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Kinase Fusion Gene:AP2A1_VRK3 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: AP2A1_VRK3 | KinaseFusionDB ID: KFG379 | FusionGDB2.0 ID: KFG379 | Hgene | Tgene | Gene symbol | AP2A1 | VRK3 | Gene ID | 160 | 51231 | |
| Gene name | adaptor related protein complex 2 subunit alpha 1 | VRK serine/threonine kinase 3 | ||||||||||
| Synonyms | ADTAA|AP2-ALPHA|CLAPA1 | - | ||||||||||
| Cytomap | 19q13.33 | 19q13.33 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | AP-2 complex subunit alpha-1100 kDa coated vesicle protein Aadapter-related protein complex 2 alpha-1 subunitadapter-related protein complex 2 subunit alpha-1adaptin, alpha Aadaptor protein complex AP-2 subunit alpha-1adaptor related protein complex | inactive serine/threonine-protein kinase VRK3serine/threonine-protein kinase VRK3serine/threonine-protein pseudokinase VRK3vaccinia related kinase 3 | ||||||||||
| Modification date | 20240407 | 20240411 | ||||||||||
| UniProtAcc | O95782 | Q8IV63 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000600199, ENST00000354293, ENST00000359032, | ENST00000316763, ENST00000377011, ENST00000443401, ENST00000594948, ENST00000599538, ENST00000601341, ENST00000424804, ENST00000593919, ENST00000594092, ENST00000601912, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: AP2A1 [Title/Abstract] AND VRK3 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | AP2A1(50295321)-VRK3(50482499), # samples:2 | |||||||||||
| 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 | AP2A1 | GO:0072583 | clathrin-dependent endocytosis | 23676497 |
| Hgene | AP2A1 | GO:1900126 | negative regulation of hyaluronan biosynthetic process | 24251095 |
| Kinase Fusion gene breakpoints across AP2A1 (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 VRK3 (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-D3-A2JN-06A | AP2A1 | chr19 | 50295321 | VRK3 | chr19 | 50482499 |
| ChimerDB4 | TCGA-IR-A3LH-01A | AP2A1 | chr19 | 50308833 | VRK3 | chr19 | 50482499 |
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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) |
| ENST00000354293 | ENST00000316763 | AP2A1 | chr19 | 50308833 | VRK3 | chr19 | 50482499 | 3112 | 870 |
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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 >ENST00000354293_ENST00000316763_AP2A1_chr19_50308833_VRK3_chr19_50482499_length(amino acids)=870 MALPGVLSARSPLASPRCSVPCPARPGADTTAIMPAVSKGDGMRGLAVFISDIRNCKSKEAEIKRINKELANIRSKFKGDKALDGYSKKK YVCKLLFIFLLGHDIDFGHMEAVNLLSSNKYTEKQIGYLFISVLVNSNSELIRLINNAIKNDLASRNPTFMCLALHCIANVGSREMGEAF AADIPRILVAGDSMDSVKQSAALCLLRLYKASPDLVPMGEWTARVVHLLNDQHMGVVTAAVSLITCLCKKNPDDFKTCVSLAVSRLSRIV SSASTDLQDYTYYFVPAPWLSVKLLRLLQCYPPPEDAAVKGRLVECLETVLNKAQEPPKSKKVQHSNAKNAILFETISLIIHYDSEPNLL VRACNQLGQFLQHRETNLRYLALESMCTLASSEFSHEAVKTHIDTVINALKTERDVSVRQRAADLLYAMCDRSNAKQIVSEMLRYLETAD YAIREEIVLKVAILAEKYAVDYSWYVDTILNLIRIAGDYVSEEVWYRVLQIVTNRDDVQGYAAKTVFEALQAPACHENMVKVGGYILGEF GNLIAGDPRSSPPVQFSLLHSKFHLCSVATRALLLSTYIKFINLFPETKATIQGVLRAGSQLRNADVELQQRAVEYLTLSSVASTDVLAT VLEEMPPFPERESSILAKLKRKKGPGAGSALDDGRRDPSSNDINGGMEPTPSTVSTPSPSADLLGLRAAPPPAAPPASAGAGNLLVDVFD GPAAQPSLGPTPEEAFLSPGPEDIGPPIPEADELLNKFVCKNNGVLFENQLLQIGVKSEFRQNLGRMYLFYGNKTSVQFQNFSPTVVHPG -------------------------------------------------------------- |
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/chr19:50295321/chr19:50482499) - 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 |
| AP2A1 | VRK3 |
| FUNCTION: Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 alpha subunit binds polyphosphoinositide-containing lipids, positioning AP-2 on the membrane. The AP-2 alpha subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity). {ECO:0000250, ECO:0000269|PubMed:14745134, ECO:0000269|PubMed:15473838, ECO:0000269|PubMed:19033387, ECO:0000269|PubMed:23676497}. | FUNCTION: Inactive kinase that suppresses ERK activity by promoting phosphatase activity of DUSP3 which specifically dephosphorylates and inactivates ERK in the nucleus. {ECO:0000250, ECO:0000269|PubMed:14645249, ECO:0000269|PubMed:19141289}. |
