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Kinase Fusion Gene:NEDD4L_ALPK2 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: NEDD4L_ALPK2 | KinaseFusionDB ID: KFG4102 | FusionGDB2.0 ID: KFG4102 | Hgene | Tgene | Gene symbol | NEDD4L | ALPK2 | Gene ID | 23327 | 115701 | |
| Gene name | NEDD4 like E3 ubiquitin protein ligase | alpha kinase 2 | ||||||||||
| Synonyms | NEDD4-2|NEDD4.2|PVNH7|RSP5|hNEDD4-2 | HAK | ||||||||||
| Cytomap | 18q21.31 | 18q21.31-q21.32 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | E3 ubiquitin-protein ligase NEDD4-likeHECT-type E3 ubiquitin transferase NED4Lneural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligaseubiquitin-protein ligase Rsp5 | alpha-protein kinase 2heart alpha-kinaseheart alpha-protein kinase | ||||||||||
| Modification date | 20240416 | 20240305 | ||||||||||
| UniProtAcc | Q96PU5 | Q86TB3 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000256830, ENST00000256832, ENST00000356462, ENST00000357895, ENST00000382850, ENST00000400345, ENST00000431212, ENST00000435432, ENST00000456173, ENST00000456986, ENST00000586263, ENST00000589054, ENST00000588516, | ENST00000587399, ENST00000361673, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: NEDD4L [Title/Abstract] AND ALPK2 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | NEDD4L(55711940)-ALPK2(56196470), # samples:5 ALPK2(56169514)-NEDD4L(55987973), # 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 | NEDD4L | GO:0003254 | regulation of membrane depolarization | 15217910 |
| Hgene | NEDD4L | GO:0006511 | ubiquitin-dependent protein catabolic process | 21463633 |
| Hgene | NEDD4L | GO:0016567 | protein ubiquitination | 15217910|18577513|25631046 |
| Hgene | NEDD4L | GO:0034765 | regulation of monoatomic ion transmembrane transport | 17289006 |
| Hgene | NEDD4L | GO:0042391 | regulation of membrane potential | 17289006 |
| Hgene | NEDD4L | GO:0043161 | proteasome-mediated ubiquitin-dependent protein catabolic process | 21463633 |
| Hgene | NEDD4L | GO:0060306 | regulation of membrane repolarization | 21463633 |
| Hgene | NEDD4L | GO:0070936 | protein K48-linked ubiquitination | 21463633 |
| Hgene | NEDD4L | GO:1901016 | regulation of potassium ion transmembrane transporter activity | 17289006 |
| Hgene | NEDD4L | GO:1901017 | negative regulation of potassium ion transmembrane transporter activity | 21463633 |
| Hgene | NEDD4L | GO:1901380 | negative regulation of potassium ion transmembrane transport | 21463633 |
| Hgene | NEDD4L | GO:1902305 | regulation of sodium ion transmembrane transport | 11244092 |
| Hgene | NEDD4L | GO:1902306 | negative regulation of sodium ion transmembrane transport | 15217910 |
| Hgene | NEDD4L | GO:1903861 | positive regulation of dendrite extension | 23999003 |
| Hgene | NEDD4L | GO:2000009 | negative regulation of protein localization to cell surface | 21463633 |
| Hgene | NEDD4L | GO:2000650 | negative regulation of sodium ion transmembrane transporter activity | 15217910 |
| Kinase Fusion gene breakpoints across NEDD4L (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 ALPK2 (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-VQ-A8PD-01A | NEDD4L | chr18 | 55711940 | ALPK2 | chr18 | 56196470 |
| ChimerDB4 | TCGA-VQ-A8PX-01A | NEDD4L | chr18 | 56033460 | ALPK2 | chr18 | 56191294 |
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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) |
