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Kinase Fusion Gene:SMYD2_WNK2 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: SMYD2_WNK2 | KinaseFusionDB ID: KFG5963 | FusionGDB2.0 ID: KFG5963 | Hgene | Tgene | Gene symbol | SMYD2 | WNK2 | Gene ID | 56950 | 65268 | |
| Gene name | SET and MYND domain containing 2 | WNK lysine deficient protein kinase 2 | ||||||||||
| Synonyms | HSKM-B|KMT3C|ZMYND14 | NY-CO-43|P/OKcl.13|PRKWNK2|SDCCAG43 | ||||||||||
| Cytomap | 1q32.3 | 9q22.31 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | N-lysine methyltransferase SMYD2SET and MYND domain-containing protein 2histone methyltransferase SMYD2lysine N-methyltransferase 3Czinc finger, MYND domain containing 14 | serine/threonine-protein kinase WNK2antigen NY-CO-43mitogen-activated protein kinase kinase kinaseprotein kinase lysine-deficient 2protein kinase with no lysine 2serologically defined colon cancer antigen 43 | ||||||||||
| Modification date | 20240403 | 20240403 | ||||||||||
| UniProtAcc | Q9NRG4 | Q9Y3S1 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000491455, ENST00000415093, ENST00000366957, | ENST00000427277, ENST00000297954, ENST00000395475, ENST00000356055, ENST00000349097, ENST00000395477, ENST00000471076, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: SMYD2 [Title/Abstract] AND WNK2 [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 | SMYD2 | GO:0018026 | peptidyl-lysine monomethylation | 17108971|20870719 |
| Tgene | WNK2 | GO:0006468 | protein phosphorylation | 21733846 |
| Tgene | WNK2 | GO:0046777 | protein autophosphorylation | 17667937 |
| Kinase Fusion gene breakpoints across SMYD2 (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 WNK2 (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 | SUP-M2 | SMYD2 | chr1 | 214503621 | WNK2 | chr9 | 96018581 |
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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/chr1:/chr9:) - 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 |
| SMYD2 | WNK2 |
| FUNCTION: Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1. Specifically trimethylates histone H3 'Lys-4' (H3K4me3) in vivo. The activity requires interaction with HSP90alpha. Shows even higher methyltransferase activity on p53/TP53. Monomethylates 'Lys-370' of p53/TP53, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity of p53/TP53. Monomethylates RB1 at 'Lys-860'. {ECO:0000269|PubMed:17108971, ECO:0000269|PubMed:17805299, ECO:0000269|PubMed:18065756, ECO:0000269|PubMed:20870719, ECO:0000269|PubMed:21782458, ECO:0000269|PubMed:21880715}. | FUNCTION: Serine/threonine-protein kinase component of the WNK2-SPAK/OSR1 kinase cascade, which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival, and proliferation (PubMed:17667937, PubMed:18593598, PubMed:21733846). The WNK2-SPAK/OSR1 kinase cascade is composed of WNK2, which mediates phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (By similarity). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters, regulating their activity (By similarity). Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively (PubMed:21733846). Activates SLC12A2, SCNN1A, SCNN1B, SCNN1D and SGK1 and inhibits SLC12A5 (PubMed:21733846). Negatively regulates the EGF-induced activation of the ERK/MAPK-pathway and the downstream cell cycle progression (PubMed:17667937, PubMed:18593598). Affects MAPK3/MAPK1 activity by modulating the activity of MAP2K1 and this modulation depends on phosphorylation of MAP2K1 by PAK1 (PubMed:17667937, PubMed:18593598). WNK2 acts by interfering with the activity of PAK1 by controlling the balance of the activity of upstream regulators of PAK1 activity, RHOA and RAC1, which display reciprocal activity (PubMed:17667937, PubMed:18593598). {ECO:0000250|UniProtKB:Q9H4A3, ECO:0000269|PubMed:17667937, ECO:0000269|PubMed:18593598, ECO:0000269|PubMed:21733846}. |
| 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 SMYD2_WNK2 |
