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Kinase Fusion Gene:MARK3_XRCC5 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: MARK3_XRCC5 | KinaseFusionDB ID: KFG3659 | FusionGDB2.0 ID: KFG3659 | Hgene | Tgene | Gene symbol | MARK3 | XRCC5 | Gene ID | 4140 | 7520 | |
| Gene name | microtubule affinity regulating kinase 3 | X-ray repair cross complementing 5 | ||||||||||
| Synonyms | CTAK1|KP78|PAR1A|Par-1a|VIPB | KARP-1|KARP1|KU80|KUB2|Ku86|NFIV | ||||||||||
| Cytomap | 14q32.32-q32.33 | 2q35 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | MAP/microtubule affinity-regulating kinase 3C-TAK1ELKL motif kinase 2EMK-2cdc25C-associated protein kinase 1protein kinase STK10ser/Thr protein kinase PAR-1serine/threonine-protein kinase p78 | X-ray repair cross-complementing protein 586 kDa subunit of Ku antigenATP-dependent DNA helicase 2 subunit 2ATP-dependent DNA helicase II 80 kDa subunitCTC box-binding factor 85 kDa subunitCTC85CTCBFDNA repair protein XRCC5Ku autoantigen, 80kDaKu | ||||||||||
| Modification date | 20240407 | 20240413 | ||||||||||
| UniProtAcc | P27448 | P13010 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000440884, ENST00000416682, ENST00000429436, ENST00000303622, ENST00000216288, ENST00000553942, ENST00000335102, ENST00000561071, | ENST00000392133, ENST00000392132, ENST00000471649, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: MARK3 [Title/Abstract] AND XRCC5 [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 | MARK3 | GO:0018105 | peptidyl-serine phosphorylation | 9543386 |
| Hgene | MARK3 | GO:0032092 | positive regulation of protein binding | 9543386 |
| Hgene | MARK3 | GO:0035331 | negative regulation of hippo signaling | 28087714 |
| Hgene | MARK3 | GO:0036289 | peptidyl-serine autophosphorylation | 9543386 |
| Hgene | MARK3 | GO:1900181 | negative regulation of protein localization to nucleus | 16822840 |
| Tgene | XRCC5 | GO:0002218 | activation of innate immune response | 28712728 |
| Tgene | XRCC5 | GO:0006303 | double-strand break repair via nonhomologous end joining | 26359349 |
| Tgene | XRCC5 | GO:0034462 | small-subunit processome assembly | 32103174 |
| Tgene | XRCC5 | GO:0045860 | positive regulation of protein kinase activity | 22504299 |
| Tgene | XRCC5 | GO:0071480 | cellular response to gamma radiation | 26359349 |
| Kinase Fusion gene breakpoints across MARK3 (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 XRCC5 (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 | SNU-81 | MARK3 | chr14 | 103941508 | XRCC5 | chr2 | 216977742 |
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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/chr14:/chr2:) - 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 |
| MARK3 | XRCC5 |
| FUNCTION: Serine/threonine-protein kinase (PubMed:16822840, PubMed:16980613, PubMed:23666762). Involved in the specific phosphorylation of microtubule-associated proteins for MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Phosphorylates CDC25C on 'Ser-216' (PubMed:12941695). Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus (PubMed:16980613). Regulates localization and activity of MITF by mediating its phosphorylation, promoting subsequent interaction between MITF and 14-3-3 and retention in the cytosol (PubMed:16822840). Negatively regulates the Hippo signaling pathway and antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase activity of STK3/MST2 toward LATS1 (PubMed:28087714). Phosphorylates PKP2 and KSR1 (PubMed:12941695). {ECO:0000269|PubMed:12941695, ECO:0000269|PubMed:16822840, ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:23666762, ECO:0000269|PubMed:28087714}. | FUNCTION: Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:11493912). Required for double-strand break repair and V(D)J recombination (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:11493912). Also has a role in chromosome translocation (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:11493912). The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:11493912). It works in the 3'-5' direction (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:11493912). During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:11493912). Binding to DNA may be mediated by XRCC6 (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:11493912). The XRCC5-XRRC6 dimer acts as a regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:20383123, PubMed:11493912). The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:20383123). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:20383123). The XRCC5-XRRC6 dimer probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks (PubMed:20383123). XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined (PubMed:20383123). The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription (PubMed:8621488). In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:12145306). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). {ECO:0000269|PubMed:11493912, ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:20383123, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:7957065, ECO:0000269|PubMed:8621488}. |
| 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 MARK3_XRCC5 |
| 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 |
| MARK3 | P27448-3 | human | MARK3 | P27448-3 | S601 | SQTRsRGstNLFsKL | |
| MARK3 | P27448-3 | human | MARK3 | P27448-3 | S598 | TPLSQTRsRGstNLF | |
| MARK3 | P27448-3 | human | MARK3 | P27448-3 | S606 | RGstNLFsKLTSKLT | |
| MARK3 | P27448-3 | human | MARK3 | P27448-3 | T602 | QTRsRGstNLFsKLT | |
| MARK3 | P27448 | human | MEF2C | Q06413 | S222 | GYGNPRNsPGLLVsP | |
| MARK3 | P27448 | human | PPP1R2 | P41236 | S72 | LMKIDEPstPyHSMM | IPP-2 |
| MARK3 | P27448 | human | CDC25C | P30307 | S216 | sGLyRsPsMPENLNR | M-inducer_phosp |
| MARK3 | P27448 | human | TNK1 | Q13470 | S502 | RMKGIsRsLEsVLsL | |
| MARK3 | P27448 | human | FEZ1 | Q99689 | S58 | SEIISFKsMEDLVNE | FEZ |
| MARK3 | P27448 | human | ARHGEF2 | Q92974 | S151 | LsLAksVsttNIAGH |
| 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 |
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Related Drugs to MARK3_XRCC5 |
| 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 MARK3-XRCC5 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 MARK3_XRCC5 |
| 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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