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Kinase Fusion Gene:BUB1B_EIF2AK4 |
Kinase Fusion Protein Summary |
Kinase Fusion gene summary |
Kinase Fusion partner gene information | Kinase Fusion gene name: BUB1B_EIF2AK4 | KinaseFusionDB ID: KFG772 | FusionGDB2.0 ID: KFG772 | Hgene | Tgene | Gene symbol | BUB1B | EIF2AK4 | Gene ID | 701 | 440275 | |
Gene name | BUB1 mitotic checkpoint serine/threonine kinase B | eukaryotic translation initiation factor 2 alpha kinase 4 | ||||||||||
Synonyms | BUB1beta|BUBR1|Bub1A|MAD3L|MVA1|SSK1|hBUBR1 | GCN2|PVOD2 | ||||||||||
Cytomap | 15q15.1 | 15q15.1 | ||||||||||
Type of gene | protein-coding | protein-coding | ||||||||||
Description | mitotic checkpoint serine/threonine-protein kinase BUB1 betaBUB1B, mitotic checkpoint serine/threonine kinaseMAD3/BUB1-related protein kinasebudding uninhibited by benzimidazoles 1 homolog betamitotic checkpoint kinase MAD3L | eIF-2-alpha kinase GCN2GCN2 eIF2alpha kinaseGCN2-like proteingeneral control nonderepressible 2 | ||||||||||
Modification date | 20240305 | 20240407 | ||||||||||
UniProtAcc | O60566 | Q9P2K8 | ||||||||||
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000560120, ENST00000287598, ENST00000412359, | ENST00000263791, ENST00000382727, ENST00000559311, ENST00000559624, ENST00000560648, | |||||||||
Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: BUB1B [Title/Abstract] AND EIF2AK4 [Title/Abstract] AND fusion [Title/Abstract] Global analysis of somatic structural genomic alterations and their impact on gene expression in diverse human cancers (pmid: 27856756) | |||||||||||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | EIF2AK4(40309443)-BUB1B(40504700), # samples:2 EIF2AK4(40309443)-BUB1B(40504699), # samples:2 BUB1B(40453456)-EIF2AK4(40314720), # 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 | BUB1B | GO:0007094 | mitotic spindle assembly checkpoint signaling | 10477750 |
Tgene | EIF2AK4 | GO:0140469 | GCN2-mediated signaling | 25329545 |
Kinase Fusion gene breakpoints across BUB1B (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 EIF2AK4 (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-36-1575-01A | BUB1B | chr15 | 40462882 | EIF2AK4 | chr15 | 40284376 |
ChimerDB4 | TCGA-36-1575 | BUB1B | chr15 | 40462882 | EIF2AK4 | chr15 | 40284375 |
ChimerDB4 | TCGA-D8-A1XT-01A | BUB1B | chr15 | 40453456 | EIF2AK4 | chr15 | 40314720 |
ChimerDB4 | TCGA-OL-A66I-01A | BUB1B | chr15 | 40453456 | EIF2AK4 | chr15 | 40321607 |
ChimerDB4 | TCGA-AO-A128-01A | BUB1B | chr15 | 40468874 | EIF2AK4 | chr15 | 40301815 |
ChimerDB4 | TCGA-N8-A56S-01A | BUB1B | chr15 | 40510763 | EIF2AK4 | chr15 | 40278006 |
CCLE | G415 | BUB1B | chr15 | 40477843 | EIF2AK4 | chr15 | 40231706 |
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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/:40309443/:40504700) - 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 |
BUB1B | EIF2AK4 |
FUNCTION: Essential component of the mitotic checkpoint. Required for normal mitosis progression. The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. One of its checkpoint functions is to inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to APC/C, independently of its kinase activity. The other is to monitor kinetochore activities that depend on the kinetochore motor CENPE. Required for kinetochore localization of CENPE. Negatively regulates PLK1 activity in interphase cells and suppresses centrosome amplification. Also implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest. May play a role for tumor suppression. {ECO:0000269|PubMed:10477750, ECO:0000269|PubMed:11702782, ECO:0000269|PubMed:14706340, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:19411850, ECO:0000269|PubMed:19503101}. | FUNCTION: Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability (PubMed:25329545, PubMed:32610081). Plays a role as an activator of the integrated stress response (ISR) required for adaptation to amino acid starvation (By similarity). