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Kinase Fusion Gene:AKAP8_BRD4 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: AKAP8_BRD4 | KinaseFusionDB ID: KFG254 | FusionGDB2.0 ID: KFG254 | Hgene | Tgene | Gene symbol | AKAP8 | BRD4 | Gene ID | 10270 | 23476 | |
| Gene name | A-kinase anchoring protein 8 | bromodomain containing 4 | ||||||||||
| Synonyms | AKAP 95|AKAP-8|AKAP-95|AKAP95 | CAP|CDLS6|FSHRG4|HUNK1|HUNKI|MCAP | ||||||||||
| Cytomap | 19p13.12 | 19p13.12 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | A-kinase anchor protein 8A kinase (PRKA) anchor protein 8A-kinase anchor protein, 95kDa | bromodomain-containing protein 4chromosome-associated proteinfemale sterile homeotic related gene 4mitotic chromosome-associated protein | ||||||||||
| Modification date | 20240305 | 20240416 | ||||||||||
| UniProtAcc | Q9ULX6 | O60885 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000269701, | ENST00000602230, ENST00000263377, ENST00000360016, ENST00000371835, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: AKAP8 [Title/Abstract] AND BRD4 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | AKAP8(15465385)-BRD4(15359824), # samples:1 AKAP8(15487787)-BRD4(15367984), # samples:1 AKAP8(15490524)-BRD4(15367984), # samples:1 AKAP8(15487787)-BRD4(15366403), # 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 | 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 AKAP8 (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 BRD4 (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-ZF-AA4V-01A | AKAP8 | chr19 | 15487787 | BRD4 | chr19 | 15367984 |
| ChimerDB4 | TCGA-ZF-AA4V-01A | AKAP8 | chr19 | 15490524 | BRD4 | chr19 | 15367984 |
| ChimerDB4 | TCGA-04-1338-01A | AKAP8 | chr19 | 15487787 | BRD4 | chr19 | 15366403 |
| ChimerDB4 | TCGA-GV-A3QI-01A | AKAP8 | chr19 | 15465385 | BRD4 | chr19 | 15359824 |
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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) |
| ENST00000269701 | ENST00000263377 | AKAP8 | chr19 | 15490524 | BRD4 | chr19 | 15367984 | 4369 | 937 |
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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 >ENST00000269701_ENST00000263377_AKAP8_chr19_15490524_BRD4_chr19_15367984_length(amino acids)=937 MWSPSKRGCWWAASKTWTRATEDVFEMRFAKMPDEPEEPVVAVSSPAVPPPTKVVAPPSSSDSSSDSSSDSDSSTDDSEEERAQRLAELQ EQLKAVHEQLAALSQPQQNKPKKKEKDKKEKKKEKHKRKEEVEENKKSKAKEPPPKKTKKNNSSNSNVSKKEPAPMKSKPPPTYESEEED KCKPMSYEEKRQLSLDINKLPGEKLGRVVHIIQSREPSLKNSNPDEIEIDFETLKPSTLRELERYVTSCLRKKRKPQAEKVDVIAGSSKM KGFSSSESESSSESSSSDSEDSETEMAPKSKKKGHPGREQKKHHHHHHQQMQQAPAPVPQQPPPPPQQPPPPPPPQQQQQPPPPPPPPSM PQQAAPAMKSSPPPFIATQVPVLEPQLPGSVFDPIGHFTQPILHLPQPELPPHLPQPPEHSTPPHLNQHAVVSPPALHNALPQQPSRPSN RAAALPPKPARPPAVSPALTQTPLLPQPPMAQPPQVLLEDEEPPAPPLTSMQMQLYLQQLQKVQPPTPLLPSVKVQSQPPPPLPPPPHPS VQQQLQQQPPPPPPPQPQPPPQQQHQPPPRPVHLQPMQFSTHIQQPPPPQGQQPPHPPPGQQPPPPQPAKPQQVIQHHHSPRHHKSDPYS TGHLREAPSPLMIHSPQMSQFQSLTHQSPPQQNVQPKKQELRAASVVQPQPLVVVKEEKIHSPIIRSEPFSPSLRPEPPKHPESIKAPVH LPQRPEMKPVDVGRPVIRPPEQNAPPPGAPDKDKQKQEPKTPVAPKKDLKIKNMGSWASLVQKHPTTPSSTAKSSSDSFEQFRRAAREKE EREKALKAQAEHAEKEKERLRQERMRSREDEDALEQARRAHEEARRRQEQQQQQRQEQQQQQQQQAAAVAAAATPQAQSSQPQSMLDQQR -------------------------------------------------------------- |
