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Kinase Fusion Gene:LIMK2_PPP2CA |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: LIMK2_PPP2CA | KinaseFusionDB ID: KFG3163 | FusionGDB2.0 ID: KFG3163 | Hgene | Tgene | Gene symbol | LIMK2 | PPP2CA | Gene ID | 3985 | 5515 | |
| Gene name | LIM domain kinase 2 | protein phosphatase 2 catalytic subunit alpha | ||||||||||
| Synonyms | - | HJS3|NEDLBA|PP2Ac|PP2CA|PP2Calpha|RP-C | ||||||||||
| Cytomap | 22q12.2 | 5q31.1 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | LIM domain kinase 2 | serine/threonine-protein phosphatase 2A catalytic subunit alpha isoformPP2A-alphaprotein phosphatase 2, catalytic subunit, alpha isozymereplication protein C | ||||||||||
| Modification date | 20240305 | 20240411 | ||||||||||
| UniProtAcc | P53671 | P67775 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000406516, ENST00000444929, ENST00000331728, ENST00000333611, ENST00000340552, ENST00000467301, | ENST00000481195, ENST00000231504, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: LIMK2 [Title/Abstract] AND PPP2CA [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 | LIMK2 | GO:0006468 | protein phosphorylation | 22328514 |
| Hgene | LIMK2 | GO:0030953 | astral microtubule organization | 22328514 |
| Tgene | PPP2CA | GO:0035970 | peptidyl-threonine dephosphorylation | 30611118 |
| Tgene | PPP2CA | GO:2000045 | regulation of G1/S transition of mitotic cell cycle | 25438055 |
| Kinase Fusion gene breakpoints across LIMK2 (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 PPP2CA (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 | JHOC-5 | LIMK2 | chr22 | 31654412 | PPP2CA | chr5 | 133541822 |
| CCLE | JHOC-5 | LIMK2 | chr22 | 31656063 | PPP2CA | chr5 | 133541822 |
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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) |
| ENST00000406516 | ENST00000481195 | LIMK2 | chr22 | 31654412 | PPP2CA | chr5 | 133541822 | 4553 | 345 |
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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 >ENST00000406516_ENST00000481195_LIMK2_chr22_31654412_PPP2CA_chr5_133541822_length(amino acids)=345 MRGAAVSPASSSPFPRSRDHVRAGGCSECQDSLTNWYYEKDGKLYCPKDYWGKFGEFCHGCSLLMTGPFMAKEILTKESNVQEVRCPVTV CGDVHGQFHDLMELFRIGGKSPDTNYLFMGDYVDRGYYSVETVTLLVALKVRYRERITILRGNHESRQITQVYGFYDECLRKYGNANVWK YFTDLFDYLPLTALVDGQIFCLHGGLSPSIDTLDHIRALDRLQEVPHEGPMCDLLWSDPDDRGGWGISPRGAGYTFGQDISETFNHANGL -------------------------------------------------------------- |
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/chr22:/chr5:) - 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 |
| LIMK2 | PPP2CA |
| FUNCTION: Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics (PubMed:10436159, PubMed:11018042). Acts downstream of several Rho family GTPase signal transduction pathways (PubMed:10436159, PubMed:11018042). Involved in astral microtubule organization and mitotic spindle orientation during early stages of mitosis by mediating phosphorylation of TPPP (PubMed:22328514). Displays serine/threonine-specific phosphorylation of myelin basic protein and histone (MBP) in vitro (PubMed:8537403). Suppresses ciliogenesis via multiple pathways; phosphorylation of CFL1, suppression of directional trafficking of ciliary vesicles to the ciliary base, and by facilitating YAP1 nuclear localization where it acts as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1 (PubMed:25849865). {ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:11018042, ECO:0000269|PubMed:22328514, ECO:0000269|PubMed:25849865, ECO:0000269|PubMed:8537403}. | FUNCTION: PP2A is the major phosphatase for microtubule-associated proteins (MAPs) (PubMed:22613722). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase (PubMed:22613722). Cooperates with SGO2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity). Can dephosphorylate SV40 large T antigen and p53/TP53 (PubMed:17245430). Activates RAF1 by dephosphorylating it at 'Ser-259' (PubMed:10801873). Mediates dephosphorylation of WEE1, preventing its ubiquitin-mediated proteolysis, increasing WEE1 protein levels, and promoting the G2/M checkpoint (PubMed:33108758). Mediates dephosphorylation of MYC; promoting its ubiquitin-mediated proteolysis: interaction with AMBRA1 enhances interaction between PPP2CA and MYC (PubMed:25438055). Mediates dephosphorylation of FOXO3; promoting its stabilization: interaction with AMBRA1 enhances interaction between PPP2CA and FOXO3 (PubMed:30513302). Catalyzes dephosphorylation of the pyrin domain of NLRP3, promoting assembly of the NLRP3 inflammasome (By similarity). {ECO:0000250|UniProtKB:P63330, ECO:0000269|PubMed:10801873, ECO:0000269|PubMed:17245430, ECO:0000269|PubMed:22613722, ECO:0000269|PubMed:25438055, ECO:0000269|PubMed:30513302, ECO:0000269|PubMed:33108758, ECO:0000269|PubMed:9920888}. |
