FusionNeoAntigen Logo

Home

Download

Statistics

Examples

Help

Contact

Terms of Use

Center for Computational Systems Medicine
leaf

Fusion Gene and Fusion Protein Summary

leaf

Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

leaf

Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

leaf

Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

leaf

Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

leaf

Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

leaf

Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

leaf

Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

leaf

Potential target of CAR-T therapy development

leaf

Information on the samples that have these potential fusion neoantigens

leaf

Fusion Protein Targeting Drugs - (Manual Curation)

leaf

Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:MAPK14-MICU2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MAPK14-MICU2
FusionPDB ID: 51520
FusionGDB2.0 ID: 51520
HgeneTgene
Gene symbol

MAPK14

MICU2

Gene ID

1432

221154

Gene namemitogen-activated protein kinase 14mitochondrial calcium uptake 2
SynonymsCSBP|CSBP1|CSBP2|CSPB1|EXIP|Mxi2|PRKM14|PRKM15|RK|SAPK2A|p38|p38ALPHA1110008L20Rik|EFHA1
Cytomap

6p21.31

13q12.11

Type of geneprotein-codingprotein-coding
Descriptionmitogen-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 kinasep3calcium uptake protein 2, mitochondrialEF hand domain family A1EF hand domain family, member A1EF-hand domain-containing family member A1Smhs2 homolog
Modification date2020032920200315
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 geneENST idsENST00000229794, ENST00000229795, 
ENST00000310795, ENST00000468133, 
ENST00000479790, ENST00000382374, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 6 X 5=21013 X 13 X 6=1014
# samples 713
** MAII scorelog2(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)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneMAPK14

GO:0035556

intracellular signal transduction

10838079

HgeneMAPK14

GO:0071222

cellular response to lipopolysaccharide

23776175

HgeneMAPK14

GO:1900015

regulation of cytokine production involved in inflammatory response

15251176

TgeneMICU2

GO:0006851

mitochondrial calcium ion transmembrane transport

24560927

TgeneMICU2

GO:0051562

negative regulation of mitochondrial calcium ion concentration

24560927



check button Four levels of functional features of fusion genes
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.
FGviewer

check buttonRetention analysis results 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, are available here.

check buttonFusion gene breakpoints across MAPK14 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across MICU2 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


Top

Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000229795MAPK14chr636044376+ENST00000382374MICU2chr1322113827-2562106632012669
ENST00000229794MAPK14chr636044376+ENST00000382374MICU2chr1322113827-250310071631953596
ENST00000468133MAPK14chr636044376+ENST00000382374MICU2chr1322113827-21856891061635509
ENST00000310795MAPK14chr636044376+ENST00000382374MICU2chr1322113827-211561901565521

check buttonDeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000229795ENST00000382374MAPK14chr636044376+MICU2chr1322113827-0.0005669090.9994331
ENST00000229794ENST00000382374MAPK14chr636044376+MICU2chr1322113827-0.0005659530.99943405
ENST00000468133ENST00000382374MAPK14chr636044376+MICU2chr1322113827-0.0004227620.9995772
ENST00000310795ENST00000382374MAPK14chr636044376+MICU2chr1322113827-0.0005538910.9994461

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

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

Top

Fusion Protein Breakpoint Sequences for MAPK14-MICU2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MAPK14chr636044376MICU2chr13221138271007282LNWMHYNQTGTDRKTSVKKLTKKDIE
MAPK14chr636044376MICU2chr13221138271066355LNWMHYNQTGTDRKTSVKKLTKKDIE
MAPK14chr636044376MICU2chr1322113827619207LNWMHYNQTGTDRKTSVKKLTKKDIE
MAPK14chr636044376MICU2chr1322113827689195LNWMHYNQTGTDRKTSVKKLTKKDIE

