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Fusion Protein:ERBB2-ZPBP2

Fusion Gene and Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: ERBB2-ZPBP2
	FusionPDB ID: 27204
	FusionGDB2.0 ID: 27204
		Hgene	Tgene
	Gene symbol	ERBB2	ZPBP2
	Gene ID	2064	124626
	Gene name	erb-b2 receptor tyrosine kinase 2	zona pellucida binding protein 2
	Synonyms	CD340\|HER-2\|HER-2/neu\|HER2\|MLN 19\|NEU\|NGL\|TKR1	ZPBPL
	Cytomap	17q12	17q21.1
	Type of gene	protein-coding	protein-coding
	Description	receptor tyrosine-protein kinase erbB-2c-erb B2/neu proteinherstatinhuman epidermal growth factor receptor 2metastatic lymph node gene 19 proteinneuro/glioblastoma derived oncogene homologneuroblastoma/glioblastoma derived oncogene homologp185erbB2	zona pellucida-binding protein 2ZPBP-like protein
	Modification date	20200329	20200313
	UniProtAcc	P04626 Main function of 5'-partner protein: FUNCTION: Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization. {ECO:0000305}.; FUNCTION: In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth. {ECO:0000269\|PubMed:10358079, ECO:0000269\|PubMed:15380516, ECO:0000269\|PubMed:21555369}.	.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000269571, ENST00000406381, ENST00000445658, ENST00000540147, ENST00000541774, ENST00000584450, ENST00000584601, ENST00000540042, ENST00000578199, ENST00000584888,	ENST00000348931, ENST00000377940, ENST00000584588,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	50 X 44 X 14=30800	8 X 8 X 6=384
	# samples	73	11
	** MAII score	log2(73/30800*10)=-5.39889007670225 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(11/384*10)=-1.8036027871965 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Fusion gene context	PubMed: ERBB2 [Title/Abstract] AND ZPBP2 [Title/Abstract] AND fusion [Title/Abstract]
Fusion neoantigen context	PubMed: ERBB2 [Title/Abstract] AND ZPBP2 [Title/Abstract] AND neoantigen [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	ERBB2(37882106)-ZPBP2(38026946), # samples:1
Anticipated loss of major functional domain due to fusion event.	ERBB2-ZPBP2 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. ERBB2-ZPBP2 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. ERBB2-ZPBP2 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. ERBB2-ZPBP2 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	ERBB2	GO:0007165	signal transduction	10572067
Hgene	ERBB2	GO:0007166	cell surface receptor signaling pathway	9685399
Hgene	ERBB2	GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway	7514177
Hgene	ERBB2	GO:0014065	phosphatidylinositol 3-kinase signaling	7556068
Hgene	ERBB2	GO:0018108	peptidyl-tyrosine phosphorylation	12000754
Hgene	ERBB2	GO:0032886	regulation of microtubule-based process	20937854
Hgene	ERBB2	GO:0035556	intracellular signal transduction	19372587
Hgene	ERBB2	GO:0042060	wound healing	12646923
Hgene	ERBB2	GO:0043406	positive regulation of MAP kinase activity	10572067
Hgene	ERBB2	GO:0045785	positive regulation of cell adhesion	7556068
Hgene	ERBB2	GO:0046777	protein autophosphorylation	7556068
Hgene	ERBB2	GO:0050679	positive regulation of epithelial cell proliferation	10572067
Hgene	ERBB2	GO:0071363	cellular response to growth factor stimulus	20010870
Hgene	ERBB2	GO:0090314	positive regulation of protein targeting to membrane	20010870

