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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:ACACA-CCL5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ACACA-CCL5
FusionPDB ID: 1144
FusionGDB2.0 ID: 1144
HgeneTgene
Gene symbol

ACACA

CCL5

Gene ID

31

6352

Gene nameacetyl-CoA carboxylase alphaC-C motif chemokine ligand 5
SynonymsACAC|ACACAD|ACC|ACC1|ACCAD17S136E|RANTES|SCYA5|SIS-delta|SISd|TCP228|eoCP
Cytomap

17q12

17q12

Type of geneprotein-codingprotein-coding
Descriptionacetyl-CoA carboxylase 1ACC-alphaacetyl-Coenzyme A carboxylase alphaC-C motif chemokine 5T-cell specific protein p288beta-chemokine RANTESchemokine (C-C motif) ligand 5eosinophil chemotactic cytokineregulated upon activation, normally T-expressed, and presumably secretedsmall inducible cytokine subfamily A (Cys-Cys)
Modification date2020031320200313
UniProtAcc

Q13085

Main function of 5'-partner protein: FUNCTION: Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis (PubMed:20952656, PubMed:20457939, PubMed:29899443). This is a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA (PubMed:20952656, PubMed:20457939, PubMed:29899443). {ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656, ECO:0000269|PubMed:29899443}.

P13501

Main function of 5'-partner protein: FUNCTION: Chemoattractant for blood monocytes, memory T-helper cells and eosinophils. Causes the release of histamine from basophils and activates eosinophils. May activate several chemokine receptors including CCR1, CCR3, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant RANTES protein induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form RANTES(3-68) acts as a natural chemotaxis inhibitor and is a more potent inhibitor of HIV-1-infection. The second processed form RANTES(4-68) exhibits reduced chemotactic and HIV-suppressive activity compared with RANTES(1-68) and RANTES(3-68) and is generated by an unidentified enzyme associated with monocytes and neutrophils (PubMed:16791620, PubMed:1380064, PubMed:8525373, PubMed:9516414, PubMed:15923218). May also be an agonist of the G protein-coupled receptor GPR75, stimulating inositol trisphosphate production and calcium mobilization through its activation. Together with GPR75, may play a role in neuron survival through activation of a downstream signaling pathway involving the PI3, Akt and MAP kinases. By activating GPR75 may also play a role in insulin secretion by islet cells (PubMed:23979485). {ECO:0000269|PubMed:1380064, ECO:0000269|PubMed:15923218, ECO:0000269|PubMed:16791620, ECO:0000269|PubMed:17001303, ECO:0000269|PubMed:23979485, ECO:0000269|PubMed:8525373, ECO:0000269|PubMed:9516414}.
Ensembl transtripts involved in fusion geneENST idsENST00000335166, ENST00000394406, 
ENST00000353139, ENST00000360679, 
ENST00000361253, ENST00000416895, 
ENST00000588142, ENST00000589665, 
ENST00000293272, ENST00000366113, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score44 X 35 X 17=261802 X 2 X 2=8
# samples 513
** MAII scorelog2(51/26180*10)=-5.68182403997375
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/8*10)=1.90689059560852
Fusion gene context

PubMed: ACACA [Title/Abstract] AND CCL5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ACACA [Title/Abstract] AND CCL5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ACACA(35478277)-CCL5(34199468), # samples:1
ACACA(35478276)-CCL5(34199468), # samples:1
Anticipated loss of major functional domain due to fusion event.ACACA-CCL5 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.
ACACA-CCL5 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.
ACACA-CCL5 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.
ACACA-CCL5 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.
ACACA-CCL5 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
ACACA-CCL5 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
ACACA-CCL5 seems lost the major protein functional domain in Tgene 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
TgeneCCL5

