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Kinase Fusion Gene:MAPK12_TMED10 |
Kinase Fusion Protein Summary |
Kinase Fusion gene summary |
Kinase Fusion partner gene information | Kinase Fusion gene name: MAPK12_TMED10 | KinaseFusionDB ID: KFG3535 | FusionGDB2.0 ID: KFG3535 | Hgene | Tgene | Gene symbol | MAPK12 | TMED10 | Gene ID | 6300 | 10972 | |
Gene name | mitogen-activated protein kinase 12 | transmembrane p24 trafficking protein 10 | ||||||||||
Synonyms | ERK-6|ERK3|ERK6|MAPK 12|P38GAMMA|PRKM12|SAPK-3|SAPK3 | P24(DELTA)|S31I125|S31III125|TMP21|Tmp-21-I|p23|p24d1 | ||||||||||
Cytomap | 22q13.33 | 14q24.3 | ||||||||||
Type of gene | protein-coding | protein-coding | ||||||||||
Description | mitogen-activated protein kinase 12MAP kinase 12MAP kinase p38 gammaextracellular signal-regulated kinase 6mitogen-activated protein kinase 3mitogen-activated protein kinase p38 gammastress-activated protein kinase 3 | transmembrane emp24 domain-containing protein 1021 kDa transmembrane trafficking proteinp24 family protein delta-1p24deltap24delta1testicular tissue protein Li 206transmembrane emp24-like trafficking protein 10transmembrane protein Tmp21 | ||||||||||
Modification date | 20240305 | 20240305 | ||||||||||
UniProtAcc | P53778 | P49755 | ||||||||||
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000497036, ENST00000395780, ENST00000215659, ENST00000395778, | ENST00000303575, ENST00000557670, | |||||||||
Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: MAPK12 [Title/Abstract] AND TMED10 [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 | MAPK12 | GO:0018105 | peptidyl-serine phosphorylation | 15850461 |
Hgene | MAPK12 | GO:0045445 | myoblast differentiation | 8633070 |
Tgene | TMED10 | GO:0006886 | intracellular protein transport | 20427317 |
Tgene | TMED10 | GO:0035964 | COPI-coated vesicle budding | 10052452 |
Kinase Fusion gene breakpoints across MAPK12 (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 TMED10 (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 | YH-13 | MAPK12 | chr22 | 50693440 | TMED10 | chr14 | 75643263 |
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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 |
MAPK12 | TMED10 |
FUNCTION: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK12 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in myoblast differentiation and also in the down-regulation of cyclin D1 in response to hypoxia in adrenal cells suggesting MAPK12 may inhibit cell proliferation while promoting differentiation. Phosphorylates DLG1. Following osmotic shock, MAPK12 in the cell nucleus increases its association with nuclear DLG1, thereby causing dissociation of DLG1-SFPQ complexes. This function is independent of its catalytic activity and could affect mRNA processing and/or gene transcription to aid cell adaptation to osmolarity changes in the environment. Regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage and G2 arrest after gamma-radiation exposure. MAPK12 is involved in the regulation of SLC2A1 expression and basal glucose uptake in L6 myotubes; and negatively regulates SLC2A4 expression and contraction-mediated glucose uptake in adult skeletal muscle. C-Jun (JUN) phosphorylation is stimulated by MAPK14 and inhibited by MAPK12, leading to a distinct AP-1 regulation. MAPK12 is required for the normal kinetochore localization of PLK1, prevents chromosomal instability and supports mitotic cell