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Kinase Fusion Gene:CDKL3_MAPKAPK5 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: CDKL3_MAPKAPK5 | KinaseFusionDB ID: KFG1221 | FusionGDB2.0 ID: KFG1221 | Hgene | Tgene | Gene symbol | CDKL3 | MAPKAPK5 | Gene ID | 51265 | 8550 | |
| Gene name | cyclin dependent kinase like 3 | MAPK activated protein kinase 5 | ||||||||||
| Synonyms | NKIAMRE | MAPKAP-K5|MK-5|MK5|NCFD|PRAK | ||||||||||
| Cytomap | 5q31.1 | 12q24.12-q24.13 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | cyclin-dependent kinase-like 3serine-threonine protein kinase NKIAMRE | MAP kinase-activated protein kinase 5MAPKAP kinase 5MAPKAPK-5mitogen-activated protein kinase-activated protein kinase 5p38-regulated/activated protein kinase | ||||||||||
| Modification date | 20240403 | 20240305 | ||||||||||
| UniProtAcc | Q8IVW4 | Q8IW41 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000265334, ENST00000435211, ENST00000435240, ENST00000521118, ENST00000521755, ENST00000522501, ENST00000523054, ENST00000523832, ENST00000536186, ENST00000609383, ENST00000609654, | ENST00000546394, ENST00000547305, ENST00000550735, ENST00000551404, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: CDKL3 [Title/Abstract] AND MAPKAPK5 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | CDKL3(133685290)-MAPKAPK5(112319509), # 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 |
| Tgene | MAPKAPK5 | GO:0006417 | regulation of translation | 21329882 |
| Tgene | MAPKAPK5 | GO:0007265 | Ras protein signal transduction | 17254968 |
| Tgene | MAPKAPK5 | GO:0046777 | protein autophosphorylation | 21329882 |
| Tgene | MAPKAPK5 | GO:0090400 | stress-induced premature senescence | 17254968 |
| Kinase Fusion gene breakpoints across CDKL3 (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 MAPKAPK5 (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 | EI790194 | CDKL3 | chr5 | 133685290 | MAPKAPK5 | chr12 | 112319509 |
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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/:133685290/:112319509) - 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 |
| CDKL3 | MAPKAPK5 |
| FUNCTION: Tumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation. Phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. Acts as a tumor suppressor by mediating Ras-induced senescence and phosphorylating p53/TP53. Involved in post-transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3, enabling expression of miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. Part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation, inducing F-actin rearrangement. {ECO:0000269|PubMed:17254968, ECO:0000269|PubMed:17728103, ECO:0000269|PubMed:19166925, ECO:0000269|PubMed:21329882, ECO:0000269|PubMed:9628874}. |
| 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 CDKL3_MAPKAPK5 |
| 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 |
| MAPKAPK5 | Q8IW41 | human | SEPTIN8 | Q92599 | S192 | IAKADTIskSELHkF | Septin |
| MAPKAPK5 | Q8IW41 | human | TP53 | P04637 | S37 | NVLsPLPsQAMDDLM | TAD2 |
| MAPKAPK5 | Q8IW41 | human | RHEB | Q15382 | S130 | LHMERVIsYEEGkAL | Ras |
| MAPKAPK5 | Q8IW41 | human | TH | P07101-3 | S19 | KGFRRAVsELDAKQA | TOH_N |
| MAPKAPK5 | Q8IW41 | human | TH | P07101-3 | S404 | GELLHCLsEEPEIRA | Biopterin_H |
| MAPKAPK5 | Q8IW41 | human | TH | P07101 | S19 | KGFRRAVsELDAKQA | TOH_N |
| MAPKAPK5 | Q8IW41 | human | KALRN | O60229 | S487 | DVLQRPLsPGNSESL | |
| MAPKAPK5 | Q8IW41 | human | DNAJB1 | P25685 | S171 | VTHDLRVsLEEIysG | DnaJ_C |
| MAPKAPK5 | Q8IW41 | human | SEPTIN8 | Q92599 | S163 | FITPTGHsLKSLDLV | Septin |
| MAPKAPK5 | Q8IW41 | human | DNAJB1 | P25685 | S151 | VNFGRsRsAQEPARK | |
| MAPKAPK5 | Q8IW41 | human | DNAJB1 | P25685 | S149 | TNVNFGRsRsAQEPA | |
| MAPKAPK5 | Q8IW41 | human | TH | P07101-3 | S40 | RFIGRRQsLIEDARK | TOH_N |
| 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 |
| MAPKAPK5 | ID | Description | 0.00e+00 |