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha into a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (PubMed:32610081). Binds uncharged tRNAs (By similarity). Required for the translational induction of protein kinase PRKCH following amino acid starvation (By similarity). Involved in cell cycle arrest by promoting cyclin D1 mRNA translation repression after the unfolded protein response pathway (UPR) activation or cell cycle inhibitor CDKN1A/p21 mRNA translation activation in response to amino acid deprivation (PubMed:26102367). Plays a role in the consolidation of synaptic plasticity, learning as well as formation of long-term memory (By similarity). Plays a role in neurite outgrowth inhibition (By similarity). Plays a proapoptotic role in response to glucose deprivation (By similarity). Promotes global cellular protein synthesis repression in response to UV irradiation independently of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAPK signaling pathways (By similarity). Plays a role in the antiviral response against alphavirus infection; impairs early viral mRNA translation of the incoming genomic virus RNA, thus preventing alphavirus replication (By similarity). {ECO:0000250|UniProtKB:P15442, ECO:0000250|UniProtKB:Q9QZ05, ECO:0000269|PubMed:25329545, ECO:0000269|PubMed:26102367, ECO:0000269|PubMed:32610081}.; FUNCTION: (Microbial infection) Plays a role in modulating the adaptive immune response to yellow fever virus infection; promotes dendritic cells to initiate autophagy and antigene presentation to both CD4(+) and CD8(+) T-cells under amino acid starvation (PubMed:24310610). {ECO:0000269|PubMed:24310610}. |
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 BUB1B_EIF2AK4 |
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 |
EIF2AK4 | Q9P2K8 | human | MARS1 | P56192 | S229 | EEELATLsEEEIAMA | |
EIF2AK4 | Q9P2K8 | human | MARS1 | P56192 | S472 | LGRTLPGsDWTPNAQ | tRNA-synt_1g |
EIF2AK4 | Q9P2K8 | human | MARS1 | P56192 | S662 | NRAGMFVskFFGGYV |
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 |
EIF2AK4 | ID | Description | 0.00e+00 |
EIF2AK4 | GO:1901838 | positive regulation of transcription of nucleolar large rRNA by RNA polymerase I | 3.72e-03 |
EIF2AK4 | GO:1901836 | regulation of transcription of nucleolar large rRNA by RNA polymerase I | 3.72e-03 |
EIF2AK4 | GO:0042790 | nucleolar large rRNA transcription by RNA polymerase I | 3.72e-03 |
EIF2AK4 | GO:0036120 | cellular response to platelet-derived growth factor stimulus | 3.72e-03 |
EIF2AK4 | GO:0036119 | response to platelet-derived growth factor | 3.72e-03 |
EIF2AK4 | GO:0045943 | positive regulation of transcription by RNA polymerase I | 3.72e-03 |
EIF2AK4 | GO:0009303 | rRNA transcription | 3.72e-03 |
EIF2AK4 | GO:0006418 | tRNA aminoacylation for protein translation | 3.72e-03 |
EIF2AK4 | GO:0071364 | cellular response to epidermal growth factor stimulus | 3.72e-03 |
EIF2AK4 | GO:0043039 | tRNA aminoacylation | 3.72e-03 |
EIF2AK4 | GO:0043038 | amino acid activation | 3.72e-03 |
EIF2AK4 | GO:0070849 | response to epidermal growth factor | 3.72e-03 |
EIF2AK4 | GO:0006356 | regulation of transcription by RNA polymerase I | 3.72e-03 |
EIF2AK4 | GO:0006360 | transcription by RNA polymerase I | 5.18e-03 |
EIF2AK4 | GO:0140747 | regulation of ncRNA transcription | 6.18e-03 |
EIF2AK4 | GO:0098781 | ncRNA transcription | 8.56e-03 |
EIF2AK4 | GO:0006399 | tRNA metabolic process | 1.17e-02 |
EIF2AK4 | GO:0016072 | rRNA metabolic process | 1.48e-02 |
EIF2AK4 | GO:0006520 | amino acid metabolic process | 1.54e-02 |
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Related Drugs to BUB1B_EIF2AK4 |
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 BUB1B-EIF2AK4 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 BUB1B_EIF2AK4 |
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 |