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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:TRA2B-BCAR1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TRA2B-BCAR1
FusionPDB ID: 93593
FusionGDB2.0 ID: 93593
HgeneTgene
Gene symbol

TRA2B

BCAR1

Gene ID

6434

9564

Gene nametransformer 2 beta homologBCAR1 scaffold protein, Cas family member
SynonymsHtra2-beta|PPP1R156|SFRS10|SRFS10|TRA2-BETA|TRAN2BCAS|CAS1|CASS1|CRKAS|P130Cas
Cytomap

3q27.2

16q23.1

Type of geneprotein-codingprotein-coding
Descriptiontransformer-2 protein homolog betaTRA-2 betaprotein phosphatase 1, regulatory subunit 156splicing factor, arginine/serine-rich 10 (transformer 2 homolog, Drosophila)transformer-2 protein homolog Bbreast cancer anti-estrogen resistance protein 1BCAR1, Cas family scaffold proteinBCAR1, Cas family scaffolding proteinCas scaffolding protein family member 1Crk-associated substrate p130Cas
Modification date2020031320200327
UniProtAcc.

P56945

Main function of 5'-partner protein: FUNCTION: Docking protein which plays a central coordinating role for tyrosine kinase-based signaling related to cell adhesion (PubMed:12832404, PubMed:12432078). Implicated in induction of cell migration and cell branching (PubMed:12432078, PubMed:12832404, PubMed:17038317). Involved in the BCAR3-mediated inhibition of TGFB signaling (By similarity). {ECO:0000250|UniProtKB:Q61140, ECO:0000269|PubMed:12432078, ECO:0000269|PubMed:12832404, ECO:0000269|PubMed:17038317}.
Ensembl transtripts involved in fusion geneENST idsENST00000342294, ENST00000453386, 
ENST00000382191, ENST00000471134, 
ENST00000546196, ENST00000393420, 
ENST00000393422, ENST00000418647, 
ENST00000420641, ENST00000535626, 
ENST00000538440, ENST00000542031, 
ENST00000566982, ENST00000162330, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score14 X 9 X 8=10086 X 4 X 4=96
# samples 156
** MAII scorelog2(15/1008*10)=-2.74846123300404
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/96*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TRA2B [Title/Abstract] AND BCAR1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TRA2B [Title/Abstract] AND BCAR1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TRA2B(185655613)-BCAR1(75276988), # samples:1
Anticipated loss of major functional domain due to fusion event.TRA2B-BCAR1 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.
TRA2B-BCAR1 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.
TRA2B-BCAR1 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.
TRA2B-BCAR1 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
HgeneTRA2B

GO:0000381

regulation of alternative mRNA splicing, via spliceosome

12165565|12761049

HgeneTRA2B

GO:0000398

mRNA splicing, via spliceosome

9546399

HgeneTRA2B

GO:0048026

positive regulation of mRNA splicing, via spliceosome

15009664

TgeneBCAR1

GO:0007015

actin filament organization

16105984

TgeneBCAR1

GO:0007229

integrin-mediated signaling pathway

8649368

TgeneBCAR1

GO:0010595

positive regulation of endothelial cell migration

21245381

TgeneBCAR1

GO:0016477

cell migration

9425168

TgeneBCAR1

GO:0030335

positive regulation of cell migration

9472046

TgeneBCAR1

GO:0050851

antigen receptor-mediated signaling pathway

10587647

TgeneBCAR1

GO:0050853

B cell receptor signaling pathway

9020138

TgeneBCAR1

GO:0086100

endothelin receptor signaling pathway

19086031



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/chr3:185655613/chr16:75276988)
- 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 TRA2B (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 BCAR1 (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)
ENST00000453386TRA2Bchr3185655613-ENST00000162330BCAR1chr1675276988-33943121922912906
ENST00000342294TRA2Bchr3185655613-ENST00000162330BCAR1chr1675276988-3271189692789906

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
ENST00000453386ENST00000162330TRA2Bchr3185655613-BCAR1chr1675276988-0.0051897450.9948102
ENST00000342294ENST00000162330TRA2Bchr3185655613-BCAR1chr1675276988-0.0056342390.9943658

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 TRA2B-BCAR1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TRA2Bchr3185655613BCAR1chr167527698818940VMSDSGEQNYGERNVLAKALYDNVAE
TRA2Bchr3185655613BCAR1chr167527698831240VMSDSGEQNYGERNVLAKALYDNVAE

