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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:SRSF4-CREB5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SRSF4-CREB5
FusionPDB ID: 86619
FusionGDB2.0 ID: 86619
HgeneTgene
Gene symbol

SRSF4

CREB5

Gene ID

6429

9586

Gene nameserine and arginine rich splicing factor 4cAMP responsive element binding protein 5
SynonymsSFRS4|SRP75CRE-BPA|CREB-5|CREBPA
Cytomap

1p35.3

7p15.1

Type of geneprotein-codingprotein-coding
Descriptionserine/arginine-rich splicing factor 4SR splicing factor 4SRP001LBpre-mRNA-splicing factor SRP75splicing factor, arginine/serine-rich 4cyclic AMP-responsive element-binding protein 5cAMP response element-binding protein CRE-BPacAMP-response element-binding protein A
Modification date2020031320200313
UniProtAcc.

Q02930

Main function of 5'-partner protein: FUNCTION: Binds to the cAMP response element and activates transcription. {ECO:0000269|PubMed:8378084}.
Ensembl transtripts involved in fusion geneENST idsENST00000373795, ENST00000546138, 
ENST00000466448, 
ENST00000482692, 
ENST00000357727, ENST00000396298, 
ENST00000396299, ENST00000396300, 
ENST00000409603, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 5 X 6=21014 X 12 X 8=1344
# samples 815
** MAII scorelog2(8/210*10)=-1.39231742277876
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(15/1344*10)=-3.16349873228288
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SRSF4 [Title/Abstract] AND CREB5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SRSF4 [Title/Abstract] AND CREB5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SRSF4(29508158)-CREB5(28843816), # samples:3
Anticipated loss of major functional domain due to fusion event.SRSF4-CREB5 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.
SRSF4-CREB5 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.
SRSF4-CREB5 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.
SRSF4-CREB5 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
HgeneSRSF4

GO:0048025

negative regulation of mRNA splicing, via spliceosome

15009664

TgeneCREB5

GO:0045893

positive regulation of transcription, DNA-templated

8378084



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/chr1:29508158/chr7:28843816)
- 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 SRSF4 (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 CREB5 (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)
ENST00000373795SRSF4chr129508158-ENST00000396299CREB5chr728843816+18883428611287
ENST00000373795SRSF4chr129508158-ENST00000357727CREB5chr728843816+77823423451166273
ENST00000373795SRSF4chr129508158-ENST00000396300CREB5chr728843816+18883428611287
ENST00000373795SRSF4chr129508158-ENST00000409603CREB5chr728843816+15253428611287
ENST00000373795SRSF4chr129508158-ENST00000396298CREB5chr728843816+18883428611287
ENST00000546138SRSF4chr129508158-ENST00000396299CREB5chr728843816+17992532561077273
ENST00000546138SRSF4chr129508158-ENST00000357727CREB5chr728843816+76932532561077273
ENST00000546138SRSF4chr129508158-ENST00000396300CREB5chr728843816+17992532561077273
ENST00000546138SRSF4chr129508158-ENST00000409603CREB5chr728843816+14362532561077273
ENST00000546138SRSF4chr129508158-ENST00000396298CREB5chr728843816+17992532561077273

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
ENST00000373795ENST00000396299SRSF4chr129508158-CREB5chr728843816+0.1215694550.8784306
ENST00000373795ENST00000357727SRSF4chr129508158-CREB5chr728843816+0.177046840.8229531
ENST00000373795ENST00000396300SRSF4chr129508158-CREB5chr728843816+0.1215694550.8784306
ENST00000373795ENST00000409603SRSF4chr129508158-CREB5chr728843816+0.05480420.9451958
ENST00000373795ENST00000396298SRSF4chr129508158-CREB5chr728843816+0.1215694550.8784306
ENST00000546138ENST00000396299SRSF4chr129508158-CREB5chr728843816+0.082781590.9172184
ENST00000546138ENST00000357727SRSF4chr129508158-CREB5chr728843816+0.16938730.83061266
ENST00000546138ENST00000396300SRSF4chr129508158-CREB5chr728843816+0.082781590.9172184
ENST00000546138ENST00000409603SRSF4chr129508158-CREB5chr728843816+0.033071910.9669281
ENST00000546138ENST00000396298SRSF4chr129508158-CREB5chr728843816+0.082781590.9172184

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 SRSF4-CREB5

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 SRSF4-CREB5 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 SRSF4-CREB5 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 SRSF4-CREB5

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 SRSF4-CREB5

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 SRSF4-CREB5

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 SRSF4-CREB5

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 SRSF4-CREB5

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 SRSF4-CREB5

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 SRSF4-CREB5

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