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Kinase Fusion Gene:ZEB1_SIK1 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: ZEB1_SIK1 | KinaseFusionDB ID: KFG7245 | FusionGDB2.0 ID: KFG7245 | Hgene | Tgene | Gene symbol | ZEB1 | SIK1 | Gene ID | 6935 | 102724428 | |
| Gene name | zinc finger E-box binding homeobox 1 | |||||||||||
| Synonyms | AREB6|BZP|DELTAEF1|FECD6|NIL2A|PPCD3|TCF8|ZFHEP|ZFHX1A | |||||||||||
| Cytomap | 10p11.22 | |||||||||||
| Type of gene | protein-coding | |||||||||||
| Description | zinc finger E-box-binding homeobox 1delta-crystallin enhancer binding factor 1negative regulator of IL2posterior polymorphous corneal dystrophy 3transcription factor 8 (represses interleukin 2 expression)zinc finger homeodomain enhancer-binding prote | |||||||||||
| Modification date | 20240407 | |||||||||||
| UniProtAcc | P37275 | P57059 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000320985, ENST00000361642, ENST00000446923, ENST00000542815, ENST00000559858, ENST00000560721, | ENST00000270162, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: ZEB1 [Title/Abstract] AND SIK1 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | ZEB1(31816308)-SIK1(44836230), # 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 | ZEB1 | GO:0000122 | negative regulation of transcription by RNA polymerase II | 23765923|23814079 |
| Hgene | ZEB1 | GO:0045892 | negative regulation of DNA-templated transcription | 20418909 |
| Kinase Fusion gene breakpoints across ZEB1 (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 SIK1 (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 |
| ChiTaRS5.0 | D15050 | ZEB1 | chr10 | 31816308 | SIK1 | chr21 | 44836230 |
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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/:31816308/:44836230) - 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 |
| ZEB1 | SIK1 |
| FUNCTION: Acts as a transcriptional repressor. Inhibits interleukin-2 (IL-2) gene expression. Enhances or represses the promoter activity of the ATP1A1 gene depending on the quantity of cDNA and on the cell type. Represses E-cadherin promoter and induces an epithelial-mesenchymal transition (EMT) by recruiting SMARCA4/BRG1. Represses BCL6 transcription in the presence of the corepressor CTBP1. Positively regulates neuronal differentiation. Represses RCOR1 transcription activation during neurogenesis. Represses transcription by binding to the E box (5'-CANNTG-3'). In the absence of TGFB1, acts as a repressor of COL1A2 transcription via binding to the E-box in the upstream enhancer region (By similarity). {ECO:0000250|UniProtKB:Q64318, ECO:0000269|PubMed:19935649, ECO:0000269|PubMed:20175752, ECO:0000269|PubMed:20418909}. | FUNCTION: Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, gluconeogenesis and lipogenesis regulation, muscle growth and differentiation and tumor suppression. Phosphorylates HDAC4, HDAC5, PPME1, SREBF1, CRTC1/TORC1. Inhibits CREB activity by phosphorylating and inhibiting activity of TORCs, the CREB-specific coactivators, like CRTC2/TORC2 and CRTC3/TORC3 in response to cAMP signaling (PubMed:29211348). Acts as a tumor suppressor and plays a key role in p53/TP53-dependent anoikis, a type of apoptosis triggered by cell detachment: required for phosphorylation of p53/TP53 in response to loss of adhesion and is able to suppress metastasis. Part of a sodium-sensing signaling network, probably by mediating phosphorylation of PPME1: following increases in intracellular sodium, SIK1 is activated by CaMK1 and phosphorylates PPME1 subunit of protein phosphatase 2A (PP2A), leading to dephosphorylation of sodium/potassium-transporting ATPase ATP1A1 and subsequent increase activity of ATP1A1. Acts as a regulator of muscle cells by phosphorylating and inhibiting class II histone deacetylases HDAC4 and HDAC5, leading to promote expression of MEF2 target genes in myocytes. Also required during cardiomyogenesis by regulating the exit of cardiomyoblasts from the cell cycle via down-regulation of CDKN1C/p57Kip2. Acts as a regulator of hepatic gluconeogenesis by phosphorylating and repressing the CREB-specific coactivators CRTC1/TORC1 and CRTC2/TORC2, leading to inhibit CREB activity. Also regulates hepatic lipogenesis by phosphorylating and inhibiting SREBF1. In concert with CRTC1/TORC1, regulates the light-induced entrainment of the circadian clock by attenuating PER1 induction; represses CREB-mediated transcription of PER1 by phosphorylating and deactivating CRTC1/TORC1 (By similarity). {ECO:0000250|UniProtKB:Q60670, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:16306228, ECO:0000269|PubMed:18348280, ECO:0000269|PubMed:19622832, ECO:0000269|PubMed:29211348}. |