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Potential FusionNeoAntigen Information of TRA2B-BCAR1 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.
TRA2B-BCAR1_185655613_75276988.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)
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B39:01ERNVLAKAL0.99780.81811120
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B45:01GERNVLAKA0.9960.83391019
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B39:06ERNVLAKAL0.99570.67411120
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B38:02ERNVLAKAL0.99510.90451120
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B14:02QNYGERNVL0.98880.8837716
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B14:01QNYGERNVL0.98880.8837716
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B50:02GERNVLAKA0.98710.65481019
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B15:18ERNVLAKAL0.56910.54881120
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B41:01GERNVLAKA0.47270.7841019
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B50:01GERNVLAKA0.11780.58481019
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B44:03GERNVLAKALY0.99960.89461021
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B39:13GEQNYGERNVL0.99270.7598516
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B73:01ERNVLAKA0.99720.6021119
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B39:12ERNVLAKAL0.99710.81881120
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B40:06GERNVLAKA0.99690.61131019
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B39:05ERNVLAKAL0.99440.79361120
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B73:01ERNVLAKAL0.93090.59021120
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B14:03QNYGERNVL0.71890.8601716
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B14:03ERNVLAKAL0.40030.79021120
TRA2B-BCAR1chr3185655613chr1675276988189HLA-C12:16ERNVLAKAL0.01780.92821120
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B39:08GEQNYGERNVL0.99630.814516
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B39:31ERNVLAKAL0.99780.81631120
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B39:02QNYGERNVL0.75460.9721716
TRA2B-BCAR1chr3185655613chr1675276988189HLA-C07:22ERNVLAKAL0.60560.64531120
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B50:05GERNVLAKA0.11780.58481019
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B50:04GERNVLAKA0.11780.58481019
TRA2B-BCAR1chr3185655613chr1675276988189HLA-C06:17ERNVLAKAL0.04470.98381120
TRA2B-BCAR1chr3185655613chr1675276988189HLA-C06:02ERNVLAKAL0.04470.98381120
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B40:04GEQNYGERNVL0.99970.6753516
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B44:13GERNVLAKALY0.99960.89461021
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B44:07GERNVLAKALY0.99960.89461021
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B44:26GERNVLAKALY0.99960.89461021
TRA2B-BCAR1chr3185655613chr1675276988189HLA-B41:03GEQNYGERNVL0.99080.6005516

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Potential FusionNeoAntigen Information of TRA2B-BCAR1 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.

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)

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Fusion breakpoint peptide structures of TRA2B-BCAR1

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
2062EQNYGERNVLAKALTRA2BBCAR1chr3185655613chr1675276988189

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TRA2B-BCAR1

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-B14:023BVN2062EQNYGERNVLAKAL-6.93921-7.05261
HLA-B14:023BVN2062EQNYGERNVLAKAL-5.28235-6.31765
HLA-B52:013W392062EQNYGERNVLAKAL-6.47863-6.59203
HLA-B52:013W392062EQNYGERNVLAKAL-5.77858-6.81388
HLA-A24:025HGA2062EQNYGERNVLAKAL-9.13182-9.24522
HLA-A24:025HGA2062EQNYGERNVLAKAL-4.34325-5.37855
HLA-B27:056PYJ2062EQNYGERNVLAKAL-7.72306-7.83646
HLA-B44:053DX82062EQNYGERNVLAKAL-5.49403-5.60743
HLA-B44:053DX82062EQNYGERNVLAKAL-5.22878-6.26408

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Vaccine Design for the FusionNeoAntigens of TRA2B-BCAR1

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
TRA2B-BCAR1chr3185655613chr16752769881019GERNVLAKAGGCGAGCGGAACGTGCTGGCCAAAGCG
TRA2B-BCAR1chr3185655613chr16752769881021GERNVLAKALYGGCGAGCGGAACGTGCTGGCCAAAGCGCTCTAT
TRA2B-BCAR1chr3185655613chr16752769881119ERNVLAKAGAGCGGAACGTGCTGGCCAAAGCG
TRA2B-BCAR1chr3185655613chr16752769881120ERNVLAKALGAGCGGAACGTGCTGGCCAAAGCGCTC
TRA2B-BCAR1chr3185655613chr1675276988516GEQNYGERNVLGGCGAGCAGAACTACGGCGAGCGGAACGTGCTG
TRA2B-BCAR1chr3185655613chr1675276988716QNYGERNVLCAGAACTACGGCGAGCGGAACGTGCTG

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

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Information of the samples that have these potential fusion neoantigens of TRA2B-BCAR1

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
STADTRA2B-BCAR1chr3185655613ENST00000342294chr1675276988ENST00000162330TCGA-HU-A4GN-01A

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Potential target of CAR-T therapy development for TRA2B-BCAR1

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 TRA2B-BCAR1

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 TRA2B-BCAR1

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