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Fusion Protein:APPL1-ABHD6 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: APPL1-ABHD6 | FusionPDB ID: 5676 | FusionGDB2.0 ID: 5676 | Hgene | Tgene | Gene symbol | APPL1 | ABHD6 | Gene ID | 26060 | 57406 |
| Gene name | adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 | abhydrolase domain containing 6, acylglycerol lipase | |
| Synonyms | APPL|DIP13alpha|MODY14 | - | |
| Cytomap | 3p14.3 | 3p14.3 | |
| Type of gene | protein-coding | protein-coding | |
| Description | DCC-interacting protein 13-alphaAKT2 interactoradapter protein containing PH domain, PTB domain and leucine zipper motif 1adaptor protein containing pH domain, PTB domain and leucine zipper motif 1adaptor protein, phosphotyrosine interaction, PH domai | monoacylglycerol lipase ABHD62-arachidonoylglycerol hydrolaseabhydrolase domain containing 6abhydrolase domain-containing protein 6lipase protein | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | Q9UKG1 | Q9BV23 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000288266, | ENST00000480457, ENST00000478253, ENST00000295962, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 6 X 5 X 6=180 | 6 X 5 X 5=150 |
| # samples | 6 | 6 | |
| ** MAII score | log2(6/180*10)=-1.58496250072116 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(6/150*10)=-1.32192809488736 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: APPL1 [Title/Abstract] AND ABHD6 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | APPL1(57294802)-ABHD6(58279316), # samples:2 | ||
| Anticipated loss of major functional domain due to fusion event. | APPL1-ABHD6 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. APPL1-ABHD6 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. APPL1-ABHD6 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. APPL1-ABHD6 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. APPL1-ABHD6 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. APPL1-ABHD6 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. | ||
| * DoF score (Degree of Frequency) = # partners X # break points X # cancer types ** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10) |
| 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 | APPL1 | GO:0006606 | protein import into nucleus | 26583432 |
| Hgene | APPL1 | GO:2000045 | regulation of G1/S transition of mitotic cell cycle | 15016378 |
| Tgene | ABHD6 | GO:0046464 | acylglycerol catabolic process | 22969151 |
| Fusion gene breakpoints across APPL1 (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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| Fusion gene breakpoints across ABHD6 (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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Fusion Gene Sample Information |
| Fusion gene information from FusionGDB2.0. |
| Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0) * 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 | Disease | Sample | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| ChimerDB4 | OV | TCGA-30-1866-01A | APPL1 | chr3 | 57294802 | + | ABHD6 | chr3 | 58279316 | + |
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Fusion ORF Analysis |
| Fusion information from ORFfinder translation from full-length transcript sequence from FusionPDB. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | Seq length (transcript) | BP loci (transcript) | Predicted start (transcript) | Predicted stop (transcript) | Seq length (amino acids) |
| ENST00000288266 | APPL1 | chr3 | 57294802 | + | ENST00000295962 | ABHD6 | chr3 | 58279316 | + | 3135 | 1989 | 9 | 2165 | 718 |
| DeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | No-coding score | Coding score |
| ENST00000288266 | ENST00000295962 | APPL1 | chr3 | 57294802 | + | ABHD6 | chr3 | 58279316 | + | 0.00140865 | 0.99859136 |
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Fusion Amino Acid Sequences |
| For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
| >FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP >5676_5676_1_APPL1-ABHD6_APPL1_chr3_57294802_ENST00000288266_ABHD6_chr3_58279316_ENST00000295962_length(amino acids)=718AA_BP=660 MEKAVRAGTAAALAGEGGPGSAAAGGPARGAVGGSCVSCHRPPSATMPGIDKLPIEETLEDSPQTRSLLGVFEEDATAISNYMNQLYQAM HRIYDAQNELSAATHLTSKLLKEYEKQRFPLGGDDEVMSSTLQQFSKVIDELSSCHAVLSTQLADAMMFPITQFKERDLKEILTLKEVFQ IASNDHDAAINRYSRLSKKRENDKVKYEVTEDVYTSRKKQHQTMMHYFCALNTLQYKKKIALLEPLLGYMQAQISFFKMGSENLNEQLEE FLANIGTSVQNVRREMDSDIETMQQTIEDLEVASDPLYVPDPDPTKFPVNRNLTRKAGYLNARNKTGLVSSTWDRQFYFTQGGNLMSQAR GDVAGGLAMDIDNCSVMAVDCEDRRYCFQITSFDGKKSSILQAESKKDHEEWICTINNISKQIYLSENPEETAARVNQSALEAVTPSPSF QQRHESLRPAAGQSRPPTARTSSSGSLGSESTNLAALSLDSLVAPDTPIQFDIISPVCEDQPGQAKAFGQGGRRTNPFGESGGSTKSETE DSILHQLFIVRFLGSMEVKSDDHPDVVYETMRQILAARAIHNIFRMTESHLLVTCDCLKLIDPQTQVTRLTFPLPCVVLYATHQENKRLF -------------------------------------------------------------- |
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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/chr3:57294802/chr3:58279316) - 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 |
| APPL1 | ABHD6 |
