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Fusion Protein:MAPK14-MICU2 |
Fusion Gene and Fusion Protein Summary |
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Fusion partner gene information | Fusion gene name: MAPK14-MICU2 | FusionPDB ID: 51520 | FusionGDB2.0 ID: 51520 | Hgene | Tgene | Gene symbol | MAPK14 | MICU2 | Gene ID | 1432 | 221154 |
Gene name | mitogen-activated protein kinase 14 | mitochondrial calcium uptake 2 | |
Synonyms | CSBP|CSBP1|CSBP2|CSPB1|EXIP|Mxi2|PRKM14|PRKM15|RK|SAPK2A|p38|p38ALPHA | 1110008L20Rik|EFHA1 | |
Cytomap | 6p21.31 | 13q12.11 | |
Type of gene | protein-coding | protein-coding | |
Description | mitogen-activated protein kinase 14CSAID-binding proteinMAP kinase 14MAP kinase Mxi2MAP kinase p38 alphaMAX-interacting protein 2cytokine suppressive anti-inflammatory drug binding proteinmitogen-activated protein kinase p38 alphap38 MAP kinasep3 | calcium uptake protein 2, mitochondrialEF hand domain family A1EF hand domain family, member A1EF-hand domain-containing family member A1Smhs2 homolog | |
Modification date | 20200329 | 20200315 | |
UniProtAcc | Q16539 Main function of 5'-partner protein: FUNCTION: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. 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 which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. MAPK14 interacts also with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3. MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9. Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation. Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation. The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression. Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113'. {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:10747897, ECO:0000269|PubMed:10943842, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11333986, ECO:0000269|PubMed:15905572, ECO:0000269|PubMed:16932740, ECO:0000269|PubMed:17003045, ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:19893488, ECO:0000269|PubMed:20188673, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000269|PubMed:9792677, ECO:0000269|PubMed:9858528}.; FUNCTION: (Microbial infection) Activated by phosphorylation by M.tuberculosis EsxA in T-cells leading to inhibition of IFN-gamma production; phosphorylation is apparent within 15 minute and is inhibited by kinase-specific inhibitors SB203580 and siRNA (PubMed:21586573). {ECO:0000269|PubMed:21586573}. | Q8IYU8 Main function of 5'-partner protein: FUNCTION: Key regulator of mitochondrial calcium uniporter (MCU) required to limit calcium uptake by MCU when cytoplasmic calcium is low (PubMed:24503055, PubMed:24560927, PubMed:26903221). MICU1 and MICU2 form a disulfide-linked heterodimer that stimulate and inhibit MCU activity, depending on the concentration of calcium (PubMed:24560927). MICU2 acts as a gatekeeper of MCU that senses calcium level via its EF-hand domains: prevents channel opening at resting calcium, avoiding energy dissipation and cell-death triggering (PubMed:24560927). {ECO:0000269|PubMed:24503055, ECO:0000269|PubMed:24560927, ECO:0000269|PubMed:26387864, ECO:0000269|PubMed:26903221}. | |
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000229794, ENST00000229795, ENST00000310795, ENST00000468133, | ENST00000479790, ENST00000382374, |
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 7 X 6 X 5=210 | 13 X 13 X 6=1014 |
# samples | 7 | 13 | |
** MAII score | log2(7/210*10)=-1.58496250072116 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(13/1014*10)=-2.96347412397489 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
Fusion gene context | PubMed: MAPK14 [Title/Abstract] AND MICU2 [Title/Abstract] AND fusion [Title/Abstract] | ||
Fusion neoantigen context | PubMed: MAPK14 [Title/Abstract] AND MICU2 [Title/Abstract] AND neoantigen [Title/Abstract] | ||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | MAPK14(36044376)-MICU2(22113827), # samples:1 | ||
Anticipated loss of major functional domain due to fusion event. | MAPK14-MICU2 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. MAPK14-MICU2 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. MAPK14-MICU2 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. MAPK14-MICU2 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. |
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types ** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10) |
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Partner | Gene | GO ID | GO term | PubMed ID |
Hgene | MAPK14 | GO:0035556 | intracellular signal transduction | 10838079 |
