| UTHEALTH HOME ABOUT SBMI A-Z WEBMAIL INSIDE THE UNIVERSITY |
|
|||||||
|
Kinase Fusion Gene:EIF2AK1_POU2F1 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: EIF2AK1_POU2F1 | KinaseFusionDB ID: KFG1904 | FusionGDB2.0 ID: KFG1904 | Hgene | Tgene | Gene symbol | EIF2AK1 | POU2F1 | Gene ID | 27102 | 5451 | |
| Gene name | eukaryotic translation initiation factor 2 alpha kinase 1 | POU class 2 homeobox 1 | ||||||||||
| Synonyms | HCR|HRI|LEMSPAD|hHRI | OCT1|OTF1|Oct1Z|oct-1B | ||||||||||
| Cytomap | 7p22.1 | 1q24.2 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | eukaryotic translation initiation factor 2-alpha kinase 1heme regulated initiation factor 2 alpha kinaseheme sensitive initiation factor 2a kinaseheme-controlled repressorheme-regulated eukaryotic initiation factor eIF-2-alpha kinaseheme-regulated in | POU domain, class 2, transcription factor 1NF-A1OTF-1Octamer-binding transcription factor-1oct-1octamer-binding protein 1octamer-binding transcription factor 1 | ||||||||||
| Modification date | 20240411 | 20240403 | ||||||||||
| UniProtAcc | Q9BQI3 | P14859 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000199389, ENST00000495565, ENST00000536084, | ENST00000367862, ENST00000367865, ENST00000367866, ENST00000420254, ENST00000429375, ENST00000452019, ENST00000541643, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: EIF2AK1 [Title/Abstract] AND POU2F1 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | EIF2AK1(6063471)-POU2F1(167385314), # 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 |
| Hgene | EIF2AK1 | GO:0140467 | integrated stress response signaling | 32132707 |
| Hgene | EIF2AK1 | GO:0140468 | HRI-mediated signaling | 32132706|32132707 |
| Hgene | EIF2AK1 | GO:1990641 | response to iron ion starvation | 11036079 |
| Tgene | POU2F1 | GO:0045892 | negative regulation of DNA-templated transcription | 11891224 |
| Tgene | POU2F1 | GO:0045892 | negative regulation of DNA-templated transcription | 11997177 |
| Tgene | POU2F1 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 15252056 |
| Kinase Fusion gene breakpoints across EIF2AK1 (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 POU2F1 (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-CD-A48C-01A | EIF2AK1 | chr7 | 6063471 | POU2F1 | chr1 | 167385314 |
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/:6063471/:167385314) - 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 |
| EIF2AK1 | POU2F1 |
| FUNCTION: Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress conditions (PubMed:32132706, PubMed:32132707, PubMed:37327776). Key activator of the integrated stress response (ISR) required for adaptation to various stress, such as heme deficiency, oxidative stress, osmotic shock, mitochondrial dysfunction and heat shock (PubMed:32132706, PubMed:32132707, PubMed:37327776). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming (PubMed:32132706, PubMed:32132707, PubMed:37327776). Acts as a key sensor of heme-deficiency: in normal conditions, binds hemin via a cysteine thiolate and histidine nitrogenous coordination, leading to inhibit the protein kinase activity (By similarity). This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell: heme depletion relieves inhibition and stimulates kinase activity, activating the ISR (By similarity). Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions (By similarity). In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties (By similarity). It thereby plays an essential protective role for RBC survival in anemias of iron deficiency (By similarity). Iron deficiency also triggers activation by full-length DELE1 (PubMed:37327776). Also activates the ISR in response to mitochondrial dysfunction: HRI/EIF2AK1 protein kinase activity is activated upon binding to the processed form of DELE1 (S-DELE1), thereby promoting the ATF4-mediated reprogramming (PubMed:32132706, PubMed:32132707). {ECO:0000250|UniProtKB:Q9Z2R9, ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707, ECO:0000269|PubMed:32197074}. | FUNCTION: Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3') and activates the promoters of the genes for some small nuclear RNAs (snRNA) and of genes such as those for histone H2B and immunoglobulins. Modulates transcription transactivation by NR3C1, AR and PGR. {ECO:0000269|PubMed:10480874, ECO:0000269|PubMed:1684878, ECO:0000269|PubMed:7859290}.; FUNCTION: (Microbial infection) In case of human herpes simplex virus (HSV) infection, POU2F1 forms a multiprotein-DNA complex with the viral transactivator protein VP16 and HCFC1 thereby enabling the transcription of the viral immediate early genes. {ECO:0000305|PubMed:12826401}. |
