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Kinase Fusion Gene:NLK_SMURF2 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: NLK_SMURF2 | KinaseFusionDB ID: KFG4212 | FusionGDB2.0 ID: KFG4212 | Hgene | Tgene | Gene symbol | NLK | SMURF2 | Gene ID | 51701 | 64750 | |
| Gene name | nemo like kinase | SMAD specific E3 ubiquitin protein ligase 2 | ||||||||||
| Synonyms | - | - | ||||||||||
| Cytomap | 17q11.2 | 17q23.3-q24.1 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | serine/threonine-protein kinase NLK | E3 ubiquitin-protein ligase SMURF2E3 ubiquitin ligase SMURF2HECT-type E3 ubiquitin transferase SMURF2SMAD ubiquitination regulatory factor 2hSMURF2 | ||||||||||
| Modification date | 20240403 | 20240411 | ||||||||||
| UniProtAcc | Q9UBE8 | Q9HAU4 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000583517, ENST00000407008, ENST00000582037, | ENST00000262435, ENST00000578200, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: NLK [Title/Abstract] AND SMURF2 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | NLK(26370357)-SMURF2(62542456), # 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 | NLK | GO:0050821 | protein stabilization | 25512613 |
| Hgene | NLK | GO:0071470 | cellular response to osmotic stress | 26588989 |
| Hgene | NLK | GO:1904262 | negative regulation of TORC1 signaling | 26588989 |
| Tgene | SMURF2 | GO:0006511 | ubiquitin-dependent protein catabolic process | 14755250 |
| Tgene | SMURF2 | GO:0030512 | negative regulation of transforming growth factor beta receptor signaling pathway | 19255252 |
| Tgene | SMURF2 | GO:1901165 | positive regulation of trophoblast cell migration | 19255252 |
| Kinase Fusion gene breakpoints across NLK (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 SMURF2 (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-ZF-A9RM-01A | NLK | chr17 | 26370357 | SMURF2 | chr17 | 62542456 |
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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/:26370357/:62542456) - 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 |
| NLK | SMURF2 |
| FUNCTION: Serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination (PubMed:14960582, PubMed:12482967, PubMed:15004007, PubMed:15764709, PubMed:20061393, PubMed:20874444, PubMed:21454679). Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2 (PubMed:15004007, PubMed:15764709). Negative regulator of the canonical Wnt/beta-catenin signaling pathway (PubMed:12482967). Binds to and phosphorylates TCF7L2/TCF4 and LEF1, promoting the dissociation of the TCF7L2/LEF1/beta-catenin complex from DNA, as well as the ubiquitination and subsequent proteolysis of LEF1 (PubMed:21454679). Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes (PubMed:12482967, PubMed:21454679). Negative regulator of the Notch signaling pathway (PubMed:20118921). Binds to and phosphorylates NOTCH1, thereby preventing the formation of a transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1 (PubMed:20118921). Negative regulator of the MYB family of transcription factors (PubMed:15082531). Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP (PubMed:15082531). Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself (PubMed:15082531). Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1 (PubMed:15004007, PubMed:15764709). Upon IL1B stimulus, cooperates with ATF5 to activate the transactivation activity of C/EBP subfamily members (PubMed:25512613). Phosphorylates ATF5 but also stabilizes ATF5 protein levels in a kinase-independent manner (PubMed:25512613). Acts as an inhibitor of the mTORC1 complex in response to osmotic stress by mediating phosphorylation of RPTOR, thereby preventing recruitment of the mTORC1 complex to lysosomes (PubMed:26588989). {ECO:0000269|PubMed:12482967, ECO:0000269|PubMed:14960582, ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:15082531, ECO:0000269|PubMed:15764709, ECO:0000269|PubMed:20061393, ECO:0000269|PubMed:20118921, ECO:0000269|PubMed:20874444, ECO:0000269|PubMed:21454679, ECO:0000269|PubMed:25512613, ECO:0000269|PubMed:26588989}. | FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:11016919). Interacts with SMAD7 to trigger SMAD7-mediated transforming growth factor beta/TGF-beta receptor ubiquitin-dependent degradation, thereby down-regulating TGF-beta signaling (PubMed:11163210, PubMed:12717440, PubMed:21791611). In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with AIMP1 (PubMed:18448069). Also forms a stable complex with TGF-beta receptor-mediated phosphorylated SMAD1, SMAD2 and SMAD3, and targets SMAD1 and SMAD2 for ubiquitination and proteasome-mediated degradation (PubMed:11016919, PubMed:11158580, PubMed:11389444). SMAD2 may recruit substrates, such as SNON, for ubiquitin-dependent degradation (PubMed:11389444). Negatively regulates TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation (PubMed:30696809). {ECO:0000269|PubMed:11016919, ECO:0000269|PubMed:11158580, ECO:0000269|PubMed:11163210, ECO:0000269|PubMed:11389444, ECO:0000269|PubMed:12717440, ECO:0000269|PubMed:18448069, ECO:0000269|PubMed:21791611, ECO:0000269|PubMed:30696809}.; FUNCTION: (Microbial infection) In case of filoviruses Ebola/EBOV and Marburg/MARV infection, the complex formed by viral matrix protein VP40 and SMURF2 facilitates virus budding. {ECO:0000269|PubMed:33673144}. |
| 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 NLK_SMURF2 |
| 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 |
| NLK | Q9UBE8 | human | NCOA3 | Q9Y6Q9 | S857 | PPYNRAVsLDsPVsV | |
| NLK | Q9UBE8 | human | LEF1 | Q9UJU2 | S166 | tysDEHFsPGSHPSH | CTNNB1_binding |
| NLK | Q9UBE8 | human | SMAD4 | Q13485 | S138 | YHYERVVsPGIDLSG | |
| NLK | Q9UBE8 | human | TCF7L2 | Q9NQB0 | T212 | TYSNEHFtPGNPPPH | CTNNB1_binding |
| NLK | Q9UBE8 | human | ESR1 | P03372 | S104 | FPPLNsVsPsPLMLL | Oest_recep |
| NLK | Q9UBE8 | human | LEF1 | Q9UJU2 | S132 | YMSNGSLsPPIPRTS | CTNNB1_binding |
| NLK | Q9UBE8 | human | LEF1 | Q9UJU2 | S200 | IPtFyPLsPGGVGQI | CTNNB1_binding |
| NLK | Q9UBE8 | human | NCOA3 | Q9Y6Q9 | S860 | NRAVsLDsPVsVGss | |
| NLK | Q9UBE8 | human | SMAD2 | Q15796 | S250 | TGsPAELsPTTLsPV | |
| NLK | Q9UBE8 | human | NCOA3 | Q9Y6Q9 | S543 | SLLSTLSsPGPKLDN | NCOA_u2 |
| NLK | Q9UBE8 | human | SMAD4 | Q13485 | T9 | DNMSITNtPTSNDAC | |
| NLK | Q9UBE8 | human | YAP1 | P46937 | S128 | QHVRAHssPAsLQLG | |
| NLK | Q9UBE8 | human | FOXO1 | Q12778 | S329 | stIsGRLsPIMtEQD | |
| NLK | Q9UBE8 | human | NCOA3 | Q9Y6Q9 | T24 | KRKLPCDtPGQGLtC | |
| NLK | Q9UBE8 | human | TCF7L2 | Q9NQB0 | T201 | PHHVHPLtPLITYSN | CTNNB1_binding |
| NLK | Q9UBE8 | human | ESR1 | P03372 | S118 | LHPPPQLsPFLQPHG | Oest_recep |
| NLK | Q9UBE8 | human | SMAD3 | P84022 | S208 | DAGsPNLsPNPMsPA | |
| NLK | Q9UBE8 | human | ESR1 | P03372 | S106 | PLNsVsPsPLMLLHP | Oest_recep |
| NLK | Q9UBE8 | human | NCOA3 | Q9Y6Q9 | S867 | sPVsVGssPPVKNIS | |
| NLK | Q9UBE8 | human | ESR1 | P03372 | S167 | GGRERLAsTNDkGSM | Oest_recep |
| NLK | Q9UBE8 | human | RPTOR | Q8N122 | S863 | LtQsAPAsPtNkGVH | |
| NLK | Q9UBE8 | human | LEF1 | Q9UJU2 | T265 | IPHPAIVtPQVKQEH | |
| NLK | Q9UBE8 | human | LEF1 | Q9UJU2 | T155 | SHAVHPLtPLItysD | CTNNB1_binding |
| NLK | Q9UBE8 | human | NCOA3 | Q9Y6Q9 | S505 | SPVAGVHsPMAsSGN | NCOA_u2 |
