVLTGHTDIVTHVKLLVNDMVVDSVGGYLYWTTLYSVE STRLNGESSLVLQTQPWFSGKKVIALTLDLSDGLLYWLVQDSQCIHLYTAVLRGQRVTGTGGPVFWAGCDQAGSGPSPHVRAAEAVFNIL -------------------------------------------------------------- |
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/chr6:149784243/chr5:117645578) - 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 |
| ROS1 | CD74 |
| FUNCTION: Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. NELL2 is an endogenous ligand for ROS1. Upon endogenous stimulation by NELL2, ROS1 activates the intracellular signaling pathway and triggers epididymal epithelial differentiation and subsequent sperm maturation (By similarity). May activate several downstream signaling pathways related to cell differentiation, proliferation, growth and survival including the PI3 kinase-mTOR signaling pathway. Mediates the phosphorylation of PTPN11, an activator of this pathway. May also phosphorylate and activate the transcription factor STAT3 to control anchorage-independent cell growth. Mediates the phosphorylation and the activation of VAV3, a guanine nucleotide exchange factor regulating cell morphology. May activate other downstream signaling proteins including AKT1, MAPK1, MAPK3, IRS1 and PLCG2. {ECO:0000250|UniProtKB:Q78DX7, ECO:0000269|PubMed:11094073, ECO:0000269|PubMed:16885344}. | FUNCTION: Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex from the endoplasmic reticulum to the endosomal/lysosomal system where the antigen processing and binding of antigenic peptides to MHC class II takes place. Serves as cell surface receptor for the cytokine MIF.; FUNCTION: [Class-II-associated invariant chain peptide]: Binds to the peptide-binding site of MHC class II alpha/beta heterodimers forming an alpha-beta-CLIP complex, thereby preventing the loading of antigenic peptides to the MHC class II complex until its release by HLA-DM in the endosome. {ECO:0000269|PubMed:1448172}.; FUNCTION: [Isoform p41]: Stabilizes the conformation of mature CTSL by binding to its active site and serving as a chaperone to help maintain a pool of mature enzyme in endocytic compartments and extracellular space of antigen-presenting cells (APCs). Has antiviral activity by stymieing the endosomal entry of Ebola virus and coronaviruses, including SARS-CoV-2 (PubMed:32855215). Disrupts cathepsin-mediated Ebola virus glycoprotein processing, which prevents viral fusion and entry. This antiviral activity is specific to p41 isoform (PubMed:32855215). {ECO:0000250|UniProtKB:P04441, ECO:0000269|PubMed:32855215}. |
| 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 |
| Hgene | ROS1 | 117700221 | CD74 | 149782187 | ENST00000368508 | 17 | 43 | 101_196 | 8651 | 2348 | Domain | Note=Fibronectin type-III 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316 |
| Hgene | ROS1 | 117700221 | CD74 | 149782188 | ENST00000368508 | 17 | 43 | 101_196 | 8651 | 2348 | Domain | Note=Fibronectin type-III 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316 |
| Hgene | ROS1 | 117700222 | CD74 | 149782188 | ENST00000368508 | 17 | 43 | 101_196 | 8651 | 2348 | Domain | Note=Fibronectin type-III 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316 |