| ENST00000356462 | ENST00000361673 | NEDD4L | chr18 | 56033460 | ALPK2 | chr18 | 56191294 | 3753 | 988 |
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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 >ENST00000356462_ENST00000361673_NEDD4L_chr18_56033460_ALPK2_chr18_56191294_length(amino acids)=988 MEAEGRTGRPRRSTAAGSASDPARGAGSMATGLGEPVYGLSEDEGESRILRVKVVSGIDLAKKDIFGASDPYVKLSLYVADENRELALVQ TKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVPLSHLPTEDPTMERPYTFKDFLLRPRSHKSRVKGFLRLKMAY MPKNGGQDEENSDQRDDMEHGWEVVDSNDSASQHQEELPPPPLPPGWEEKVDNLGRTYYVNHNNRTTQWHRPSLMDVSSESDNNIRQINQ EAAHRRFRSRRHISEDLEPEPSEGGDVPEPWETISEEVNIAGDSLGLALPPPPASPGSRTSPQELSEELSRRLQITPDSNGEQFSSLIQR EPSSRLRSCSVTDAVAEQGHLPPLAEDGASGSATNSNNHLIEPQIRRPRSLSSPTVTLSAPLEGAKDSPVRRAVKDTLSNPQSPQPSPYN SPKPQHKVTQSFLPPGWEMRIAPNGRPFFIDHNTKTTTWEDPRLKFPVHMRSKTSLNPNDLGPLPPGWEERIHLDGRTFYIDHNSKITQW EDPRLQNPAITGPAVPYSREFKQKYDYFRKKLKKPADIPNRFEMKLHRNNIFEESYRRIMSVKRPDVLKARLWIEFESEKGLDYGGVARE WFFLLSKEMFNPYYGLFEYSATAGDNSTVSFAIVQASPKDQGLYYCCIKNSYGKVTAEFNLTAEVLKQLSSRQDTKGCEEIEFSQLIFKE DFLHDSYFGGRLRGQIATEELHFGEGVHRKAFRSTVMHGLMPVFKPGHACVLKVHNAIAYGTRNNDELIQRNYKLAAQECYVQNTARYYA KIYAAEAQPLEGFGEVPEIIPIFLIHRPENNIPYATVEEELIGEFVKYSIRDGKEINFLRRESEAGQKCCTFQHWVYQKTSGCLLVTDMQ -------------------------------------------------------------- |
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/chr18:55711940/chr18:56196470) - 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 |
| NEDD4L | ALPK2 |
| FUNCTION: E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins and is thereby implicated in the regulation of various signaling pathways including autophagy, innate immunity or DNA repair (PubMed:31959741, PubMed:33608556, PubMed:20064473). Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation (PubMed:15496141). Downregulates autophagy and cell growth by ubiquitinating and reducing cellular ULK1 or ASCT2 levels (PubMed:28820317, PubMed:31959741). Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN5A/Nav1.5, SCN9A/Nav1.7, SCN10A/Nav1.8, KCNA3/Kv1.3, KCNH2, EAAT1, KCNQ2/Kv7.2, KCNQ3/Kv7.3 or CLC5 (PubMed:26363003, PubMed:27445338). Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Plays a role in dendrite formation by melanocytes (PubMed:23999003). Involved in the regulation of TOR signaling (PubMed:27694961). Ubiquitinates and regulates protein levels of NTRK1 once this one is activated by NGF (PubMed:27445338). Plays a role in antiviral innate immunity by catalyzing 'Lys-29'-linked cysteine ubiquitination of TRAF3, resulting in enhanced 'Lys-48' and 'Lys-63'-linked ubiquitination of TRAF3 (PubMed:33608556). {ECO:0000250|UniProtKB:Q8CFI0, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:15040001, ECO:0000269|PubMed:15217910, ECO:0000269|PubMed:15489223, ECO:0000269|PubMed:15496141, ECO:0000269|PubMed:15576372, ECO:0000269|PubMed:19144635, ECO:0000269|PubMed:23999003, ECO:0000269|PubMed:25631046, ECO:0000269|PubMed:26363003, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:27694961, ECO:0000269|PubMed:33608556}. | FUNCTION: Protein kinase that recognizes phosphorylation sites in which the surrounding peptides have an alpha-helical conformation (PubMed:10021370). Regulates cardiac development and cardiomyocyte differentiation by negatively regulating Wnt/beta-catenin signaling (PubMed:29888752). {ECO:0000269|PubMed:29888752, ECO:0000303|PubMed:10021370}. |
