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Kinase Fusion Gene:SERPINA3_EIF2AK2 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: SERPINA3_EIF2AK2 | KinaseFusionDB ID: KFG5750 | FusionGDB2.0 ID: KFG5750 | Hgene | Tgene | Gene symbol | SERPINA3 | EIF2AK2 | Gene ID | 12 | 5610 | |
| Gene name | serpin family A member 3 | eukaryotic translation initiation factor 2 alpha kinase 2 | ||||||||||
| Synonyms | AACT|ACT|GIG24|GIG25 | DYT33|EIF2AK1|LEUDEN|PKR|PPP1R83|PRKR | ||||||||||
| Cytomap | 14q32.13 | 2p22.2 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | alpha-1-antichymotrypsincell growth-inhibiting gene 24/25 proteingrowth-inhibiting protein 24growth-inhibiting protein 25serine (or cysteine) proteinase inhibitor, clade A, member 3serpin A3serpin peptidase inhibitor, clade A (alpha-1 antiproteinase | 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 RNA-regulatedp | ||||||||||
| Modification date | 20240317 | 20240411 | ||||||||||
| UniProtAcc | P01011 | P19525 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000393078, ENST00000393080, ENST00000467132, ENST00000482740, ENST00000485588, | ENST00000233057, ENST00000395127, ENST00000405334, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: SERPINA3 [Title/Abstract] AND EIF2AK2 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | SERPINA3(95090389)-EIF2AK2(37342384), # 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 |
| Tgene | EIF2AK2 | GO:0006468 | protein phosphorylation | 19189853 |
| Tgene | EIF2AK2 | GO:0017148 | negative regulation of translation | 12882984 |
| Tgene | EIF2AK2 | GO:0035455 | response to interferon-alpha | 19840259 |
| Tgene | EIF2AK2 | GO:0046777 | protein autophosphorylation | 22801494 |
| Tgene | EIF2AK2 | GO:0051092 | positive regulation of NF-kappaB transcription factor activity | 15121867 |
| Tgene | EIF2AK2 | GO:0140374 | antiviral innate immune response | 22948139 |
| Kinase Fusion gene breakpoints across SERPINA3 (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 EIF2AK2 (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-K7-A6G5-01A | SERPINA3 | chr14 | 95090389 | EIF2AK2 | chr2 | 37342384 |
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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/:95090389/:37342384) - 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 |
| SERPINA3 | EIF2AK2 |
| FUNCTION: Although its physiological function is unclear, it can inhibit neutrophil cathepsin G and mast cell chymase, both of which can convert angiotensin-1 to the active angiotensin-2. {ECO:0000269|PubMed:2404007}. | 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 proteasomal 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 pro-inflammatory 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}. |
| 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 SERPINA3_EIF2AK2 |
| 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 |
| EIF2AK2 | P19525 | human | EIF2AK2 | P19525 | S242 | NQRKAKRsLAPRFDL | |
| EIF2AK2 | P19525 | human | EIF2AK2 | P19525 | S83 | NkEKkAVsPLLLttt | |
| EIF2AK2 | P19525 | human | EIF2AK2 | P19525 | T451 | kRtRSKGtLRyMsPE | Pkinase |
| EIF2AK2 | P19525 | human | CDK1 | P06493 | Y4 | ____MEDytkIEkIG | Pkinase |
| EIF2AK2 | P19525 | human | EIF2AK2 | P19525 | Y293 | HRIDGKTyVIKRVkY | Pkinase |
| EIF2AK2 | P19525 | human | MAPT | P10636-8 | S262 | NVKskIGstENLkHQ | Tubulin-binding |
| EIF2AK2 | P19525 | human | KDM4C | Q9H3R0 | S918 | MFDDGsFsRDTFPED | |
| EIF2AK2 | P19525 | human | TP53 | P04637 | S392 | FktEGPDsD______ | |
| EIF2AK2 | P19525 | human | EIF2AK2 | P19525 | T446 | LkNDGkRtRSKGtLR | Pkinase |
| EIF2AK2 | P19525 | human | EIF2AK2 | P19525 | S6 | __MAGDLsAGFFMEE | |
| EIF2AK2 | P19525 | human | EIF2AK2 | P19525 | Y162 | QLAAkLAyLQILSEE | dsrm |
| EIF2AK2 | P19525 | human | EIF2S1 | P05198 | S49 | IEGMILLsELsRRRI | S1 |
| EIF2AK2 | P19525 | human | EIF2AK2 | P19525 | T255 | DLPDMkEtKytVDKR | |
| EIF2AK2 | P19525 | human | MAPT | P10636-8 | S356 | rVQskIGsLDNItHV | Tubulin-binding |
| EIF2AK2 | P19525 | human | EIF2AK2 | P19525 | T89 | VsPLLLtttNssEGL | |
| EIF2AK2 | P19525 | human | EIF2AK2 | P19525 | T88 | AVsPLLLtttNssEG | |
| EIF2AK2 | P19525 | human | PPP2R5A | Q15172 | S28 | VDGFTRKsVRKAQRQ | |
| EIF2AK2 | P19525 | human | TRIM28 | Q13263 | S473 | sGVkRsRsGEGEVsG | |
| EIF2AK2 | P19525 | human | EIF2AK2 | P19525 | T90 | sPLLLtttNssEGLs | |