| Hgene | ROS1 | 117700221 | CD74 | 149782187 | ENST00000368508 | 17 | 43 | 197_285 | 8651 | 2348 | Domain | Note=Fibronectin type-III 2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316 |
| Hgene | ROS1 | 117700221 | CD74 | 149782188 | ENST00000368508 | 17 | 43 | 197_285 | 8651 | 2348 | Domain | Note=Fibronectin type-III 2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316 |
| Hgene | ROS1 | 117700222 | CD74 | 149782188 | ENST00000368508 | 17 | 43 | 197_285 | 8651 | 2348 | Domain | Note=Fibronectin type-III 2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316 |
| Hgene | ROS1 | 117700221 | CD74 | 149782187 | ENST00000368508 | 17 | 43 | 557_671 | 8651 | 2348 | Domain | Note=Fibronectin type-III 3;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316 |
| Hgene | ROS1 | 117700221 | CD74 | 149782188 | ENST00000368508 | 17 | 43 | 557_671 | 8651 | 2348 | Domain | Note=Fibronectin type-III 3;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316 |
| Hgene | ROS1 | 117700222 | CD74 | 149782188 | ENST00000368508 | 17 | 43 | 557_671 | 8651 | 2348 | Domain | Note=Fibronectin type-III 3;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316 |
| - 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 |
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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 >>>243_ROS1_CD74 | ENST00000368508 | ENST00000377795 | ROS1 | chr6 | 117700221 | CD74 | chr5 | 149782187 | MKNIYCLIPKLVNFATLGCLWISVVQCTVLNSCLKSCVTNLGQQLDLGTPHNLSEPCIQGCHFWNSVDQKNCALKCRESCEVGCSSAEGA YEEEVLENADLPTAPFASSIGSHNMTLRWKSANFSGVKYIIQWKYAQLLGSWTYTKTVSRPSYVVKPLHPFTEYIFRVVWIFTAQLQLYS PPSPSYRTHPHGVPETAPLIRNIESSSPDTVEVSWDPPQFPGGPILGYNLRLISKNQKLDAGTQRTSFQFYSTLPNTIYRFSIAAVNEVG EGPEAESSITTSSSAVQQEEQWLFLSRKTSLRKRSLKHLVDEAHCLRLDAIYHNITGISVDVHQQIVYFSEGTLIWAKKAANMSDVSDLR IFYRGSGLISSISIDWLYQRMYFIMDELVCVCDLENCSNIEEITPPSISAPQKIVADSYNGYVFYLLRDGIYRADLPVPSGRCAEAVRIV ESCTLKDFAIKPQAKRIIYFNDTAQVFMSTFLDGSASHLILPRIPFADVKSFACENNDFLVTDGKVIFQQDALSFNEFIVGCDLSHIEEF GFGNLVIFGSSSQLHPLPGRPQELSVLFGSHQALVQWKPPALAIGANVILISDIIELFELGPSAWQNWTYEVKVSTQDPPEVTHIFLNIS GTMLNVPELQSAMKYKVSVRASSPKRPGPWSEPSVGTTLVPASEPPFIMAVKEDGLWSKPLNSFGPGEFLSSDIGNVSDMDWYNNSLYYS DTKGDVFVWLLNGTDISENYHLPSIAGAGALAFEWLGHFLYWAGKTYVIQRQSVLTGHTDIVTHVKLLVNDMVVDSVGGYLYWTTLYSVE STRLNGESSLVLQTQPWFSGKKVIALTLDLSDGLLYWLVQDSQCIHLYTAVLRGQRVTGTGGPVFWAGCDQAGSGPSPHVRAAEAVFNIL | 948 |
| 3D view using mol* of 243_ROS1_CD74 | ||||||||||
| PDB file >>>HKFP_353_ROS1_CD74 | ENST00000368508 | ENST00000377795 | ROS1 | chr6 | 117700222 | CD74 | chr5 | 149782188 | MKNIYCLIPKLVNFATLGCLWISVVQCTVLNSCLKSCVTNLGQQLDLGTPHNLSEPCIQGCHFWNSVDQKNCALKCRESCEVGCSSAEGA YEEEVLENADLPTAPFASSIGSHNMTLRWKSANFSGVKYIIQWKYAQLLGSWTYTKTVSRPSYVVKPLHPFTEYIFRVVWIFTAQLQLYS PPSPSYRTHPHGVPETAPLIRNIESSSPDTVEVSWDPPQFPGGPILGYNLRLISKNQKLDAGTQRTSFQFYSTLPNTIYRFSIAAVNEVG EGPEAESSITTSSSAVQQEEQWLFLSRKTSLRKRSLKHLVDEAHCLRLDAIYHNITGISVDVHQQIVYFSEGTLIWAKKAANMSDVSDLR IFYRGSGLISSISIDWLYQRMYFIMDELVCVCDLENCSNIEEITPPSISAPQKIVADSYNGYVFYLLRDGIYRADLPVPSGRCAEAVRIV ESCTLKDFAIKPQAKRIIYFNDTAQVFMSTFLDGSASHLILPRIPFADVKSFACENNDFLVTDGKVIFQQDALSFNEFIVGCDLSHIEEF GFGNLVIFGSSSQLHPLPGRPQELSVLFGSHQALVQWKPPALAIGANVILISDIIELFELGPSAWQNWTYEVKVSTQDPPEVTHIFLNIS GTMLNVPELQSAMKYKVSVRASSPKRPGPWSEPSVGTTLVPASEPPFIMAVKEDGLWSKPLNSFGPGEFLSSDIGNVSDMDWYNNSLYYS DTKGDVFVWLLNGTDISENYHLPSIAGAGALAFEWLGHFLYWAGKTYVIQRQSVLTGHTDIVTHVKLLVNDMVVDSVGGYLYWTTLYSVE STRLNGESSLVLQTQPWFSGKKVIALTLDLSDGLLYWLVQDSQCIHLYTAVLRGQRVTGTGGPVFWAGCDQAGSGPSPHVRAAEAVFNIL | 948_ROS1_CD74 |
