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Kinase Fusion Gene:ATG3_EPHB1 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: ATG3_EPHB1 | KinaseFusionDB ID: KFG469 | FusionGDB2.0 ID: KFG469 | Hgene | Tgene | Gene symbol | ATG3 | EPHB1 | Gene ID | 64422 | 2047 | |
| Gene name | autophagy related 3 | EPH receptor B1 | ||||||||||
| Synonyms | APG3|APG3-LIKE|APG3L|PC3-96|hApg3 | ELK|EPHT2|Hek6|NET | ||||||||||
| Cytomap | 3q13.2 | 3q22.2 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | ubiquitin-like-conjugating enzyme ATG3APG3 autophagy 3-likeATG3 autophagy related 3 homologautophagy-related protein 3 | ephrin type-B receptor 1EK6EPH-like kinase 6eph tyrosine kinase 2neuronally-expressed EPH-related tyrosine kinasetyrosine-protein kinase receptor EPH-2 | ||||||||||
| Modification date | 20240411 | 20240411 | ||||||||||
| UniProtAcc | Q9NT62 | P54762 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000283290, ENST00000402314, ENST00000495756, | ENST00000488154, ENST00000493838, ENST00000398015, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: ATG3 [Title/Abstract] AND EPHB1 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | ATG3(112277222)-EPHB1(134880858), # 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 | ATG3 | GO:0016567 | protein ubiquitination | 11825910 |
| Tgene | EPHB1 | GO:0001525 | angiogenesis | 9499402 |
| Tgene | EPHB1 | GO:0031589 | cell-substrate adhesion | 9430661 |
| Tgene | EPHB1 | GO:0046328 | regulation of JNK cascade | 9430661 |
| Tgene | EPHB1 | GO:0046777 | protein autophosphorylation | 18034775 |
| Tgene | EPHB1 | GO:0048013 | ephrin receptor signaling pathway | 12925710|18034775 |
| Tgene | EPHB1 | GO:0060326 | cell chemotaxis | 12925710 |
| Tgene | EPHB1 | GO:0070372 | regulation of ERK1 and ERK2 cascade | 12925710|18034775 |
| Kinase Fusion gene breakpoints across ATG3 (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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| Kinase Fusion gene breakpoints across EPHB1 (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 | LQ657557 | ATG3 | chr3 | 112277222 | EPHB1 | chr3 | 134880858 |
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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) |
| ENST00000283290 | ENST00000398015 | ATG3 | chr3 | 112277222 | EPHB1 | chr3 | 134880858 | 3429 | 572 |
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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 >ENST00000283290_ENST00000398015_ATG3_chr3_112277222_EPHB1_chr3_134880858_length(amino acids)=572 MTPWPLTRLHFPSRRGAGRYSGPRMQNVINTVKGKALEVAEYLTPVLKESKFKETGVITPEEEHNEFNSSMARSQTNTARIDGLRPGMVY VVQVRARTVAGYGKFSGKMCFQTLTDDDYKSELREQLPLIAGSAAAGVVFVVSLVAISIVCSRKRAYSKEAVYSDKLQHYSTGRGSPGMK IYIDPFTYEDPNEAVREFAKEIDVSFVKIEEVIGAGEFGEVYKGRLKLPGKREIYVAIKTLKAGYSEKQRRDFLSEASIMGQFDHPNIIR LEGVVTKSRPVMIITEFMENGALDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLAEMNYVHRDLAARNILVNSNLVCKVSDFGLSRYLQDD TSDPTYTSSLGGKIPVRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSFGERPYWDMSNQDVINAIEQDYRLPPPMDCPAALHQLMLDCWQ KDRNSRPRFAEIVNTLDKMIRNPASLKTVATITAVPSQPLLDRSIPDFTAFTTVDDWLSAIKMVQYRDSFLTAGFTSLQLVTQMTSEDLL -------------------------------------------------------------- |
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/chr3:112277222/chr3:134880858) - 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 |
| ATG3 | EPHB1 |
| FUNCTION: E2 conjugating enzyme required for the cytoplasm to vacuole transport (Cvt), autophagy, and mitochondrial homeostasis. Responsible for the E2-like covalent binding of phosphatidylethanolamine to the C-terminal Gly of ATG8-like proteins (GABARAP, GABARAPL1, GABARAPL2 or MAP1LC3A). The ATG12-ATG5 conjugate plays a role of an E3 and promotes the transfer of ATG8-like proteins from ATG3 to phosphatidylethanolamine (PE). This step is required for the membrane association of ATG8-like proteins. The formation of the ATG8-phosphatidylethanolamine conjugates is essential for autophagy and for the cytoplasm to vacuole transport (Cvt). Preferred substrate is MAP1LC3A. Also acts as an autocatalytic E2-like enzyme, catalyzing the conjugation of ATG12 to itself, ATG12 conjugation to ATG3 playing a role in mitochondrial homeostasis but not in autophagy. ATG7 (E1-like enzyme) facilitates this reaction by forming an E1-E2 complex with ATG3. Promotes primary ciliogenesis by removing OFD1 from centriolar satellites via the autophagic