viability. MAPK12-signaling is also positively regulating the expansion of transient amplifying myogenic precursor cells during muscle growth and regeneration. {ECO:0000269|PubMed:10848581, ECO:0000269|PubMed:14592936, ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:20605917, ECO:0000269|PubMed:21172807, ECO:0000269|PubMed:8633070, ECO:0000269|PubMed:9430721}. | FUNCTION: Cargo receptor involved in protein vesicular trafficking and quality control in the endoplasmic reticulum (ER) and Golgi (PubMed:10052452, PubMed:11726511, PubMed:16641999, PubMed:17288597, PubMed:19296914, PubMed:20427317, PubMed:21219331, PubMed:27569046). The p24 protein family is a group of transmembrane proteins that bind coat protein complex I/COPI and coat protein complex II/COPII involved in vesicular trafficking between the membranes (PubMed:10052452). Acts at the lumenal side for incorporation of secretory cargo molecules into transport vesicles and involved in vesicle coat formation at the cytoplasmic side (PubMed:20427317, PubMed:27569046). Mainly functions in the early secretory pathway and cycles between the ER, ER-Golgi intermediate compartment (ERGIC) and Golgi, mediating cargo transport through COPI and COPII-coated vesicles (PubMed:10052452, PubMed:10852829, PubMed:12237308). In COPII vesicle-mediated anterograde transport, involved in the transport of GPI-anchored proteins by acting together with TMED2 as their cargo receptor; the function specifically implies SEC24C and SEC24D of the COPII vesicle coat and lipid raft-like microdomains of the ER (PubMed:20427317, PubMed:27569046). Recognizes GPI anchors structural remodeled in the ER by the GPI inositol-deacylase/PGAP1 and the metallophosphoesterase MPPE1/PGAP5 (By similarity). In COPI vesicle-mediated retrograde transport, involved in the biogenesis of COPI vesicles and vesicle coat recruitment (PubMed:11726511). Involved in trafficking of amyloid beta A4 protein and soluble APP-beta release (independent from the modulation of gamma-secretase activity) (PubMed:17288597). Involved in the KDELR2-mediated retrograde transport of the toxin A subunit (CTX-A-K63)together with COPI and the COOH terminus of KDELR2 (By similarity). On Golgi membranes, acts as a primary receptor for ARF1-GDP, a GTP-binding protein involved in COPI-vesicle formation (PubMed:11726511). Increases coatomer-dependent GTPase-activating activity of ARFGAP2 which mediates the hydrolysis of ARF1-bound GTP and therefore modulates protein trafficking from the Golgi apparatus (PubMed:19296914). Involved in the exocytic trafficking of G protein-coupled receptors F2LR1/PAR2 (trypsin and tryspin-like enzyme receptor), OPRM1 (opioid receptor) and P2RY4 (UTD and UDP receptor) from the Golgi to the plasma membrane, thus contributing to receptor resensitization (PubMed:21219331). In addition to its cargo receptor activity, may also act as a protein channel after oligomerization, facilitating the post-translational entry of leaderless cytoplasmic cargo into the ERGIC (PubMed:32272059). Involved in the translocation into ERGIC, the vesicle entry and the secretion of leaderless cargos (lacking the secretion signal sequence), including the mature form of interleukin 1/IL-1 family members, the alpha-crystallin B chain HSPB5, the carbohydrate-binding proteins galectin-1/LGALS1 and galectin-3/LGALS3, the microtubule-associated protein Tau/MAPT, and the annexin A1/ANXA1; the translocation process is dependent on cargo