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/chr19:15465385/chr19:15359824) - 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 |
| AKAP8 | BRD4 |
| FUNCTION: Could play a role in constitutive transport element (CTE)-mediated gene expression by association with DHX9. Increases CTE-dependent nuclear unspliced mRNA export (PubMed:10748171, PubMed:11402034). Proposed to target PRKACA to the nucleus but does not seem to be implicated in the binding of regulatory subunit II of PKA (PubMed:10761695, PubMed:11884601). May be involved in nuclear envelope breakdown and chromatin condensation. May be involved in anchoring nuclear membranes to chromatin in interphase and in releasing membranes from chromating at mitosis (PubMed:11034899). May regulate the initiation phase of DNA replication when associated with TMPO isoform Beta (PubMed:12538639). Required for cell cycle G2/M transition and histone deacetylation during mitosis. In mitotic cells recruits HDAC3 to the vicinity of chromatin leading to deacetylation and subsequent phosphorylation at 'Ser-10' of histone H3; in this function seems to act redundantly with AKAP8 (PubMed:16980585). May be involved in regulation of pre-mRNA splicing (PubMed:17594903). {ECO:0000269|PubMed:10748171, ECO:0000269|PubMed:11034899, ECO:0000269|PubMed:11402034, ECO:0000269|PubMed:11884601, ECO:0000269|PubMed:12538639, ECO:0000269|PubMed:16980585, ECO:0000305|PubMed:10761695}.; FUNCTION: (Microbial infection) In case of EBV infection, may target PRKACA to EBNA-LP-containing nuclear sites to modulate transcription from specific promoters. {ECO:0000269|PubMed:11884601}.; FUNCTION: (Microbial infection) Can synergize with DHX9 to activate the CTE-mediated gene expression of type D retroviruses. {ECO:0000269|PubMed:11402034}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, involved in the DHX9-promoted annealing of host tRNA(Lys3) to viral genomic RNA as a primer in reverse transcription; in vitro negatively regulates DHX9 annealing activity. {ECO:0000269|PubMed:25034436}. | 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 |
| Tgene | AKAP8 | 15490524 | BRD4 | 15367984 | ENST00000269701 | 6 | 12 | 600_682 | 447 | 723 | Domain | Note=NET;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00857 |
| Tgene | AKAP8 | 15490524 | BRD4 | 15367984 | ENST00000269701 | 6 | 12 | 600_682 | 447 | 795 | Domain | Note=NET;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00857 |
| Tgene | AKAP8 | 15490524 | BRD4 | 15367984 | ENST00000269701 | 6 | 20 | 600_682 | 447 | 1363 | Domain | Note=NET;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00857 |
