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Kinase Fusion Gene:AAK1_PAXIP1 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: AAK1_PAXIP1 | KinaseFusionDB ID: KFG16 | FusionGDB2.0 ID: KFG16 | Hgene | Tgene | Gene symbol | AAK1 | PAXIP1 | Gene ID | 22848 | 22976 | |
| Gene name | AP2 associated kinase 1 | PAX interacting protein 1 | ||||||||||
| Synonyms | - | CAGF28|CAGF29|PACIP1|PAXIP1L|PTIP|TNRC2 | ||||||||||
| Cytomap | 2p13.3 | 7q36.2 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | AP2-associated protein kinase 1adaptor-associated kinase 1alternative protein AAK1 | PAX-interacting protein 1PAX interacting (with transcription-activation domain) protein 1PAX transcription activation domain interacting protein 1 likeprotein encoded by CAG trinucleotide repeats | ||||||||||
| Modification date | 20240403 | 20240416 | ||||||||||
| UniProtAcc | Q2M2I8 | Q6ZW49 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000406297, ENST00000409068, ENST00000409085, ENST00000470281, | ENST00000473219, ENST00000397192, ENST00000404141, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: AAK1 [Title/Abstract] AND PAXIP1 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | AAK1(69870009)-PAXIP1(154755476), # 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 | AAK1 | GO:0006468 | protein phosphorylation | 17494869|18657069 |
| Hgene | AAK1 | GO:0032880 | regulation of protein localization | 18657069 |
| Hgene | AAK1 | GO:0045747 | positive regulation of Notch signaling pathway | 21464124 |
| Hgene | AAK1 | GO:0050821 | protein stabilization | 21464124 |
| Hgene | AAK1 | GO:2000369 | regulation of clathrin-dependent endocytosis | 18657069 |
| Tgene | PAXIP1 | GO:0006338 | chromatin remodeling | 17178841 |
| Tgene | PAXIP1 | GO:0010212 | response to ionizing radiation | 15456759 |
| Kinase Fusion gene breakpoints across AAK1 (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 PAXIP1 (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-X8-AAAR | AAK1 | chr2 | 69870009 | PAXIP1 | chr7 | 154755476 |
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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/:69870009/:154755476) - 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 |
| AAK1 | PAXIP1 |
| FUNCTION: Regulates clathrin-mediated endocytosis by phosphorylating the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2) which ensures high affinity binding of AP-2 to cargo membrane proteins during the initial stages of endocytosis (PubMed:17494869, PubMed:11877457, PubMed:11877461, PubMed:12952931, PubMed:14617351, PubMed:25653444). Isoform 1 and isoform 2 display similar levels of kinase activity towards AP2M1 (PubMed:17494869). Preferentially, may phosphorylate substrates on threonine residues (PubMed:11877457, PubMed:18657069). Regulates phosphorylation of other AP-2 subunits as well as AP-2 localization and AP-2-mediated internalization of ligand complexes (PubMed:12952931). Phosphorylates NUMB and regulates its cellular localization, promoting NUMB localization to endosomes (PubMed:18657069). Binds to and stabilizes the activated form of NOTCH1, increases its localization in endosomes and regulates its transcriptional activity (PubMed:21464124). {ECO:0000269|PubMed:11877457, ECO:0000269|PubMed:11877461, ECO:0000269|PubMed:12952931, ECO:0000269|PubMed:14617351, ECO:0000269|PubMed:17494869, ECO:0000269|PubMed:18657069, ECO:0000269|PubMed:21464124, ECO:0000269|PubMed:25653444}.; FUNCTION: (Microbial infection) By regulating clathrin-mediated endocytosis, AAK1 plays a role in the entry of hepatitis C virus as well as for the lifecycle of other viruses such as Ebola and Dengue. {ECO:0000269|PubMed:25653444, ECO:0000305|PubMed:31136173}. | FUNCTION: Involved in DNA damage response and in transcriptional regulation through histone methyltransferase (HMT) complexes. Plays a role in early development. In DNA damage response is required for cell survival after ionizing radiation. In vitro shown to be involved in the homologous recombination mechanism for the repair of double-strand breaks (DSBs). Its localization to DNA damage foci requires RNF8 and UBE2N. Recruits TP53BP1 to DNA damage foci and, at least in particular repair processes, effective DNA damage response appears to require the association with TP53BP1 phosphorylated by ATM at 'Ser-25'. Together with TP53BP1 regulates ATM association. Proposed to recruit PAGR1 to sites of DNA damage and the PAGR1:PAXIP1 complex is required for cell survival in response to DNA damage; the function is probably independent of MLL-containing histone methyltransferase (HMT) complexes. However, this function has been questioned (By similarity). Promotes ubiquitination of PCNA following UV irradiation and may regulate recruitment of polymerase eta and RAD51 to chromatin after DNA damage. Proposed to be involved in transcriptional regulation by linking MLL-containing histone methyltransferase (HMT) complexes to gene promoters by interacting with promoter-bound transcription factors such as PAX2. Associates