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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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

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

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

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

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:MAP2K3-FAM133B

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MAP2K3-FAM133B
FusionPDB ID: 51195
FusionGDB2.0 ID: 51195
HgeneTgene
Gene symbol

MAP2K3

FAM133B

Gene ID

5606

257415

Gene namemitogen-activated protein kinase kinase 3family with sequence similarity 133 member B
SynonymsMAPKK3|MEK3|MKK3|PRKMK3|SAPKK-2|SAPKK2-
Cytomap

17p11.2

7q21.2

Type of geneprotein-codingprotein-coding
Descriptiondual specificity mitogen-activated protein kinase kinase 3MAP kinase kinase 3MAPK/ERK kinase 3MAPKK 3MEK 3SAPK kinase 2stress-activated protein kinase kinase 2protein FAM133B
Modification date2020032720200313
UniProtAcc

P46734

Main function of 5'-partner protein: FUNCTION: Dual specificity kinase. Is activated by cytokines and environmental stress in vivo. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. {ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:8622669}.

Q5BKY9

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000316920, ENST00000342679, 
ENST00000361818, ENST00000534743, 
ENST00000427372, ENST00000438306, 
ENST00000445716, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 6 X 5=2703 X 2 X 3=18
# samples 103
** MAII scorelog2(10/270*10)=-1.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/18*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: MAP2K3 [Title/Abstract] AND FAM133B [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MAP2K3 [Title/Abstract] AND FAM133B [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MAP2K3(21216849)-FAM133B(92207031), # samples:1
Anticipated loss of major functional domain due to fusion event.MAP2K3-FAM133B 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.
MAP2K3-FAM133B 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
HgeneMAP2K3

GO:0045860

positive regulation of protein kinase activity

11980910

HgeneMAP2K3

GO:0045893

positive regulation of transcription, DNA-templated

11980910



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/chr17:21216849/chr7:92207031)
- 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 MAP2K3 (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 FAM133B (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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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)
ENST00000342679MAP2K3chr1721216849+ENST00000438306FAM133Bchr792207031-313312092491643464
ENST00000342679MAP2K3chr1721216849+ENST00000445716FAM133Bchr792207031-282312092491643464
ENST00000342679MAP2K3chr1721216849+ENST00000427372FAM133Bchr792207031-164412092491643464
ENST00000361818MAP2K3chr1721216849+ENST00000438306FAM133Bchr792207031-2891967941401435
ENST00000361818MAP2K3chr1721216849+ENST00000445716FAM133Bchr792207031-2581967941401435
ENST00000361818MAP2K3chr1721216849+ENST00000427372FAM133Bchr792207031-1402967941401436
ENST00000316920MAP2K3chr1721216849+ENST00000438306FAM133Bchr792207031-30061082981516472
ENST00000316920MAP2K3chr1721216849+ENST00000445716FAM133Bchr792207031-26961082981516472
ENST00000316920MAP2K3chr1721216849+ENST00000427372FAM133Bchr792207031-15171082981516473

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
ENST00000342679ENST00000438306MAP2K3chr1721216849+FAM133Bchr792207031-0.0008273140.9991726
ENST00000342679ENST00000445716MAP2K3chr1721216849+FAM133Bchr792207031-0.0015510880.99844885
ENST00000342679ENST00000427372MAP2K3chr1721216849+FAM133Bchr792207031-0.0074161160.9925839
ENST00000361818ENST00000438306MAP2K3chr1721216849+FAM133Bchr792207031-0.0013974320.99860257
ENST00000361818ENST00000445716MAP2K3chr1721216849+FAM133Bchr792207031-0.0021048610.9978951
ENST00000361818ENST00000427372MAP2K3chr1721216849+FAM133Bchr792207031-0.0145070160.985493
ENST00000316920ENST00000438306MAP2K3chr1721216849+FAM133Bchr792207031-0.0014527420.99854726
ENST00000316920ENST00000445716MAP2K3chr1721216849+FAM133Bchr792207031-0.0024541940.9975458
ENST00000316920ENST00000427372MAP2K3chr1721216849+FAM133Bchr792207031-0.0108259470.989174

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

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Fusion Protein Breakpoint Sequences for MAP2K3-FAM133B

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MAP2K3chr1721216849FAM133Bchr7922070311082328KNPAERMSYLELMYSSSSSSSSDSSS
MAP2K3chr1721216849FAM133Bchr7922070311209320KNPAERMSYLELMYSSSSSSSSDSSS
MAP2K3chr1721216849FAM133Bchr792207031967291KNPAERMSYLELMYSSSSSSSSDSSS