Hgene | MAPK14 | GO:0071222 | cellular response to lipopolysaccharide | 23776175 |
Hgene | MAPK14 | GO:1900015 | regulation of cytokine production involved in inflammatory response | 15251176 |
Tgene | MICU2 | GO:0006851 | mitochondrial calcium ion transmembrane transport | 24560927 |
Tgene | MICU2 | GO:0051562 | negative regulation of mitochondrial calcium ion concentration | 24560927 |
![]() Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr6:36044376/chr13:22113827) - 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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![]() * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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![]() * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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Fusion Amino Acid Sequences |
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Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | Seq length (transcript) | BP loci (transcript) | Predicted start (transcript) | Predicted stop (transcript) | Seq length (amino acids) |
ENST00000229795 | MAPK14 | chr6 | 36044376 | + | ENST00000382374 | MICU2 | chr13 | 22113827 | - | 2562 | 1066 | 3 | 2012 | 669 |
ENST00000229794 | MAPK14 | chr6 | 36044376 | + | ENST00000382374 | MICU2 | chr13 | 22113827 | - | 2503 | 1007 | 163 | 1953 | 596 |
ENST00000468133 | MAPK14 | chr6 | 36044376 | + | ENST00000382374 | MICU2 | chr13 | 22113827 | - | 2185 | 689 | 106 | 1635 | 509 |
ENST00000310795 | MAPK14 | chr6 | 36044376 | + | ENST00000382374 | MICU2 | chr13 | 22113827 | - | 2115 | 619 | 0 | 1565 | 521 |
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Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | No-coding score | Coding score |
ENST00000229795 | ENST00000382374 | MAPK14 | chr6 | 36044376 | + | MICU2 | chr13 | 22113827 | - | 0.000566909 | 0.9994331 |
ENST00000229794 | ENST00000382374 | MAPK14 | chr6 | 36044376 | + | MICU2 | chr13 | 22113827 | - | 0.000565953 | 0.99943405 |
ENST00000468133 | ENST00000382374 | MAPK14 | chr6 | 36044376 | + | MICU2 | chr13 | 22113827 | - | 0.000422762 | 0.9995772 |
ENST00000310795 | ENST00000382374 | MAPK14 | chr6 | 36044376 | + | MICU2 | chr13 | 22113827 | - | 0.000553891 | 0.9994461 |
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Get the fusion protein sequences from here. |
Fusion protein sequence information is available in the fasta format. >FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP |
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Fusion Protein Breakpoint Sequences for MAPK14-MICU2 |
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Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Length(fusion protein) | BP in fusion protein | Peptide |
MAPK14 | chr6 | 36044376 | MICU2 | chr13 | 22113827 | 1007 | 282 | LNWMHYNQTGTDRKTSVKKLTKKDIE |
MAPK14 | chr6 | 36044376 | MICU2 | chr13 | 22113827 | 1066 | 355 | LNWMHYNQTGTDRKTSVKKLTKKDIE |
MAPK14 | chr6 | 36044376 | MICU2 | chr13 | 22113827 | 619 | 207 | LNWMHYNQTGTDRKTSVKKLTKKDIE |
MAPK14 | chr6 | 36044376 | MICU2 | chr13 | 22113827 | 689 | 195 | LNWMHYNQTGTDRKTSVKKLTKKDIE |
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Potential FusionNeoAntigen Information of MAPK14-MICU2 in HLA I |
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MAPK14-MICU2_36044376_22113827.msa |
![]() * We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5) |
Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA I | FusionNeoAntigen peptide | Binding score | Immunogenic score | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 1007 | HLA-B14:02 | DRKTSVKKL | 0.9857 | 0.5776 | 11 | 20 |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 1007 | HLA-B14:01 | DRKTSVKKL | 0.9857 | 0.5776 | 11 | 20 |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 1007 | HLA-A30:08 | GTDRKTSVKK | 0.9385 | 0.7173 | 9 | 19 |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 1007 | HLA-A30:08 | RKTSVKKLTK | 0.8925 | 0.777 | 12 | 22 |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 1007 | HLA-B39:12 | DRKTSVKKL | 0.6179 | 0.8422 | 11 | 20 |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 1007 | HLA-C07:05 | DRKTSVKKL | 0.565 | 0.9362 | 11 | 20 |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 1007 | HLA-B14:03 | DRKTSVKKL | 0.1269 | 0.7444 | 11 | 20 |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 1007 | HLA-C12:16 | DRKTSVKKL | 0.0089 | 0.9436 | 11 | 20 |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 1007 | HLA-C07:01 | DRKTSVKKL | 0.6211 | 0.5931 | 11 | 20 |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 1007 | HLA-C07:22 | DRKTSVKKL | 0.397 | 0.7117 | 11 | 20 |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 1007 | HLA-C06:08 | DRKTSVKKL | 0.2419 | 0.9887 | 11 | 20 |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 1007 | HLA-C06:02 | DRKTSVKKL | 0.0132 | 0.9906 | 11 | 20 |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 1007 | HLA-C06:17 | DRKTSVKKL | 0.0132 | 0.9906 | 11 | 20 |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 1007 | HLA-A30:01 | GTDRKTSVKK | 0.9383 | 0.8167 | 9 | 19 |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 1007 | HLA-A30:01 | RKTSVKKLTK | 0.8976 | 0.8607 | 12 | 22 |