pathway. {ECO:0000269|PubMed:11825910, ECO:0000269|PubMed:12207896, ECO:0000269|PubMed:12890687, ECO:0000269|PubMed:16704426, ECO:0000269|PubMed:20723759}. | FUNCTION: Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B 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. Cognate/functional ephrin ligands for this receptor include EFNB1, EFNB2 and EFNB3. During nervous system development, regulates retinal axon guidance redirecting ipsilaterally ventrotemporal retinal ganglion cells axons at the optic chiasm midline. This probably requires repulsive interaction with EFNB2. In the adult nervous system together with EFNB3, regulates chemotaxis, proliferation and polarity of the hippocampus neural progenitors. In addition to its role in axon guidance also plays an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and synapse formation. May also regulate angiogenesis. More generally, may play a role in targeted cell migration and adhesion. Upon activation by EFNB1 and probably other ephrin-B ligands activates the MAPK/ERK and the JNK signaling cascades to regulate cell migration and adhesion respectively. Involved in the maintenance of the pool of satellite cells (muscle stem cells) by promoting their self-renewal and reducing their activation and differentiation (By similarity). {ECO:0000250|UniProtKB:Q8CBF3, ECO:0000269|PubMed:12223469, ECO:0000269|PubMed:12925710, ECO:0000269|PubMed:18034775, ECO:0000269|PubMed:9430661, ECO:0000269|PubMed:9499402}. |
| 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 |
| Tgene | ATG3 | 112277222 | EPHB1 | 134880858 | ENST00000283290 | 5 | 16 | 619_882 | 474 | 985 | Domain | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Tgene | ATG3 | 112277222 | EPHB1 | 134880858 | ENST00000283290 | 5 | 16 | 911_975 | 474 | 985 | Domain | Note=SAM;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00184 |
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Kinase Fusion Protein Structures |
| CIF files of the predicted kinase 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. |
| Kinase Fusion protein CIF link (fusion AA seq ID in KinaseFusionDB) | Henst | Tenst | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | AA seq | Len(AA seq) |
| PDB file >>>38_ATG3_EPHB1 | ENST00000283290 | ENST00000398015 | ATG3 | chr3 | 112277222 | EPHB1 | chr3 | 134880858 | MTPWPLTRLHFPSRRGAGRYSGPRMQNVINTVKGKALEVAEYLTPVLKESKFKETGVITPEEEHNEFNSSMARSQTNTARIDGLRPGMVY VVQVRARTVAGYGKFSGKMCFQTLTDDDYKSELREQLPLIAGSAAAGVVFVVSLVAISIVCSRKRAYSKEAVYSDKLQHYSTGRGSPGMK IYIDPFTYEDPNEAVREFAKEIDVSFVKIEEVIGAGEFGEVYKGRLKLPGKREIYVAIKTLKAGYSEKQRRDFLSEASIMGQFDHPNIIR LEGVVTKSRPVMIITEFMENGALDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLAEMNYVHRDLAARNILVNSNLVCKVSDFGLSRYLQDD TSDPTYTSSLGGKIPVRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSFGERPYWDMSNQDVINAIEQDYRLPPPMDCPAALHQLMLDCWQ KDRNSRPRFAEIVNTLDKMIRNPASLKTVATITAVPSQPLLDRSIPDFTAFTTVDDWLSAIKMVQYRDSFLTAGFTSLQLVTQMTSEDLL | 572 |
| 3D view using mol* of 38_ATG3_EPHB1 | ||||||||||
| PDB file >>>TKFP_59_ATG3_EPHB1 | ENST00000283290 | ENST00000398015 | ATG3 | chr3 | 112277222 | EPHB1 | chr3 | 134880858 | MTPWPLTRLHFPSRRGAGRYSGPRMQNVINTVKGKALEVAEYLTPVLKESKFKETGVITPEEEHNEFNSSMARSQTNTARIDGLRPGMVY VVQVRARTVAGYGKFSGKMCFQTLTDDDYKSELREQLPLIAGSAAAGVVFVVSLVAISIVCSRKRAYSKEAVYSDKLQHYSTGRGSPGMK IYIDPFTYEDPNEAVREFAKEIDVSFVKIEEVIGAGEFGEVYKGRLKLPGKREIYVAIKTLKAGYSEKQRRDFLSEASIMGQFDHPNIIR LEGVVTKSRPVMIITEFMENGALDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLAEMNYVHRDLAARNILVNSNLVCKVSDFGLSRYLQDD TSDPTYTSSLGGKIPVRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSFGERPYWDMSNQDVINAIEQDYRLPPPMDCPAALHQLMLDCWQ KDRNSRPRFAEIVNTLDKMIRNPASLKTVATITAVPSQPLLDRSIPDFTAFTTVDDWLSAIKMVQYRDSFLTAGFTSLQLVTQMTSEDLL | 572_ATG3_EPHB1 |
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Comparison of Fusion Protein Isoforms |
| Superimpose the 3D Structures Among All Fusion Protein Isoforms * Download the pdb file and open it from the molstar online viewer. |
| Comparison of the Secondary Structures of Fusion Protein Isoforms |
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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB |
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pLDDT score distribution |
| pLDDT score distribution of the predicted fusion protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. * The blue color at the bottom marks the best active site residues. |
| 38_ATG3_EPHB1.png |