| 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 |
| WNK2 | Q9Y3S1 | human | WNK1 | Q9H4A3 | S382 | kRAsFAKsVIGTPEF | Pkinase |
| WNK2 | Q9Y3S1 | human | STK39 | Q9UEW8 | T354 | IEkLLtRtPDIAQRA | |
| WNK2 | Q9Y3S1 | human | STK39 | Q9UEW8 | S371 | VRRVPGssGHLHKTE |
| 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 |
| WNK2 | ID | Description | 0.00e+00 |
| WNK2 | GO:0030002 | intracellular monoatomic anion homeostasis | 2.36e-05 |
| WNK2 | GO:0030644 | intracellular chloride ion homeostasis | 2.36e-05 |
| WNK2 | GO:0030157 | pancreatic juice secretion | 2.36e-05 |
| WNK2 | GO:0060457 | negative regulation of digestive system process | 2.57e-05 |
| WNK2 | GO:0010820 | positive regulation of T cell chemotaxis | 2.57e-05 |
| WNK2 | GO:0010819 | regulation of T cell chemotaxis | 2.57e-05 |
| WNK2 | GO:0055064 | chloride ion homeostasis | 2.70e-05 |
| WNK2 | GO:0071474 | cellular hyperosmotic response | 2.70e-05 |
| WNK2 | GO:0140131 | positive regulation of lymphocyte chemotaxis | 2.70e-05 |
| WNK2 | GO:0055081 | monoatomic anion homeostasis | 2.70e-05 |
| WNK2 | GO:1901623 | regulation of lymphocyte chemotaxis | 3.47e-05 |
| WNK2 | GO:0006972 | hyperosmotic response | 3.47e-05 |
| WNK2 | GO:0010818 | T cell chemotaxis | 3.47e-05 |
| WNK2 | GO:0006884 | cell volume homeostasis | 5.10e-05 |
| WNK2 | GO:2000406 | positive regulation of T cell migration | 5.10e-05 |
| WNK2 | GO:0044058 | regulation of digestive system process | 5.35e-05 |
| WNK2 | GO:0032941 | secretion by tissue | 6.15e-05 |
| WNK2 | GO:2000403 | positive regulation of lymphocyte migration | 6.15e-05 |
| WNK2 | GO:2000404 | regulation of T cell migration | 7.96e-05 |
| WNK2 | GO:0071470 | cellular response to osmotic stress | 8.53e-05 |
| WNK2 | GO:1902305 | regulation of sodium ion transmembrane transport | 1.08e-04 |
| WNK2 | GO:0048247 | lymphocyte chemotaxis | 1.18e-04 |
| WNK2 | GO:2000401 | regulation of lymphocyte migration | 1.31e-04 |
| WNK2 | GO:0071677 | positive regulation of mononuclear cell migration | 1.35e-04 |
| WNK2 | GO:0072678 | T cell migration | 1.35e-04 |
| WNK2 | GO:0006970 | response to osmotic stress | 1.60e-04 |
| WNK2 | GO:0002028 | regulation of sodium ion transport | 1.70e-04 |
| WNK2 | GO:0007589 | body fluid secretion | 1.82e-04 |
| WNK2 | GO:0070098 | chemokine-mediated signaling pathway | 1.82e-04 |
| WNK2 | GO:0002690 | positive regulation of leukocyte chemotaxis | 1.93e-04 |
| WNK2 | GO:1990868 | response to chemokine | 1.93e-04 |
| WNK2 | GO:1990869 | cellular response to chemokine | 1.93e-04 |
| WNK2 | GO:0018107 | peptidyl-threonine phosphorylation | 1.93e-04 |
| WNK2 | GO:0022600 | digestive system process | 1.99e-04 |
| WNK2 | GO:0018210 | peptidyl-threonine modification | 2.20e-04 |
| WNK2 | GO:0072676 | lymphocyte migration | 2.67e-04 |
| WNK2 | GO:0071675 | regulation of mononuclear cell migration | 2.67e-04 |
| WNK2 | GO:0002688 | regulation of leukocyte chemotaxis | 2.67e-04 |
| WNK2 | GO:0007586 | digestion | 2.94e-04 |
| WNK2 | GO:0050921 | positive regulation of chemotaxis | 3.36e-04 |
| WNK2 | GO:0002687 | positive regulation of leukocyte migration | 3.46e-04 |
| WNK2 | GO:0051048 | negative regulation of secretion | 4.50e-04 |
| WNK2 | GO:0035725 | sodium ion transmembrane transport | 4.82e-04 |
| WNK2 | GO:0008217 | regulation of blood pressure | 4.97e-04 |
| WNK2 | GO:0008361 | regulation of cell size | 4.97e-04 |
| WNK2 | GO:0071674 | mononuclear cell migration | 5.96e-04 |
| WNK2 | GO:0002685 | regulation of leukocyte migration | 7.18e-04 |
| WNK2 | GO:0050920 | regulation of chemotaxis | 7.18e-04 |
| WNK2 | GO:0030595 | leukocyte chemotaxis | 7.53e-04 |
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Related Drugs to SMYD2_WNK2 |
| 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 SMYD2-WNK2 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 SMYD2_WNK2 |
| 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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