GO:0006816

calcium ion transport

10734056

TgeneCCL5

GO:0006874

cellular calcium ion homeostasis

10734056

TgeneCCL5

GO:0006887

exocytosis

10734056

TgeneCCL5

GO:0006954

inflammatory response

21147091

TgeneCCL5

GO:0007159

leukocyte cell-cell adhesion

8558019

TgeneCCL5

GO:0007186

G protein-coupled receptor signaling pathway

17001303|23979485

TgeneCCL5

GO:0007267

cell-cell signaling

8558019

TgeneCCL5

GO:0009636

response to toxic substance

10841574

TgeneCCL5

GO:0010759

positive regulation of macrophage chemotaxis

16778803

TgeneCCL5

GO:0010820

positive regulation of T cell chemotaxis

1699135|7544376|16778803|18337562

TgeneCCL5

GO:0014068

positive regulation of phosphatidylinositol 3-kinase signaling

7544376

TgeneCCL5

GO:0014911

positive regulation of smooth muscle cell migration

21297082

TgeneCCL5

GO:0030335

positive regulation of cell migration

7545673

TgeneCCL5

GO:0031328

positive regulation of cellular biosynthetic process

18337562

TgeneCCL5

GO:0031584

activation of phospholipase D activity

9469451

TgeneCCL5

GO:0031663

lipopolysaccharide-mediated signaling pathway

21147091

TgeneCCL5

GO:0033634

positive regulation of cell-cell adhesion mediated by integrin

8558019

TgeneCCL5

GO:0034112

positive regulation of homotypic cell-cell adhesion

10488085

TgeneCCL5

GO:0042102

positive regulation of T cell proliferation

18832695

TgeneCCL5

GO:0042119

neutrophil activation

10488085

TgeneCCL5

GO:0042327

positive regulation of phosphorylation

18337562

TgeneCCL5

GO:0042531

positive regulation of tyrosine phosphorylation of STAT protein

9417081

TgeneCCL5

GO:0043922

negative regulation by host of viral transcription

10841574

TgeneCCL5

GO:0045071

negative regulation of viral genome replication

10490959

TgeneCCL5

GO:0045744

negative regulation of G protein-coupled receptor signaling pathway

10734056

TgeneCCL5

GO:0045785

positive regulation of cell adhesion

10910894

TgeneCCL5

GO:0048245

eosinophil chemotaxis

16778803

TgeneCCL5

GO:0048661

positive regulation of smooth muscle cell proliferation

21297082

TgeneCCL5

GO:0050796

regulation of insulin secretion

23979485

TgeneCCL5

GO:0050863

regulation of T cell activation

10488085

TgeneCCL5

GO:0051928

positive regulation of calcium ion transport

8699119

TgeneCCL5

GO:0070098

chemokine-mediated signaling pathway

17001303

TgeneCCL5

GO:0070233

negative regulation of T cell apoptotic process

10488085

TgeneCCL5

GO:0070234

positive regulation of T cell apoptotic process

10488085

TgeneCCL5

GO:0071407

cellular response to organic cyclic compound

21147091

TgeneCCL5

GO:0090026

positive regulation of monocyte chemotaxis

1699135|19779041

TgeneCCL5

GO:1901214

regulation of neuron death

17001303

TgeneCCL5

GO:2000406

positive regulation of T cell migration

23620790

TgeneCCL5

GO:2000503

positive regulation of natural killer cell chemotaxis

7545673



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/chr17:35478277/chr17:34199468)
- 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 ACACA (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 CCL5 (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)
ENST00000353139ACACAchr1735478277-ENST00000293272CCL5chr1734199468-7730675646168382125
ENST00000353139ACACAchr1735478277-ENST00000366113CCL5chr1734199468-7730675646168382125
ENST00000360679ACACAchr1735478277-ENST00000293272CCL5chr1734199468-7398642429765062069
ENST00000360679ACACAchr1735478277-ENST00000366113CCL5chr1734199468-7398642429765062069
ENST00000361253ACACAchr1735478277-ENST00000293272CCL5chr1734199468-1833859195941248
ENST00000361253ACACAchr1735478277-ENST00000366113CCL5chr1734199468-1833859195941248
ENST00000353139ACACAchr1735478276-ENST00000293272CCL5chr1734199468-7730675646168382125
ENST00000353139ACACAchr1735478276-ENST00000366113CCL5chr1734199468-7730675646168382125
ENST00000360679ACACAchr1735478276-ENST00000293272CCL5chr1734199468-7398642429765062069
ENST00000360679ACACAchr1735478276-ENST00000366113CCL5chr1734199468-7398642429765062069
ENST00000361253ACACAchr1735478276-ENST00000293272CCL5chr1734199468-1833859195941248
ENST00000361253ACACAchr1735478276-ENST00000366113CCL5chr1734199468-1833859195941248

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
ENST00000353139ENST00000293272ACACAchr1735478277-CCL5chr1734199468-0.0011292160.9988708
ENST00000353139ENST00000366113ACACAchr1735478277-CCL5chr1734199468-0.0011292160.9988708
ENST00000360679ENST00000293272ACACAchr1735478277-CCL5chr1734199468-0.0011239460.99887604
ENST00000360679ENST00000366113ACACAchr1735478277-CCL5chr1734199468-0.0011239460.99887604
ENST00000361253ENST00000293272ACACAchr1735478277-CCL5chr1734199468-0.069444960.9305551
ENST00000361253ENST00000366113ACACAchr1735478277-CCL5chr1734199468-0.069444960.9305551
ENST00000353139ENST00000293272ACACAchr1735478276-CCL5chr1734199468-0.0011292160.9988708
ENST00000353139ENST00000366113ACACAchr1735478276-CCL5chr1734199468-0.0011292160.9988708
ENST00000360679ENST00000293272ACACAchr1735478276-CCL5chr1734199468-0.0011239460.99887604
ENST00000360679ENST00000366113ACACAchr1735478276-CCL5chr1734199468-0.0011239460.99887604
ENST00000361253ENST00000293272ACACAchr1735478276-CCL5chr1734199468-0.069444960.9305551
ENST00000361253ENST00000366113ACACAchr1735478276-CCL5chr1734199468-0.069444960.9305551