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Potential FusionNeoAntigen Information of MAP2K3-FAM133B 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.
MAP2K3-FAM133B_21216849_92207031.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)
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B15:01RMSYLELMY0.99730.9283514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B15:25RMSYLELMY0.9960.9249514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-A32:13RMSYLELMY0.90660.8972514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B15:03RMSYLELMY0.78690.8059514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B27:04ERMSYLELMY0.99970.6696414
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B44:03AERMSYLELMY0.99920.9404314
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B15:07RMSYLELMY0.97920.7673514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B15:05RMSYLELMY0.96520.908514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B15:04RMSYLELMY0.82720.936514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B27:03ERMSYLELMY0.99870.854414
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B15:27RMSYLELMY0.99750.9321514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B15:33RMSYLELMY0.99730.9283514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B15:125RMSYLELMY0.99730.9283514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B15:34RMSYLELMY0.99730.9283514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B15:50RMSYLELMY0.99680.9146514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B15:135RMSYLELMY0.99660.9306514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B15:39RMSYLELMY0.99580.8652514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B15:12RMSYLELMY0.99570.849514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B15:24RMSYLELMY0.99190.9244514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B15:35RMSYLELMY0.98650.9252514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-A32:01RMSYLELMY0.96840.9621514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B15:20RMSYLELMY0.96540.933514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B35:28RMSYLELMY0.93890.9332514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B15:68RMSYLELMY0.28990.6815514
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B44:07AERMSYLELMY0.99920.9404314
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B44:26AERMSYLELMY0.99920.9404314
MAP2K3-FAM133Bchr1721216849chr7922070311082HLA-B44:13AERMSYLELMY0.99920.9404314

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Potential FusionNeoAntigen Information of MAP2K3-FAM133B 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.
MAP2K3-FAM133B_21216849_92207031.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)
MAP2K3-FAM133Bchr1721216849chr7922070311082DRB1-0407ELMYSSSSSSSSDSS1025
MAP2K3-FAM133Bchr1721216849chr7922070311082DRB1-0407LELMYSSSSSSSSDS924
MAP2K3-FAM133Bchr1721216849chr7922070311082DRB1-0474ELMYSSSSSSSSDSS1025
MAP2K3-FAM133Bchr1721216849chr7922070311082DRB1-0474LELMYSSSSSSSSDS924

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Fusion breakpoint peptide structures of MAP2K3-FAM133B

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
6026MSYLELMYSSSSSSMAP2K3FAM133Bchr1721216849chr7922070311082

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MAP2K3-FAM133B

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-B14:023BVN6026MSYLELMYSSSSSS-7.60305-7.71645
HLA-B14:023BVN6026MSYLELMYSSSSSS-5.05941-6.09471
HLA-B52:013W396026MSYLELMYSSSSSS-6.15021-6.26361
HLA-B52:013W396026MSYLELMYSSSSSS-5.02075-6.05605
HLA-A11:014UQ26026MSYLELMYSSSSSS-11.7385-11.8519
HLA-A11:014UQ26026MSYLELMYSSSSSS-5.92038-6.95568
HLA-A24:025HGA6026MSYLELMYSSSSSS-7.83733-8.87263
HLA-A24:025HGA6026MSYLELMYSSSSSS-6.03481-6.14821
HLA-B27:056PYJ6026MSYLELMYSSSSSS-4.50818-5.54348
HLA-B44:053DX86026MSYLELMYSSSSSS-7.35685-8.39215
HLA-B44:053DX86026MSYLELMYSSSSSS-6.69772-6.81112

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Vaccine Design for the FusionNeoAntigens of MAP2K3-FAM133B

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
MAP2K3-FAM133Bchr1721216849chr792207031314AERMSYLELMYGCAGAGCGTATGAGCTACCTGGAGCTGATGTAT
MAP2K3-FAM133Bchr1721216849chr792207031414ERMSYLELMYGAGCGTATGAGCTACCTGGAGCTGATGTAT
MAP2K3-FAM133Bchr1721216849chr792207031514RMSYLELMYCGTATGAGCTACCTGGAGCTGATGTAT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
MAP2K3-FAM133Bchr1721216849chr7922070311025ELMYSSSSSSSSDSSGAGCTGATGTATTCATCTTCTTCTTCATCAAGCTCTGATTCTTCC
MAP2K3-FAM133Bchr1721216849chr792207031924LELMYSSSSSSSSDSCTGGAGCTGATGTATTCATCTTCTTCTTCATCAAGCTCTGATTCT

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Information of the samples that have these potential fusion neoantigens of MAP2K3-FAM133B

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
SARCMAP2K3-FAM133Bchr1721216849ENST00000316920chr792207031ENST00000427372TCGA-DX-A8BM-01A

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Potential target of CAR-T therapy development for MAP2K3-FAM133B

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

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Related Drugs to MAP2K3-FAM133B

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

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Related Diseases to MAP2K3-FAM133B

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