protein unfolding and enhanced by chaperones HSP90AB1 and HSP90B1/GRP9 (PubMed:32272059). Could also associates with the presenilin-dependent gamma-secretase complex in order to regulate gamma-cleavages of the amyloid beta A4 protein to yield amyloid-beta 40/Abeta40 (PubMed:16641999). {ECO:0000250|UniProtKB:Q28735, ECO:0000250|UniProtKB:Q63584, ECO:0000269|PubMed:10052452, ECO:0000269|PubMed:10852829, ECO:0000269|PubMed:11726511, ECO:0000269|PubMed:12237308, ECO:0000269|PubMed:16641999, ECO:0000269|PubMed:17288597, ECO:0000269|PubMed:19296914, ECO:0000269|PubMed:20427317, ECO:0000269|PubMed:21219331, ECO:0000269|PubMed:27569046, ECO:0000269|PubMed:32272059, ECO:0000303|PubMed:10052452}. |
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 MAPK12_TMED10 |
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 |
MAPK12 | P53778 | human | MYOD1 | P15172 | S201 | SGDSDAssPRsNCsD | Myf5 |
MAPK12 | P53778 | human | ATF2 | P15336 | T71 | IVADQtPtPtRFLkN | |
MAPK12 | P53778 | human | NUP62 | P37198 | T269 | GAASGTStTTsTAAT | |
MAPK12 | P53778 | human | DLG1 | Q12959 | S443 | FLGQtPAsPARysPV | PDZ_assoc |
MAPK12 | P53778 | human | MAPT | P10636-8 | S396 | GAEIVyKsPVVsGDt | |
MAPK12 | P53778 | human | MAPT | P10636-8 | S404 | PVVsGDtsPRHLsNV | |
MAPK12 | P53778 | human | DLG1 | Q12959 | T209 | VNTDSLEtPTYVNGT | MAGUK_N_PEST |
MAPK12 | P53778 | human | STAT2 | P52630 | Y690 | NLQERRKyLKHRLIV | |
MAPK12 | P53778 | human | PTPN3 | P26045 | S459 | QKSsSSVsPSSNAPG | |
MAPK12 | P53778 | human | HTRA2 | O43464 | S142 | VPSPPPAsPRSQYNF | Peptidase_M50 |
MAPK12 | P53778 | human | HSP90AA1 | P07900 | S595 | VsNRLVTsPCCIVts | HSP90 |
MAPK12 | P53778 | human | NUP62 | P37198 | S272 | SGTStTTsTAATATA | |
MAPK12 | P53778 | human | TP53 | P04637 | S33 | LPENNVLsPLPsQAM | |
MAPK12 | P53778 | human | MAPK12 | P53778 | S3 | _____MSsPPPARSG | |
MAPK12 | P53778 | human | SQSTM1 | Q13501 | T269 | GGkRsRLtPVsPEss | |
MAPK12 | P53778 | human | SREBF1 | P36956 | S63 | AGGtDPAsPDTSSPG | |
MAPK12 | P53778 | human | SREBF1 | P36956 | T426 | TEVEDTLtPPPsDAG | |
MAPK12 | P53778 | human | CCND3 | P30281 | T283 | QGPsQtstPtDVtAI | |
MAPK12 | P53778 | human | GYS1 | P13807 | S723 | sssLStPsEPLsPts | |
MAPK12 | P53778 | human | HSF1 | Q00613 | S307 | EPPsPPQsPRVEEAs | Vert_HS_TF |
MAPK12 | P53778 | human | CTNNB1 | P35222 | S605 | LFVQLLYsPIENIQR | Arm |
MAPK12 | P53778 | human | MYOD1 | P15172 | S200 | YSGDSDAssPRsNCs | Myf5 |
MAPK12 | P53778 | human | DLG1 | Q12959 | S158 | FVsHsHIsPIKPTEA | MAGUK_N_PEST |
MAPK12 | P53778 | human | NLRP1 | Q9C000 | S107 | PSEPHLGsPSQPTST | |
MAPK12 | P53778 | human | MEF2D | Q14814 | S444 | SIkSEPVsPsRERsP | |
MAPK12 | P53778 | human | HSF1 | Q00613 | S303 | RVkEEPPsPPQsPRV | Vert_HS_TF |
MAPK12 | P53778 | human | KAT5 | Q92993-2 | T106 | VEVVsPAtPVPSETA | |
MAPK12 | P53778 | human | GYS1 | P13807 | S727 | StPsEPLsPtssLGE | |
MAPK12 | P53778 | human | HSF1 | Q00613 | S326 | ssVDtLLsPTALIDs | Vert_HS_TF |
MAPK12 | P53778 | human | GYS1 | P13807 | T278 | kRkPDIVtPNGLNVk | Glycogen_syn |
MAPK12 | P53778 | human | SQSTM1 | Q13501 | S272 | RsRLtPVsPEssstE | |
MAPK12 | P53778 | human | KAT5 | Q92993 | T158 | VEVVsPAtPVPSETA |
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 |
MAPK12 | ID | Description | 0.00e+00 |
MAPK12 | GO:0010821 | regulation of mitochondrion organization | 9.30e-06 |
MAPK12 | GO:0072594 | establishment of protein localization to organelle | 9.30e-06 |