| 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 |
| NLK | ID | Description | 0.00e+00 |
| NLK | GO:0010718 | positive regulation of epithelial to mesenchymal transition | 6.04e-08 |
| NLK | GO:0048339 | paraxial mesoderm development | 6.04e-08 |
| NLK | GO:0010717 | regulation of epithelial to mesenchymal transition | 5.26e-07 |
| NLK | GO:0007498 | mesoderm development | 1.02e-06 |
| NLK | GO:0060485 | mesenchyme development | 1.02e-06 |
| NLK | GO:0048340 | paraxial mesoderm morphogenesis | 2.13e-06 |
| NLK | GO:0072132 | mesenchyme morphogenesis | 2.13e-06 |
| NLK | GO:0001837 | epithelial to mesenchymal transition | 2.13e-06 |
| NLK | GO:0048762 | mesenchymal cell differentiation | 1.31e-05 |
| NLK | GO:0062009 | secondary palate development | 2.72e-05 |
| NLK | GO:0060070 | canonical Wnt signaling pathway | 2.72e-05 |
| NLK | GO:0030325 | adrenal gland development | 2.80e-05 |
| NLK | GO:0060562 | epithelial tube morphogenesis | 2.80e-05 |
| NLK | GO:0030111 | regulation of Wnt signaling pathway | 2.80e-05 |
| NLK | GO:0003299 | muscle hypertrophy in response to stress | 2.80e-05 |
| NLK | GO:0014887 | cardiac muscle adaptation | 2.80e-05 |
| NLK | GO:0014898 | cardiac muscle hypertrophy in response to stress | 2.80e-05 |
| NLK | GO:1904019 | epithelial cell apoptotic process | 3.64e-05 |
| NLK | GO:0010614 | negative regulation of cardiac muscle hypertrophy | 3.64e-05 |
| NLK | GO:0072073 | kidney epithelium development | 3.87e-05 |
| NLK | GO:0014741 | negative regulation of muscle hypertrophy | 3.91e-05 |
| NLK | GO:0001701 | in utero embryonic development | 3.93e-05 |
| NLK | GO:0048754 | branching morphogenesis of an epithelial tube | 3.93e-05 |
| NLK | GO:0048732 | gland development | 6.62e-05 |
| NLK | GO:0061138 | morphogenesis of a branching epithelium | 6.93e-05 |
| NLK | GO:0016055 | Wnt signaling pathway | 6.93e-05 |
| NLK | GO:0198738 | cell-cell signaling by wnt | 6.93e-05 |
| NLK | GO:0032924 | activin receptor signaling pathway | 6.93e-05 |
| NLK | GO:0007369 | gastrulation | 7.85e-05 |
| NLK | GO:0050673 | epithelial cell proliferation | 7.85e-05 |
| NLK | GO:0001763 | morphogenesis of a branching structure | 8.34e-05 |
| NLK | GO:0014888 | striated muscle adaptation | 8.63e-05 |
| NLK | GO:0009952 | anterior/posterior pattern specification | 1.06e-04 |
| NLK | GO:0045599 | negative regulation of fat cell differentiation | 1.11e-04 |
| NLK | GO:0001756 | somitogenesis | 1.37e-04 |
| NLK | GO:0010611 | regulation of cardiac muscle hypertrophy | 1.40e-04 |
| NLK | GO:0045444 | fat cell differentiation | 1.47e-04 |
| NLK | GO:0014743 | regulation of muscle hypertrophy | 1.47e-04 |
| NLK | GO:1902893 | regulation of miRNA transcription | 1.47e-04 |
| NLK | GO:0061614 | miRNA transcription | 1.50e-04 |
| NLK | GO:0001649 | osteoblast differentiation | 1.59e-04 |
| NLK | GO:0009880 | embryonic pattern specification | 1.59e-04 |
| NLK | GO:0001707 | mesoderm formation | 1.59e-04 |
| NLK | GO:0060828 | regulation of canonical Wnt signaling pathway | 1.59e-04 |
| NLK | GO:0003007 | heart morphogenesis | 1.59e-04 |
| NLK | GO:0014706 | striated muscle tissue development | 1.59e-04 |
| NLK | GO:0048332 | mesoderm morphogenesis | 1.63e-04 |
| NLK | GO:0007492 | endoderm development | 2.00e-04 |
| NLK | GO:0060395 | SMAD protein signal transduction | 2.03e-04 |
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Related Drugs to NLK_SMURF2 |
| 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 NLK-SMURF2 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 NLK_SMURF2 |
| 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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