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Fusion Protein:ZEB1-RSU1

Fusion Gene and Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: ZEB1-RSU1
	FusionPDB ID: 100858
	FusionGDB2.0 ID: 100858
		Hgene	Tgene
	Gene symbol	ZEB1	RSU1
	Gene ID	6935	6251
	Gene name	zinc finger E-box binding homeobox 1	Ras suppressor protein 1
	Synonyms	AREB6\|BZP\|DELTAEF1\|FECD6\|NIL2A\|PPCD3\|TCF8\|ZFHEP\|ZFHX1A	RSP-1
	Cytomap	10p11.22	10p13
	Type of gene	protein-coding	protein-coding
	Description	zinc finger E-box-binding homeobox 1delta-crystallin enhancer binding factor 1negative regulator of IL2posterior polymorphous corneal dystrophy 3transcription factor 8 (represses interleukin 2 expression)zinc finger homeodomain enhancer-binding prote	ras suppressor protein 1ras suppressor protein 1 variant 1ras suppressor protein 1 variant 2ras suppressor protein 1 variant 3ras suppressor protein 1 variant 5rsu-1
	Modification date	20200329	20200327
	UniProtAcc	.	.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000559858, ENST00000320985, ENST00000361642, ENST00000542815, ENST00000560721, ENST00000446923,	ENST00000345264, ENST00000377921, ENST00000602389, ENST00000464074,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	11 X 5 X 8=440	12 X 9 X 4=432
	# samples	13	12
	** MAII score	log2(13/440*10)=-1.7589919004962 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(12/432*10)=-1.84799690655495 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Fusion gene context	PubMed: ZEB1 [Title/Abstract] AND RSU1 [Title/Abstract] AND fusion [Title/Abstract]
Fusion neoantigen context	PubMed: ZEB1 [Title/Abstract] AND RSU1 [Title/Abstract] AND neoantigen [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	ZEB1(31608221)-RSU1(16737154), # samples:1
Anticipated loss of major functional domain due to fusion event.	ZEB1-RSU1 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. ZEB1-RSU1 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
Hgene	ZEB1	GO:0000122	negative regulation of transcription by RNA polymerase II	23765923\|23814079
Hgene	ZEB1	GO:0045892	negative regulation of transcription, DNA-templated	20418909

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr10:31608221/chr10:16737154)
- 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 ZEB1 (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 RSU1 (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)
ENST00000320985	ZEB1	chr10	31608221	+	ENST00000377921	RSU1	chr10	16737154	-	3187	168	1513	1890	125
ENST00000320985	ZEB1	chr10	31608221	+	ENST00000345264	RSU1	chr10	16737154	-	3187	168	1513	1890	125
ENST00000320985	ZEB1	chr10	31608221	+	ENST00000602389	RSU1	chr10	16737154	-	3178	168	1513	1890	125
ENST00000361642	ZEB1	chr10	31608221	+	ENST00000377921	RSU1	chr10	16737154	-	3140	121	1466	1843	125
ENST00000361642	ZEB1	chr10	31608221	+	ENST00000345264	RSU1	chr10	16737154	-	3140	121	1466	1843	125
ENST00000361642	ZEB1	chr10	31608221	+	ENST00000602389	RSU1	chr10	16737154	-	3131	121	1466	1843	125
ENST00000560721	ZEB1	chr10	31608221	+	ENST00000377921	RSU1	chr10	16737154	-	3100	81	1426	1803	125
ENST00000560721	ZEB1	chr10	31608221	+	ENST00000345264	RSU1	chr10	16737154	-	3100	81	1426	1803	125
ENST00000560721	ZEB1	chr10	31608221	+	ENST00000602389	RSU1	chr10	16737154	-	3091	81	1426	1803	125
ENST00000542815	ZEB1	chr10	31608221	+	ENST00000377921	RSU1	chr10	16737154	-	3090	71	1416	1793	125
ENST00000542815	ZEB1	chr10	31608221	+	ENST00000345264	RSU1	chr10	16737154	-	3090	71	1416	1793	125
ENST00000542815	ZEB1	chr10	31608221	+	ENST00000602389	RSU1	chr10	16737154	-	3081	71	1416	1793	125

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
ENST00000320985	ENST00000377921	ZEB1	chr10	31608221	+	RSU1	chr10	16737154	-	0.65587956	0.34412047
ENST00000320985	ENST00000345264	ZEB1	chr10	31608221	+	RSU1	chr10	16737154	-	0.65587956	0.34412047
ENST00000320985	ENST00000602389	ZEB1	chr10	31608221	+	RSU1	chr10	16737154	-	0.63549453	0.36450547
ENST00000361642	ENST00000377921	ZEB1	chr10	31608221	+	RSU1	chr10	16737154	-	0.6378058	0.36219418
ENST00000361642	ENST00000345264	ZEB1	chr10	31608221	+	RSU1	chr10	16737154	-	0.6378058	0.36219418
ENST00000361642	ENST00000602389	ZEB1	chr10	31608221	+	RSU1	chr10	16737154	-	0.61657655	0.38342345
ENST00000560721	ENST00000377921	ZEB1	chr10	31608221	+	RSU1	chr10	16737154	-	0.6354366	0.36456338
ENST00000560721	ENST00000345264	ZEB1	chr10	31608221	+	RSU1	chr10	16737154	-	0.6354366	0.36456338
ENST00000560721	ENST00000602389	ZEB1	chr10	31608221	+	RSU1	chr10	16737154	-	0.6141893	0.3858106
ENST00000542815	ENST00000377921	ZEB1	chr10	31608221	+	RSU1	chr10	16737154	-	0.63728154	0.36271852
ENST00000542815	ENST00000345264	ZEB1	chr10	31608221	+	RSU1	chr10	16737154	-	0.63728154	0.36271852
ENST00000542815	ENST00000602389	ZEB1	chr10	31608221	+	RSU1	chr10	16737154	-	0.6160923	0.38390774

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 ZEB1-RSU1

+/-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 ZEB1-RSU1 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 ZEB1-RSU1 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 ZEB1-RSU1

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 ZEB1-RSU1

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 ZEB1-RSU1

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 ZEB1-RSU1

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 ZEB1-RSU1

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 ZEB1-RSU1

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 ZEB1-RSU1

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)