| 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 | NEDD4L | 56033460 | ALPK2 | 56191294 | ENST00000356462 | 5 | 13 | 1901_2133 | 1833 | 2171 | Domain | Note=Alpha-type protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00501 |
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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 >>>332_NEDD4L_ALPK2 | ENST00000356462 | ENST00000361673 | NEDD4L | chr18 | 56033460 | ALPK2 | chr18 | 56191294 | MEAEGRTGRPRRSTAAGSASDPARGAGSMATGLGEPVYGLSEDEGESRILRVKVVSGIDLAKKDIFGASDPYVKLSLYVADENRELALVQ TKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVPLSHLPTEDPTMERPYTFKDFLLRPRSHKSRVKGFLRLKMAY MPKNGGQDEENSDQRDDMEHGWEVVDSNDSASQHQEELPPPPLPPGWEEKVDNLGRTYYVNHNNRTTQWHRPSLMDVSSESDNNIRQINQ EAAHRRFRSRRHISEDLEPEPSEGGDVPEPWETISEEVNIAGDSLGLALPPPPASPGSRTSPQELSEELSRRLQITPDSNGEQFSSLIQR EPSSRLRSCSVTDAVAEQGHLPPLAEDGASGSATNSNNHLIEPQIRRPRSLSSPTVTLSAPLEGAKDSPVRRAVKDTLSNPQSPQPSPYN SPKPQHKVTQSFLPPGWEMRIAPNGRPFFIDHNTKTTTWEDPRLKFPVHMRSKTSLNPNDLGPLPPGWEERIHLDGRTFYIDHNSKITQW EDPRLQNPAITGPAVPYSREFKQKYDYFRKKLKKPADIPNRFEMKLHRNNIFEESYRRIMSVKRPDVLKARLWIEFESEKGLDYGGVARE WFFLLSKEMFNPYYGLFEYSATAGDNSTVSFAIVQASPKDQGLYYCCIKNSYGKVTAEFNLTAEVLKQLSSRQDTKGCEEIEFSQLIFKE DFLHDSYFGGRLRGQIATEELHFGEGVHRKAFRSTVMHGLMPVFKPGHACVLKVHNAIAYGTRNNDELIQRNYKLAAQECYVQNTARYYA KIYAAEAQPLEGFGEVPEIIPIFLIHRPENNIPYATVEEELIGEFVKYSIRDGKEINFLRRESEAGQKCCTFQHWVYQKTSGCLLVTDMQ | 988 |
| 3D view using mol* of 332_NEDD4L_ALPK2 | ||||||||||
| PDB file >>>TKFP_569_NEDD4L_ALPK2 | ENST00000356462 | ENST00000361673 | NEDD4L | chr18 | 56033460 | ALPK2 | chr18 | 56191294 | MEAEGRTGRPRRSTAAGSASDPARGAGSMATGLGEPVYGLSEDEGESRILRVKVVSGIDLAKKDIFGASDPYVKLSLYVADENRELALVQ TKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVPLSHLPTEDPTMERPYTFKDFLLRPRSHKSRVKGFLRLKMAY MPKNGGQDEENSDQRDDMEHGWEVVDSNDSASQHQEELPPPPLPPGWEEKVDNLGRTYYVNHNNRTTQWHRPSLMDVSSESDNNIRQINQ EAAHRRFRSRRHISEDLEPEPSEGGDVPEPWETISEEVNIAGDSLGLALPPPPASPGSRTSPQELSEELSRRLQITPDSNGEQFSSLIQR EPSSRLRSCSVTDAVAEQGHLPPLAEDGASGSATNSNNHLIEPQIRRPRSLSSPTVTLSAPLEGAKDSPVRRAVKDTLSNPQSPQPSPYN SPKPQHKVTQSFLPPGWEMRIAPNGRPFFIDHNTKTTTWEDPRLKFPVHMRSKTSLNPNDLGPLPPGWEERIHLDGRTFYIDHNSKITQW EDPRLQNPAITGPAVPYSREFKQKYDYFRKKLKKPADIPNRFEMKLHRNNIFEESYRRIMSVKRPDVLKARLWIEFESEKGLDYGGVARE WFFLLSKEMFNPYYGLFEYSATAGDNSTVSFAIVQASPKDQGLYYCCIKNSYGKVTAEFNLTAEVLKQLSSRQDTKGCEEIEFSQLIFKE DFLHDSYFGGRLRGQIATEELHFGEGVHRKAFRSTVMHGLMPVFKPGHACVLKVHNAIAYGTRNNDELIQRNYKLAAQECYVQNTARYYA KIYAAEAQPLEGFGEVPEIIPIFLIHRPENNIPYATVEEELIGEFVKYSIRDGKEINFLRRESEAGQKCCTFQHWVYQKTSGCLLVTDMQ | 988_NEDD4L_ALPK2 |
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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. |
| 332_NEDD4L_ALPK2.png |
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| 332_NEDD4L_ALPK2.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. |
| 332_NEDD4L_ALPK2_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 |
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Kinase-Substrate Information of NEDD4L_ALPK2 |
| 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 |
| 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 |
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Related Drugs to NEDD4L_ALPK2 |
| 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 NEDD4L-ALPK2 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 NEDD4L_ALPK2 |
| 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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