| FUNCTION: Multifunctional adapter protein that binds to various membrane receptors, nuclear factors and signaling proteins to regulate many processes, such as cell proliferation, immune response, endosomal trafficking and cell metabolism (PubMed:26583432, PubMed:15016378, PubMed:26073777, PubMed:19661063, PubMed:10490823). Regulates signaling pathway leading to cell proliferation through interaction with RAB5A and subunits of the NuRD/MeCP1 complex (PubMed:15016378). Functions as a positive regulator of innate immune response via activation of AKT1 signaling pathway by forming a complex with APPL1 and PIK3R1 (By similarity). Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). Regulates TLR4 signaling in activated macrophages (By similarity). Involved in trafficking of the TGFBR1 from the endosomes to the nucleus via microtubules in a TRAF6-dependent manner (PubMed:26583432). Plays a role in cell metabolism by regulating adiponecting and insulin signaling pathways (PubMed:26073777, PubMed:19661063, PubMed:24879834). Required for fibroblast migration through HGF cell signaling (By similarity). Positive regulator of beta-catenin/TCF-dependent transcription through direct interaction with RUVBL2/reptin resulting in the relief of RUVBL2-mediated repression of beta-catenin/TCF target genes by modulating the interactions within the beta-catenin-reptin-HDAC complex (PubMed:19433865). {ECO:0000250|UniProtKB:Q8K3H0, ECO:0000269|PubMed:10490823, ECO:0000269|PubMed:15016378, ECO:0000269|PubMed:19433865, ECO:0000269|PubMed:19661063, ECO:0000269|PubMed:24879834, ECO:0000269|PubMed:26073777, ECO:0000269|PubMed:26583432}. | FUNCTION: Lipase that preferentially hydrolysis medium-chain saturated monoacylglycerols including 2-arachidonoylglycerol (PubMed:22969151). Through 2-arachidonoylglycerol degradation may regulate endocannabinoid signaling pathways (By similarity). Also has a lysophosphatidyl lipase activity with a preference for lysophosphatidylglycerol among other lysophospholipids (By similarity). Also able to degrade bis(monoacylglycero)phosphate (BMP) and constitutes the major enzyme for BMP catabolism (PubMed:26491015). BMP, also known as lysobisphosphatidic acid, is enriched in late endosomes and lysosomes and plays a key role in the formation of intraluminal vesicles and in lipid sorting (PubMed:26491015). {ECO:0000250|UniProtKB:Q8R2Y0, ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:26491015}. |
| 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 protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Hgene | APPL1 | chr3:57294802 | chr3:58279316 | ENST00000288266 | + | 19 | 22 | 215_259 | 614.0 | 710.0 | Coiled coil | Ontology_term=ECO:0000255 |
| Hgene | APPL1 | chr3:57294802 | chr3:58279316 | ENST00000288266 | + | 19 | 22 | 277_375 | 614.0 | 710.0 | Domain | PH |
| Hgene | APPL1 | chr3:57294802 | chr3:58279316 | ENST00000288266 | + | 19 | 22 | 3_268 | 614.0 | 710.0 | Domain | BAR |
| Hgene | APPL1 | chr3:57294802 | chr3:58279316 | ENST00000288266 | + | 19 | 22 | 403_414 | 614.0 | 710.0 | Motif | Note=F%26H |
| Hgene | APPL1 | chr3:57294802 | chr3:58279316 | ENST00000288266 | + | 19 | 22 | 1_428 | 614.0 | 710.0 | Region | Note=Required for RAB5A binding |
| - Not-retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Hgene | APPL1 | chr3:57294802 | chr3:58279316 | ENST00000288266 | + | 19 | 22 | 621_673 | 614.0 | 710.0 | Coiled coil | Ontology_term=ECO:0000255 |
| Hgene | APPL1 | chr3:57294802 | chr3:58279316 | ENST00000288266 | + | 19 | 22 | 496_656 | 614.0 | 710.0 | Domain | PID |
| Tgene | ABHD6 | chr3:57294802 | chr3:58279316 | ENST00000295962 | 7 | 9 | 72_313 | 279.0 | 338.0 | Domain | AB hydrolase-1 | |
| Tgene | ABHD6 | chr3:57294802 | chr3:58279316 | ENST00000478253 | 8 | 10 | 72_313 | 279.0 | 338.0 | Domain | AB hydrolase-1 | |
| Tgene | ABHD6 | chr3:57294802 | chr3:58279316 | ENST00000295962 | 7 | 9 | 1_8 | 279.0 | 338.0 | Topological domain | Extracellular | |
| Tgene | ABHD6 | chr3:57294802 | chr3:58279316 | ENST00000295962 | 7 | 9 | 30_337 | 279.0 | 338.0 | Topological domain | Cytoplasmic | |
| Tgene | ABHD6 | chr3:57294802 | chr3:58279316 | ENST00000478253 | 8 | 10 | 1_8 | 279.0 | 338.0 | Topological domain | Extracellular | |
| Tgene | ABHD6 | chr3:57294802 | chr3:58279316 | ENST00000478253 | 8 | 10 | 30_337 | 279.0 | 338.0 | Topological domain | Cytoplasmic | |
| Tgene | ABHD6 | chr3:57294802 | chr3:58279316 | ENST00000295962 | 7 | 9 | 9_29 | 279.0 | 338.0 | Transmembrane | Helical%3B Signal-anchor for type II membrane protein | |
| Tgene | ABHD6 | chr3:57294802 | chr3:58279316 | ENST00000478253 | 8 | 10 | 9_29 | 279.0 | 338.0 | Transmembrane | Helical%3B Signal-anchor for type II membrane protein |
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Fusion Protein-Protein Interaction |
| Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in |
| Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160) |
| Gene | PPI interactors |
| Protein-protein interactors based on sequence similarity (STRING) |
| Gene | STRING network |
| APPL1 | |
| ABHD6 |
| - Retained interactions in fusion protein (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
| - Lost interactions due to fusion (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
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Related Drugs to APPL1-ABHD6 |
| Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Drug | Source | PMID |
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Related Diseases to APPL1-ABHD6 |
| Diseases that have this fusion gene. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Disease | Source | PMID |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
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