| 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 |
| Hgene | LIMK2 | 31654412 | PPP2CA | 133541822 | ENST00000406516 | 2 | 15 | 12_63 | 631 | 618 | Domain | Note=LIM zinc-binding 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00125 |
| Hgene | LIMK2 | 31654412 | PPP2CA | 133541822 | ENST00000406516 | 2 | 15 | 12_63 | 631 | 687 | Domain | Note=LIM zinc-binding 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00125 |
| Hgene | LIMK2 | 31654412 | PPP2CA | 133541822 | ENST00000406516 | 3 | 16 | 12_63 | 841 | 639 | Domain | Note=LIM zinc-binding 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00125 |
| - 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 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 >>>145_LIMK2_PPP2CA | ENST00000406516 | ENST00000481195 | LIMK2 | chr22 | 31654412 | PPP2CA | chr5 | 133541822 | MRGAAVSPASSSPFPRSRDHVRAGGCSECQDSLTNWYYEKDGKLYCPKDYWGKFGEFCHGCSLLMTGPFMAKEILTKESNVQEVRCPVTV CGDVHGQFHDLMELFRIGGKSPDTNYLFMGDYVDRGYYSVETVTLLVALKVRYRERITILRGNHESRQITQVYGFYDECLRKYGNANVWK YFTDLFDYLPLTALVDGQIFCLHGGLSPSIDTLDHIRALDRLQEVPHEGPMCDLLWSDPDDRGGWGISPRGAGYTFGQDISETFNHANGL | 345 |
| 3D view using mol* of 145_LIMK2_PPP2CA | ||||||||||
| PDB file >>>HKFP_217_LIMK2_PPP2CA | ENST00000406516 | ENST00000481195 | LIMK2 | chr22 | 31654412 | PPP2CA | chr5 | 133541822 | MRGAAVSPASSSPFPRSRDHVRAGGCSECQDSLTNWYYEKDGKLYCPKDYWGKFGEFCHGCSLLMTGPFMAKEILTKESNVQEVRCPVTV CGDVHGQFHDLMELFRIGGKSPDTNYLFMGDYVDRGYYSVETVTLLVALKVRYRERITILRGNHESRQITQVYGFYDECLRKYGNANVWK YFTDLFDYLPLTALVDGQIFCLHGGLSPSIDTLDHIRALDRLQEVPHEGPMCDLLWSDPDDRGGWGISPRGAGYTFGQDISETFNHANGL | 345_LIMK2_PPP2CA |
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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. |
| 145_LIMK2_PPP2CA.png |
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| 145_LIMK2_PPP2CA.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. |
| 145_LIMK2_PPP2CA_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 |
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| 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 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Lapatinib | -7.245889999999999 | -7.334689999999999 | -60.4174 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Pazopanib | -6.95937 | -6.96627 | -52.9375 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Pazopanib | -6.95937 | -6.96627 | -52.9375 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Netarsudil | -6.31775 | -6.32885 | -46.1309 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Netarsudil | -6.31775 | -6.32885 | -46.1309 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Afatinib | -6.0749 | -6.2572 | -55.6117 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Afatinib | -6.0749 | -6.2572 | -55.6117 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Afatinib | -6.0735 | -6.2572 | -55.6117 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Dacomitinib | -6.0360000000000005 | -6.1443 | -51.3177 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Dacomitinib | -6.0360000000000005 | -6.1443 | -51.3177 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Dacomitinib | -5.918740000000001 | -6.0277400000000005 | -52.5651 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Dacomitinib | -5.87672 | -5.98502 | -52.158 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Dacomitinib | -5.87672 | -5.98502 | -52.158 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Dacomitinib | -5.87602 | -5.98502 | -52.158 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Baricitinib | -5.77315 | -5.77315 | -40.9357 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Bosutinib | -5.7685 | -5.8817 | -39.9247 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Bosutinib | -5.7685 | -5.8817 | -39.9247 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Bosutinib | -5.7685 | -5.8817 | -39.9247 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Afatinib | -5.7479 | -5.9302 | -53.0622 |
