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Kinase Fusion Gene:VRK2_JAG1 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: VRK2_JAG1 | KinaseFusionDB ID: KFG7090 | FusionGDB2.0 ID: KFG7090 | Hgene | Tgene | Gene symbol | VRK2 | JAG1 | Gene ID | 7444 | 182 | |
| Gene name | VRK serine/threonine kinase 2 | jagged canonical Notch ligand 1 | ||||||||||
| Synonyms | - | AGS|AGS1|AHD|AWS|CD339|CMT2HH|DCHE|HJ1|JAGL1 | ||||||||||
| Cytomap | 2p16.1 | 20p12.2 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | serine/threonine-protein kinase VRK2vaccinia related kinase 2vaccinia virus B1R-related kinase 2 | protein jagged-1 | ||||||||||
| Modification date | 20240403 | 20240317 | ||||||||||
| UniProtAcc | Q86Y07 | P78504 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000340157, ENST00000412104, ENST00000417641, ENST00000435505, ENST00000440705, ENST00000478687, | ENST00000423891, ENST00000488480, ENST00000254958, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: VRK2 [Title/Abstract] AND JAG1 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | VRK2(58276102)-JAG1(10639370), # 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 | VRK2 | GO:0046777 | protein autophosphorylation | 14645249|16704422 |
| Tgene | JAG1 | GO:0001953 | negative regulation of cell-matrix adhesion | 11549580 |
| Tgene | JAG1 | GO:0022408 | negative regulation of cell-cell adhesion | 11549580 |
| Tgene | JAG1 | GO:0030336 | negative regulation of cell migration | 11549580 |
| Kinase Fusion gene breakpoints across VRK2 (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 JAG1 (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-VR-AA7B | VRK2 | chr2 | 58276102 | JAG1 | chr20 | 10639370 |
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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) |
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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 |
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/chr2:58276102/chr20:10639370) - 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 |
| VRK2 | JAG1 |
| FUNCTION: Serine/threonine kinase that regulates several signal transduction pathways (PubMed:16704422, PubMed:14645249, PubMed:16495336, PubMed:17709393, PubMed:18617507, PubMed:18286207, PubMed:20679487). Isoform 1 modulates the stress response to hypoxia and cytokines, such as interleukin-1 beta (IL1B) and this is dependent on its interaction with MAPK8IP1, which assembles mitogen-activated protein kinase (MAPK) complexes (PubMed:17709393). Inhibition of signal transmission mediated by the assembly of MAPK8IP1-MAPK complexes reduces JNK phosphorylation and JUN-dependent transcription (PubMed:18286207). Phosphorylates 'Thr-18' of p53/TP53, histone H3, and may also phosphorylate MAPK8IP1 (PubMed:16704422). Phosphorylates BANF1 and disrupts its ability to bind DNA and reduces its binding to LEM domain-containing proteins (PubMed:16495336). Down-regulates the transactivation of transcription induced by ERBB2, HRAS, BRAF, and MEK1 (PubMed:20679487). Blocks the phosphorylation of ERK in response to ERBB2 and HRAS (PubMed:20679487). Can also phosphorylate the following substrates that are commonly used to establish in vitro kinase activity: casein, MBP and histone H2B, but it is not sure that this is physiologically relevant (PubMed:14645249). {ECO:0000269|PubMed:14645249, ECO:0000269|PubMed:16495336, ECO:0000269|PubMed:16704422, ECO:0000269|PubMed:17709393, ECO:0000269|PubMed:18286207, ECO:0000269|PubMed:18617507, ECO:0000269|PubMed:20679487}.; FUNCTION: [Isoform 2]: Phosphorylates 'Thr-18' of p53/TP53, as well as histone H3. Reduces p53/TP53 ubiquitination by MDM2, promotes p53/TP53 acetylation by EP300 and thereby increases p53/TP53 stability and activity. {ECO:0000269|PubMed:16704422}. | FUNCTION: Ligand for multiple Notch receptors and involved in the mediation of Notch signaling (PubMed:18660822, PubMed:20437614). May be involved in cell-fate decisions during hematopoiesis (PubMed:9462510). Seems to be involved in early and late stages of mammalian cardiovascular development. Inhibits myoblast differentiation (By similarity). Enhances fibroblast growth factor-induced angiogenesis (in vitro). {ECO:0000250, ECO:0000269|PubMed:18660822, ECO:0000269|PubMed:20437614, ECO:0000269|PubMed:9462510}. |
| 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 |
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Kinase-Substrate Information of VRK2_JAG1 |
| 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 |
| VRK2 | Q86Y07 | human | COIL | P38432 | S184 | NEEAKRKsPKKKEKC | Coilin_N |
| VRK2 | Q86Y07 | human | GAPDH | P04406 | S151 | LkIIsNAsCttNCLA | |
| VRK2 | Q86Y07 | human | USP25 | Q9UHP3 | T680 | QPLVGIEtLPPDLRD | |
| VRK2 | Q86Y07 | human | USP25 | Q9UHP3 | S745 | PEyLEQPsRSDFSKH | |
