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Kinase Fusion Gene:AP2A2_ACVRL1 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: AP2A2_ACVRL1 | KinaseFusionDB ID: KFG380 | FusionGDB2.0 ID: KFG380 | Hgene | Tgene | Gene symbol | AP2A2 | ACVRL1 | Gene ID | 161 | 94 | |
| Gene name | adaptor related protein complex 2 subunit alpha 2 | activin A receptor like type 1 | ||||||||||
| Synonyms | ADTAB|CLAPA2|HIP-9|HIP9|HYPJ | ACVRLK1|ALK-1|ALK1|HHT|HHT2|ORW2|SKR3|TSR-I | ||||||||||
| Cytomap | 11p15.5 | 12q13.13 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | AP-2 complex subunit alpha-2100 kDa coated vesicle protein Cadapter-related protein complex 2 subunit alpha-2adaptin, alpha Badaptor related protein complex 2 alpha 2 subunitalpha-adaptin C; Huntingtin interacting protein Jalpha2-adaptinclathrin as | serine/threonine-protein kinase receptor R3TGF-B superfamily receptor type Iactivin A receptor type II-like 1activin A receptor type ILactivin A receptor, type II-like kinase 1 | ||||||||||
| Modification date | 20240403 | 20240403 | ||||||||||
| UniProtAcc | O94973 | P37023 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000332231, ENST00000448903, ENST00000525891, ENST00000534328, | ENST00000388922, ENST00000419526, ENST00000550683, ENST00000550084, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: AP2A2 [Title/Abstract] AND ACVRL1 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | AP2A2(1006527)-ACVRL1(52312792), # 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 | AP2A2 | GO:0072583 | clathrin-dependent endocytosis | 23676497 |
| Tgene | ACVRL1 | GO:0007165 | signal transduction | 15702480 |
| Tgene | ACVRL1 | GO:0007179 | transforming growth factor beta receptor signaling pathway | 15702480 |
| Tgene | ACVRL1 | GO:0010596 | negative regulation of endothelial cell migration | 17068149 |
| Tgene | ACVRL1 | GO:0030308 | negative regulation of cell growth | 17068149 |
| Tgene | ACVRL1 | GO:0030509 | BMP signaling pathway | 12065756|22718755 |
| Tgene | ACVRL1 | GO:0030513 | positive regulation of BMP signaling pathway | 17068149 |
| Tgene | ACVRL1 | GO:0045893 | positive regulation of DNA-templated transcription | 12393874 |
| Tgene | ACVRL1 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 19366699 |
| Tgene | ACVRL1 | GO:0071560 | cellular response to transforming growth factor beta stimulus | 19494318 |
| Kinase Fusion gene breakpoints across AP2A2 (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 ACVRL1 (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 | AA368346 | AP2A2 | chr11 | 1006527 | ACVRL1 | chr12 | 52312792 |
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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/:1006527/:52312792) - 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 |
| AP2A2 | ACVRL1 |
| 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:12960147, ECO:0000269|PubMed:14745134, ECO:0000269|PubMed:15473838, ECO:0000269|PubMed:19033387, ECO:0000269|PubMed:23676497}. | FUNCTION: Type I receptor for TGF-beta family ligands BMP9/GDF2 and BMP10 and important regulator of normal blood vessel development. On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. May bind activin as well. {ECO:0000269|PubMed:22718755, ECO:0000269|PubMed:22799562, ECO:0000269|PubMed:26176610}. |
| 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 AP2A2_ACVRL1 |
| 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 |
| ACVRL1 | P37023 | human | ENG | P17813 | S646 | StNHSIGsTQstPCS | |
| ACVRL1 | P37023 | human | ENG | P17813 | T640 | AssESSStNHSIGsT | |
| ACVRL1 | P37023 | human | ENG | P17813 | T654 | TQstPCStSSMA___ | |
| ACVRL1 | P37023 | human | ENG | P17813 | S649 | HSIGsTQstPCStSS |
| 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 |
| ACVRL1 | ID | Description | 0.00e+00 |
| ACVRL1 | GO:0035907 | dorsal aorta development | 8.94e-03 |
| ACVRL1 | GO:0062042 | regulation of cardiac epithelial to mesenchymal transition | 8.94e-03 |
