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Fusion Protein:AKAP8-BRD4 |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: AKAP8-BRD4 | FusionPDB ID: 3365 | FusionGDB2.0 ID: 3365 | 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|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 proteinmitotic chromosome-associated protein | |
| Modification date | 20200313 | 20200329 | |
| UniProtAcc | Q9ULX6 Main function of 5'-partner protein: 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}. | O60885 Main function of 5'-partner protein: 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}. | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000269701, | ENST00000602230, ENST00000263377, ENST00000360016, ENST00000371835, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 13 X 14 X 9=1638 | 15 X 19 X 13=3705 |
| # samples | 17 | 28 | |
| ** MAII score | log2(17/1638*10)=-3.26832870550331 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(28/3705*10)=-3.72597481024823 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Fusion gene context | PubMed: AKAP8 [Title/Abstract] AND BRD4 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: AKAP8 [Title/Abstract] AND BRD4 [Title/Abstract] AND neoantigen [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 | ||
| Anticipated loss of major functional domain due to fusion event. | AKAP8-BRD4 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. AKAP8-BRD4 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. AKAP8-BRD4 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. AKAP8-BRD4 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. AKAP8-BRD4 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. AKAP8-BRD4 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF. AKAP8-BRD4 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF. AKAP8-BRD4 seems lost the major protein functional domain in Tgene partner, which is a epigenetic factor due to the frame-shifted ORF. AKAP8-BRD4 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. AKAP8-BRD4 seems lost the major protein functional domain in Tgene partner, which is a kinase 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 |
| Tgene | BRD4 | GO:0032968 | positive regulation of transcription elongation from RNA polymerase II promoter | 19103749|23086925 |
| Tgene | BRD4 | GO:0043123 | positive regulation of I-kappaB kinase/NF-kappaB signaling | 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 |
| Tgene | BRD4 | GO:1901407 | regulation of phosphorylation of RNA polymerase II C-terminal domain | 23086925 |
| 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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| Retention analysis results 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, are available here. |
| 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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| 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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Fusion Amino Acid Sequences |
| 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) |
| ENST00000269701 | AKAP8 | chr19 | 15490524 | - | ENST00000263377 | BRD4 | chr19 | 15367984 | - | 4369 | 80 | 14 | 2827 | 937 |
| ENST00000269701 | AKAP8 | chr19 | 15490524 | - | ENST00000371835 | BRD4 | chr19 | 15367984 | - | 3131 | 80 | 14 | 907 | 297 |
| ENST00000269701 | AKAP8 | chr19 | 15490524 | - | ENST00000360016 | BRD4 | chr19 | 15367984 | - | 1689 | 80 | 14 | 1123 | 369 |
| 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 |
| ENST00000269701 | ENST00000263377 | AKAP8 | chr19 | 15490524 | - | BRD4 | chr19 | 15367984 | - | 0.010930412 | 0.98906964 |
| ENST00000269701 | ENST00000371835 | AKAP8 | chr19 | 15490524 | - | BRD4 | chr19 | 15367984 | - | 0.00372581 | 0.99627423 |
| ENST00000269701 | ENST00000360016 | AKAP8 | chr19 | 15490524 | - | BRD4 | chr19 | 15367984 | - | 0.007903014 | 0.992097 |
| Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones. |
Get the fusion protein sequences from here. |
| Fusion protein sequence information is available in the fasta format. >FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP |
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Fusion Protein Breakpoint Sequences for AKAP8-BRD4 |
| +/-13 AA sequence from the breakpoints of the fusion protein sequences. |
| Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Length(fusion protein) | BP in fusion protein | Peptide |
| AKAP8 | chr19 | 15490524 | BRD4 | chr19 | 15367984 | 80 | 43 | KMPDEPEEPVVAVSSPAVPPPTKVVA |
| AKAP8 | chr19 | 15490524 | BRD4 | chr19 | 15367984 | 80 | 547 | PPPHPSVQQQLQQQPPPPPPPQPQPP |
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Potential FusionNeoAntigen Information of AKAP8-BRD4 in HLA I |
| Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific. |
| Potential FusionNeoAntigen Information * We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5) |
| Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA I | FusionNeoAntigen peptide | Binding score | Immunogenic score | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
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Potential FusionNeoAntigen Information of AKAP8-BRD4 in HLA II |
| Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific. |
