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Fusion Protein:EIF2AK2-RMDN2 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: EIF2AK2-RMDN2 | FusionPDB ID: 25664 | FusionGDB2.0 ID: 25664 | Hgene | Tgene | Gene symbol | EIF2AK2 | RMDN2 | Gene ID | 5610 | 151393 |
| Gene name | eukaryotic translation initiation factor 2 alpha kinase 2 | regulator of microtubule dynamics 2 | |
| Synonyms | EIF2AK1|PKR|PPP1R83|PRKR | BLOCK18|FAM82A|FAM82A1|PRO34163|PYST9371|RMD-2|RMD2|RMD4 | |
| Cytomap | 2p22.2 | 2p22.2 | |
| Type of gene | protein-coding | protein-coding | |
| Description | interferon-induced, double-stranded RNA-activated protein kinaseP1/eIF-2A protein kinasedouble stranded RNA activated protein kinaseeIF-2A protein kinase 2interferon-inducible elF2alpha kinasep68 kinaseprotein kinase Rprotein kinase, interferon-ind | regulator of microtubule dynamics protein 2family with sequence similarity 82, member Afamily with sequence similarity 82, member A1microtubule-associated protein | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | P19525 | . | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000233057, ENST00000395127, ENST00000405334, | ENST00000354545, ENST00000402091, ENST00000406384, ENST00000407257, ENST00000417700, ENST00000469469, ENST00000234195, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 6 X 8 X 4=192 | 8 X 7 X 2=112 |
| # samples | 9 | 9 | |
| ** MAII score | log2(9/192*10)=-1.09310940439148 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(9/112*10)=-0.315501825727929 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: EIF2AK2 [Title/Abstract] AND RMDN2 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | EIF2AK2(37362627)-RMDN2(38216684), # samples:2 | ||
| Anticipated loss of major functional domain due to fusion event. | EIF2AK2-RMDN2 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. EIF2AK2-RMDN2 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. EIF2AK2-RMDN2 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. EIF2AK2-RMDN2 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. EIF2AK2-RMDN2 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. EIF2AK2-RMDN2 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. EIF2AK2-RMDN2 seems lost the major protein functional domain in Hgene 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 | EIF2AK2 | GO:0006468 | protein phosphorylation | 19189853 |
| Hgene | EIF2AK2 | GO:0017148 | negative regulation of translation | 12882984 |
| Hgene | EIF2AK2 | GO:0035455 | response to interferon-alpha | 19840259 |
| Hgene | EIF2AK2 | GO:0046777 | protein autophosphorylation | 22801494 |
| Hgene | EIF2AK2 | GO:0051092 | positive regulation of NF-kappaB transcription factor activity | 15121867 |
| Fusion gene breakpoints across EIF2AK2 (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 RMDN2 (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 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 | BRCA | TCGA-D8-A142-01A | EIF2AK2 | chr2 | 37362627 | - | RMDN2 | chr2 | 38216684 | + |
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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) |
| ENST00000405334 | EIF2AK2 | chr2 | 37362627 | - | ENST00000234195 | RMDN2 | chr2 | 38216684 | + | 1329 | 785 | 0 | 1181 | 393 |
| 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 |
| ENST00000405334 | ENST00000234195 | EIF2AK2 | chr2 | 37362627 | - | RMDN2 | chr2 | 38216684 | + | 0.0004878 | 0.9995122 |
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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 >25664_25664_1_EIF2AK2-RMDN2_EIF2AK2_chr2_37362627_ENST00000405334_RMDN2_chr2_38216684_ENST00000234195_length(amino acids)=393AA_BP=261 MAGDLSAGFFMEELNTYRQKQGVVLKYQELPNSGPPHDRRFTFQVIIDGREFPEGEGRSKKEAKNAAAKLAVEILNKEKKAVSPLLLTTT NSSEGLSMGNYIGLINRIAQKKRLTVNYEQCASGVHGPEGFHYKCKMGQKEYSIGTGSTKQEAKQLAAKLAYLQILSEETSVKSDYLSSG SFATTCESQSNSLVTSTLASESSSEGDFSADTSEINSNSDSLNSSSLLMNGLRNNQRKAKRSLAPRFDLPDMKETKYTVDKRYAVLCGYV SEFEGLQNKINYGHLFKEHLDIAIKLLPEEPFLYYLKGRYCYTVSKLSWIEKKMAATLFGKIPSSTVQEALHNFLKAEELCPGYSNPNYM -------------------------------------------------------------- |