| VRK2 | Q86Y07 | human | BANF1 | O75531 | S4 | ____MttsQkHRDFV | BAF |
| VRK2 | Q86Y07 | human | DTNBP1 | Q96EV8 | S299 | RAKPPsSssTCtDSA | Dysbindin |
| VRK2 | Q86Y07 | human | BANF1 | O75531 | T3 | _____MttsQkHRDF | BAF |
| VRK2 | Q86Y07 | human | PLK1 | P53350 | T210 | YDGERKktLCGtPNy | Pkinase |
| VRK2 | Q86Y07 | human | USP25 | Q9UHP3 | T727 | QkLRESEtSVTTAQA | |
| VRK2 | Q86Y07 | human | IKBKB | O14920 | S177 | AkELDQGsLCtsFVG | Pkinase |
| VRK2 | Q86Y07 | human | BANF1 | O75531 | T2 | ______MttsQkHRD | BAF |
| VRK2 | Q86Y07 | human | IKBKB | O14920 | S181 | DQGsLCtsFVGTLQy | Pkinase |
| VRK2 | Q86Y07 | human | DTNBP1 | Q96EV8 | S297 | ELRAKPPsSssTCtD | Dysbindin |
| 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 |
| VRK2 | ID | Description | 0.00e+00 |
| VRK2 | GO:0043086 | negative regulation of catalytic activity | 9.49e-05 |
| VRK2 | GO:0051348 | negative regulation of transferase activity | 1.28e-02 |
| VRK2 | GO:0071763 | nuclear membrane organization | 1.52e-02 |
| VRK2 | GO:0006998 | nuclear envelope organization | 1.52e-02 |
| VRK2 | GO:0031647 | regulation of protein stability | 1.52e-02 |
| VRK2 | GO:0045936 | negative regulation of phosphate metabolic process | 1.68e-02 |
| VRK2 | GO:0010563 | negative regulation of phosphorus metabolic process | 1.68e-02 |
| VRK2 | GO:0031400 | negative regulation of protein modification process | 2.28e-02 |
| VRK2 | GO:0032479 | regulation of type I interferon production | 3.92e-02 |
| VRK2 | GO:0032606 | type I interferon production | 3.92e-02 |
| VRK2 | GO:0006997 | nucleus organization | 4.87e-02 |
| VRK2 | GO:0006469 | negative regulation of protein kinase activity | 5.90e-02 |
| VRK2 | GO:0033673 | negative regulation of kinase activity | 5.90e-02 |
| VRK2 | GO:0043123 | positive regulation of canonical NF-kappaB signal transduction | 5.90e-02 |
| VRK2 | GO:0061136 | regulation of proteasomal protein catabolic process | 5.90e-02 |
| VRK2 | GO:0051346 | negative regulation of hydrolase activity | 5.90e-02 |
| VRK2 | GO:0045861 | negative regulation of proteolysis | 5.90e-02 |
| VRK2 | GO:1903050 | regulation of proteolysis involved in protein catabolic process | 5.90e-02 |
| VRK2 | GO:0007084 | mitotic nuclear membrane reassembly | 5.90e-02 |
| VRK2 | GO:0051081 | nuclear membrane disassembly | 5.90e-02 |
| VRK2 | GO:0101024 | mitotic nuclear membrane organization | 5.90e-02 |
| VRK2 | GO:0043122 | regulation of canonical NF-kappaB signal transduction | 5.90e-02 |
| VRK2 | GO:0014049 | positive regulation of glutamate secretion | 5.90e-02 |
| VRK2 | GO:0030397 | membrane disassembly | 5.90e-02 |
| VRK2 | GO:0035666 | TRIF-dependent toll-like receptor signaling pathway | 5.90e-02 |
| VRK2 | GO:0060159 | regulation of dopamine receptor signaling pathway | 5.90e-02 |
| VRK2 | GO:0072697 | protein localization to cell cortex | 5.90e-02 |
| VRK2 | GO:0140014 | mitotic nuclear division | 5.90e-02 |
| VRK2 | GO:0015074 | DNA integration | 5.90e-02 |
| VRK2 | GO:0061000 | negative regulation of dendritic spine development | 5.90e-02 |
| VRK2 | GO:0090435 | protein localization to nuclear envelope | 5.90e-02 |
| VRK2 | GO:0018105 | peptidyl-serine phosphorylation | 5.90e-02 |
| VRK2 | GO:0007249 | canonical NF-kappaB signal transduction | 5.90e-02 |
| VRK2 | GO:0001933 | negative regulation of protein phosphorylation | 5.90e-02 |
| VRK2 | GO:0018209 | peptidyl-serine modification | 5.90e-02 |
| VRK2 | GO:0048308 | organelle inheritance | 5.90e-02 |
| VRK2 | GO:0048313 | Golgi inheritance | 5.90e-02 |
| VRK2 | GO:0002756 | MyD88-independent toll-like receptor signaling pathway | 5.90e-02 |
| VRK2 | GO:0017014 | protein nitrosylation | 5.90e-02 |
| VRK2 | GO:0018119 | peptidyl-cysteine S-nitrosylation | 5.90e-02 |
| VRK2 | GO:0042326 | negative regulation of phosphorylation | 5.90e-02 |
| VRK2 | GO:0001956 | positive regulation of neurotransmitter secretion | 5.90e-02 |
| VRK2 | GO:1901550 | regulation of endothelial cell development | 5.90e-02 |
| VRK2 | GO:1903140 | regulation of establishment of endothelial barrier | 5.90e-02 |
| VRK2 | GO:0048490 | anterograde synaptic vesicle transport | 5.90e-02 |
| VRK2 | GO:0099514 | synaptic vesicle cytoskeletal transport | 5.90e-02 |
| VRK2 | GO:0099517 | synaptic vesicle transport along microtubule | 5.90e-02 |
| VRK2 | GO:1904666 | regulation of ubiquitin protein ligase activity | 5.90e-02 |
| VRK2 | GO:1990778 | protein localization to cell periphery | 5.90e-02 |
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Related Drugs to VRK2_JAG1 |
| 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 VRK2-JAG1 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 VRK2_JAG1 |
| 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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