| Potential FusionNeoAntigen Information * We used NetMHCIIpan v4.1 (%rank<0.5). |
| Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA II | FusionNeoAntigen peptide | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
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Fusion breakpoint peptide structures of AKAP8-BRD4 |
| 3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens * The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA. |
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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of AKAP8-BRD4 |
| Virtual screening between 25 HLAs (from PDB) and FusionNeoAntigens * We used Glide to predict the interaction between HLAs and neoantigens. |
| HLA allele | PDB ID | File name | BPseq | Docking score | Glide score |
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Vaccine Design for the FusionNeoAntigens of AKAP8-BRD4 |
| mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is. |
| Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide sequence | FusionNeoAntigen RNA sequence |
| mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs. |
| Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide | FusionNEoAntigen RNA sequence |
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Information of the samples that have these potential fusion neoantigens of AKAP8-BRD4 |
| These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens. |
| Cancer type | Fusion gene | Hchr | Hbp | Henst | Tchr | Tbp | Tenst | Sample |
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Potential target of CAR-T therapy development for AKAP8-BRD4 |
| Predicted 3D structure. We used RoseTTAFold. |
| 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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features * Minus value of BPloci means that the break point is located before the CDS. |
| - In-frame and retained 'Transmembrane'. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Subcellular localization prediction of the transmembrane domain retained fusion proteins * We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image. |
| Hgene | Hchr | Hbp | Henst | Tgene | Tchr | Tbp | Tenst | DeepLoc result |
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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 |
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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 |
| 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 |
| Tgene | BRD4 | C0002170 | Alopecia | 1 | CTD_human |
| Tgene | BRD4 | C0007102 | Malignant tumor of colon | 1 | CTD_human |
| Tgene | BRD4 | C0009375 | Colonic Neoplasms | 1 | CTD_human |
| Tgene | BRD4 | C0018798 | Congenital Heart Defects | 1 | GENOMICS_ENGLAND |
| Tgene | BRD4 | C0019193 | Hepatitis, Toxic | 1 | CTD_human |
| Tgene | BRD4 | C0020507 | Hyperplasia | 1 | CTD_human |
| Tgene | BRD4 | C0020542 | Pulmonary Hypertension | 1 | CTD_human |
| Tgene | BRD4 | C0025149 | Medulloblastoma | 1 | CTD_human |
| Tgene | BRD4 | C0025958 | Microcephaly | 1 | GENOMICS_ENGLAND |
| Tgene | BRD4 | C0029463 | Osteosarcoma | 1 | CTD_human |
| Tgene | BRD4 | C0033578 | Prostatic Neoplasms | 1 | CTD_human |
| Tgene | BRD4 | C0040136 | Thyroid Neoplasm | 1 | CTD_human |
| Tgene | BRD4 | C0085413 | Polycystic Kidney, Autosomal Dominant | 1 | CTD_human |
| Tgene | BRD4 | C0086873 | Pseudopelade | 1 | CTD_human |
| Tgene | BRD4 | C0151468 | Thyroid Gland Follicular Adenoma | 1 | CTD_human |
| Tgene | BRD4 | C0162311 | Androgenetic Alopecia | 1 | CTD_human |
| Tgene | BRD4 | C0205833 | Medullomyoblastoma | 1 | CTD_human |
| Tgene | BRD4 | C0263477 | Female pattern alopecia (disorder) | 1 | CTD_human |
| Tgene | BRD4 | C0270972 | Cornelia De Lange Syndrome | 1 | CTD_human |
| Tgene | BRD4 | C0278510 | Childhood Medulloblastoma | 1 | CTD_human |
| Tgene | BRD4 | C0278876 | Adult Medulloblastoma | 1 | CTD_human |
| Tgene | BRD4 | C0376358 | Malignant neoplasm of prostate | 1 | CTD_human |
| Tgene | BRD4 | C0549473 | Thyroid carcinoma | 1 | CTD_human |
| Tgene | BRD4 | C0751291 | Desmoplastic Medulloblastoma | 1 | CTD_human |
| Tgene | BRD4 | C0860207 | Drug-Induced Liver Disease | 1 | CTD_human |
| Tgene | BRD4 | C0887850 | Polycystic Kidney, Type 1 Autosomal Dominant Disease | 1 | CTD_human |
| Tgene | BRD4 | C1262760 | Hepatitis, Drug-Induced | 1 | CTD_human |
| Tgene | BRD4 | C1275668 | Melanotic medulloblastoma | 1 | CTD_human |
| Tgene | BRD4 | C1707291 | NUT midline carcinoma | 1 | ORPHANET |
| Tgene | BRD4 | C1802395 | Congenital muscular hypertrophy-cerebral syndrome | 1 | CTD_human |
| Tgene | BRD4 | C1853099 | Cornelia de Lange Syndrome 3 | 1 | CTD_human |
| Tgene | BRD4 | C2751306 | Polycystic kidney disease, type 2 | 1 | CTD_human |
| Tgene | BRD4 | C3658290 | Drug-Induced Acute Liver Injury | 1 | CTD_human |
| Tgene | BRD4 | C3714756 | Intellectual Disability | 1 | GENOMICS_ENGLAND |
| Tgene | BRD4 | C4025871 | Abnormality of the face | 1 | GENOMICS_ENGLAND |
| Tgene | BRD4 | C4083212 | Alopecia, Male Pattern | 1 | CTD_human |
| Tgene | BRD4 | C4277682 | Chemical and Drug Induced Liver Injury | 1 | CTD_human |
| Tgene | BRD4 | C4279912 | Chemically-Induced Liver Toxicity | 1 | CTD_human |
| Tgene | BRD4 | C4551851 | Cornelia de Lange Syndrome 1 | 1 | CTD_human |
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