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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/chr2:37362627/chr2:38216684) - 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 |
| EIF2AK2 | . |
| FUNCTION: IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection (PubMed:18835251, PubMed:19507191, PubMed:19189853, PubMed:21123651, PubMed:21072047, PubMed:22948139, PubMed:23229543, PubMed:22381929). Inhibits viral replication via the integrated stress response (ISR): EIF2S1/eIF-2-alpha phosphorylation in response to viral infection converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, resulting to a shutdown of cellular and viral protein synthesis, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4 (PubMed:19189853, PubMed:21123651, PubMed:22948139, PubMed:23229543). Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1) (PubMed:11836380, PubMed:19189853, PubMed:20171114, PubMed:19840259, PubMed:21710204, PubMed:23115276, PubMed:23399035). Also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation: phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11 (PubMed:11836380, PubMed:22214662, PubMed:19229320). In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteosomal degradation (PubMed:20395957). Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding proinflammatory cytokines and IFNs (PubMed:22948139, PubMed:23084476, PubMed:23372823). Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6 (PubMed:10848580, PubMed:15121867, PubMed:15229216). Can act as both a positive and negative regulator of the insulin signaling pathway (ISP) (PubMed:20685959). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2) (PubMed:20685959). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes (PubMed:22801494). Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin (By similarity). {ECO:0000250|UniProtKB:Q03963, ECO:0000269|PubMed:10848580, ECO:0000269|PubMed:11836380, ECO:0000269|PubMed:15121867, ECO:0000269|PubMed:15229216, ECO:0000269|PubMed:18835251, ECO:0000269|PubMed:19189853, ECO:0000269|PubMed:19229320, ECO:0000269|PubMed:19507191, ECO:0000269|PubMed:19840259, ECO:0000269|PubMed:20171114, ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:20685959, ECO:0000269|PubMed:21072047, ECO:0000269|PubMed:21123651, ECO:0000269|PubMed:21710204, ECO:0000269|PubMed:22214662, ECO:0000269|PubMed:22381929, ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:22948139, ECO:0000269|PubMed:23084476, ECO:0000269|PubMed:23115276, ECO:0000269|PubMed:23229543, ECO:0000269|PubMed:23372823, ECO:0000269|PubMed:23399035, ECO:0000269|PubMed:32197074}. | FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes. |
| 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 | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000233057 | - | 10 | 17 | 100_167 | 261.6666666666667 | 552.0 | Domain | DRBM 2 |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000233057 | - | 10 | 17 | 9_77 | 261.6666666666667 | 552.0 | Domain | DRBM 1 |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000395127 | - | 10 | 17 | 100_167 | 261.6666666666667 | 552.0 | Domain | DRBM 2 |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000395127 | - | 10 | 17 | 9_77 | 261.6666666666667 | 552.0 | Domain | DRBM 1 |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000405334 | - | 8 | 14 | 100_167 | 261.6666666666667 | 511.0 | Domain | DRBM 2 |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000405334 | - | 8 | 14 | 9_77 | 261.6666666666667 | 511.0 | Domain | DRBM 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 | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000233057 | - | 10 | 17 | 267_538 | 261.6666666666667 | 552.0 | Domain | Protein kinase |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000395127 | - | 10 | 17 | 267_538 | 261.6666666666667 | 552.0 | Domain | Protein kinase |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000405334 | - | 8 | 14 | 267_538 | 261.6666666666667 | 511.0 | Domain | Protein kinase |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000233057 | - | 10 | 17 | 273_281 | 261.6666666666667 | 552.0 | Nucleotide binding | ATP |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000395127 | - | 10 | 17 | 273_281 | 261.6666666666667 | 552.0 | Nucleotide binding | ATP |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000405334 | - | 8 | 14 | 273_281 | 261.6666666666667 | 511.0 | Nucleotide binding | ATP |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000233057 | - | 10 | 17 | 331_357 | 261.6666666666667 | 552.0 | Region | Note=2 X 13 AA approximate repeats |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000395127 | - | 10 | 17 | 331_357 | 261.6666666666667 | 552.0 | Region | Note=2 X 13 AA approximate repeats |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000405334 | - | 8 | 14 | 331_357 | 261.6666666666667 | 511.0 | Region | Note=2 X 13 AA approximate repeats |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000233057 | - | 10 | 17 | 331_343 | 261.6666666666667 | 552.0 | Repeat | Note=1 |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000233057 | - | 10 | 17 | 345_357 | 261.6666666666667 | 552.0 | Repeat | Note=2 |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000395127 | - | 10 | 17 | 331_343 | 261.6666666666667 | 552.0 | Repeat | Note=1 |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000395127 | - | 10 | 17 | 345_357 | 261.6666666666667 | 552.0 | Repeat | Note=2 |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000405334 | - | 8 | 14 | 331_343 | 261.6666666666667 | 511.0 | Repeat | Note=1 |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000405334 | - | 8 | 14 | 345_357 | 261.6666666666667 | 511.0 | Repeat | Note=2 |
| Tgene | RMDN2 | chr2:37362627 | chr2:38216684 | ENST00000234195 | 4 | 11 | 68_110 | 441.6666666666667 | 574.0 | Coiled coil | Ontology_term=ECO:0000255 | |
| Tgene | RMDN2 | chr2:37362627 | chr2:38216684 | ENST00000354545 | 4 | 11 | 68_110 | 263.6666666666667 | 411.0 | Coiled coil | Ontology_term=ECO:0000255 | |
| Tgene | RMDN2 | chr2:37362627 | chr2:38216684 | ENST00000406384 | 4 | 11 | 68_110 | 263.6666666666667 | 411.0 | Coiled coil | Ontology_term=ECO:0000255 | |
| Tgene | RMDN2 | chr2:37362627 | chr2:38216684 | ENST00000407257 | 4 | 12 | 68_110 | 441.6666666666667 | 641.6666666666666 | Coiled coil | Ontology_term=ECO:0000255 | |
| Tgene | RMDN2 | chr2:37362627 | chr2:38216684 | ENST00000417700 | 3 | 10 | 68_110 | 118.66666666666667 | 266.0 | Coiled coil | Ontology_term=ECO:0000255 | |
| Tgene | RMDN2 | chr2:37362627 | chr2:38216684 | ENST00000234195 | 4 | 11 | 9_28 | 441.6666666666667 | 574.0 | Transmembrane | Helical | |
| Tgene | RMDN2 | chr2:37362627 | chr2:38216684 | ENST00000354545 | 4 | 11 | 9_28 | 263.6666666666667 | 411.0 | Transmembrane | Helical | |
| Tgene | RMDN2 | chr2:37362627 | chr2:38216684 | ENST00000406384 | 4 | 11 | 9_28 | 263.6666666666667 | 411.0 | Transmembrane | Helical | |
| Tgene | RMDN2 | chr2:37362627 | chr2:38216684 | ENST00000407257 | 4 | 12 | 9_28 | 441.6666666666667 | 641.6666666666666 | Transmembrane | Helical | |
| Tgene | RMDN2 | chr2:37362627 | chr2:38216684 | ENST00000417700 | 3 | 10 | 9_28 | 118.66666666666667 | 266.0 | Transmembrane | Helical |
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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 |
| EIF2AK2 | |
| RMDN2 |
| - 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 |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000233057 | - | 10 | 17 | 266_551 | 261.6666666666667 | 552.0 | TRAF5 |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000395127 | - | 10 | 17 | 266_551 | 261.6666666666667 | 552.0 | TRAF5 |
| Hgene | EIF2AK2 | chr2:37362627 | chr2:38216684 | ENST00000405334 | - | 8 | 14 | 266_551 | 261.6666666666667 | 511.0 | TRAF5 |
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Related Drugs to EIF2AK2-RMDN2 |
| 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 EIF2AK2-RMDN2 |
| 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 |
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