| PDB file >>>HKFP_354_ROS1_CD74 | ENST00000368508 | ENST00000377795 | ROS1 | chr6 | 117700221 | CD74 | chr5 | 149782188 | MKNIYCLIPKLVNFATLGCLWISVVQCTVLNSCLKSCVTNLGQQLDLGTPHNLSEPCIQGCHFWNSVDQKNCALKCRESCEVGCSSAEGA YEEEVLENADLPTAPFASSIGSHNMTLRWKSANFSGVKYIIQWKYAQLLGSWTYTKTVSRPSYVVKPLHPFTEYIFRVVWIFTAQLQLYS PPSPSYRTHPHGVPETAPLIRNIESSSPDTVEVSWDPPQFPGGPILGYNLRLISKNQKLDAGTQRTSFQFYSTLPNTIYRFSIAAVNEVG EGPEAESSITTSSSAVQQEEQWLFLSRKTSLRKRSLKHLVDEAHCLRLDAIYHNITGISVDVHQQIVYFSEGTLIWAKKAANMSDVSDLR IFYRGSGLISSISIDWLYQRMYFIMDELVCVCDLENCSNIEEITPPSISAPQKIVADSYNGYVFYLLRDGIYRADLPVPSGRCAEAVRIV ESCTLKDFAIKPQAKRIIYFNDTAQVFMSTFLDGSASHLILPRIPFADVKSFACENNDFLVTDGKVIFQQDALSFNEFIVGCDLSHIEEF GFGNLVIFGSSSQLHPLPGRPQELSVLFGSHQALVQWKPPALAIGANVILISDIIELFELGPSAWQNWTYEVKVSTQDPPEVTHIFLNIS GTMLNVPELQSAMKYKVSVRASSPKRPGPWSEPSVGTTLVPASEPPFIMAVKEDGLWSKPLNSFGPGEFLSSDIGNVSDMDWYNNSLYYS DTKGDVFVWLLNGTDISENYHLPSIAGAGALAFEWLGHFLYWAGKTYVIQRQSVLTGHTDIVTHVKLLVNDMVVDSVGGYLYWTTLYSVE STRLNGESSLVLQTQPWFSGKKVIALTLDLSDGLLYWLVQDSQCIHLYTAVLRGQRVTGTGGPVFWAGCDQAGSGPSPHVRAAEAVFNIL | 948_ROS1_CD74 |
| PDB file >>>HKFP_355_ROS1_CD74 | ENST00000368508 | ENST00000377795 | ROS1 | chr6 | 117700221 | CD74 | chr5 | 149782187 | MKNIYCLIPKLVNFATLGCLWISVVQCTVLNSCLKSCVTNLGQQLDLGTPHNLSEPCIQGCHFWNSVDQKNCALKCRESCEVGCSSAEGA YEEEVLENADLPTAPFASSIGSHNMTLRWKSANFSGVKYIIQWKYAQLLGSWTYTKTVSRPSYVVKPLHPFTEYIFRVVWIFTAQLQLYS PPSPSYRTHPHGVPETAPLIRNIESSSPDTVEVSWDPPQFPGGPILGYNLRLISKNQKLDAGTQRTSFQFYSTLPNTIYRFSIAAVNEVG EGPEAESSITTSSSAVQQEEQWLFLSRKTSLRKRSLKHLVDEAHCLRLDAIYHNITGISVDVHQQIVYFSEGTLIWAKKAANMSDVSDLR IFYRGSGLISSISIDWLYQRMYFIMDELVCVCDLENCSNIEEITPPSISAPQKIVADSYNGYVFYLLRDGIYRADLPVPSGRCAEAVRIV ESCTLKDFAIKPQAKRIIYFNDTAQVFMSTFLDGSASHLILPRIPFADVKSFACENNDFLVTDGKVIFQQDALSFNEFIVGCDLSHIEEF GFGNLVIFGSSSQLHPLPGRPQELSVLFGSHQALVQWKPPALAIGANVILISDIIELFELGPSAWQNWTYEVKVSTQDPPEVTHIFLNIS GTMLNVPELQSAMKYKVSVRASSPKRPGPWSEPSVGTTLVPASEPPFIMAVKEDGLWSKPLNSFGPGEFLSSDIGNVSDMDWYNNSLYYS DTKGDVFVWLLNGTDISENYHLPSIAGAGALAFEWLGHFLYWAGKTYVIQRQSVLTGHTDIVTHVKLLVNDMVVDSVGGYLYWTTLYSVE STRLNGESSLVLQTQPWFSGKKVIALTLDLSDGLLYWLVQDSQCIHLYTAVLRGQRVTGTGGPVFWAGCDQAGSGPSPHVRAAEAVFNIL | 948_ROS1_CD74 |
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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. |
| 3D view using mol* of viewer/superimpose_isoforms/TKFP_154_CD74_ROS1_vs_TKFP_155_CD74_ROS1_superimposed.pdb.html |
| 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. |
| 243_ROS1_CD74.png |
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| 243_ROS1_CD74.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. |
| 243_ROS1_CD74_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 |