| 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 EIF2AK1_POU2F1 |
| 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 |
| EIF2AK1 | Q9BQI3 | human | EIF2S1 | P05198 | S52 | MILLsELsRRRIRsI | S1 |
| EIF2AK1 | Q9BQI3 | human | EIF2S1 | P05198 | S49 | IEGMILLsELsRRRI | S1 |
| 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 |
| EIF2AK1 | ID | Description | 0.00e+00 |
| EIF2AK1 | GO:0071287 | cellular response to manganese ion | 7.58e-03 |
| EIF2AK1 | GO:0097050 | type B pancreatic cell apoptotic process | 7.58e-03 |
| EIF2AK1 | GO:0036490 | regulation of translation in response to endoplasmic reticulum stress | 7.58e-03 |
| EIF2AK1 | GO:0043558 | regulation of translational initiation in response to stress | 7.58e-03 |
| EIF2AK1 | GO:0010042 | response to manganese ion | 7.58e-03 |
| EIF2AK1 | GO:0036499 | PERK-mediated unfolded protein response | 7.58e-03 |
| EIF2AK1 | GO:0043555 | regulation of translation in response to stress | 7.58e-03 |
| EIF2AK1 | GO:0045947 | negative regulation of translational initiation | 7.58e-03 |
| EIF2AK1 | GO:0034063 | stress granule assembly | 9.49e-03 |
| EIF2AK1 | GO:0140467 | integrated stress response signaling | 1.06e-02 |
| EIF2AK1 | GO:1904037 | positive regulation of epithelial cell apoptotic process | 1.06e-02 |
| EIF2AK1 | GO:0006984 | ER-nucleus signaling pathway | 1.06e-02 |
| EIF2AK1 | GO:0034198 | cellular response to amino acid starvation | 1.06e-02 |
| EIF2AK1 | GO:1990928 | response to amino acid starvation | 1.06e-02 |
| EIF2AK1 | GO:0034605 | cellular response to heat | 1.21e-02 |
| EIF2AK1 | GO:0030968 | endoplasmic reticulum unfolded protein response | 1.29e-02 |
| EIF2AK1 | GO:0006446 | regulation of translational initiation | 1.31e-02 |
| EIF2AK1 | GO:0034620 | cellular response to unfolded protein | 1.31e-02 |
| EIF2AK1 | GO:0034644 | cellular response to UV | 1.31e-02 |
| EIF2AK1 | GO:0009408 | response to heat | 1.39e-02 |
| EIF2AK1 | GO:0035967 | cellular response to topologically incorrect protein | 1.39e-02 |
| EIF2AK1 | GO:1904035 | regulation of epithelial cell apoptotic process | 1.39e-02 |
| EIF2AK1 | GO:0006413 | translational initiation | 1.39e-02 |
| EIF2AK1 | GO:0071482 | cellular response to light stimulus | 1.39e-02 |
| EIF2AK1 | GO:0043200 | response to amino acid | 1.39e-02 |
| EIF2AK1 | GO:0006986 | response to unfolded protein | 1.42e-02 |
| EIF2AK1 | GO:0001101 | response to acid chemical | 1.42e-02 |
| EIF2AK1 | GO:1904019 | epithelial cell apoptotic process | 1.42e-02 |
| EIF2AK1 | GO:0009411 | response to UV | 1.44e-02 |
| EIF2AK1 | GO:0035966 | response to topologically incorrect protein | 1.46e-02 |
| EIF2AK1 | GO:0009266 | response to temperature stimulus | 1.51e-02 |
| EIF2AK1 | GO:0009267 | cellular response to starvation | 1.51e-02 |
| EIF2AK1 | GO:0071478 | cellular response to radiation | 1.51e-02 |
| EIF2AK1 | GO:0071248 | cellular response to metal ion | 1.62e-02 |
| EIF2AK1 | GO:0042594 | response to starvation | 1.72e-02 |
| EIF2AK1 | GO:0071241 | cellular response to inorganic substance | 1.75e-02 |
| EIF2AK1 | GO:0031669 | cellular response to nutrient levels | 1.85e-02 |
| EIF2AK1 | GO:0034599 | cellular response to oxidative stress | 1.85e-02 |
| EIF2AK1 | GO:0034976 | response to endoplasmic reticulum stress | 1.88e-02 |
| EIF2AK1 | GO:0031668 | cellular response to extracellular stimulus | 1.94e-02 |
| EIF2AK1 | GO:0017148 | negative regulation of translation | 2.03e-02 |
| EIF2AK1 | GO:0062197 | cellular response to chemical stress | 2.03e-02 |
| EIF2AK1 | GO:0009416 | response to light stimulus | 2.03e-02 |
| EIF2AK1 | GO:0071214 | cellular response to abiotic stimulus | 2.03e-02 |
| EIF2AK1 | GO:0104004 | cellular response to environmental stimulus | 2.03e-02 |
| EIF2AK1 | GO:0034249 | negative regulation of amide metabolic process | 2.03e-02 |
| EIF2AK1 | GO:0071496 | cellular response to external stimulus | 2.03e-02 |
| EIF2AK1 | GO:0010038 | response to metal ion | 2.06e-02 |
| EIF2AK1 | GO:0006979 | response to oxidative stress | 2.25e-02 |
Top |
Related Drugs to EIF2AK1_POU2F1 |
| 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 EIF2AK1-POU2F1 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 EIF2AK1_POU2F1 |
| 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 |
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 |
Copyright 2024-Present -The University of Texas Health Science Center at Houston
Web File Viewing | Emergency Information |Campus Carry|Site Policies |