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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:USP22-ATP2A3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: USP22-ATP2A3
FusionPDB ID: 97270
FusionGDB2.0 ID: 97270
HgeneTgene
Gene symbol

USP22

ATP2A3

Gene ID

23326

489

Gene nameubiquitin specific peptidase 22ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3
SynonymsUSP3LSERCA3
Cytomap

17p11.2

17p13.2

Type of geneprotein-codingprotein-coding
Descriptionubiquitin carboxyl-terminal hydrolase 22deubiquitinating enzyme 22ubiquitin specific protease 22ubiquitin thioesterase 22ubiquitin thiolesterase 22ubiquitin-specific processing protease 22sarcoplasmic/endoplasmic reticulum calcium ATPase 3ATPase, Ca(2+)-transporting, ubiquitousATPase, Ca++ transporting, ubiquitousSR Ca(2+)-ATPase 3adenosine triphosphatase, calciumcalcium pump 3calcium-translocating P-type ATPasesarco/endoplasmic ret
Modification date2020031320200313
UniProtAcc.

Q93084

Main function of 5'-partner protein: FUNCTION: This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium. Transports calcium ions from the cytosol into the sarcoplasmic/endoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction. {ECO:0000269|PubMed:11956212, ECO:0000269|PubMed:15028735}.
Ensembl transtripts involved in fusion geneENST idsENST00000261497, ENST00000455117, 
ENST00000537526, 
ENST00000352011, 
ENST00000359983, ENST00000397039, 
ENST00000397043, ENST00000309890, 
ENST00000397035, ENST00000397041, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 14 X 7=14705 X 3 X 5=75
# samples 225
** MAII scorelog2(22/1470*10)=-2.74024072619907
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/75*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: USP22 [Title/Abstract] AND ATP2A3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: USP22 [Title/Abstract] AND ATP2A3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)USP22(20945978)-ATP2A3(3848442), # samples:2
Anticipated loss of major functional domain due to fusion event.USP22-ATP2A3 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.
USP22-ATP2A3 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.
USP22-ATP2A3 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.
USP22-ATP2A3 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
HgeneUSP22

GO:0016574

histone ubiquitination

18469533

HgeneUSP22

GO:0016578

histone deubiquitination

18206972|18206973

HgeneUSP22

GO:0016579

protein deubiquitination

16378762

TgeneATP2A3

GO:0006919

activation of cysteine-type endopeptidase activity involved in apoptotic process

16725111

TgeneATP2A3

GO:0070059

intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress

16725111

TgeneATP2A3

GO:0070588

calcium ion transmembrane transport

9843705|11956212

TgeneATP2A3

GO:1903515

calcium ion transport from cytosol to endoplasmic reticulum

15028735



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/chr17:20945978/chr17:3848442)
- 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 USP22 (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 ATP2A3 (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)
ENST00000261497USP22chr1720945978-ENST00000397035ATP2A3chr173848442-3334375242369781
ENST00000261497USP22chr1720945978-ENST00000397041ATP2A3chr173848442-3827375242279751
ENST00000261497USP22chr1720945978-ENST00000309890ATP2A3chr173848442-3928375242369781

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
ENST00000261497ENST00000397035USP22chr1720945978-ATP2A3chr173848442-0.0102866740.9897133
ENST00000261497ENST00000397041USP22chr1720945978-ATP2A3chr173848442-0.0069362070.99306375
ENST00000261497ENST00000309890USP22chr1720945978-ATP2A3chr173848442-0.0075949040.9924051

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 USP22-ATP2A3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
USP22chr1720945978ATP2A3chr173848442375117FVWSGTAEARKRKMFVVAEADAGSCL