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 ACACA-CCL5

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ACACAchr1735478276CCL5chr173419946864242042VFANWRGFSGGMKALSPERTAKCVPT
ACACAchr1735478276CCL5chr173419946867562098VFANWRGFSGGMKALSPERTAKCVPT
ACACAchr1735478276CCL5chr1734199468859221VFANWRGFSGGMKALSPERTAKCVPT
ACACAchr1735478277CCL5chr173419946864242042VFANWRGFSGGMKALSPERTAKCVPT
ACACAchr1735478277CCL5chr173419946867562098VFANWRGFSGGMKALSPERTAKCVPT
ACACAchr1735478277CCL5chr1734199468859221VFANWRGFSGGMKALSPERTAKCVPT

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Potential FusionNeoAntigen Information of ACACA-CCL5 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.
ACACA-CCL5_35478276_34199468.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)
ACACA-CCL5chr1735478276chr17341994686756HLA-A31:02GMKALSPER0.88880.50431019
ACACA-CCL5chr1735478276chr17341994686756HLA-A30:08KALSPERTAK0.99420.75281222
ACACA-CCL5chr1735478276chr17341994686756HLA-B39:06WRGFSGGMKA0.94940.976414
ACACA-CCL5chr1735478276chr17341994686756HLA-B27:14WRGFSGGMKA0.9960.8371414
ACACA-CCL5chr1735478276chr17341994686756HLA-B73:01WRGFSGGMKA0.99020.9266414
ACACA-CCL5chr1735478276chr17341994686756HLA-C14:02GFSGGMKAL0.04810.9809615
ACACA-CCL5chr1735478276chr17341994686756HLA-C14:03GFSGGMKAL0.04810.9809615
ACACA-CCL5chr1735478276chr17341994686756HLA-A30:01KALSPERTAK0.99420.85461222

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Potential FusionNeoAntigen Information of ACACA-CCL5 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.
ACACA-CCL5_35478276_34199468.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)
ACACA-CCL5chr1735478276chr17341994686756DRB1-0102FSGGMKALSPERTAK722
ACACA-CCL5chr1735478276chr17341994686756DRB1-0123FSGGMKALSPERTAK722
ACACA-CCL5chr1735478276chr17341994686756DRB1-1001FSGGMKALSPERTAK722
ACACA-CCL5chr1735478276chr17341994686756DRB1-1002FSGGMKALSPERTAK722
ACACA-CCL5chr1735478276chr17341994686756DRB1-1002SGGMKALSPERTAKC823
ACACA-CCL5chr1735478276chr17341994686756DRB1-1003FSGGMKALSPERTAK722

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Fusion breakpoint peptide structures of ACACA-CCL5

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
2786GFSGGMKALSPERTACACACCL5chr1735478276chr17341994686756

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ACACA-CCL5

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-B14:023BVN2786GFSGGMKALSPERT-5.49802-5.50512
HLA-B52:013W392786GFSGGMKALSPERT-4.88484-4.89194
HLA-A24:025HGA2786GFSGGMKALSPERT-9.7287-9.7358
HLA-B44:053DX82786GFSGGMKALSPERT-6.55078-6.55788
HLA-A02:016TDR2786GFSGGMKALSPERT-1.02296-1.03006

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Vaccine Design for the FusionNeoAntigens of ACACA-CCL5

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
ACACA-CCL5chr1735478276chr17341994681019GMKALSPERGAATGAAAGCTTTGTCACCCGAAAGAA
ACACA-CCL5chr1735478276chr17341994681222KALSPERTAKAAGCTTTGTCACCCGAAAGAACCGCCAAGT
ACACA-CCL5chr1735478276chr1734199468414WRGFSGGMKAGGAGAGGCTTCTCTGGTGGAATGAAAGCTT
ACACA-CCL5chr1735478276chr1734199468615GFSGGMKALGCTTCTCTGGTGGAATGAAAGCTTTGT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ACACA-CCL5chr1735478276chr1734199468722FSGGMKALSPERTAKTCTCTGGTGGAATGAAAGCTTTGTCACCCGAAAGAACCGCCAAGT
ACACA-CCL5chr1735478276chr1734199468823SGGMKALSPERTAKCCTGGTGGAATGAAAGCTTTGTCACCCGAAAGAACCGCCAAGTGTG

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Information of the samples that have these potential fusion neoantigens of ACACA-CCL5

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
SARCACACA-CCL5chr1735478276ENST00000353139chr1734199468ENST00000293272TCGA-IE-A3OV

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Potential target of CAR-T therapy development for ACACA-CCL5

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 ACACA-CCL5

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 ACACA-CCL5

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