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Kinase Fusion Gene:EPHA4_HSPD1 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: EPHA4_HSPD1 | KinaseFusionDB ID: KFG2001 | FusionGDB2.0 ID: KFG2001 | Hgene | Tgene | Gene symbol | EPHA4 | HSPD1 | Gene ID | 2043 | 3329 | |
| Gene name | EPH receptor A4 | heat shock protein family D (Hsp60) member 1 | ||||||||||
| Synonyms | EK8|HEK8|SEK|TYRO1 | CPN60|GROEL|HLD4|HSP-60|HSP60|HSP65|HuCHA60|SPG13 | ||||||||||
| Cytomap | 2q36.1 | 2q33.1 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | ephrin type-A receptor 4EPH-like kinase 8TYRO1 protein tyrosine kinasereceptor protein-tyrosine kinase HEK8tyrosine-protein kinase TYRO1tyrosine-protein kinase receptor SEK | 60 kDa heat shock protein, mitochondrial60 kDa chaperoninP60 lymphocyte proteinchaperonin 60epididymis secretory sperm binding proteinheat shock 60kDa protein 1 (chaperonin)heat shock protein 65mitochondrial matrix protein P1short heat shock prote | ||||||||||
| Modification date | 20240411 | 20240413 | ||||||||||
| UniProtAcc | P54764 | P10809 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000281821, ENST00000392071, ENST00000409854, ENST00000409938, ENST00000469354, | ENST00000345042, ENST00000388968, ENST00000544407, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: EPHA4 [Title/Abstract] AND HSPD1 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | EPHA4(222358152)-HSPD1(198351308), # 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 | EPHA4 | GO:0018108 | peptidyl-tyrosine phosphorylation | 12775584 |
| Hgene | EPHA4 | GO:0030335 | positive regulation of cell migration | 28795314 |
| Hgene | EPHA4 | GO:0046777 | protein autophosphorylation | 12775584 |
| Hgene | EPHA4 | GO:0070373 | negative regulation of ERK1 and ERK2 cascade | 29093007 |
| Hgene | EPHA4 | GO:2001108 | positive regulation of Rho guanyl-nucleotide exchange factor activity | 12775584 |
| Tgene | HSPD1 | GO:0002755 | MyD88-dependent toll-like receptor signaling pathway | 16148103 |
| Tgene | HSPD1 | GO:0002842 | positive regulation of T cell mediated immune response to tumor cell | 10663613 |
| Tgene | HSPD1 | GO:0006919 | activation of cysteine-type endopeptidase activity involved in apoptotic process | 17823127 |
| Tgene | HSPD1 | GO:0006986 | response to unfolded protein | 11050098 |
| Tgene | HSPD1 | GO:0032727 | positive regulation of interferon-alpha production | 17164250 |
| Tgene | HSPD1 | GO:0032729 | positive regulation of type II interferon production | 17164250 |
| Tgene | HSPD1 | GO:0032729 | positive regulation of type II interferon production | 17164250 |
| Tgene | HSPD1 | GO:0032733 | positive regulation of interleukin-10 production | 16148103 |
| Tgene | HSPD1 | GO:0032735 | positive regulation of interleukin-12 production | 17164250 |
| Tgene | HSPD1 | GO:0032755 | positive regulation of interleukin-6 production | 16148103 |
| Tgene | HSPD1 | GO:0042026 | protein refolding | 11050098 |
| Tgene | HSPD1 | GO:0042100 | B cell proliferation | 16148103 |
| Tgene | HSPD1 | GO:0042110 | T cell activation | 15371451|17164250 |
| Tgene | HSPD1 | GO:0042113 | B cell activation | 16148103 |
| Tgene | HSPD1 | GO:0043032 | positive regulation of macrophage activation | 17164250 |
| Tgene | HSPD1 | GO:0044406 | adhesion of symbiont to host | 20633027 |
| Tgene | HSPD1 | GO:0048291 | isotype switching to IgG isotypes | 16148103 |
| Tgene | HSPD1 | GO:0050870 | positive regulation of T cell activation | 16148103|17164250 |
| Kinase Fusion gene breakpoints across EPHA4 (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 HSPD1 (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 |
| ChiTaRS5.0 | AV697583 | EPHA4 | chr2 | 222358152 | HSPD1 | chr2 | 198351308 |
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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/:222358152/:198351308) - 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 |
| EPHA4 | HSPD1 |
| FUNCTION: Receptor tyrosine kinase which binds membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections. May also control the segregation of motor and sensory axons during neuromuscular circuit development. In addition to its role in axonal guidance plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at 'Tyr-15' which in turn phosphorylates NGEF regulating RHOA and dendritic spine morphogenesis. In the nervous system, also plays a role in repair after injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation. Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for instance the development of the thymic epithelium. During development of the cochlear organ of Corti, regulates pillar cell separation by forming a ternary complex with ADAM10 and CADH1 which facilitates the cleavage of CADH1 by ADAM10 and disruption of adherens junctions (By similarity). Phosphorylates CAPRIN1, promoting CAPRIN1-dependent formation of a membraneless compartment (By similarity). {ECO:0000250|UniProtKB:Q03137, ECO:0000269|PubMed:17143272}. | FUNCTION: Chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp10, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix (PubMed:1346131, PubMed:11422376). The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein (Probable). {ECO:0000269|PubMed:11422376, ECO:0000269|PubMed:1346131, ECO:0000305|PubMed:25918392}. |