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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 >>>18_AKAP8_BRD4 | ENST00000269701 | ENST00000263377 | AKAP8 | chr19 | 15490524 | BRD4 | chr19 | 15367984 | MWSPSKRGCWWAASKTWTRATEDVFEMRFAKMPDEPEEPVVAVSSPAVPPPTKVVAPPSSSDSSSDSSSDSDSSTDDSEEERAQRLAELQ EQLKAVHEQLAALSQPQQNKPKKKEKDKKEKKKEKHKRKEEVEENKKSKAKEPPPKKTKKNNSSNSNVSKKEPAPMKSKPPPTYESEEED KCKPMSYEEKRQLSLDINKLPGEKLGRVVHIIQSREPSLKNSNPDEIEIDFETLKPSTLRELERYVTSCLRKKRKPQAEKVDVIAGSSKM KGFSSSESESSSESSSSDSEDSETEMAPKSKKKGHPGREQKKHHHHHHQQMQQAPAPVPQQPPPPPQQPPPPPPPQQQQQPPPPPPPPSM PQQAAPAMKSSPPPFIATQVPVLEPQLPGSVFDPIGHFTQPILHLPQPELPPHLPQPPEHSTPPHLNQHAVVSPPALHNALPQQPSRPSN RAAALPPKPARPPAVSPALTQTPLLPQPPMAQPPQVLLEDEEPPAPPLTSMQMQLYLQQLQKVQPPTPLLPSVKVQSQPPPPLPPPPHPS VQQQLQQQPPPPPPPQPQPPPQQQHQPPPRPVHLQPMQFSTHIQQPPPPQGQQPPHPPPGQQPPPPQPAKPQQVIQHHHSPRHHKSDPYS TGHLREAPSPLMIHSPQMSQFQSLTHQSPPQQNVQPKKQELRAASVVQPQPLVVVKEEKIHSPIIRSEPFSPSLRPEPPKHPESIKAPVH LPQRPEMKPVDVGRPVIRPPEQNAPPPGAPDKDKQKQEPKTPVAPKKDLKIKNMGSWASLVQKHPTTPSSTAKSSSDSFEQFRRAAREKE EREKALKAQAEHAEKEKERLRQERMRSREDEDALEQARRAHEEARRRQEQQQQQRQEQQQQQQQQAAAVAAAATPQAQSSQPQSMLDQQR | 937 |
| 3D view using mol* of 18_AKAP8_BRD4 | ||||||||||
| PDB file >>>TKFP_31_AKAP8_BRD4 | ENST00000269701 | ENST00000263377 | AKAP8 | chr19 | 15490524 | BRD4 | chr19 | 15367984 | MWSPSKRGCWWAASKTWTRATEDVFEMRFAKMPDEPEEPVVAVSSPAVPPPTKVVAPPSSSDSSSDSSSDSDSSTDDSEEERAQRLAELQ EQLKAVHEQLAALSQPQQNKPKKKEKDKKEKKKEKHKRKEEVEENKKSKAKEPPPKKTKKNNSSNSNVSKKEPAPMKSKPPPTYESEEED KCKPMSYEEKRQLSLDINKLPGEKLGRVVHIIQSREPSLKNSNPDEIEIDFETLKPSTLRELERYVTSCLRKKRKPQAEKVDVIAGSSKM KGFSSSESESSSESSSSDSEDSETEMAPKSKKKGHPGREQKKHHHHHHQQMQQAPAPVPQQPPPPPQQPPPPPPPQQQQQPPPPPPPPSM PQQAAPAMKSSPPPFIATQVPVLEPQLPGSVFDPIGHFTQPILHLPQPELPPHLPQPPEHSTPPHLNQHAVVSPPALHNALPQQPSRPSN RAAALPPKPARPPAVSPALTQTPLLPQPPMAQPPQVLLEDEEPPAPPLTSMQMQLYLQQLQKVQPPTPLLPSVKVQSQPPPPLPPPPHPS VQQQLQQQPPPPPPPQPQPPPQQQHQPPPRPVHLQPMQFSTHIQQPPPPQGQQPPHPPPGQQPPPPQPAKPQQVIQHHHSPRHHKSDPYS TGHLREAPSPLMIHSPQMSQFQSLTHQSPPQQNVQPKKQELRAASVVQPQPLVVVKEEKIHSPIIRSEPFSPSLRPEPPKHPESIKAPVH LPQRPEMKPVDVGRPVIRPPEQNAPPPGAPDKDKQKQEPKTPVAPKKDLKIKNMGSWASLVQKHPTTPSSTAKSSSDSFEQFRRAAREKE EREKALKAQAEHAEKEKERLRQERMRSREDEDALEQARRAHEEARRRQEQQQQQRQEQQQQQQQQAAAVAAAATPQAQSSQPQSMLDQQR | 937_AKAP8_BRD4 |
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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. |
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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. |
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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 AKAP8_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 |
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Related Drugs to AKAP8_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 AKAP8-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 |
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Related Diseases to AKAP8_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 |
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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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