| UTHEALTH HOME ABOUT SBMI A-Z WEBMAIL INSIDE THE UNIVERSITY |
|
|||||||
|
Fusion Protein:EIF2AK1-MAP2K5 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: EIF2AK1-MAP2K5 | FusionPDB ID: 25655 | FusionGDB2.0 ID: 25655 | Hgene | Tgene | Gene symbol | EIF2AK1 | MAP2K5 | Gene ID | 27102 | 5607 |
| Gene name | eukaryotic translation initiation factor 2 alpha kinase 1 | mitogen-activated protein kinase kinase 5 | |
| Synonyms | HCR|HRI | HsT17454|MAPKK5|MEK5|PRKMK5 | |
| Cytomap | 7p22.1 | 15q23 | |
| 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 | dual specificity mitogen-activated protein kinase kinase 5MAP kinase kinase 5MAP kinase kinase MEK5bMAPK/ERK kinase 5MAPKK 5MEK 5 | |
| Modification date | 20200313 | 20200327 | |
| UniProtAcc | Q9BQI3 | Q13163 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000199389, ENST00000536084, ENST00000495565, | ENST00000340972, ENST00000354498, ENST00000395476, ENST00000560591, ENST00000178640, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 11 X 8 X 8=704 | 13 X 18 X 12=2808 |
| # samples | 11 | 19 | |
| ** MAII score | log2(11/704*10)=-2.67807190511264 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(19/2808*10)=-3.88547161197361 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: EIF2AK1 [Title/Abstract] AND MAP2K5 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | EIF2AK1(6077055)-MAP2K5(68098984), # samples:3 | ||
| Anticipated loss of major functional domain due to fusion event. | EIF2AK1-MAP2K5 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. EIF2AK1-MAP2K5 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. EIF2AK1-MAP2K5 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. EIF2AK1-MAP2K5 seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF. EIF2AK1-MAP2K5 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. EIF2AK1-MAP2K5 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 |
| Hgene | EIF2AK1 | GO:1990641 | response to iron ion starvation | 11036079 |
| 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. |
 |
| Fusion gene breakpoints across MAP2K5 (3'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
 |
Top |
Fusion Gene Sample Information |
| Fusion gene information from FusionGDB2.0. |
| Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0) * 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 | Disease | Sample | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| ChimerDB4 | PRAD | TCGA-V1-A8WV-01A | EIF2AK1 | chr7 | 6077055 | - | MAP2K5 | chr15 | 68098984 | + |
| ChimerDB4 | PRAD | TCGA-V1-A8WV | EIF2AK1 | chr7 | 6077055 | - | MAP2K5 | chr15 | 68098984 | + |
Top |
Fusion ORF Analysis |
| 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) |
| ENST00000536084 | EIF2AK1 | chr7 | 6077055 | - | ENST00000178640 | MAP2K5 | chr15 | 68098984 | + | 1757 | 1279 | 319 | 1383 | 354 |
| 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 |
| ENST00000536084 | ENST00000178640 | EIF2AK1 | chr7 | 6077055 | - | MAP2K5 | chr15 | 68098984 | + | 0.001619109 | 0.9983809 |
Top |
Fusion Amino Acid Sequences |
| For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
| >FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP >25655_25655_1_EIF2AK1-MAP2K5_EIF2AK1_chr7_6077055_ENST00000536084_MAP2K5_chr15_68098984_ENST00000178640_length(amino acids)=354AA_BP=320 MNQTHFVQDRCLSDPCEDISRIQKIRSREVALEAQTSRYLNEFEELAILGKGGYGRVYKVRNKLDGQYYAIKKILIKGATKTVCMKVLRE VKVLAGLQHPNIVGYHTAWIEHVHVIQPRADRAAIELPSLEVLSDQEEDREQCGVKNDESSSSSIIFAEPTPEKEKRFGESDTENQNNKS VKYTTNLVIRESGELESTLELQENGLAGLSASSIVEQQLPLRRNSHLEESFTSTEESSEENVNFLGQTEAQYHLMLHIQMQLCELSLWDW -------------------------------------------------------------- |
Top |
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/chr7:6077055/chr15:68098984) - 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 | MAP2K5 |
| 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). 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). 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). 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). Similarly, in hepatocytes, involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes (By similarity). May also regulate endoplasmic reticulum (ER) stress during acute heme-deficient conditions (By similarity). 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: Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appears to play a critical role in protecting cells from stress-induced apoptosis, neuronal survival and cardiac development and angiogenesis. {ECO:0000269|PubMed:7759517, ECO:0000269|PubMed:9384584}. |
| 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 protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Hgene | EIF2AK1 | chr7:6077055 | chr15:68098984 | ENST00000199389 | - | 11 | 15 | 173_181 | 444.0 | 631.0 | Nucleotide binding | ATP |
