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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:ACSL1-HERC5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ACSL1-HERC5
FusionPDB ID: 1493
FusionGDB2.0 ID: 1493
HgeneTgene
Gene symbol

ACSL1

HERC5

Gene ID

2180

51191

Gene nameacyl-CoA synthetase long chain family member 1HECT and RLD domain containing E3 ubiquitin protein ligase 5
SynonymsACS1|FACL1|FACL2|LACS|LACS1|LACS2CEB1|CEBP1
Cytomap

4q35.1

4q22.1

Type of geneprotein-codingprotein-coding
Descriptionlong-chain-fatty-acid--CoA ligase 1LACS 1LACS 2acyl-CoA synthetase 1arachidonate--CoA ligasefatty-acid-Coenzyme A ligase, long-chain 1fatty-acid-Coenzyme A ligase, long-chain 2lignoceroyl-CoA synthaselong-chain acyl-CoA synthetase 1long-chain acyE3 ISG15--protein ligase HERC5HECT domain and RCC1-like domain-containing protein 5cyclin-E-binding protein 1hect domain and RLD 5probable E3 ubiquitin-protein ligase HERC5
Modification date2020031320200313
UniProtAcc

P33121

Main function of 5'-partner protein: FUNCTION: Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:24269233, PubMed:22633490, PubMed:21242590). Preferentially uses palmitoleate, oleate and linoleate (PubMed:24269233). Preferentially activates arachidonate than epoxyeicosatrienoic acids (EETs) or hydroxyeicosatrienoic acids (HETEs) (By similarity). {ECO:0000250|UniProtKB:P18163, ECO:0000269|PubMed:21242590, ECO:0000269|PubMed:22633490, ECO:0000269|PubMed:24269233}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000281455, ENST00000437665, 
ENST00000454703, ENST00000504342, 
ENST00000504900, ENST00000507295, 
ENST00000513317, ENST00000515030, 
ENST00000508695, ENST00000264350, 
ENST00000508159, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score2 X 2 X 2=81 X 1 X 1=1
# samples 21
** MAII scorelog2(2/8*10)=1.32192809488736log2(1/1*10)=3.32192809488736
Fusion gene context

PubMed: ACSL1 [Title/Abstract] AND HERC5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ACSL1 [Title/Abstract] AND HERC5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ACSL1(185698038)-HERC5(89407266), # samples:1
Anticipated loss of major functional domain due to fusion event.ACSL1-HERC5 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.
ACSL1-HERC5 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.
ACSL1-HERC5 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
ACSL1-HERC5 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted 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
HgeneACSL1

GO:0001676

long-chain fatty acid metabolic process

22022213|24269233

HgeneACSL1

GO:0008610

lipid biosynthetic process

21242590

HgeneACSL1

GO:0044539

long-chain fatty acid import

22022213

TgeneHERC5

GO:0016567

protein ubiquitination

15331633

TgeneHERC5

GO:0032020

ISG15-protein conjugation

20308324

TgeneHERC5

GO:0050688

regulation of defense response to virus

20308324



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/chr4:185698038/chr4:89407266)
- 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 ACSL1 (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 HERC5 (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)
ENST00000515030ACSL1chr4185698038-ENST00000264350HERC5chr489407266+25269039572240427
ENST00000515030ACSL1chr4185698038-ENST00000508159HERC5chr489407266+23859039572240427
ENST00000281455ACSL1chr4185698038-ENST00000264350HERC5chr489407266+24117888422125427
ENST00000281455ACSL1chr4185698038-ENST00000508159HERC5chr489407266+22707888422125427
ENST00000507295ACSL1chr4185698038-ENST00000264350HERC5chr489407266+22496266801963427
ENST00000507295ACSL1chr4185698038-ENST00000508159HERC5chr489407266+21086266801963427
ENST00000437665ACSL1chr4185698038-ENST00000264350HERC5chr489407266+25279049582241427
ENST00000437665ACSL1chr4185698038-ENST00000508159HERC5chr489407266+23869049582241427
ENST00000504900ACSL1chr4185698038-ENST00000264350HERC5chr489407266+23697468002083427
ENST00000504900ACSL1chr4185698038-ENST00000508159HERC5chr489407266+22287468002083427

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
ENST00000515030ENST00000264350ACSL1chr4185698038-HERC5chr489407266+0.00033560.9996644
ENST00000515030ENST00000508159ACSL1chr4185698038-HERC5chr489407266+0.0003961360.9996039
ENST00000281455ENST00000264350ACSL1chr4185698038-HERC5chr489407266+0.00030050.9996995
ENST00000281455ENST00000508159ACSL1chr4185698038-HERC5chr489407266+0.000343580.99965644
ENST00000507295ENST00000264350ACSL1chr4185698038-HERC5chr489407266+0.0002352410.99976474
ENST00000507295ENST00000508159ACSL1chr4185698038-HERC5chr489407266+0.0002656590.99973434
ENST00000437665ENST00000264350ACSL1chr4185698038-HERC5chr489407266+0.0002034260.99979657
ENST00000437665ENST00000508159ACSL1chr4185698038-HERC5chr489407266+0.000230.99977
ENST00000504900ENST00000264350ACSL1chr4185698038-HERC5chr489407266+0.0002715460.9997284
ENST00000504900ENST00000508159ACSL1chr4185698038-HERC5chr489407266+0.0003104050.9996896

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 ACSL1-HERC5

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

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Potential FusionNeoAntigen Information of ACSL1-HERC5 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 ACSL1-HERC5 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 ACSL1-HERC5

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 ACSL1-HERC5

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 ACSL1-HERC5

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 ACSL1-HERC5

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 ACSL1-HERC5

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
HgeneACSL1chr4:185698038chr4:89407266ENST00000281455-62125_45192699.0TransmembraneHelical%3B Signal-anchor for type III membrane protein
HgeneACSL1chr4:185698038chr4:89407266ENST00000504342-62125_45192699.0TransmembraneHelical%3B Signal-anchor for type III membrane protein
HgeneACSL1chr4:185698038chr4:89407266ENST00000515030-62125_45192699.0TransmembraneHelical%3B Signal-anchor for type III membrane protein

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 ACSL1-HERC5

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 ACSL1-HERC5

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