| EIF2AK2 | P19525 | human | EIF2S1 | P05198 | S52 | MILLsELsRRRIRsI | S1 |
| EIF2AK2 | P19525 | human | EIF2AK2 | P19525 | Y101 | EGLsMGNyIGLINRI | dsrm |
| EIF2AK2 | P19525 | human | EIF2AK2 | P19525 | T258 | DMkEtKytVDKRFGM |
| 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 |
| EIF2AK2 | ID | Description | 0.00e+00 |
| EIF2AK2 | GO:0034599 | cellular response to oxidative stress | 1.67e-03 |
| EIF2AK2 | GO:0062197 | cellular response to chemical stress | 1.98e-03 |
| EIF2AK2 | GO:0006979 | response to oxidative stress | 3.31e-03 |
| EIF2AK2 | GO:0016032 | viral process | 3.36e-03 |
| EIF2AK2 | GO:0072594 | establishment of protein localization to organelle | 3.42e-03 |
| EIF2AK2 | GO:0006606 | protein import into nucleus | 3.95e-03 |
| EIF2AK2 | GO:0051170 | import into nucleus | 3.95e-03 |
| EIF2AK2 | GO:0009267 | cellular response to starvation | 4.33e-03 |
| EIF2AK2 | GO:0034063 | stress granule assembly | 5.56e-03 |
| EIF2AK2 | GO:0042594 | response to starvation | 5.56e-03 |
| EIF2AK2 | GO:0051348 | negative regulation of transferase activity | 5.56e-03 |
| EIF2AK2 | GO:0060218 | hematopoietic stem cell differentiation | 5.56e-03 |
| EIF2AK2 | GO:0043550 | regulation of lipid kinase activity | 5.56e-03 |
| EIF2AK2 | GO:0048863 | stem cell differentiation | 5.56e-03 |
| EIF2AK2 | GO:0033044 | regulation of chromosome organization | 5.56e-03 |
| EIF2AK2 | GO:0042307 | positive regulation of protein import into nucleus | 5.56e-03 |
| EIF2AK2 | GO:0031669 | cellular response to nutrient levels | 5.56e-03 |
| EIF2AK2 | GO:0034976 | response to endoplasmic reticulum stress | 6.24e-03 |
| EIF2AK2 | GO:0006984 | ER-nucleus signaling pathway | 6.48e-03 |
| EIF2AK2 | GO:0031668 | cellular response to extracellular stimulus | 6.60e-03 |
| EIF2AK2 | GO:0034198 | cellular response to amino acid starvation | 7.06e-03 |
| EIF2AK2 | GO:0010823 | negative regulation of mitochondrion organization | 7.06e-03 |
| EIF2AK2 | GO:1990928 | response to amino acid starvation | 7.06e-03 |
| EIF2AK2 | GO:0045071 | negative regulation of viral genome replication | 7.06e-03 |
| EIF2AK2 | GO:0034504 | protein localization to nucleus | 7.06e-03 |
| EIF2AK2 | GO:0019058 | viral life cycle | 7.26e-03 |
| EIF2AK2 | GO:0042306 | regulation of protein import into nucleus | 7.26e-03 |
| EIF2AK2 | GO:0006913 | nucleocytoplasmic transport | 7.32e-03 |
| EIF2AK2 | GO:0051169 | nuclear transport | 7.32e-03 |
| EIF2AK2 | GO:0046824 | positive regulation of nucleocytoplasmic transport | 7.34e-03 |
| EIF2AK2 | GO:0042063 | gliogenesis | 7.34e-03 |
| EIF2AK2 | GO:0071496 | cellular response to external stimulus | 7.62e-03 |
| EIF2AK2 | GO:0034605 | cellular response to heat | 7.70e-03 |
| EIF2AK2 | GO:2000379 | positive regulation of reactive oxygen species metabolic process | 7.77e-03 |
| EIF2AK2 | GO:0010038 | response to metal ion | 7.77e-03 |
| EIF2AK2 | GO:0045936 | negative regulation of phosphate metabolic process | 8.48e-03 |
| EIF2AK2 | GO:0010563 | negative regulation of phosphorus metabolic process | 8.48e-03 |
| EIF2AK2 | GO:0030968 | endoplasmic reticulum unfolded protein response | 8.63e-03 |
| EIF2AK2 | GO:0001701 | in utero embryonic development | 8.87e-03 |
| EIF2AK2 | GO:2000736 | regulation of stem cell differentiation | 8.87e-03 |
| EIF2AK2 | GO:0044773 | mitotic DNA damage checkpoint signaling | 9.79e-03 |
| EIF2AK2 | GO:0045069 | regulation of viral genome replication | 9.94e-03 |
| EIF2AK2 | GO:0043254 | regulation of protein-containing complex assembly | 9.94e-03 |
| EIF2AK2 | GO:0044774 | mitotic DNA integrity checkpoint signaling | 1.00e-02 |
| EIF2AK2 | GO:0034620 | cellular response to unfolded protein | 1.03e-02 |
| EIF2AK2 | GO:0034644 | cellular response to UV | 1.03e-02 |
| EIF2AK2 | GO:0048525 | negative regulation of viral process | 1.05e-02 |
| EIF2AK2 | GO:1900182 | positive regulation of protein localization to nucleus | 1.05e-02 |
| EIF2AK2 | GO:0072091 | regulation of stem cell proliferation | 1.07e-02 |
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Related Drugs to SERPINA3_EIF2AK2 |
| 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 SERPINA3-EIF2AK2 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 SERPINA3_EIF2AK2 |
| 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 |
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