| 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 | AP2A1 | 50308833 | VRK3 | 50482499 | ENST00000354293 | 0 | 13 | 166_457 | 0 | 413 | Domain | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
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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 >>>29_AP2A1_VRK3 | ENST00000354293 | ENST00000316763 | AP2A1 | chr19 | 50308833 | VRK3 | chr19 | 50482499 | MALPGVLSARSPLASPRCSVPCPARPGADTTAIMPAVSKGDGMRGLAVFISDIRNCKSKEAEIKRINKELANIRSKFKGDKALDGYSKKK YVCKLLFIFLLGHDIDFGHMEAVNLLSSNKYTEKQIGYLFISVLVNSNSELIRLINNAIKNDLASRNPTFMCLALHCIANVGSREMGEAF AADIPRILVAGDSMDSVKQSAALCLLRLYKASPDLVPMGEWTARVVHLLNDQHMGVVTAAVSLITCLCKKNPDDFKTCVSLAVSRLSRIV SSASTDLQDYTYYFVPAPWLSVKLLRLLQCYPPPEDAAVKGRLVECLETVLNKAQEPPKSKKVQHSNAKNAILFETISLIIHYDSEPNLL VRACNQLGQFLQHRETNLRYLALESMCTLASSEFSHEAVKTHIDTVINALKTERDVSVRQRAADLLYAMCDRSNAKQIVSEMLRYLETAD YAIREEIVLKVAILAEKYAVDYSWYVDTILNLIRIAGDYVSEEVWYRVLQIVTNRDDVQGYAAKTVFEALQAPACHENMVKVGGYILGEF GNLIAGDPRSSPPVQFSLLHSKFHLCSVATRALLLSTYIKFINLFPETKATIQGVLRAGSQLRNADVELQQRAVEYLTLSSVASTDVLAT VLEEMPPFPERESSILAKLKRKKGPGAGSALDDGRRDPSSNDINGGMEPTPSTVSTPSPSADLLGLRAAPPPAAPPASAGAGNLLVDVFD GPAAQPSLGPTPEEAFLSPGPEDIGPPIPEADELLNKFVCKNNGVLFENQLLQIGVKSEFRQNLGRMYLFYGNKTSVQFQNFSPTVVHPG | 870 |
| 3D view using mol* of 29_AP2A1_VRK3 | ||||||||||
| PDB file >>>TKFP_45_AP2A1_VRK3 | ENST00000354293 | ENST00000316763 | AP2A1 | chr19 | 50308833 | VRK3 | chr19 | 50482499 | MALPGVLSARSPLASPRCSVPCPARPGADTTAIMPAVSKGDGMRGLAVFISDIRNCKSKEAEIKRINKELANIRSKFKGDKALDGYSKKK YVCKLLFIFLLGHDIDFGHMEAVNLLSSNKYTEKQIGYLFISVLVNSNSELIRLINNAIKNDLASRNPTFMCLALHCIANVGSREMGEAF AADIPRILVAGDSMDSVKQSAALCLLRLYKASPDLVPMGEWTARVVHLLNDQHMGVVTAAVSLITCLCKKNPDDFKTCVSLAVSRLSRIV SSASTDLQDYTYYFVPAPWLSVKLLRLLQCYPPPEDAAVKGRLVECLETVLNKAQEPPKSKKVQHSNAKNAILFETISLIIHYDSEPNLL VRACNQLGQFLQHRETNLRYLALESMCTLASSEFSHEAVKTHIDTVINALKTERDVSVRQRAADLLYAMCDRSNAKQIVSEMLRYLETAD YAIREEIVLKVAILAEKYAVDYSWYVDTILNLIRIAGDYVSEEVWYRVLQIVTNRDDVQGYAAKTVFEALQAPACHENMVKVGGYILGEF GNLIAGDPRSSPPVQFSLLHSKFHLCSVATRALLLSTYIKFINLFPETKATIQGVLRAGSQLRNADVELQQRAVEYLTLSSVASTDVLAT VLEEMPPFPERESSILAKLKRKKGPGAGSALDDGRRDPSSNDINGGMEPTPSTVSTPSPSADLLGLRAAPPPAAPPASAGAGNLLVDVFD GPAAQPSLGPTPEEAFLSPGPEDIGPPIPEADELLNKFVCKNNGVLFENQLLQIGVKSEFRQNLGRMYLFYGNKTSVQFQNFSPTVVHPG | 870_AP2A1_VRK3 |
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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. |
| 29_AP2A1_VRK3.png |
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| 29_AP2A1_VRK3.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. |
| 29_AP2A1_VRK3_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 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Lapatinib | -8.33191 | -8.42071 | -59.049 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Lapatinib | -8.31136 | -8.400160000000001 | -58.1586 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Netarsudil | -7.329289999999999 | -7.340389999999999 | -49.028 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Netarsudil | -7.329289999999999 | -7.340389999999999 | -49.028 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Trametinib | -7.25553 | -7.25553 | -45.5568 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Mobocertinib | -7.1311800000000005 | -7.13888 | -54.1342 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Gilteritinib | -7.114439999999999 | -7.14084 | -52.6277 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Gilteritinib | -7.114439999999999 | -7.14084 | -52.6277 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Larotrectinib | -7.11335 | -7.11335 | -46.4588 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Tepotinib | -7.00317 | -7.00427 | -56.5679 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Osimertinib | -6.88997 | -6.89767 | -55.8718 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Crizotinib | -6.876519999999999 | -7.37242 | -41.5569 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Crizotinib | -6.876519999999999 | -7.37242 | -41.5569 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Axitinib | -6.87193 | -6.87513 | -46.9754 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Crizotinib | -6.78185 | -7.27775 | -41.7355 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Crizotinib | -6.78185 | -7.27775 | -41.7355 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Pazopanib | -6.754289999999999 | -6.761189999999999 | -47.7993 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Pazopanib | -6.754289999999999 | -6.761189999999999 | -47.7993 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Tepotinib | -6.7492600000000005 | -6.750360000000001 | -54.293 |
| 29_AP2A1_VRK3-DOCK_HTVS_1-001 | Tepotinib | -6.6958899999999995 | -6.6969899999999996 | -53.7768 |
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Kinase-Substrate Information of AP2A1_VRK3 |
| 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 |
| VRK3 | Q8IV63 | human | BANF1 | O75531 | S4 | ____MttsQkHRDFV | BAF |
| 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 |
| VRK3 | ID | Description | 0.00e+00 |
| VRK3 | GO:0007084 | mitotic nuclear membrane reassembly | 7.81e-03 |
| VRK3 | GO:0101024 | mitotic nuclear membrane organization | 7.81e-03 |
| VRK3 | GO:0015074 | DNA integration | 7.81e-03 |
| VRK3 | GO:0031468 | nuclear membrane reassembly | 1.15e-02 |
| VRK3 | GO:0071763 | nuclear membrane organization | 1.15e-02 |
| VRK3 | GO:0032480 | negative regulation of type I interferon production | 1.15e-02 |
| VRK3 | GO:0006998 | nuclear envelope organization | 1.15e-02 |
| VRK3 | GO:0045071 | negative regulation of viral genome replication | 1.15e-02 |
| VRK3 | GO:0071709 | membrane assembly | 1.15e-02 |
| VRK3 | GO:0044091 | membrane biogenesis | 1.15e-02 |
| VRK3 | GO:0045069 | regulation of viral genome replication | 1.29e-02 |
| VRK3 | GO:0045824 | negative regulation of innate immune response | 1.29e-02 |
| VRK3 | GO:0048525 | negative regulation of viral process | 1.29e-02 |
| VRK3 | GO:0032479 | regulation of type I interferon production | 1.42e-02 |
| VRK3 | GO:0032606 | type I interferon production | 1.42e-02 |
| VRK3 | GO:0019079 | viral genome replication | 1.42e-02 |
| VRK3 | GO:1903900 | regulation of viral life cycle | 1.42e-02 |
| VRK3 | GO:0006997 | nucleus organization | 1.42e-02 |
| VRK3 | GO:0002832 | negative regulation of response to biotic stimulus | 1.42e-02 |
| VRK3 | GO:0050792 | regulation of viral process | 1.51e-02 |
| VRK3 | GO:0050777 | negative regulation of immune response | 1.76e-02 |
| VRK3 | GO:0051348 | negative regulation of transferase activity | 1.84e-02 |
| VRK3 | GO:0140014 | mitotic nuclear division | 2.15e-02 |
| VRK3 | GO:0019058 | viral life cycle | 2.31e-02 |
| VRK3 | GO:0031348 | negative regulation of defense response | 2.31e-02 |
| VRK3 | GO:0001818 | negative regulation of cytokine production | 2.56e-02 |
| VRK3 | GO:0006979 | response to oxidative stress | 2.56e-02 |
| VRK3 | GO:0045088 | regulation of innate immune response | 2.56e-02 |
| VRK3 | GO:0016032 | viral process | 2.56e-02 |
| VRK3 | GO:0009615 | response to virus | 2.56e-02 |
| VRK3 | GO:0000280 | nuclear division | 2.56e-02 |
| VRK3 | GO:0043086 | negative regulation of catalytic activity | 2.59e-02 |
| VRK3 | GO:0032102 | negative regulation of response to external stimulus | 2.59e-02 |
| VRK3 | GO:0048285 | organelle fission | 2.59e-02 |
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Related Drugs to AP2A1_VRK3 |
| 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 AP2A1-VRK3 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 AP2A1_VRK3 |
| 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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