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Kinase Fusion Gene:LIMK1_TOP2A |
Kinase Fusion Protein Summary |
Kinase Fusion gene summary |
Kinase Fusion partner gene information | Kinase Fusion gene name: LIMK1_TOP2A | KinaseFusionDB ID: KFG3154 | FusionGDB2.0 ID: KFG3154 | Hgene | Tgene | Gene symbol | LIMK1 | TOP2A | Gene ID | 3984 | 7153 | |
Gene name | LIM domain kinase 1 | DNA topoisomerase II alpha | ||||||||||
Synonyms | LIMK|LIMK-1 | TOP2|TOP2alpha|TOPIIA|TP2A | ||||||||||
Cytomap | 7q11.23 | 17q21.2 | ||||||||||
Type of gene | protein-coding | protein-coding | ||||||||||
Description | LIM domain kinase 1LIM motif-containing protein kinase | DNA topoisomerase 2-alphaDNA gyraseDNA topoisomerase (ATP-hydrolyzing)DNA topoisomerase II, 170 kDDNA topoisomerase II, alpha isozymetopoisomerase (DNA) II alpha 170kDa | ||||||||||
Modification date | 20240305 | 20240413 | ||||||||||
UniProtAcc | P53667 | P11388 | ||||||||||
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000418310, ENST00000336180, ENST00000538333, ENST00000491052, | ENST00000423485, | |||||||||
Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: LIMK1 [Title/Abstract] AND TOP2A [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 | LIMK1 | GO:0006468 | protein phosphorylation | 17512523|22328514 |
Hgene | LIMK1 | GO:0032233 | positive regulation of actin filament bundle assembly | 17512523 |
Hgene | LIMK1 | GO:0051444 | negative regulation of ubiquitin-protein transferase activity | 17512523 |
Tgene | TOP2A | GO:0006265 | DNA topological change | 22323612 |
Tgene | TOP2A | GO:0006266 | DNA ligation | 15491148 |
Tgene | TOP2A | GO:0006974 | DNA damage response | 16611985 |
Tgene | TOP2A | GO:0030263 | apoptotic chromosome condensation | 10959840 |
Tgene | TOP2A | GO:0043065 | positive regulation of apoptotic process | 16611985 |
Kinase Fusion gene breakpoints across LIMK1 (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 TOP2A (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 | TE-14 | LIMK1 | chr7 | 73522292 | TOP2A | chr17 | 38574118 |
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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/:/:) - 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. |
Main function of each fusion partner protein. (from UniProt) |
Hgene | Tgene |
LIMK1 | TOP2A |
FUNCTION: Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics. Acts downstream of several Rho family GTPase signal transduction pathways (PubMed:10436159, PubMed:11832213, PubMed:12807904, PubMed:15660133, PubMed:16230460, PubMed:18028908, PubMed:22328514, PubMed:23633677). Activated by upstream kinases including ROCK1, PAK1 and PAK4, which phosphorylate LIMK1 on a threonine residue located in its activation loop (PubMed:10436159). LIMK1 subsequently phosphorylates and inactivates the actin binding/depolymerizing factors cofilin-1/CFL1, cofilin-2/CFL2 and destrin/DSTN, thereby preventing the cleavage of filamentous actin (F-actin), and stabilizing the actin cytoskeleton (PubMed:11832213, PubMed:15660133, PubMed:16230460, PubMed:23633677). In this way LIMK1 regulates several actin-dependent biological processes including cell motility, cell cycle progression, and differentiation (PubMed:11832213, PubMed:15660133, PubMed:16230460, PubMed:23633677). Phosphorylates TPPP on serine residues, thereby promoting microtubule disassembly (PubMed:18028908). Stimulates axonal outgrowth and may be involved in brain development (PubMed:18028908). {ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:11832213, ECO:0000269|PubMed:12807904, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:16230460, ECO:0000269|PubMed:18028908, ECO:0000269|PubMed:22328514, ECO:0000269|PubMed:23633677}.; FUNCTION: [Isoform 3]: Has a dominant negative effect on actin cytoskeletal changes. Required for atypical chemokine receptor ACKR2-induced phosphorylation of cofilin (CFL1). {ECO:0000269|PubMed:10196227}. | FUNCTION: Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand (PubMed:17567603, PubMed:18790802, PubMed:22013166, PubMed:22323612). May play a role in regulating the period length of BMAL1 transcriptional oscillation (By similarity). {ECO:0000250|UniProtKB:Q01320, ECO:0000269|PubMed:17567603, ECO:0000269|PubMed:18790802, ECO:0000269|PubMed:22013166, ECO:0000269|PubMed:22323612}. |