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Potential FusionNeoAntigen Information of MAPK14-MICU2 in HLA II |
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MAPK14-MICU2_36044376_22113827.msa |
![]() * We used NetMHCIIpan v4.1 (%rank<0.5). |
Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA II | FusionNeoAntigen peptide | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 1007 | DRB1-1220 | DRKTSVKKLTKKDIE | 11 | 26 |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 1007 | DRB1-1354 | DRKTSVKKLTKKDIE | 11 | 26 |
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Fusion breakpoint peptide structures of MAPK14-MICU2 |
![]() * The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA. |
File name | BPseq | Hgene | Tgene | Hchr | Hbp | Tchr | Tbp | AAlen |
6344 | NQTGTDRKTSVKKL | MAPK14 | MICU2 | chr6 | 36044376 | chr13 | 22113827 | 1007 |
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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MAPK14-MICU2 |
![]() * We used Glide to predict the interaction between HLAs and neoantigens. |
HLA allele | PDB ID | File name | BPseq | Docking score | Glide score |
HLA-B14:02 | 3BVN | 6344 | NQTGTDRKTSVKKL | -6.66111 | -6.77451 |
HLA-B14:02 | 3BVN | 6344 | NQTGTDRKTSVKKL | -6.49216 | -7.52746 |
HLA-B52:01 | 3W39 | 6344 | NQTGTDRKTSVKKL | -5.57342 | -5.68682 |
HLA-B52:01 | 3W39 | 6344 | NQTGTDRKTSVKKL | -3.59959 | -4.63489 |
HLA-A11:01 | 4UQ2 | 6344 | NQTGTDRKTSVKKL | -3.54213 | -3.65553 |
HLA-A24:02 | 5HGA | 6344 | NQTGTDRKTSVKKL | -7.6647 | -7.7781 |
HLA-A24:02 | 5HGA | 6344 | NQTGTDRKTSVKKL | -4.05482 | -5.09012 |
HLA-B44:05 | 3DX8 | 6344 | NQTGTDRKTSVKKL | -5.24587 | -5.35927 |
HLA-B44:05 | 3DX8 | 6344 | NQTGTDRKTSVKKL | -4.91507 | -5.95037 |
HLA-A02:01 | 6TDR | 6344 | NQTGTDRKTSVKKL | -3.67735 | -4.71265 |
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Vaccine Design for the FusionNeoAntigens of MAPK14-MICU2 |
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Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide sequence | FusionNeoAntigen RNA sequence |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 11 | 20 | DRKTSVKKL | CAGACCGTAAAACTTCAGTCAAGAAGC |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 12 | 22 | RKTSVKKLTK | ACCGTAAAACTTCAGTCAAGAAGCTGACAA |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 9 | 19 | GTDRKTSVKK | CAGGTACAGACCGTAAAACTTCAGTCAAGA |
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Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide | FusionNEoAntigen RNA sequence |
MAPK14-MICU2 | chr6 | 36044376 | chr13 | 22113827 | 11 | 26 | DRKTSVKKLTKKDIE | CAGACCGTAAAACTTCAGTCAAGAAGCTGACAAAAAAGGACATCG |
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Information of the samples that have these potential fusion neoantigens of MAPK14-MICU2 |
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Cancer type | Fusion gene | Hchr | Hbp | Henst | Tchr | Tbp | Tenst | Sample |
BRCA | MAPK14-MICU2 | chr6 | 36044376 | ENST00000229794 | chr13 | 22113827 | ENST00000382374 | TCGA-AO-A129-01A |
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Potential target of CAR-T therapy development for MAPK14-MICU2 |
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![]() * Minus value of BPloci means that the break point is located before the CDS. |
- In-frame and retained 'Transmembrane'. |
Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
![]() * We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image. |
Hgene | Hchr | Hbp | Henst | Tgene | Tchr | Tbp | Tenst | DeepLoc result |
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Related Drugs to MAPK14-MICU2 |
![]() (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
Hgene | Tgene | Drug | Source | PMID |
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Related Diseases to MAPK14-MICU2 |
![]() (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
Hgene | Tgene | Disease | Source | PMID |
![]() (DisGeNet 4.0) |
Partner | Gene | Disease ID | Disease name | # pubmeds | Source |