| Hgene | EIF2AK1 | chr7:6077055 | chr15:68098984 | ENST00000199389 | - | 11 | 15 | 410_415 | 444.0 | 631.0 | Repeat | Note=HRM 1 |
| - Not-retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Hgene | EIF2AK1 | chr7:6077055 | chr15:68098984 | ENST00000199389 | - | 11 | 15 | 167_583 | 444.0 | 631.0 | Domain | Protein kinase |
| Hgene | EIF2AK1 | chr7:6077055 | chr15:68098984 | ENST00000199389 | - | 11 | 15 | 552_557 | 444.0 | 631.0 | Repeat | Note=HRM 2 |
| Tgene | MAP2K5 | chr7:6077055 | chr15:68098984 | ENST00000178640 | 20 | 22 | 166_409 | 414.0 | 449.0 | Domain | Protein kinase | |
| Tgene | MAP2K5 | chr7:6077055 | chr15:68098984 | ENST00000178640 | 20 | 22 | 18_109 | 414.0 | 449.0 | Domain | PB1 | |
| Tgene | MAP2K5 | chr7:6077055 | chr15:68098984 | ENST00000354498 | 20 | 22 | 166_409 | 378.0 | 413.0 | Domain | Protein kinase | |
| Tgene | MAP2K5 | chr7:6077055 | chr15:68098984 | ENST00000354498 | 20 | 22 | 18_109 | 378.0 | 413.0 | Domain | PB1 | |
| Tgene | MAP2K5 | chr7:6077055 | chr15:68098984 | ENST00000395476 | 19 | 21 | 166_409 | 404.0 | 439.0 | Domain | Protein kinase | |
| Tgene | MAP2K5 | chr7:6077055 | chr15:68098984 | ENST00000395476 | 19 | 21 | 18_109 | 404.0 | 439.0 | Domain | PB1 | |
| Tgene | MAP2K5 | chr7:6077055 | chr15:68098984 | ENST00000178640 | 20 | 22 | 172_180 | 414.0 | 449.0 | Nucleotide binding | ATP | |
| Tgene | MAP2K5 | chr7:6077055 | chr15:68098984 | ENST00000354498 | 20 | 22 | 172_180 | 378.0 | 413.0 | Nucleotide binding | ATP | |
| Tgene | MAP2K5 | chr7:6077055 | chr15:68098984 | ENST00000395476 | 19 | 21 | 172_180 | 404.0 | 439.0 | Nucleotide binding | ATP |
Top |
Fusion Protein Structures |
| PDB and CIF files of the predicted 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. |
| Fusion protein PDB link (fusion AA seq ID in FusionPDB) | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | AA seq | Len(AA seq) |
| PDB file >>>688_EIF2AK1_6077055_MAP2K5_68098984_ranked_0.pdb | EIF2AK1 | 6077055 | 6077055 | ENST00000178640 | MAP2K5 | chr15 | 68098984 | + | MNQTHFVQDRCLSDPCEDISRIQKIRSREVALEAQTSRYLNEFEELAILGKGGYGRVYKVRNKLDGQYYAIKKILIKGATKTVCMKVLRE VKVLAGLQHPNIVGYHTAWIEHVHVIQPRADRAAIELPSLEVLSDQEEDREQCGVKNDESSSSSIIFAEPTPEKEKRFGESDTENQNNKS VKYTTNLVIRESGELESTLELQENGLAGLSASSIVEQQLPLRRNSHLEESFTSTEESSEENVNFLGQTEAQYHLMLHIQMQLCELSLWDW | 354 |
Top |
pLDDT score distribution |
| pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
EIF2AK1_pLDDT.png  |
MAP2K5_pLDDT.png  |
| pLDDT score distribution of the predicted fusion protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
 |
Top |
Ramachandran Plot of 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. |
| Fusion AA seq ID in FusionPDB and their Ramachandran plots |
Top |
Fusion Protein-Protein Interaction |
| Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in |
| Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160) |
| Gene | PPI interactors |
| Protein-protein interactors based on sequence similarity (STRING) |
| Gene | STRING network |
| EIF2AK1 | |
| MAP2K5 |
| - Retained interactions in fusion protein (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
| - Lost interactions due to fusion (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
| Tgene | MAP2K5 | chr7:6077055 | chr15:68098984 | ENST00000178640 | 20 | 22 | 64_68 | 414.0 | 449.0 | MAP3K2/MAP3K3 | |
| Tgene | MAP2K5 | chr7:6077055 | chr15:68098984 | ENST00000354498 | 20 | 22 | 64_68 | 378.0 | 413.0 | MAP3K2/MAP3K3 | |
| Tgene | MAP2K5 | chr7:6077055 | chr15:68098984 | ENST00000395476 | 19 | 21 | 64_68 | 404.0 | 439.0 | MAP3K2/MAP3K3 | |
| Tgene | MAP2K5 | chr7:6077055 | chr15:68098984 | ENST00000178640 | 20 | 22 | 117_131 | 414.0 | 449.0 | MAPK7 | |
| Tgene | MAP2K5 | chr7:6077055 | chr15:68098984 | ENST00000178640 | 20 | 22 | 18_25 | 414.0 | 449.0 | MAPK7 | |
| Tgene | MAP2K5 | chr7:6077055 | chr15:68098984 | ENST00000354498 | 20 | 22 | 117_131 | 378.0 | 413.0 | MAPK7 | |
| Tgene | MAP2K5 | chr7:6077055 | chr15:68098984 | ENST00000354498 | 20 | 22 | 18_25 | 378.0 | 413.0 | MAPK7 | |
| Tgene | MAP2K5 | chr7:6077055 | chr15:68098984 | ENST00000395476 | 19 | 21 | 117_131 | 404.0 | 439.0 | MAPK7 | |
| Tgene | MAP2K5 | chr7:6077055 | chr15:68098984 | ENST00000395476 | 19 | 21 | 18_25 | 404.0 | 439.0 | MAPK7 |
Top |
Related Drugs to EIF2AK1-MAP2K5 |
| Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Drug | Source | PMID |
Top |
Related Diseases to EIF2AK1-MAP2K5 |
| 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 |
Copyright 2021-Present -The University of Texas Health Science Center at Houston (UTHealth)
Web File Viewing | Emergency Information |Campus Carry|Site Policies