Top

Potential FusionNeoAntigen Information of MAPK14-MICU2 in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
MAPK14-MICU2_36044376_22113827.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
MAPK14-MICU2chr636044376chr13221138271007HLA-B14:02DRKTSVKKL0.98570.57761120
MAPK14-MICU2chr636044376chr13221138271007HLA-B14:01DRKTSVKKL0.98570.57761120
MAPK14-MICU2chr636044376chr13221138271007HLA-A30:08GTDRKTSVKK0.93850.7173919
MAPK14-MICU2chr636044376chr13221138271007HLA-A30:08RKTSVKKLTK0.89250.7771222
MAPK14-MICU2chr636044376chr13221138271007HLA-B39:12DRKTSVKKL0.61790.84221120
MAPK14-MICU2chr636044376chr13221138271007HLA-C07:05DRKTSVKKL0.5650.93621120
MAPK14-MICU2chr636044376chr13221138271007HLA-B14:03DRKTSVKKL0.12690.74441120
MAPK14-MICU2chr636044376chr13221138271007HLA-C12:16DRKTSVKKL0.00890.94361120
MAPK14-MICU2chr636044376chr13221138271007HLA-C07:01DRKTSVKKL0.62110.59311120
MAPK14-MICU2chr636044376chr13221138271007HLA-C07:22DRKTSVKKL0.3970.71171120
MAPK14-MICU2chr636044376chr13221138271007HLA-C06:08DRKTSVKKL0.24190.98871120
MAPK14-MICU2chr636044376chr13221138271007HLA-C06:02DRKTSVKKL0.01320.99061120
MAPK14-MICU2chr636044376chr13221138271007HLA-C06:17DRKTSVKKL0.01320.99061120
MAPK14-MICU2chr636044376chr13221138271007HLA-A30:01GTDRKTSVKK0.93830.8167919
MAPK14-MICU2chr636044376chr13221138271007HLA-A30:01RKTSVKKLTK0.89760.86071222

Top

Potential FusionNeoAntigen Information of MAPK14-MICU2 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
MAPK14-MICU2_36044376_22113827.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)
MAPK14-MICU2chr636044376chr13221138271007DRB1-1220DRKTSVKKLTKKDIE1126
MAPK14-MICU2chr636044376chr13221138271007DRB1-1354DRKTSVKKLTKKDIE1126

Top

Fusion breakpoint peptide structures of MAPK14-MICU2

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* 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 nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
6344NQTGTDRKTSVKKLMAPK14MICU2chr636044376chr13221138271007

Top

Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MAPK14-MICU2

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN6344NQTGTDRKTSVKKL-6.66111-6.77451
HLA-B14:023BVN6344NQTGTDRKTSVKKL-6.49216-7.52746
HLA-B52:013W396344NQTGTDRKTSVKKL-5.57342-5.68682
HLA-B52:013W396344NQTGTDRKTSVKKL-3.59959-4.63489
HLA-A11:014UQ26344NQTGTDRKTSVKKL-3.54213-3.65553
HLA-A24:025HGA6344NQTGTDRKTSVKKL-7.6647-7.7781
HLA-A24:025HGA6344NQTGTDRKTSVKKL-4.05482-5.09012
HLA-B44:053DX86344NQTGTDRKTSVKKL-5.24587-5.35927
HLA-B44:053DX86344NQTGTDRKTSVKKL-4.91507-5.95037
HLA-A02:016TDR6344NQTGTDRKTSVKKL-3.67735-4.71265

Top

Vaccine Design for the FusionNeoAntigens of MAPK14-MICU2

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
MAPK14-MICU2chr636044376chr13221138271120DRKTSVKKLCAGACCGTAAAACTTCAGTCAAGAAGC
MAPK14-MICU2chr636044376chr13221138271222RKTSVKKLTKACCGTAAAACTTCAGTCAAGAAGCTGACAA
MAPK14-MICU2chr636044376chr1322113827919GTDRKTSVKKCAGGTACAGACCGTAAAACTTCAGTCAAGA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
MAPK14-MICU2chr636044376chr13221138271126DRKTSVKKLTKKDIECAGACCGTAAAACTTCAGTCAAGAAGCTGACAAAAAAGGACATCG

Top

Information of the samples that have these potential fusion neoantigens of MAPK14-MICU2

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
BRCAMAPK14-MICU2chr636044376ENST00000229794chr1322113827ENST00000382374TCGA-AO-A129-01A

Top

Potential target of CAR-T therapy development for MAPK14-MICU2

check button Predicted 3D structure. We used RoseTTAFold.

check buttonRetention 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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* 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.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

Top

Related Drugs to MAPK14-MICU2

check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

Top

Related Diseases to MAPK14-MICU2

check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource