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Kinase Fusion Gene:TTBK2_VPS39 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: TTBK2_VPS39 | KinaseFusionDB ID: KFG6883 | FusionGDB2.0 ID: KFG6883 | Hgene | Tgene | Gene symbol | TTBK2 | VPS39 | Gene ID | 146057 | 23339 | |
| Gene name | tau tubulin kinase 2 | VPS39 subunit of HOPS complex | ||||||||||
| Synonyms | SCA11|TTBK | TLP|VAM6|hVam6p | ||||||||||
| Cytomap | 15q15.2 | 15q15.1 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | tau-tubulin kinase 2 | vam6/Vps39-like proteinTRAP1-like proteinVPS39, HOPS complex subunitvacuolar protein sorting 39 homolog | ||||||||||
| Modification date | 20240323 | 20240407 | ||||||||||
| UniProtAcc | Q6IQ55 | Q96JC1 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000267890, ENST00000567840, ENST00000567274, ENST00000567485, | ENST00000318006, ENST00000348544, ENST00000568357, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: TTBK2 [Title/Abstract] AND VPS39 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | ||||||||||||
| 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 | TTBK2 | GO:0007026 | negative regulation of microtubule depolymerization | 26323690 |
| Hgene | TTBK2 | GO:0018105 | peptidyl-serine phosphorylation | 21548880|26323690|30375385 |
| Hgene | TTBK2 | GO:1904527 | negative regulation of microtubule binding | 26323690 |
| Tgene | VPS39 | GO:0034058 | endosomal vesicle fusion | 23167963 |
| Tgene | VPS39 | GO:0061909 | autophagosome-lysosome fusion | 33422265 |
| Tgene | VPS39 | GO:1902774 | late endosome to lysosome transport | 23167963 |
| Kinase Fusion gene breakpoints across TTBK2 (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 VPS39 (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 |
| CCLE | U-BLC1 | TTBK2 | chr15 | 43212636 | VPS39 | chr15 | 42476898 |
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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/:/:) - 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 |
| TTBK2 | VPS39 |
| FUNCTION: Serine/threonine kinase that acts as a key regulator of ciliogenesis: controls the initiation of ciliogenesis by binding to the distal end of the basal body and promoting the removal of CCP110, which caps the mother centriole, leading to the recruitment of IFT proteins, which build the ciliary axoneme. Has some substrate preference for proteins that are already phosphorylated on a Tyr residue at the +2 position relative to the phosphorylation site. Able to phosphorylate tau on serines in vitro (PubMed:23141541). Phosphorylates MPHOSPH9 which promotes its ubiquitination and proteasomal degradation, loss of MPHOSPH9 facilitates the removal of the CP110-CEP97 complex (a negative regulator of ciliogenesis) from the mother centrioles, promoting the initiation of ciliogenesis (PubMed:30375385). {ECO:0000269|PubMed:21548880, ECO:0000269|PubMed:23141541, ECO:0000269|PubMed:30375385}. | FUNCTION: Regulator of TGF-beta/activin signaling, inhibiting SMAD3- and activating SMAD2-dependent transcription. Acts by interfering with SMAD3/SMAD4 complex formation, this would lead to inhibition of SMAD3-dependent transcription and relieve SMAD3 inhibition of SMAD2-dependent promoters, thus increasing SMAD2-dependent transcription. Does not affect TGF-beta-induced SMAD2 or SMAD3 phosphorylation, nor SMAD2/SMAD4 complex formation. {ECO:0000269|PubMed:12941698}.; FUNCTION: Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Acts as a component of the putative HOPS endosomal tethering complex which is proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes (PubMed:23351085). Involved in homotypic vesicle fusions between late endosomes and in heterotypic fusions between late endosomes and lysosomes (PubMed:11448994, PubMed:23351085, PubMed:23167963). Required for fusion of endosomes and autophagosomes with lysosomes (PubMed:25783203). {ECO:0000269|PubMed:11448994, ECO:0000269|PubMed:23167963, ECO:0000269|PubMed:25783203, ECO:0000269|PubMed:33422265, ECO:0000305|PubMed:23351085}. |
| 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 TTBK2_VPS39 |
| 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 |