| 145_LIMK2_PPP2CA-DOCK_HTVS_1-001 | Afatinib | -5.7479 | -5.9302 | -53.0622 |
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Kinase-Substrate Information of LIMK2_PPP2CA |
| 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 |
| LIMK2 | P53671 | human | DSTN | P60981 | S3 | _____MAsGVQVADE | |
| LIMK2 | P53671 | human | CFL1 | P23528 | S3 | _____MAsGVAVsDG | |
| LIMK2 | P53671 | human | G3BP1 | Q13283 | S149 | VtEPQEEsEEEVEEP |
| 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 |
| LIMK2 | ID | Description | 0.00e+00 |
| LIMK2 | GO:0051014 | actin filament severing | 1.50e-04 |
| LIMK2 | GO:0030042 | actin filament depolymerization | 1.03e-03 |
| LIMK2 | GO:0051261 | protein depolymerization | 2.71e-03 |
| LIMK2 | GO:0008154 | actin polymerization or depolymerization | 5.92e-03 |
| LIMK2 | GO:0032984 | protein-containing complex disassembly | 7.39e-03 |
| LIMK2 | GO:0007265 | Ras protein signal transduction | 1.19e-02 |
| LIMK2 | GO:0009615 | response to virus | 1.39e-02 |
| LIMK2 | GO:0007015 | actin filament organization | 1.39e-02 |
| LIMK2 | GO:0007264 | small GTPase mediated signal transduction | 1.39e-02 |
| LIMK2 | GO:0022411 | cellular component disassembly | 1.39e-02 |
| LIMK2 | GO:0030836 | positive regulation of actin filament depolymerization | 1.39e-02 |
| LIMK2 | GO:1901881 | positive regulation of protein depolymerization | 1.86e-02 |
| LIMK2 | GO:0044794 | positive regulation by host of viral process | 1.90e-02 |
| LIMK2 | GO:0040019 | positive regulation of embryonic development | 1.93e-02 |
| LIMK2 | GO:0034063 | stress granule assembly | 2.43e-02 |
| LIMK2 | GO:0043243 | positive regulation of protein-containing complex disassembly | 2.72e-02 |
| LIMK2 | GO:0061001 | regulation of dendritic spine morphogenesis | 2.90e-02 |
| LIMK2 | GO:0044788 | modulation by host of viral process | 3.18e-02 |
| LIMK2 | GO:0030834 | regulation of actin filament depolymerization | 3.18e-02 |
| LIMK2 | GO:0060997 | dendritic spine morphogenesis | 3.18e-02 |
| LIMK2 | GO:0051293 | establishment of spindle localization | 3.18e-02 |
| LIMK2 | GO:0051653 | spindle localization | 3.27e-02 |
| LIMK2 | GO:0032481 | positive regulation of type I interferon production | 3.27e-02 |
| LIMK2 | GO:0032508 | DNA duplex unwinding | 3.27e-02 |
| LIMK2 | GO:0097061 | dendritic spine organization | 3.27e-02 |
| LIMK2 | GO:1902117 | positive regulation of organelle assembly | 3.27e-02 |
| LIMK2 | GO:0032392 | DNA geometric change | 3.27e-02 |
| LIMK2 | GO:1901879 | regulation of protein depolymerization | 3.27e-02 |
| LIMK2 | GO:0051851 | modulation by host of symbiont process | 3.27e-02 |
| LIMK2 | GO:0000281 | mitotic cytokinesis | 3.27e-02 |
| LIMK2 | GO:0106027 | neuron projection organization | 3.27e-02 |
| LIMK2 | GO:0071103 | DNA conformation change | 3.27e-02 |
| LIMK2 | GO:0045995 | regulation of embryonic development | 3.27e-02 |
| LIMK2 | GO:0060996 | dendritic spine development | 3.27e-02 |
| LIMK2 | GO:0099175 | regulation of postsynapse organization | 3.44e-02 |
| LIMK2 | GO:0061640 | cytoskeleton-dependent cytokinesis | 3.59e-02 |
| LIMK2 | GO:0051702 | biological process involved in interaction with symbiont | 3.59e-02 |
| LIMK2 | GO:0032479 | regulation of type I interferon production | 3.59e-02 |
| LIMK2 | GO:0032606 | type I interferon production | 3.59e-02 |
| LIMK2 | GO:0043244 | regulation of protein-containing complex disassembly | 3.59e-02 |
| LIMK2 | GO:0007266 | Rho protein signal transduction | 3.80e-02 |
| LIMK2 | GO:0048813 | dendrite morphogenesis | 3.80e-02 |
| LIMK2 | GO:0090090 | negative regulation of canonical Wnt signaling pathway | 3.80e-02 |
| LIMK2 | GO:0008064 | regulation of actin polymerization or depolymerization | 4.07e-02 |
| LIMK2 | GO:0030832 | regulation of actin filament length | 4.07e-02 |
| LIMK2 | GO:0030178 | negative regulation of Wnt signaling pathway | 4.34e-02 |
| LIMK2 | GO:1902905 | positive regulation of supramolecular fiber organization | 4.34e-02 |
| LIMK2 | GO:0051495 | positive regulation of cytoskeleton organization | 4.47e-02 |
| LIMK2 | GO:0000910 | cytokinesis | 4.47e-02 |
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Related Drugs to LIMK2_PPP2CA |
| 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 LIMK2-PPP2CA 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 LIMK2_PPP2CA |
| 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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