MAPK12 | GO:0045786 | negative regulation of cell cycle | 6.92e-05 |
MAPK12 | GO:0034599 | cellular response to oxidative stress | 7.85e-05 |
MAPK12 | GO:1903008 | organelle disassembly | 1.21e-04 |
MAPK12 | GO:0006606 | protein import into nucleus | 1.27e-04 |
MAPK12 | GO:0034605 | cellular response to heat | 1.27e-04 |
MAPK12 | GO:0062197 | cellular response to chemical stress | 1.27e-04 |
MAPK12 | GO:0051170 | import into nucleus | 1.27e-04 |
MAPK12 | GO:0009267 | cellular response to starvation | 1.66e-04 |
MAPK12 | GO:0010506 | regulation of autophagy | 1.86e-04 |
MAPK12 | GO:0006839 | mitochondrial transport | 1.86e-04 |
MAPK12 | GO:2000291 | regulation of myoblast proliferation | 2.92e-04 |
MAPK12 | GO:0006979 | response to oxidative stress | 2.92e-04 |
MAPK12 | GO:0042594 | response to starvation | 2.92e-04 |
MAPK12 | GO:0000422 | autophagy of mitochondrion | 3.02e-04 |
MAPK12 | GO:0061726 | mitochondrion disassembly | 3.02e-04 |
MAPK12 | GO:0009408 | response to heat | 3.48e-04 |
MAPK12 | GO:0045930 | negative regulation of mitotic cell cycle | 4.32e-04 |
MAPK12 | GO:0031669 | cellular response to nutrient levels | 4.32e-04 |
MAPK12 | GO:0032355 | response to estradiol | 4.32e-04 |
MAPK12 | GO:0051450 | myoblast proliferation | 4.49e-04 |
MAPK12 | GO:1903829 | positive regulation of protein localization | 5.05e-04 |
MAPK12 | GO:0072655 | establishment of protein localization to mitochondrion | 5.05e-04 |
MAPK12 | GO:0071392 | cellular response to estradiol stimulus | 5.05e-04 |
MAPK12 | GO:0051402 | neuron apoptotic process | 5.05e-04 |
MAPK12 | GO:0031667 | response to nutrient levels | 5.05e-04 |
MAPK12 | GO:0000423 | mitophagy | 5.05e-04 |
MAPK12 | GO:0031668 | cellular response to extracellular stimulus | 5.05e-04 |
MAPK12 | GO:0022411 | cellular component disassembly | 5.05e-04 |
MAPK12 | GO:1903146 | regulation of autophagy of mitochondrion | 5.10e-04 |
MAPK12 | GO:0070585 | protein localization to mitochondrion | 5.10e-04 |
MAPK12 | GO:0034504 | protein localization to nucleus | 7.30e-04 |
MAPK12 | GO:0051972 | regulation of telomerase activity | 7.30e-04 |
MAPK12 | GO:0009299 | mRNA transcription | 8.86e-04 |
MAPK12 | GO:0006913 | nucleocytoplasmic transport | 8.86e-04 |
MAPK12 | GO:0051169 | nuclear transport | 8.86e-04 |
MAPK12 | GO:1903747 | regulation of establishment of protein localization to mitochondrion | 8.93e-04 |
MAPK12 | GO:0010659 | cardiac muscle cell apoptotic process | 1.03e-03 |
MAPK12 | GO:0071496 | cellular response to external stimulus | 1.03e-03 |
MAPK12 | GO:0010658 | striated muscle cell apoptotic process | 1.08e-03 |
MAPK12 | GO:0010952 | positive regulation of peptidase activity | 1.08e-03 |
MAPK12 | GO:0009266 | response to temperature stimulus | 1.08e-03 |
MAPK12 | GO:0042770 | signal transduction in response to DNA damage | 1.57e-03 |
MAPK12 | GO:0031334 | positive regulation of protein-containing complex assembly | 1.84e-03 |
MAPK12 | GO:0043254 | regulation of protein-containing complex assembly | 2.23e-03 |
MAPK12 | GO:0042098 | T cell proliferation | 2.34e-03 |
MAPK12 | GO:0009410 | response to xenobiotic stimulus | 2.53e-03 |
MAPK12 | GO:0010720 | positive regulation of cell development | 2.73e-03 |
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Related Drugs to MAPK12_TMED10 |
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 MAPK12-TMED10 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 MAPK12_TMED10 |
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 |