| TTBK2 | Q6IQ55 | human | SV2A | Q7L0J3 | S47 | EysRRsYsRFEEEDD | |
| TTBK2 | Q6IQ55 | human | SV2A | Q7L0J3 | T84 | GGAssDAtEGHDEDD | |
| TTBK2 | Q6IQ55 | human | SV2A | Q7L0J3 | S45 | QDEysRRsYsRFEEE | |
| TTBK2 | Q6IQ55 | human | CEP83 | Q9Y592 | S698 | KQLEELGsSGE____ | |
| TTBK2 | Q6IQ55 | human | SV2A | Q7L0J3 | S80 | DEEEGGAssDAtEGH | |
| TTBK2 | Q6IQ55 | human | SV2A | Q7L0J3 | S81 | EEEGGAssDAtEGHD | |
| TTBK2 | Q6IQ55 | human | SV2A | Q7L0J3 | S42 | DRVQDEysRRsYsRF | |
| TTBK2 | Q6IQ55 | human | KIF2A | O00139 | S135 | SSAQQNGsVsDIsPV |
| 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 |
| TTBK2 | ID | Description | 0.00e+00 |
| TTBK2 | GO:0051660 | establishment of centrosome localization | 3.70e-02 |
| TTBK2 | GO:0014051 | gamma-aminobutyric acid secretion | 3.70e-02 |
| TTBK2 | GO:0016082 | synaptic vesicle priming | 3.70e-02 |
| TTBK2 | GO:0015812 | gamma-aminobutyric acid transport | 3.70e-02 |
| TTBK2 | GO:0051642 | centrosome localization | 3.70e-02 |
| TTBK2 | GO:0061842 | microtubule organizing center localization | 3.70e-02 |
| TTBK2 | GO:0071539 | protein localization to centrosome | 3.70e-02 |
| TTBK2 | GO:1905508 | protein localization to microtubule organizing center | 3.70e-02 |
| TTBK2 | GO:0046717 | acid secretion | 3.70e-02 |
| TTBK2 | GO:0051955 | regulation of amino acid transport | 3.70e-02 |
| TTBK2 | GO:0007019 | microtubule depolymerization | 3.70e-02 |
| TTBK2 | GO:0072698 | protein localization to microtubule cytoskeleton | 4.10e-02 |
| TTBK2 | GO:0044380 | protein localization to cytoskeleton | 4.10e-02 |
| TTBK2 | GO:0048278 | vesicle docking | 4.11e-02 |
| TTBK2 | GO:0090307 | mitotic spindle assembly | 4.11e-02 |
| TTBK2 | GO:0032890 | regulation of organic acid transport | 4.11e-02 |
| TTBK2 | GO:0140029 | exocytic process | 4.11e-02 |
| TTBK2 | GO:0140056 | organelle localization by membrane tethering | 4.11e-02 |
| TTBK2 | GO:0022406 | membrane docking | 4.16e-02 |
| TTBK2 | GO:0016079 | synaptic vesicle exocytosis | 4.16e-02 |
| TTBK2 | GO:0051952 | regulation of amine transport | 4.16e-02 |
| TTBK2 | GO:0015837 | amine transport | 4.42e-02 |
| TTBK2 | GO:0051261 | protein depolymerization | 4.50e-02 |
| TTBK2 | GO:0007052 | mitotic spindle organization | 4.63e-02 |
| TTBK2 | GO:0051225 | spindle assembly | 4.63e-02 |
| TTBK2 | GO:0031109 | microtubule polymerization or depolymerization | 4.63e-02 |
| TTBK2 | GO:0007269 | neurotransmitter secretion | 4.63e-02 |
| TTBK2 | GO:0099643 | signal release from synapse | 4.63e-02 |
| TTBK2 | GO:0006865 | amino acid transport | 4.65e-02 |
| TTBK2 | GO:1902850 | microtubule cytoskeleton organization involved in mitosis | 4.88e-02 |
| TTBK2 | GO:0000070 | mitotic sister chromatid segregation | 5.27e-02 |
| TTBK2 | GO:0001505 | regulation of neurotransmitter levels | 5.27e-02 |
| TTBK2 | GO:0099504 | synaptic vesicle cycle | 5.30e-02 |
| TTBK2 | GO:0007051 | spindle organization | 5.30e-02 |
| TTBK2 | GO:0006836 | neurotransmitter transport | 5.30e-02 |
| TTBK2 | GO:0099003 | vesicle-mediated transport in synapse | 5.35e-02 |
| TTBK2 | GO:0000819 | sister chromatid segregation | 5.35e-02 |
| TTBK2 | GO:0045055 | regulated exocytosis | 5.35e-02 |
| TTBK2 | GO:0032984 | protein-containing complex disassembly | 5.62e-02 |
| TTBK2 | GO:0140014 | mitotic nuclear division | 6.12e-02 |
| TTBK2 | GO:0006874 | intracellular calcium ion homeostasis | 6.62e-02 |
| TTBK2 | GO:0098813 | nuclear chromosome segregation | 6.62e-02 |
| TTBK2 | GO:0055074 | calcium ion homeostasis | 6.81e-02 |
| TTBK2 | GO:0006887 | exocytosis | 6.81e-02 |
| TTBK2 | GO:0046942 | carboxylic acid transport | 6.81e-02 |
| TTBK2 | GO:0015849 | organic acid transport | 6.81e-02 |
| TTBK2 | GO:0060271 | cilium assembly | 7.14e-02 |
| TTBK2 | GO:0044782 | cilium organization | 7.37e-02 |
| TTBK2 | GO:0140694 | non-membrane-bounded organelle assembly | 7.37e-02 |
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Related Drugs to TTBK2_VPS39 |
| 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 TTBK2-VPS39 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 TTBK2_VPS39 |
| 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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