| 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 EPHA4_HSPD1 |
| 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 |
| EPHA4 | P54764 | human | EPHA4 | P54764 | Y779 | EDDPEAAyTtRGGKI | PK_Tyr_Ser-Thr |
| EPHA4 | P54764 | human | EPHA4 | P54764 | Y602 | tyVDPFtyEDPNQAV | EphA2_TM |
| EPHA4 | P54764 | human | GMPR | P36959 | Y267 | GRKLKLFyGMssDtA | IMPDH |
| EPHA4 | P54764 | human | EPHA4 | P54764 | Y596 | LNQGVRtyVDPFtyE | EphA2_TM |
| 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 |
| EPHA4 | ID | Description | 0.00e+00 |
| EPHA4 | GO:1905245 | regulation of aspartic-type peptidase activity | 1.99e-02 |
| EPHA4 | GO:0072178 | nephric duct morphogenesis | 1.99e-02 |
| EPHA4 | GO:1900038 | negative regulation of cellular response to hypoxia | 1.99e-02 |
| EPHA4 | GO:1904424 | regulation of GTP binding | 1.99e-02 |
| EPHA4 | GO:0048681 | negative regulation of axon regeneration | 1.99e-02 |
| EPHA4 | GO:1900272 | negative regulation of long-term synaptic potentiation | 1.99e-02 |
| EPHA4 | GO:1905244 | regulation of modification of synaptic structure | 1.99e-02 |
| EPHA4 | GO:0070571 | negative regulation of neuron projection regeneration | 1.99e-02 |
| EPHA4 | GO:0098883 | synapse pruning | 1.99e-02 |
| EPHA4 | GO:0072176 | nephric duct development | 1.99e-02 |
| EPHA4 | GO:0006144 | purine nucleobase metabolic process | 1.99e-02 |
| EPHA4 | GO:1900037 | regulation of cellular response to hypoxia | 1.99e-02 |
| EPHA4 | GO:1902004 | positive regulation of amyloid-beta formation | 1.99e-02 |
| EPHA4 | GO:0007413 | axonal fasciculation | 1.99e-02 |
| EPHA4 | GO:0106030 | neuron projection fasciculation | 1.99e-02 |
| EPHA4 | GO:0008045 | motor neuron axon guidance | 1.99e-02 |
| EPHA4 | GO:1902993 | positive regulation of amyloid precursor protein catabolic process | 1.99e-02 |
| EPHA4 | GO:0150146 | cell junction disassembly | 1.99e-02 |
| EPHA4 | GO:0099563 | modification of synaptic structure | 1.99e-02 |
| EPHA4 | GO:0021952 | central nervous system projection neuron axonogenesis | 1.99e-02 |
| EPHA4 | GO:0048679 | regulation of axon regeneration | 1.99e-02 |
| EPHA4 | GO:0061098 | positive regulation of protein tyrosine kinase activity | 1.99e-02 |
| EPHA4 | GO:0007628 | adult walking behavior | 1.99e-02 |
| EPHA4 | GO:0048710 | regulation of astrocyte differentiation | 1.99e-02 |
| EPHA4 | GO:0070570 | regulation of neuron projection regeneration | 1.99e-02 |
| EPHA4 | GO:0050775 | positive regulation of dendrite morphogenesis | 1.99e-02 |
| EPHA4 | GO:0009112 | nucleobase metabolic process | 1.99e-02 |
| EPHA4 | GO:0090659 | walking behavior | 1.99e-02 |
| EPHA4 | GO:0010770 | positive regulation of cell morphogenesis | 1.99e-02 |
| EPHA4 | GO:0021955 | central nervous system neuron axonogenesis | 1.99e-02 |
| EPHA4 | GO:0061001 | regulation of dendritic spine morphogenesis | 1.99e-02 |
| EPHA4 | GO:0010719 | negative regulation of epithelial to mesenchymal transition | 1.99e-02 |
| EPHA4 | GO:1904646 | cellular response to amyloid-beta | 1.99e-02 |
| EPHA4 | GO:0009409 | response to cold | 1.99e-02 |
| EPHA4 | GO:0008038 | neuron recognition | 1.99e-02 |
| EPHA4 | GO:1900271 | regulation of long-term synaptic potentiation | 1.99e-02 |
| EPHA4 | GO:0090102 | cochlea development | 1.99e-02 |
| EPHA4 | GO:1902003 | regulation of amyloid-beta formation | 1.99e-02 |
| EPHA4 | GO:0048013 | ephrin receptor signaling pathway | 1.99e-02 |
| EPHA4 | GO:0031103 | axon regeneration | 1.99e-02 |
| EPHA4 | GO:1904645 | response to amyloid-beta | 1.99e-02 |
| EPHA4 | GO:1902991 | regulation of amyloid precursor protein catabolic process | 1.99e-02 |
| EPHA4 | GO:0034205 | amyloid-beta formation | 1.99e-02 |
| EPHA4 | GO:0060997 | dendritic spine morphogenesis | 1.99e-02 |
| EPHA4 | GO:0061097 | regulation of protein tyrosine kinase activity | 1.99e-02 |
| EPHA4 | GO:0034332 | adherens junction organization | 1.99e-02 |
| EPHA4 | GO:0031102 | neuron projection regeneration | 1.99e-02 |
| EPHA4 | GO:0008347 | glial cell migration | 2.01e-02 |
| EPHA4 | GO:0048814 | regulation of dendrite morphogenesis | 2.09e-02 |
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Related Drugs to EPHA4_HSPD1 |
| 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 EPHA4-HSPD1 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 EPHA4_HSPD1 |
| 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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