with gene promoters that are known to be regulated by KMT2D/MLL2. During immunoglobulin class switching in activated B-cells is involved in trimethylation of histone H3 at 'Lys-4' and in transcription initiation of downstream switch regions at the immunoglobulin heavy-chain (Igh) locus; this function appears to involve the recruitment of MLL-containing HMT complexes. Conflictingly, its function in transcriptional regulation during immunoglobulin class switching is reported to be independent of the MLL2/MLL3 complex (By similarity). {ECO:0000250|UniProtKB:Q6NZQ4, ECO:0000269|PubMed:14576432, ECO:0000269|PubMed:15456759, ECO:0000269|PubMed:17690115, ECO:0000269|PubMed:17925232, ECO:0000269|PubMed:18353733, ECO:0000269|PubMed:20088963, ECO:0000269|PubMed:23727112}. |
| 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 AAK1_PAXIP1 |
| 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 |
| AAK1 | Q2M2I8 | human | AP2M1 | Q96CW1 | T156 | SQItsQVtGQIGWRR | |
| AAK1 | Q2M2I8 | human | NUMB | P49757 | T102 | LRVVDEKtKDLIVDQ | PID |
| 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 |
| AAK1 | ID | Description | 0.00e+00 |
| AAK1 | GO:0098884 | postsynaptic neurotransmitter receptor internalization | 2.66e-05 |
| AAK1 | GO:0140239 | postsynaptic endocytosis | 2.66e-05 |
| AAK1 | GO:1903077 | negative regulation of protein localization to plasma membrane | 2.66e-05 |
| AAK1 | GO:1904376 | negative regulation of protein localization to cell periphery | 2.66e-05 |
| AAK1 | GO:0099590 | neurotransmitter receptor internalization | 2.66e-05 |
| AAK1 | GO:1905476 | negative regulation of protein localization to membrane | 3.18e-05 |
| AAK1 | GO:0002090 | regulation of receptor internalization | 7.99e-05 |
| AAK1 | GO:0099072 | regulation of postsynaptic membrane neurotransmitter receptor levels | 1.37e-04 |
| AAK1 | GO:1903076 | regulation of protein localization to plasma membrane | 1.84e-04 |
| AAK1 | GO:0048259 | regulation of receptor-mediated endocytosis | 1.88e-04 |
| AAK1 | GO:0031623 | receptor internalization | 2.12e-04 |
| AAK1 | GO:1904375 | regulation of protein localization to cell periphery | 2.22e-04 |
| AAK1 | GO:1905475 | regulation of protein localization to membrane | 3.59e-04 |
| AAK1 | GO:0031503 | protein-containing complex localization | 3.60e-04 |
| AAK1 | GO:1903828 | negative regulation of protein localization | 4.31e-04 |
| AAK1 | GO:0099003 | vesicle-mediated transport in synapse | 4.31e-04 |
| AAK1 | GO:0006898 | receptor-mediated endocytosis | 5.59e-04 |
| AAK1 | GO:0072659 | protein localization to plasma membrane | 6.36e-04 |
| AAK1 | GO:0030100 | regulation of endocytosis | 6.36e-04 |
| AAK1 | GO:1990778 | protein localization to cell periphery | 8.90e-04 |
| AAK1 | GO:0021670 | lateral ventricle development | 3.09e-03 |
| AAK1 | GO:0055057 | neuroblast division | 3.44e-03 |
| AAK1 | GO:0099149 | regulation of postsynaptic neurotransmitter receptor internalization | 3.76e-03 |
| AAK1 | GO:0097494 | regulation of vesicle size | 4.11e-03 |
| AAK1 | GO:1900242 | regulation of synaptic vesicle endocytosis | 4.11e-03 |
| AAK1 | GO:1903421 | regulation of synaptic vesicle recycling | 5.21e-03 |
| AAK1 | GO:0002092 | positive regulation of receptor internalization | 5.21e-03 |
| AAK1 | GO:0021846 | cell proliferation in forebrain | 5.21e-03 |
| AAK1 | GO:0021591 | ventricular system development | 6.15e-03 |
| AAK1 | GO:0072583 | clathrin-dependent endocytosis | 8.46e-03 |
| AAK1 | GO:0048260 | positive regulation of receptor-mediated endocytosis | 9.23e-03 |
| AAK1 | GO:0034332 | adherens junction organization | 9.61e-03 |
| AAK1 | GO:0048488 | synaptic vesicle endocytosis | 1.14e-02 |
| AAK1 | GO:0140238 | presynaptic endocytosis | 1.14e-02 |
| AAK1 | GO:0007405 | neuroblast proliferation | 1.22e-02 |
| AAK1 | GO:0036465 | synaptic vesicle recycling | 1.22e-02 |
| AAK1 | GO:0006900 | vesicle budding from membrane | 1.22e-02 |
| AAK1 | GO:0045807 | positive regulation of endocytosis | 2.20e-02 |
| AAK1 | GO:0061351 | neural precursor cell proliferation | 2.29e-02 |
| AAK1 | GO:0099504 | synaptic vesicle cycle | 2.66e-02 |
| AAK1 | GO:0045216 | cell-cell junction organization | 2.81e-02 |
| AAK1 | GO:0050769 | positive regulation of neurogenesis | 3.09e-02 |
| AAK1 | GO:0021537 | telencephalon development | 3.44e-02 |
| AAK1 | GO:0051962 | positive regulation of nervous system development | 3.54e-02 |
| AAK1 | GO:0016050 | vesicle organization | 4.31e-02 |
| AAK1 | GO:0032535 | regulation of cellular component size | 4.31e-02 |
| AAK1 | GO:0050767 | regulation of neurogenesis | 4.44e-02 |
| AAK1 | GO:0030900 | forebrain development | 4.53e-02 |
| AAK1 | GO:0010720 | positive regulation of cell development | 4.79e-02 |
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Related Drugs to AAK1_PAXIP1 |
| 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 AAK1-PAXIP1 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 AAK1_PAXIP1 |
| 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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