UTHEALTH HOME ABOUT SBMI A-Z WEBMAIL INSIDE THE UNIVERSITY |
|
Kinase Fusion Gene:NOTCH3_BRD4 |
Kinase Fusion Protein Summary |
Kinase Fusion gene summary |
Kinase Fusion partner gene information | Kinase Fusion gene name: NOTCH3_BRD4 | KinaseFusionDB ID: KFG4234 | FusionGDB2.0 ID: KFG4234 | Hgene | Tgene | Gene symbol | NOTCH3 | BRD4 | Gene ID | 4854 | 23476 | |
Gene name | notch receptor 3 | bromodomain containing 4 | ||||||||||
Synonyms | CADASIL|CADASIL1|CASIL|IMF2|LMNS | CAP|CDLS6|FSHRG4|HUNK1|HUNKI|MCAP | ||||||||||
Cytomap | 19p13.12 | 19p13.12 | ||||||||||
Type of gene | protein-coding | protein-coding | ||||||||||
Description | neurogenic locus notch homolog protein 3Notch homolog 3notch 3 | bromodomain-containing protein 4chromosome-associated proteinfemale sterile homeotic related gene 4mitotic chromosome-associated protein | ||||||||||
Modification date | 20240408 | 20240416 | ||||||||||
UniProtAcc | Q9UM47 | O60885 | ||||||||||
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000263388, | ENST00000263377, ENST00000360016, ENST00000371835, ENST00000602230, | |||||||||
Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: NOTCH3 [Title/Abstract] AND BRD4 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | BRD4(15443101)-NOTCH3(15281636), # samples:3 NOTCH3(15308311)-BRD4(15360101), # 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 |
Tgene | BRD4 | GO:0032968 | positive regulation of transcription elongation by RNA polymerase II | 19103749 |
Tgene | BRD4 | GO:0043123 | positive regulation of canonical NF-kappaB signal transduction | 19103749 |
Tgene | BRD4 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 23086925|23317504|24360279 |
Tgene | BRD4 | GO:0050727 | regulation of inflammatory response | 19103749 |
Kinase Fusion gene breakpoints across NOTCH3 (5'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
Kinase Fusion gene breakpoints across BRD4 (3'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
Top |
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-B5-A0JN-01A | NOTCH3 | chr19 | 15299800 | BRD4 | chr19 | 15360101 |
ChimerDB4 | TCGA-HM-A6W2-01A | NOTCH3 | chr19 | 15308311 | BRD4 | chr19 | 15360101 |
ChimerDB4 | TCGA-HM-A6W2-01A | NOTCH3 | chr19 | 15308311 | BRD4 | chr19 | 15355573 |
Top |
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) |
Top |
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 |
Top |
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/:15443101/:15281636) - 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. |
Main function of each fusion partner protein. (from UniProt) |
Hgene | Tgene |
NOTCH3 | BRD4 |
FUNCTION: Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity). {ECO:0000250|UniProtKB:Q9R172, ECO:0000269|PubMed:15350543}. | FUNCTION: Chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation. Remains associated with acetylated chromatin throughout the entire cell cycle and provides epigenetic memory for postmitotic G1 gene transcription by preserving acetylated chromatin status and maintaining high-order chromatin structure (PubMed:23589332, PubMed:23317504, PubMed:22334664). During interphase, plays a key role in regulating the transcription of signal-inducible genes by associating with the P-TEFb complex and recruiting it to promoters. Also recruits P-TEFb complex to distal enhancers, so called anti-pause enhancers in collaboration with JMJD6. BRD4 and JMJD6 are required to form the transcriptionally active P-TEFb complex by displacing negative regulators such as HEXIM1 and 7SKsnRNA complex from P-TEFb, thereby transforming it into an active form that can then phosphorylate the C-terminal domain (CTD) of RNA polymerase II (PubMed:23589332, PubMed:19596240, PubMed:16109377, PubMed:16109376, PubMed:24360279). Promotes phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II (PubMed:23086925). According to a report, directly acts as an atypical protein kinase and mediates phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II; these data however need additional evidences in vivo (PubMed:22509028). In addition to acetylated histones, also recognizes and binds acetylated RELA, leading to further recruitment of the P-TEFb complex and subsequent activation of NF-kappa-B (PubMed:19103749). Also acts as a regulator of p53/TP53-mediated transcription: following phosphorylation by CK2, recruited to p53/TP53 specific target promoters (PubMed:23317504). {ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:19103749, ECO:0000269|PubMed:19596240, ECO:0000269|PubMed:22334664, ECO:0000269|PubMed:22509028, ECO:0000269|PubMed:23086925, ECO:0000269|PubMed:23317504, ECO:0000269|PubMed:23589332, ECO:0000269|PubMed:24360279}.; FUNCTION: [Isoform B]: Acts as a chromatin insulator in the DNA damage response pathway. Inhibits DNA damage response signaling by recruiting the condensin-2 complex to acetylated histones, leading to chromatin structure remodeling, insulating the region from DNA damage response by limiting spreading of histone H2AX/H2A.x phosphorylation. {ECO:0000269|PubMed:23728299}. |
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 |
Top |
Kinase-Substrate Information of NOTCH3_BRD4 |
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 |
BRD4 | O60885 | human | POLR2A | P24928 | S1616 | TPQSPSysPtsPsYS | RNA_pol_Rpb1_R |
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 |
BRD4 | ID | Description | 0.00e+00 |
BRD4 | GO:0006353 | DNA-templated transcription termination | 4.88e-03 |
BRD4 | GO:0033120 | positive regulation of RNA splicing | 4.88e-03 |
BRD4 | GO:0043484 | regulation of RNA splicing | 1.28e-02 |
BRD4 | GO:0008380 | RNA splicing | 2.53e-02 |
Top |
Related Drugs to NOTCH3_BRD4 |
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 NOTCH3-BRD4 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 |
Top |
Related Diseases to NOTCH3_BRD4 |
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 |
Tgene | BRD4 | C0017636 | Glioblastoma | 2 | CTD_human |
Tgene | BRD4 | C0334588 | Giant Cell Glioblastoma | 2 | CTD_human |
Tgene | BRD4 | C1621958 | Glioblastoma Multiforme | 2 | CTD_human |
Top |
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 |