| MAPKAPK5 | GO:0009651 | response to salt stress | 1.24e-02 |
| MAPKAPK5 | GO:0048512 | circadian behavior | 1.41e-02 |
| MAPKAPK5 | GO:0007622 | rhythmic behavior | 1.41e-02 |
| MAPKAPK5 | GO:0043462 | regulation of ATP-dependent activity | 2.25e-02 |
| MAPKAPK5 | GO:0006970 | response to osmotic stress | 2.58e-02 |
| MAPKAPK5 | GO:0007264 | small GTPase mediated signal transduction | 2.58e-02 |
| MAPKAPK5 | GO:0031667 | response to nutrient levels | 2.58e-02 |
| MAPKAPK5 | GO:0014013 | regulation of gliogenesis | 3.32e-02 |
| MAPKAPK5 | GO:0016241 | regulation of macroautophagy | 4.26e-02 |
| MAPKAPK5 | GO:0071466 | cellular response to xenobiotic stimulus | 4.26e-02 |
| MAPKAPK5 | GO:0007623 | circadian rhythm | 4.26e-02 |
| MAPKAPK5 | GO:0031669 | cellular response to nutrient levels | 4.26e-02 |
| MAPKAPK5 | GO:0003007 | heart morphogenesis | 4.26e-02 |
| MAPKAPK5 | GO:0061418 | regulation of transcription from RNA polymerase II promoter in response to hypoxia | 4.26e-02 |
| MAPKAPK5 | GO:0071287 | cellular response to manganese ion | 4.26e-02 |
| MAPKAPK5 | GO:1900543 | negative regulation of purine nucleotide metabolic process | 4.26e-02 |
| MAPKAPK5 | GO:1903799 | negative regulation of miRNA processing | 4.26e-02 |
| MAPKAPK5 | GO:0031668 | cellular response to extracellular stimulus | 4.26e-02 |
| MAPKAPK5 | GO:0006983 | ER overload response | 4.26e-02 |
| MAPKAPK5 | GO:0007406 | negative regulation of neuroblast proliferation | 4.26e-02 |
| MAPKAPK5 | GO:0045980 | negative regulation of nucleotide metabolic process | 4.26e-02 |
| MAPKAPK5 | GO:0051095 | regulation of helicase activity | 4.26e-02 |
| MAPKAPK5 | GO:0062100 | positive regulation of programmed necrotic cell death | 4.26e-02 |
| MAPKAPK5 | GO:1990440 | positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress | 4.26e-02 |
| MAPKAPK5 | GO:0048511 | rhythmic process | 4.26e-02 |
| MAPKAPK5 | GO:0001666 | response to hypoxia | 4.26e-02 |
| MAPKAPK5 | GO:0042416 | dopamine biosynthetic process | 4.26e-02 |
| MAPKAPK5 | GO:0045472 | response to ether | 4.26e-02 |
| MAPKAPK5 | GO:0060965 | negative regulation of miRNA-mediated gene silencing | 4.26e-02 |
| MAPKAPK5 | GO:0071236 | cellular response to antibiotic | 4.26e-02 |
| MAPKAPK5 | GO:0090084 | negative regulation of inclusion body assembly | 4.26e-02 |
| MAPKAPK5 | GO:0036293 | response to decreased oxygen levels | 4.26e-02 |
| MAPKAPK5 | GO:0009416 | response to light stimulus | 4.26e-02 |
| MAPKAPK5 | GO:0060149 | negative regulation of post-transcriptional gene silencing | 4.26e-02 |
| MAPKAPK5 | GO:0060967 | negative regulation of gene silencing by regulatory ncRNA | 4.26e-02 |
| MAPKAPK5 | GO:0070234 | positive regulation of T cell apoptotic process | 4.26e-02 |
| MAPKAPK5 | GO:1900369 | negative regulation of post-transcriptional gene silencing by regulatory ncRNA | 4.26e-02 |
| MAPKAPK5 | GO:0016236 | macroautophagy | 4.26e-02 |
| MAPKAPK5 | GO:0009404 | toxin metabolic process | 4.26e-02 |
| MAPKAPK5 | GO:0010225 | response to UV-C | 4.26e-02 |
| MAPKAPK5 | GO:0035542 | regulation of SNARE complex assembly | 4.26e-02 |
| MAPKAPK5 | GO:0042136 | neurotransmitter biosynthetic process | 4.26e-02 |
| MAPKAPK5 | GO:0042415 | norepinephrine metabolic process | 4.26e-02 |
| MAPKAPK5 | GO:0051412 | response to corticosterone | 4.26e-02 |
| MAPKAPK5 | GO:0070243 | regulation of thymocyte apoptotic process | 4.26e-02 |
| MAPKAPK5 | GO:0042063 | gliogenesis | 4.26e-02 |
| MAPKAPK5 | GO:0070482 | response to oxygen levels | 4.26e-02 |
| MAPKAPK5 | GO:0071496 | cellular response to external stimulus | 4.26e-02 |
| MAPKAPK5 | GO:0010506 | regulation of autophagy | 4.26e-02 |
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Related Drugs to CDKL3_MAPKAPK5 |
| 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 CDKL3-MAPKAPK5 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 CDKL3_MAPKAPK5 |
| 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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