| 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 ZEB1_SIK1 |
| 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 |
| SIK1 | P57059 | human | HDAC5 | Q9UQL6 | S661 | QALGRTQsSPAAPGG | |
| SIK1 | P57059 | human | NCOR2 | Q9Y618 | T1383 | KLLKREGtPPPPPPs |
| 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 |
| SIK1 | ID | Description | 0.00e+00 |
| SIK1 | GO:0044849 | estrous cycle | 3.20e-02 |
| SIK1 | GO:0060766 | negative regulation of androgen receptor signaling pathway | 3.20e-02 |
| SIK1 | GO:0010832 | negative regulation of myotube differentiation | 3.20e-02 |
| SIK1 | GO:1902894 | negative regulation of miRNA transcription | 3.20e-02 |
| SIK1 | GO:2000629 | negative regulation of miRNA metabolic process | 3.20e-02 |
| SIK1 | GO:0060765 | regulation of androgen receptor signaling pathway | 3.20e-02 |
| SIK1 | GO:0033144 | negative regulation of intracellular steroid hormone receptor signaling pathway | 3.20e-02 |
| SIK1 | GO:0051154 | negative regulation of striated muscle cell differentiation | 3.20e-02 |
| SIK1 | GO:0007595 | lactation | 3.20e-02 |
| SIK1 | GO:0090051 | negative regulation of cell migration involved in sprouting angiogenesis | 3.20e-02 |
| SIK1 | GO:0010830 | regulation of myotube differentiation | 3.20e-02 |
| SIK1 | GO:0042220 | response to cocaine | 3.20e-02 |
| SIK1 | GO:0030521 | androgen receptor signaling pathway | 3.20e-02 |
| SIK1 | GO:0051148 | negative regulation of muscle cell differentiation | 3.20e-02 |
| SIK1 | GO:1902893 | regulation of miRNA transcription | 3.20e-02 |
| SIK1 | GO:0042698 | ovulation cycle | 3.20e-02 |
| SIK1 | GO:0061614 | miRNA transcription | 3.20e-02 |
| SIK1 | GO:0014823 | response to activity | 3.20e-02 |
| SIK1 | GO:0033143 | regulation of intracellular steroid hormone receptor signaling pathway | 3.20e-02 |
| SIK1 | GO:0043537 | negative regulation of blood vessel endothelial cell migration | 3.20e-02 |
| SIK1 | GO:0090049 | regulation of cell migration involved in sprouting angiogenesis | 3.20e-02 |
| SIK1 | GO:2000628 | regulation of miRNA metabolic process | 3.20e-02 |
| SIK1 | GO:0007589 | body fluid secretion | 3.20e-02 |
| SIK1 | GO:0140747 | regulation of ncRNA transcription | 3.20e-02 |
| SIK1 | GO:0043279 | response to alkaloid | 3.20e-02 |
| SIK1 | GO:0002042 | cell migration involved in sprouting angiogenesis | 3.20e-02 |
| SIK1 | GO:0051153 | regulation of striated muscle cell differentiation | 3.20e-02 |
| SIK1 | GO:0010596 | negative regulation of endothelial cell migration | 3.20e-02 |
| SIK1 | GO:0021549 | cerebellum development | 3.20e-02 |
| SIK1 | GO:0010586 | miRNA metabolic process | 3.20e-02 |
| SIK1 | GO:0032355 | response to estradiol | 3.20e-02 |
| SIK1 | GO:0022037 | metencephalon development | 3.20e-02 |
| SIK1 | GO:0010633 | negative regulation of epithelial cell migration | 3.20e-02 |
| SIK1 | GO:0045814 | negative regulation of gene expressio | 1.27e-02 |
| SIK1 | GO:0014902 | myotube differentiation | 3.23e-02 |
| SIK1 | GO:0030879 | mammary gland development | 3.23e-02 |
| SIK1 | GO:0098781 | ncRNA transcription | 3.23e-02 |
| SIK1 | GO:0043401 | steroid hormone mediated signaling pathway | 3.23e-02 |
| SIK1 | GO:0043393 | regulation of protein binding | 3.23e-02 |
| SIK1 | GO:0010565 | regulation of cellular ketone metabolic process | 3.23e-02 |
| SIK1 | GO:0030183 | B cell differentiation | 3.27e-02 |
| SIK1 | GO:0043535 | regulation of blood vessel endothelial cell migration | 3.27e-02 |
| SIK1 | GO:0030902 | hindbrain development | 3.28e-02 |
| SIK1 | GO:0051147 | regulation of muscle cell differentiation | 3.31e-02 |
| SIK1 | GO:0043534 | blood vessel endothelial cell migration | 3.61e-02 |
| SIK1 | GO:0002040 | sprouting angiogenesis | 3.69e-02 |
| SIK1 | GO:0009755 | hormone-mediated signaling pathway | 3.69e-02 |
| SIK1 | GO:0032869 | cellular response to insulin stimulus | 3.81e-02 |
| SIK1 | GO:0071383 | cellular response to steroid hormone stimulus | 3.81e-02 |
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Related Drugs to ZEB1_SIK1 |
| 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 ZEB1-SIK1 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 ZEB1_SIK1 |
| 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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