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Fusion Protein:E2F5-CA3

Fusion Gene and Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: E2F5-CA3
	FusionPDB ID: 24786
	FusionGDB2.0 ID: 24786
		Hgene	Tgene
	Gene symbol	E2F5	CA3
	Gene ID	1875	761
	Gene name	E2F transcription factor 5	carbonic anhydrase 3
	Synonyms	E2F-5	CAIII\|Car3
	Cytomap	8q21.2	8q21.2
	Type of gene	protein-coding	protein-coding
	Description	transcription factor E2F5E2F transcription factor 5, p130-binding	carbonic anhydrase 3CA-IIIHEL-S-167mPcarbonate dehydratase IIIcarbonic anhydrase III, muscle specificcarbonic anhydrase IIIIepididymis secretory sperm binding protein Li 167mP
	Modification date	20200313	20200313
	UniProtAcc	Q15329 Main function of 5'-partner protein: FUNCTION: Transcriptional activator that binds to E2F sites, these sites are present in the promoter of many genes whose products are involved in cell proliferation. May mediate growth factor-initiated signal transduction. It is likely involved in the early responses of resting cells to growth factor stimulation. Specifically required for multiciliate cell differentiation: together with MCIDAS and E2F5, binds and activate genes required for centriole biogenesis. {ECO:0000250\|UniProtKB:Q6DE14}.	P07451 Main function of 5'-partner protein: FUNCTION: Reversible hydration of carbon dioxide.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000519128, ENST00000256117, ENST00000416274, ENST00000418930, ENST00000517476, ENST00000521429,	ENST00000285381,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	5 X 5 X 4=100	7 X 7 X 8=392
	# samples	7	13
	** MAII score	log2(7/100*10)=-0.514573172829758 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(13/392*10)=-1.59234203108675 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Fusion gene context	PubMed: E2F5 [Title/Abstract] AND CA3 [Title/Abstract] AND fusion [Title/Abstract]
Fusion neoantigen context	PubMed: E2F5 [Title/Abstract] AND CA3 [Title/Abstract] AND neoantigen [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	E2F5(86124439)-CA3(86351941), # samples:2
Anticipated loss of major functional domain due to fusion event.	E2F5-CA3 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. E2F5-CA3 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. E2F5-CA3 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. E2F5-CA3 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)

Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner

Gene

GO ID

GO term

PubMed ID

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr8:86124439/chr8:86351941)
- 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.

Retention 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.

Fusion gene breakpoints across E2F5 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Fusion gene breakpoints across CA3 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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Fusion Amino Acid Sequences

Fusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.

Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	Seq length (transcript)	BP loci (transcript)	Predicted start (transcript)	Predicted stop (transcript)	Seq length (amino acids)
ENST00000418930	E2F5	chr8	86124439	+	ENST00000285381	CA3	chr8	86351941	+	2760	1124	196	1872	558
ENST00000256117	E2F5	chr8	86124439	+	ENST00000285381	CA3	chr8	86351941	+	2607	971	37	1719	560
ENST00000416274	E2F5	chr8	86124439	+	ENST00000285381	CA3	chr8	86351941	+	2601	965	34	1713	559
ENST00000517476	E2F5	chr8	86124439	+	ENST00000285381	CA3	chr8	86351941	+	2445	809	124	1557	477
ENST00000521429	E2F5	chr8	86124439	+	ENST00000285381	CA3	chr8	86351941	+	2449	813	401	1561	386
ENST00000418930	E2F5	chr8	86121644	+	ENST00000285381	CA3	chr8	86351941	+	2715	1079	196	1827	543
ENST00000256117	E2F5	chr8	86121644	+	ENST00000285381	CA3	chr8	86351941	+	2559	923	37	1671	544
ENST00000416274	E2F5	chr8	86121644	+	ENST00000285381	CA3	chr8	86351941	+	2553	917	34	1665	543
ENST00000517476	E2F5	chr8	86121644	+	ENST00000285381	CA3	chr8	86351941	+	2397	761	124	1509	461
ENST00000521429	E2F5	chr8	86121644	+	ENST00000285381	CA3	chr8	86351941	+	2401	765	401	1513	370
ENST00000418930	E2F5	chr8	86124439	+	ENST00000285381	CA3	chr8	86351940	+	2760	1124	196	1872	558
ENST00000256117	E2F5	chr8	86124439	+	ENST00000285381	CA3	chr8	86351940	+	2607	971	37	1719	560
ENST00000416274	E2F5	chr8	86124439	+	ENST00000285381	CA3	chr8	86351940	+	2601	965	34	1713	559
ENST00000517476	E2F5	chr8	86124439	+	ENST00000285381	CA3	chr8	86351940	+	2445	809	124	1557	477
ENST00000521429	E2F5	chr8	86124439	+	ENST00000285381	CA3	chr8	86351940	+	2449	813	401	1561	386

DeepORF 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.

Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	No-coding score	Coding score
ENST00000418930	ENST00000285381	E2F5	chr8	86124439	+	CA3	chr8	86351941	+	0.002987025	0.997013
ENST00000256117	ENST00000285381	E2F5	chr8	86124439	+	CA3	chr8	86351941	+	0.002712615	0.9972874
ENST00000416274	ENST00000285381	E2F5	chr8	86124439	+	CA3	chr8	86351941	+	0.002740985	0.997259
ENST00000517476	ENST00000285381	E2F5	chr8	86124439	+	CA3	chr8	86351941	+	0.001000282	0.9989998
ENST00000521429	ENST00000285381	E2F5	chr8	86124439	+	CA3	chr8	86351941	+	0.001306774	0.9986933
ENST00000418930	ENST00000285381	E2F5	chr8	86121644	+	CA3	chr8	86351941	+	0.002957543	0.9970425
ENST00000256117	ENST00000285381	E2F5	chr8	86121644	+	CA3	chr8	86351941	+	0.002887748	0.9971123
ENST00000416274	ENST00000285381	E2F5	chr8	86121644	+	CA3	chr8	86351941	+	0.002373196	0.99762684
ENST00000517476	ENST00000285381	E2F5	chr8	86121644	+	CA3	chr8	86351941	+	0.001480601	0.99851936
ENST00000521429	ENST00000285381	E2F5	chr8	86121644	+	CA3	chr8	86351941	+	0.001041265	0.9989587
ENST00000418930	ENST00000285381	E2F5	chr8	86124439	+	CA3	chr8	86351940	+	0.002987025	0.997013
ENST00000256117	ENST00000285381	E2F5	chr8	86124439	+	CA3	chr8	86351940	+	0.002712615	0.9972874
ENST00000416274	ENST00000285381	E2F5	chr8	86124439	+	CA3	chr8	86351940	+	0.002740985	0.997259
ENST00000517476	ENST00000285381	E2F5	chr8	86124439	+	CA3	chr8	86351940	+	0.001000282	0.9989998
ENST00000521429	ENST00000285381	E2F5	chr8	86124439	+	CA3	chr8	86351940	+	0.001306774	0.9986933

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 E2F5-CA3

+/-13 AA sequence from the breakpoints of the fusion protein sequences.

Hgene

Hchr

Hbp

Tgene

Tchr

Tbp

Length(fusion protein)

BP in fusion protein

Peptide

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Potential FusionNeoAntigen Information of E2F5-CA3 in HLA I

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.

Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)

Fusion gene

Hchr

Hbp

Tgene

Tchr

Tbp

HLA I

FusionNeoAntigen peptide

Binding score

Immunogenic score

Neoantigen start (at BP 13)

Neoantigen end (at BP 13)

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Potential FusionNeoAntigen Information of E2F5-CA3 in HLA II

Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).

Fusion gene

Hchr

Hbp

Tgene

Tchr

Tbp

HLA II

FusionNeoAntigen peptide

Neoantigen start (at BP 13)

Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of E2F5-CA3

3D 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 E2F5-CA3

Virtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.

HLA allele

PDB ID

File name

BPseq

Docking score

Glide score

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Vaccine Design for the FusionNeoAntigens of E2F5-CA3

mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.

Fusion gene

Hchr

Hbp

Tchr

Tbp

Start in +/-13AA

End in +/-13AA

FusionNeoAntigen peptide sequence

FusionNeoAntigen RNA sequence

mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.

Fusion gene

Hchr

Hbp

Tchr

Tbp

Start in +/-13AA

End in +/-13AA

FusionNeoAntigen peptide

FusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of E2F5-CA3

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 type

Fusion gene

Hchr

Hbp

Henst

Tchr

Tbp

Tenst

Sample

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Potential target of CAR-T therapy development for E2F5-CA3

Predicted 3D structure. We used RoseTTAFold.

Retention 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'.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

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.

Hgene

Hchr

Hbp

Henst

Tgene

Tchr

Tbp

Tenst

DeepLoc result

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Related Drugs to E2F5-CA3

Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Drug

Source

PMID

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Related Diseases to E2F5-CA3

Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Disease

Source

PMID

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source

	Fusion Gene and Fusion Protein Summary
	Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)
	Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)
	Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)
	Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)
	Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)
	Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)
	Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)
	Potential target of CAR-T therapy development
	Information on the samples that have these potential fusion neoantigens
	Fusion Protein Targeting Drugs - (Manual Curation)
	Fusion Protein Related diseases - (Manual Curation)