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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:ABL2-XRRA1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ABL2-XRRA1
FusionPDB ID: 505
FusionGDB2.0 ID: 505
HgeneTgene
Gene symbol

ABL2

XRRA1

Gene ID

27

143570

Gene nameABL proto-oncogene 2, non-receptor tyrosine kinaseX-ray radiation resistance associated 1
SynonymsABLL|ARG-
Cytomap

1q25.2

11q13.4

Type of geneprotein-codingprotein-coding
Descriptiontyrosine-protein kinase ABL2Abelson tyrosine-protein kinase 2abelson-related gene proteinc-abl oncogene 2, non-receptor tyrosine kinasetyrosine-protein kinase ARGv-abl Abelson murine leukemia viral oncogene homolog 2X-ray radiation resistance-associated protein 1
Modification date2020032720200313
UniProtAcc

P42684

Main function of 5'-partner protein: FUNCTION: Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 acts also as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. {ECO:0000269|PubMed:15735735, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:18945674}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000367623, ENST00000392043, 
ENST00000502732, ENST00000507173, 
ENST00000511413, ENST00000344730, 
ENST00000408940, ENST00000504405, 
ENST00000512653, 
ENST00000533598, 
ENST00000321448, ENST00000340360, 
ENST00000527087, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 6 X 6=2887 X 9 X 6=378
# samples 89
** MAII scorelog2(8/288*10)=-1.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/378*10)=-2.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ABL2 [Title/Abstract] AND XRRA1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ABL2 [Title/Abstract] AND XRRA1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ABL2(179198376)-XRRA1(74559507), # samples:1
Anticipated loss of major functional domain due to fusion event.ABL2-XRRA1 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.
ABL2-XRRA1 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
HgeneABL2

GO:0018108

peptidyl-tyrosine phosphorylation

15886098

HgeneABL2

GO:0051353

positive regulation of oxidoreductase activity

12893824

TgeneXRRA1

GO:0010165

response to X-ray

12908878



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/chr1:179198376/chr11:74559507)
- 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 ABL2 (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 XRRA1 (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)
ENST00000502732ABL2chr1179198376-ENST00000340360XRRA1chr1174559507-43543611031383426
ENST00000502732ABL2chr1179198376-ENST00000321448XRRA1chr1174559507-36743611031383426
ENST00000502732ABL2chr1179198376-ENST00000527087XRRA1chr1174559507-15103611031062319
ENST00000367623ABL2chr1179198376-ENST00000340360XRRA1chr1174559507-41501571541179341
ENST00000367623ABL2chr1179198376-ENST00000321448XRRA1chr1174559507-34701571541179341
ENST00000367623ABL2chr1179198376-ENST00000527087XRRA1chr1174559507-1306157154858234
ENST00000507173ABL2chr1179198376-ENST00000340360XRRA1chr1174559507-41501571541179341
ENST00000507173ABL2chr1179198376-ENST00000321448XRRA1chr1174559507-34701571541179341
ENST00000507173ABL2chr1179198376-ENST00000527087XRRA1chr1174559507-1306157154858234
ENST00000511413ABL2chr1179198376-ENST00000340360XRRA1chr1174559507-41501571541179341
ENST00000511413ABL2chr1179198376-ENST00000321448XRRA1chr1174559507-34701571541179341
ENST00000511413ABL2chr1179198376-ENST00000527087XRRA1chr1174559507-1306157154858234
ENST00000392043ABL2chr1179198376-ENST00000340360XRRA1chr1174559507-44374441861466426
ENST00000392043ABL2chr1179198376-ENST00000321448XRRA1chr1174559507-37574441861466426
ENST00000392043ABL2chr1179198376-ENST00000527087XRRA1chr1174559507-15934441861145319

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
ENST00000502732ENST00000340360ABL2chr1179198376-XRRA1chr1174559507-0.000896120.99910384
ENST00000502732ENST00000321448ABL2chr1179198376-XRRA1chr1174559507-0.0012731070.9987269
ENST00000502732ENST00000527087ABL2chr1179198376-XRRA1chr1174559507-0.0098748630.9901252
ENST00000367623ENST00000340360ABL2chr1179198376-XRRA1chr1174559507-0.0007582490.9992418
ENST00000367623ENST00000321448ABL2chr1179198376-XRRA1chr1174559507-0.0010565640.9989435
ENST00000367623ENST00000527087ABL2chr1179198376-XRRA1chr1174559507-0.0104220260.989578
ENST00000507173ENST00000340360ABL2chr1179198376-XRRA1chr1174559507-0.0007582490.9992418
ENST00000507173ENST00000321448ABL2chr1179198376-XRRA1chr1174559507-0.0010565640.9989435
ENST00000507173ENST00000527087ABL2chr1179198376-XRRA1chr1174559507-0.0104220260.989578
ENST00000511413ENST00000340360ABL2chr1179198376-XRRA1chr1174559507-0.0007582490.9992418
ENST00000511413ENST00000321448ABL2chr1179198376-XRRA1chr1174559507-0.0010565640.9989435
ENST00000511413ENST00000527087ABL2chr1179198376-XRRA1chr1174559507-0.0104220260.989578
ENST00000392043ENST00000340360ABL2chr1179198376-XRRA1chr1174559507-0.0008482180.9991518
ENST00000392043ENST00000321448ABL2chr1179198376-XRRA1chr1174559507-0.0012227030.99877733
ENST00000392043ENST00000527087ABL2chr1179198376-XRRA1chr1174559507-0.0084277010.99157226

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 ABL2-XRRA1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ABL2chr1179198376XRRA1chr117455950736167GSGAAVQPGPPAAGGTRRGAPQRPAS
ABL2chr1179198376XRRA1chr117455950744467GSGAAVQPGPPAAGGTRRGAPQRPAS

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Potential FusionNeoAntigen Information of ABL2-XRRA1 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.

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)

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Potential FusionNeoAntigen Information of ABL2-XRRA1 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 ABL2-XRRA1

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ABL2-XRRA1

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

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Vaccine Design for the FusionNeoAntigens of ABL2-XRRA1

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

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 ABL2-XRRA1

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

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Potential target of CAR-T therapy development for ABL2-XRRA1

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 ABL2-XRRA1

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 ABL2-XRRA1

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