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Potential FusionNeoAntigen Information of USP22-ATP2A3 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.
USP22-ATP2A3_20945978_3848442.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)
USP22-ATP2A3chr1720945978chr173848442375HLA-B27:04ARKRKMFVV0.99350.655817
USP22-ATP2A3chr1720945978chr173848442375HLA-B08:09EARKRKMFV0.98820.7954716
USP22-ATP2A3chr1720945978chr173848442375HLA-B44:03AEARKRKMF0.9690.9627615
USP22-ATP2A3chr1720945978chr173848442375HLA-B39:06RKMFVVAEA0.93690.83491120
USP22-ATP2A3chr1720945978chr173848442375HLA-B47:01AEARKRKMF0.75710.5248615
USP22-ATP2A3chr1720945978chr173848442375HLA-B73:01RKMFVVAEA0.96780.70861120
USP22-ATP2A3chr1720945978chr173848442375HLA-C07:05ARKRKMFVV0.8240.961817
USP22-ATP2A3chr1720945978chr173848442375HLA-B27:06ARKRKMFVV0.99570.666817
USP22-ATP2A3chr1720945978chr173848442375HLA-B27:10ARKRKMFVV0.99380.806817
USP22-ATP2A3chr1720945978chr173848442375HLA-B44:13AEARKRKMF0.9690.9627615
USP22-ATP2A3chr1720945978chr173848442375HLA-B44:07AEARKRKMF0.9690.9627615
USP22-ATP2A3chr1720945978chr173848442375HLA-B44:26AEARKRKMF0.9690.9627615
USP22-ATP2A3chr1720945978chr173848442375HLA-C06:08ARKRKMFVV0.69380.98817
USP22-ATP2A3chr1720945978chr173848442375HLA-C06:17ARKRKMFVV0.13020.9856817
USP22-ATP2A3chr1720945978chr173848442375HLA-C06:02ARKRKMFVV0.13020.9856817
USP22-ATP2A3chr1720945978chr173848442375HLA-B41:03AEARKRKMF0.06540.6326615
USP22-ATP2A3chr1720945978chr173848442375HLA-C16:02TAEARKRKM0.03980.9935514
USP22-ATP2A3chr1720945978chr173848442375HLA-B15:53AEARKRKMF0.02910.9122615
USP22-ATP2A3chr1720945978chr173848442375HLA-C16:01TAEARKRKM0.02540.9861514

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Potential FusionNeoAntigen Information of USP22-ATP2A3 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.
USP22-ATP2A3_20945978_3848442.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)
USP22-ATP2A3chr1720945978chr173848442375DRB1-0902RKRKMFVVAEADAGS924

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Fusion breakpoint peptide structures of USP22-ATP2A3

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
137AEARKRKMFVVAEAUSP22ATP2A3chr1720945978chr173848442375

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of USP22-ATP2A3

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-B14:023BVN137AEARKRKMFVVAEA-4.83882-4.84592
HLA-B52:013W39137AEARKRKMFVVAEA-7.55694-7.56404
HLA-A11:014UQ2137AEARKRKMFVVAEA-11.141-11.1481
HLA-A24:025HGA137AEARKRKMFVVAEA-6.61984-6.62694
HLA-B44:053DX8137AEARKRKMFVVAEA-5.13965-5.14675
HLA-A02:016TDR137AEARKRKMFVVAEA-9.32603-9.33313

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Vaccine Design for the FusionNeoAntigens of USP22-ATP2A3

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
USP22-ATP2A3chr1720945978chr1738484421120RKMFVVAEACGCAAGATGTTCGTGGTAGCCGAGGCC
USP22-ATP2A3chr1720945978chr173848442514TAEARKRKMACGGCTGAGGCCCGCAAGCGCAAGATG
USP22-ATP2A3chr1720945978chr173848442615AEARKRKMFGCTGAGGCCCGCAAGCGCAAGATGTTC
USP22-ATP2A3chr1720945978chr173848442716EARKRKMFVGAGGCCCGCAAGCGCAAGATGTTCGTG
USP22-ATP2A3chr1720945978chr173848442817ARKRKMFVVGCCCGCAAGCGCAAGATGTTCGTGGTA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
USP22-ATP2A3chr1720945978chr173848442924RKRKMFVVAEADAGSCGCAAGCGCAAGATGTTCGTGGTAGCCGAGGCCGATGCGGGCTCC

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Information of the samples that have these potential fusion neoantigens of USP22-ATP2A3

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
PRADUSP22-ATP2A3chr1720945978ENST00000261497chr173848442ENST00000309890TCGA-HC-A6AN-01A

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Potential target of CAR-T therapy development for USP22-ATP2A3