| ACVRL1 | GO:0031953 | negative regulation of protein autophosphorylation | 8.94e-03 |
| ACVRL1 | GO:0097084 | vascular associated smooth muscle cell development | 8.94e-03 |
| ACVRL1 | GO:0036302 | atrioventricular canal development | 8.94e-03 |
| ACVRL1 | GO:0070278 | extracellular matrix constituent secretion | 8.94e-03 |
| ACVRL1 | GO:1905065 | positive regulation of vascular associated smooth muscle cell differentiation | 8.94e-03 |
| ACVRL1 | GO:0003222 | ventricular trabecula myocardium morphogenesis | 8.94e-03 |
| ACVRL1 | GO:0003198 | epithelial to mesenchymal transition involved in endocardial cushion formation | 8.94e-03 |
| ACVRL1 | GO:0060841 | venous blood vessel development | 8.94e-03 |
| ACVRL1 | GO:0051152 | positive regulation of smooth muscle cell differentiation | 8.94e-03 |
| ACVRL1 | GO:0060973 | cell migration involved in heart development | 8.94e-03 |
| ACVRL1 | GO:0003228 | atrial cardiac muscle tissue development | 8.94e-03 |
| ACVRL1 | GO:0003148 | outflow tract septum morphogenesis | 8.94e-03 |
| ACVRL1 | GO:1905063 | regulation of vascular associated smooth muscle cell differentiation | 8.94e-03 |
| ACVRL1 | GO:0032967 | positive regulation of collagen biosynthetic process | 8.94e-03 |
| ACVRL1 | GO:0010714 | positive regulation of collagen metabolic process | 8.94e-03 |
| ACVRL1 | GO:0048745 | smooth muscle tissue development | 8.94e-03 |
| ACVRL1 | GO:0003272 | endocardial cushion formation | 8.94e-03 |
| ACVRL1 | GO:0003209 | cardiac atrium morphogenesis | 8.94e-03 |
| ACVRL1 | GO:0061384 | heart trabecula morphogenesis | 8.94e-03 |
| ACVRL1 | GO:0060317 | cardiac epithelial to mesenchymal transition | 8.94e-03 |
| ACVRL1 | GO:0001569 | branching involved in blood vessel morphogenesis | 8.94e-03 |
| ACVRL1 | GO:0003230 | cardiac atrium development | 8.94e-03 |
| ACVRL1 | GO:0032965 | regulation of collagen biosynthetic process | 8.94e-03 |
| ACVRL1 | GO:0035909 | aorta morphogenesis | 8.94e-03 |
| ACVRL1 | GO:0035886 | vascular associated smooth muscle cell differentiation | 8.94e-03 |
| ACVRL1 | GO:0003203 | endocardial cushion morphogenesis | 8.94e-03 |
| ACVRL1 | GO:0031952 | regulation of protein autophosphorylation | 8.94e-03 |
| ACVRL1 | GO:0030513 | positive regulation of BMP signaling pathway | 8.94e-03 |
| ACVRL1 | GO:0010712 | regulation of collagen metabolic process | 8.94e-03 |
| ACVRL1 | GO:0051150 | regulation of smooth muscle cell differentiation | 8.94e-03 |
| ACVRL1 | GO:0055010 | ventricular cardiac muscle tissue morphogenesis | 8.94e-03 |
| ACVRL1 | GO:0061383 | trabecula morphogenesis | 8.94e-03 |
| ACVRL1 | GO:0032964 | collagen biosynthetic process | 8.94e-03 |
| ACVRL1 | GO:0003197 | endocardial cushion development | 9.42e-03 |
| ACVRL1 | GO:0072132 | mesenchyme morphogenesis | 9.86e-03 |
| ACVRL1 | GO:0003229 | ventricular cardiac muscle tissue development | 9.86e-03 |
| ACVRL1 | GO:0010718 | positive regulation of epithelial to mesenchymal transition | 9.86e-03 |
| ACVRL1 | GO:0055008 | cardiac muscle tissue morphogenesis | 9.94e-03 |
| ACVRL1 | GO:0001947 | heart looping | 9.99e-03 |
| ACVRL1 | GO:0035904 | aorta development | 9.99e-03 |
| ACVRL1 | GO:0061371 | determination of heart left/right asymmetry | 9.99e-03 |
| ACVRL1 | GO:0003143 | embryonic heart tube morphogenesis | 9.99e-03 |
| ACVRL1 | GO:0003208 | cardiac ventricle morphogenesis | 9.99e-03 |
| ACVRL1 | GO:0060411 | cardiac septum morphogenesis | 9.99e-03 |
| ACVRL1 | GO:0071260 | cellular response to mechanical stimulus | 9.99e-03 |
| ACVRL1 | GO:0060415 | muscle tissue morphogenesis | 1.00e-02 |
| ACVRL1 | GO:0051145 | smooth muscle cell differentiation | 1.00e-02 |
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Related Drugs to AP2A2_ACVRL1 |
| 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 AP2A2-ACVRL1 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 AP2A2_ACVRL1 |
| 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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