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| 38_ATG3_EPHB1.png |
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Potential Active Site Information |
| The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite. |
| Kinase Fusion AA seq ID in KinaseFusionDB | Site score | Size | Dscore | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
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Ramachandran Plot of Kinase 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. |
| 38_ATG3_EPHB1_ramachandran.png |
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Virtual Screening Results |
| Distribution of the average docking score across all approved kinase inhibitors. Distribution of the number of occurrence across all approved kinase inhibitors. |
| 5'-kinase fusion protein case |
| 3'-kinase fusion protein case |
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| Drug information from DrugBank of the top 20 interacting small molecules. * The detailed information of individual kinase inhibitors are available in the download page. |
| Fusion gene name info | Drug | Docking score | Glide g score | Glide energy |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Pacritinib | -7.00617 | -7.01127 | -45.4731 |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Gilteritinib | -6.5176 | -6.544 | -51.2158 |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Gilteritinib | -6.5176 | -6.544 | -51.2158 |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Gilteritinib | -6.5176 | -6.544 | -51.2158 |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Gilteritinib | -6.5176 | -6.544 | -51.2158 |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Encorafenib | -6.43561 | -6.824110000000001 | -58.6633 |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Pazopanib | -6.4131 | -6.42 | -47.3278 |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Pazopanib | -6.4131 | -6.42 | -47.3278 |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Lapatinib | -6.3025400000000005 | -6.3913400000000005 | -62.0101 |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Lapatinib | -6.29138 | -6.38018 | -61.2563 |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Encorafenib | -6.14433 | -6.532830000000001 | -57.3102 |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Vemurafenib | -5.81154 | -6.19074 | -49.6153 |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Vemurafenib | -5.81154 | -6.19074 | -49.6153 |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Pacritinib | -5.804119999999999 | -5.80922 | -40.4311 |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Netarsudil | -5.80002 | -5.81112 | -47.9485 |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Netarsudil | -5.80002 | -5.81112 | -47.9485 |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Avapritinib | -5.61641 | -5.94771 | -44.2511 |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Avapritinib | -5.61641 | -5.94771 | -44.2511 |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Avapritinib | -5.61641 | -5.94771 | -44.2511 |
| 38_ATG3_EPHB1-DOCK_HTVS_1-001 | Avapritinib | -5.61641 | -5.94771 | -44.2511 |
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Kinase-Substrate Information of ATG3_EPHB1 |
| 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 |
| EPHB1 | P54762 | human | GJB1 | P08034 | Y243 | GHRLsPEyKQNEINk |
| 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 |
| EPHB1 | ID | Description | 0.00e+00 |
| EPHB1 | GO:0016264 | gap junction assembly | 5.83e-03 |
| EPHB1 | GO:0015868 | purine ribonucleotide transport | 5.83e-03 |
| EPHB1 | GO:0015865 | purine nucleotide transport | 5.83e-03 |
| EPHB1 | GO:0006862 | nucleotide transport | 5.83e-03 |
| EPHB1 | GO:1901264 | carbohydrate derivative transport | 9.01e-03 |
| EPHB1 | GO:0015748 | organophosphate ester transport | 1.19e-02 |
| EPHB1 | GO:0007043 | cell-cell junction assembly | 1.19e-02 |
| EPHB1 | GO:0045216 | cell-cell junction organization | 1.32e-02 |
| EPHB1 | GO:0015931 | nucleobase-containing compound transport | 1.32e-02 |
| EPHB1 | GO:0034329 | cell junction assembly | 2.36e-02 |
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Related Drugs to ATG3_EPHB1 |
| 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 ATG3-EPHB1 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 ATG3_EPHB1 |
| 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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