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
TgeneATP2A3chr17:20945978chr17:3848442ENST00000309890722758_77701030.0TransmembraneHelical%3B Name%3D5
TgeneATP2A3chr17:20945978chr17:3848442ENST00000309890722829_85101030.0TransmembraneHelical%3B Name%3D7
TgeneATP2A3chr17:20945978chr17:3848442ENST00000309890722898_91701030.0TransmembraneHelical%3B Name%3D8
TgeneATP2A3chr17:20945978chr17:3848442ENST00000309890722931_94901030.0TransmembraneHelical%3B Name%3D9
TgeneATP2A3chr17:20945978chr17:3848442ENST00000309890722965_98501030.0TransmembraneHelical%3B Name%3D10
TgeneATP2A3chr17:20945978chr17:3848442ENST00000352011722758_77701044.0TransmembraneHelical%3B Name%3D5
TgeneATP2A3chr17:20945978chr17:3848442ENST00000352011722829_85101044.0TransmembraneHelical%3B Name%3D7
TgeneATP2A3chr17:20945978chr17:3848442ENST00000352011722898_91701044.0TransmembraneHelical%3B Name%3D8
TgeneATP2A3chr17:20945978chr17:3848442ENST00000352011722931_94901044.0TransmembraneHelical%3B Name%3D9
TgeneATP2A3chr17:20945978chr17:3848442ENST00000352011722965_98501044.0TransmembraneHelical%3B Name%3D10
TgeneATP2A3chr17:20945978chr17:3848442ENST00000359983723758_77701053.0TransmembraneHelical%3B Name%3D5
TgeneATP2A3chr17:20945978chr17:3848442ENST00000359983723829_85101053.0TransmembraneHelical%3B Name%3D7
TgeneATP2A3chr17:20945978chr17:3848442ENST00000359983723898_91701053.0TransmembraneHelical%3B Name%3D8
TgeneATP2A3chr17:20945978chr17:3848442ENST00000359983723931_94901053.0TransmembraneHelical%3B Name%3D9
TgeneATP2A3chr17:20945978chr17:3848442ENST00000359983723965_98501053.0TransmembraneHelical%3B Name%3D10
TgeneATP2A3chr17:20945978chr17:3848442ENST00000397035723758_77701266.3333333333333TransmembraneHelical%3B Name%3D5
TgeneATP2A3chr17:20945978chr17:3848442ENST00000397035723829_85101266.3333333333333TransmembraneHelical%3B Name%3D7
TgeneATP2A3chr17:20945978chr17:3848442ENST00000397035723898_91701266.3333333333333TransmembraneHelical%3B Name%3D8
TgeneATP2A3chr17:20945978chr17:3848442ENST00000397035723931_94901266.3333333333333TransmembraneHelical%3B Name%3D9
TgeneATP2A3chr17:20945978chr17:3848442ENST00000397035723965_98501266.3333333333333TransmembraneHelical%3B Name%3D10
TgeneATP2A3chr17:20945978chr17:3848442ENST00000397041721758_77701000.0TransmembraneHelical%3B Name%3D5
TgeneATP2A3chr17:20945978chr17:3848442ENST00000397041721829_85101000.0TransmembraneHelical%3B Name%3D7
TgeneATP2A3chr17:20945978chr17:3848442ENST00000397041721898_91701000.0TransmembraneHelical%3B Name%3D8
TgeneATP2A3chr17:20945978chr17:3848442ENST00000397041721931_94901000.0TransmembraneHelical%3B Name%3D9
TgeneATP2A3chr17:20945978chr17:3848442ENST00000397041721965_98501000.0TransmembraneHelical%3B Name%3D10
TgeneATP2A3chr17:20945978chr17:3848442ENST00000397043721758_7770999.0TransmembraneHelical%3B Name%3D5
TgeneATP2A3chr17:20945978chr17:3848442ENST00000397043721829_8510999.0TransmembraneHelical%3B Name%3D7
TgeneATP2A3chr17:20945978chr17:3848442ENST00000397043721898_9170999.0TransmembraneHelical%3B Name%3D8
TgeneATP2A3chr17:20945978chr17:3848442ENST00000397043721931_9490999.0TransmembraneHelical%3B Name%3D9
TgeneATP2A3chr17:20945978chr17:3848442ENST00000397043721965_9850999.0TransmembraneHelical%3B Name%3D10

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 USP22-ATP2A3

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 USP22-ATP2A3

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