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 LIMK1_TOP2A |
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 |
LIMK1 | P53667 | human | DSTN | P60981 | S3 | _____MAsGVQVADE | |
LIMK1 | P53667 | human | CFL1 | P23528 | S3 | _____MAsGVAVsDG |
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 |
LIMK1 | ID | Description | 0.00e+00 |
LIMK1 | GO:0051014 | actin filament severing | 3.64e-05 |
LIMK1 | GO:0030042 | actin filament depolymerization | 2.51e-04 |
LIMK1 | GO:0051261 | protein depolymerization | 6.63e-04 |
LIMK1 | GO:0008154 | actin polymerization or depolymerization | 1.45e-03 |
LIMK1 | GO:0032984 | protein-containing complex disassembly | 1.81e-03 |
LIMK1 | GO:0007015 | actin filament organization | 5.34e-03 |
LIMK1 | GO:0022411 | cellular component disassembly | 5.34e-03 |
LIMK1 | GO:0030836 | positive regulation of actin filament depolymerization | 9.30e-03 |
LIMK1 | GO:1901881 | positive regulation of protein depolymerization | 1.20e-02 |
LIMK1 | GO:0044794 | positive regulation by host of viral process | 1.20e-02 |
LIMK1 | GO:0040019 | positive regulation of embryonic development | 1.20e-02 |
LIMK1 | GO:0043243 | positive regulation of protein-containing complex disassembly | 1.76e-02 |
LIMK1 | GO:0061001 | regulation of dendritic spine morphogenesis | 1.85e-02 |
LIMK1 | GO:0044788 | modulation by host of viral process | 1.92e-02 |
LIMK1 | GO:0030834 | regulation of actin filament depolymerization | 1.92e-02 |
LIMK1 | GO:0060997 | dendritic spine morphogenesis | 1.92e-02 |
LIMK1 | GO:0051293 | establishment of spindle localization | 1.92e-02 |
LIMK1 | GO:0051653 | spindle localization | 1.97e-02 |
LIMK1 | GO:0097061 | dendritic spine organization | 2.17e-02 |
LIMK1 | GO:1901879 | regulation of protein depolymerization | 2.17e-02 |
LIMK1 | GO:0051851 | modulation by host of symbiont process | 2.17e-02 |
LIMK1 | GO:0000281 | mitotic cytokinesis | 2.17e-02 |
LIMK1 | GO:0106027 | neuron projection organization | 2.17e-02 |
LIMK1 | GO:0045995 | regulation of embryonic development | 2.17e-02 |
LIMK1 | GO:0060996 | dendritic spine development | 2.17e-02 |
LIMK1 | GO:0099175 | regulation of postsynapse organization | 2.26e-02 |
LIMK1 | GO:0061640 | cytoskeleton-dependent cytokinesis | 2.42e-02 |
LIMK1 | GO:0051702 | biological process involved in interaction with symbiont | 2.42e-02 |
LIMK1 | GO:0043244 | regulation of protein-containing complex disassembly | 2.42e-02 |
LIMK1 | GO:0007266 | Rho protein signal transduction | 2.56e-02 |
LIMK1 | GO:0048813 | dendrite morphogenesis | 2.56e-02 |
LIMK1 | GO:0008064 | regulation of actin polymerization or depolymerization | 2.71e-02 |
LIMK1 | GO:0030832 | regulation of actin filament length | 2.71e-02 |
LIMK1 | GO:1902905 | positive regulation of supramolecular fiber organization | 2.93e-02 |
LIMK1 | GO:0051495 | positive regulation of cytoskeleton organization | 2.97e-02 |
LIMK1 | GO:0000910 | cytokinesis | 2.97e-02 |
LIMK1 | GO:0099173 | postsynapse organization | 3.02e-02 |
LIMK1 | GO:0016358 | dendrite development | 3.47e-02 |
LIMK1 | GO:0050807 | regulation of synapse organization | 3.47e-02 |
LIMK1 | GO:0022604 | regulation of cell morphogenesis | 3.47e-02 |
LIMK1 | GO:0050803 | regulation of synapse structure or activity | 3.47e-02 |
LIMK1 | GO:0110053 | regulation of actin filament organization | 3.69e-02 |
LIMK1 | GO:0044403 | biological process involved in symbiotic interaction | 4.25e-02 |
LIMK1 | GO:0032956 | regulation of actin cytoskeleton organization | 4.30e-02 |
LIMK1 | GO:0007265 | Ras protein signal transduction | 4.30e-02 |
LIMK1 | GO:0032535 | regulation of cellular component size | 4.56e-02 |
LIMK1 | GO:0032970 | regulation of actin filament-based process | 4.57e-02 |
LIMK1 | GO:1902903 | regulation of supramolecular fiber organization | 4.59e-02 |
LIMK1 | GO:0016032 | viral process | 4.93e-02 |
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Related Drugs to LIMK1_TOP2A |
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 LIMK1-TOP2A 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 LIMK1_TOP2A |
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 |