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| 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 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Netarsudil | -8.47668 | -8.48778 | -59.0628 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Netarsudil | -8.47668 | -8.48778 | -59.0628 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Lapatinib | -7.65263 | -7.74143 | -64.5846 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Zanubrutinib | -7.46409 | -7.46409 | -48.4729 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Pralsetinib | -7.30708 | -7.39858 | -53.5496 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Axitinib | -7.22238 | -7.22558 | -47.9864 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Avapritinib | -6.87454 | -7.672039999999999 | -45.9004 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Avapritinib | -6.87454 | -7.672039999999999 | -45.9004 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Avapritinib | -6.87454 | -7.672039999999999 | -45.9004 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Avapritinib | -6.87454 | -7.672039999999999 | -45.9004 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Cobimetinib | -6.84975 | -6.85255 | -57.5914 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Futibatinib | -6.82163 | -6.82163 | -45.6138 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Bosutinib | -6.7 | -6.8132 | -39.1716 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Bosutinib | -6.7 | -6.8132 | -39.1716 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Bosutinib | -6.7 | -6.8132 | -39.1716 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Zanubrutinib | -6.686960000000001 | -6.686960000000001 | -49.3184 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Ibrutinib | -6.639289999999999 | -6.639289999999999 | -48.7012 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Lapatinib | -6.59761 | -6.68641 | -64.0775 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Cobimetinib | -6.51923 | -6.52203 | -53.8569 |
| 243_ROS1_CD74-DOCK_HTVS_1-001 | Pralsetinib | -6.5124699999999995 | -6.6039699999999995 | -55.0944 |
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Kinase-Substrate Information of ROS1_CD74 |
| 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 |
| 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 |
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Related Drugs to ROS1_CD74 |
| 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 ROS1-CD74 and kinase inhibitors the PubMed Abstract (04-01-2024) |
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| Fusion gene - drug pair 1 | Fusion gene - drug pair 2 | PMID | Publication date | DOI | Study title |
| ROS1-CD74 AND Brigatinib | 32462394 | 2020-05-27 | 10.1007/s12094-020-02376-w | Clinical activity of brigatinib in ROS1-rearranged non-small cell lung cancer. |
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Related Diseases to ROS1_CD74 |
| 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 |
| Hgene | ROS1 | C0007131 | Non-Small Cell Lung Carcinoma | 4 | CTD_human |
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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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