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr17:37882106/chr17:38026946)
- 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 ERBB2 (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 ZPBP2 (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)
ENST00000584601	ERBB2	chr17	37882106	+	ENST00000348931	ZPBP2	chr17	38026946	+	4813	3579	752	4477	1241
ENST00000584601	ERBB2	chr17	37882106	+	ENST00000584588	ZPBP2	chr17	38026946	+	4599	3579	752	4258	1168
ENST00000584601	ERBB2	chr17	37882106	+	ENST00000377940	ZPBP2	chr17	38026946	+	5565	3579	752	4477	1241
ENST00000406381	ERBB2	chr17	37882106	+	ENST00000348931	ZPBP2	chr17	38026946	+	4526	3292	510	4190	1226
ENST00000406381	ERBB2	chr17	37882106	+	ENST00000584588	ZPBP2	chr17	38026946	+	4312	3292	510	3971	1153
ENST00000406381	ERBB2	chr17	37882106	+	ENST00000377940	ZPBP2	chr17	38026946	+	5278	3292	510	4190	1226
ENST00000541774	ERBB2	chr17	37882106	+	ENST00000348931	ZPBP2	chr17	38026946	+	4061	2827	0	3725	1241
ENST00000541774	ERBB2	chr17	37882106	+	ENST00000584588	ZPBP2	chr17	38026946	+	3847	2827	0	3506	1168
ENST00000541774	ERBB2	chr17	37882106	+	ENST00000377940	ZPBP2	chr17	38026946	+	4813	2827	0	3725	1241
ENST00000445658	ERBB2	chr17	37882106	+	ENST00000348931	ZPBP2	chr17	38026946	+	3541	2307	50	3205	1051
ENST00000445658	ERBB2	chr17	37882106	+	ENST00000584588	ZPBP2	chr17	38026946	+	3327	2307	50	2986	978
ENST00000445658	ERBB2	chr17	37882106	+	ENST00000377940	ZPBP2	chr17	38026946	+	4293	2307	50	3205	1051
ENST00000540147	ERBB2	chr17	37882106	+	ENST00000348931	ZPBP2	chr17	38026946	+	4344	3110	25	4008	1327
ENST00000540147	ERBB2	chr17	37882106	+	ENST00000584588	ZPBP2	chr17	38026946	+	4130	3110	25	3789	1254
ENST00000540147	ERBB2	chr17	37882106	+	ENST00000377940	ZPBP2	chr17	38026946	+	5096	3110	25	4008	1327
ENST00000584450	ERBB2	chr17	37882106	+	ENST00000348931	ZPBP2	chr17	38026946	+	4321	3087	2	3985	1327
ENST00000584450	ERBB2	chr17	37882106	+	ENST00000584588	ZPBP2	chr17	38026946	+	4107	3087	2	3766	1254
ENST00000584450	ERBB2	chr17	37882106	+	ENST00000377940	ZPBP2	chr17	38026946	+	5073	3087	2	3985	1327
ENST00000269571	ERBB2	chr17	37882106	+	ENST00000348931	ZPBP2	chr17	38026946	+	4265	3031	57	3929	1290
ENST00000269571	ERBB2	chr17	37882106	+	ENST00000584588	ZPBP2	chr17	38026946	+	4051	3031	57	3710	1217
ENST00000269571	ERBB2	chr17	37882106	+	ENST00000377940	ZPBP2	chr17	38026946	+	5017	3031	57	3929	1290

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
ENST00000584601	ENST00000348931	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.001146086	0.9988539
ENST00000584601	ENST00000584588	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.001304786	0.9986952
ENST00000584601	ENST00000377940	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.000603169	0.9993968
ENST00000406381	ENST00000348931	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.000859056	0.999141
ENST00000406381	ENST00000584588	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.000971933	0.9990281
ENST00000406381	ENST00000377940	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.000441389	0.9995586
ENST00000541774	ENST00000348931	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.00046363	0.9995364
ENST00000541774	ENST00000584588	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.000539952	0.99946004
ENST00000541774	ENST00000377940	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.000233956	0.99976605
ENST00000445658	ENST00000348931	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.000298394	0.99970156
ENST00000445658	ENST00000584588	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.000431475	0.9995685
ENST00000445658	ENST00000377940	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.000146488	0.9998535
ENST00000540147	ENST00000348931	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.000729055	0.999271
ENST00000540147	ENST00000584588	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.000877539	0.99912244
ENST00000540147	ENST00000377940	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.000380715	0.99961925
ENST00000584450	ENST00000348931	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.000718789	0.9992812
ENST00000584450	ENST00000584588	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.000861626	0.99913836
ENST00000584450	ENST00000377940	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.000371375	0.99962866
ENST00000269571	ENST00000348931	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.000668666	0.99933136
ENST00000269571	ENST00000584588	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.000802631	0.9991974
ENST00000269571	ENST00000377940	ERBB2	chr17	37882106	+	ZPBP2	chr17	38026946	+	0.000346764	0.9996532

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 ERBB2-ZPBP2

+/-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 ERBB2-ZPBP2 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 ERBB2-ZPBP2 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 ERBB2-ZPBP2

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 ERBB2-ZPBP2

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 ERBB2-ZPBP2

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 ERBB2-ZPBP2

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 ERBB2-ZPBP2

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

Hgene

ERBB2

chr17:37882106

chr17:38026946

ENST00000269571

653_675

957

1256.0

Transmembrane

Helical

Hgene

ERBB2

chr17:37882106

chr17:38026946

ENST00000541774

653_675

942

1241.0

Transmembrane

Helical

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 ERBB2-ZPBP2

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 ERBB2-ZPBP2

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)