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	Fusion Gene Summary
	Fusion Gene Sample Information
	Fusion ORF Analysis
	Fusion Amino Acid Sequences
	Fusion Protein Functional Features
	Fusion Protein Structure
	pLDDT scores
	Ramachandran Plot of Fusion Protein Structure
	Fusion Protein-Protein Interaction
	Related drugs with this fusion protein
	Related disease with this fusion protein

Fusion Protein:ERBB3-EGFR

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: ERBB3-EGFR
	FusionPDB ID: 27211
	FusionGDB2.0 ID: 27211
		Hgene	Tgene
	Gene symbol	ERBB3	EGFR
	Gene ID	2065	1956
	Gene name	erb-b2 receptor tyrosine kinase 3	epidermal growth factor receptor
	Synonyms	ErbB-3\|FERLK\|HER3\|LCCS2\|MDA-BF-1\|c-erbB-3\|c-erbB3\|erbB3-S\|p180-ErbB3\|p45-sErbB3\|p85-sErbB3	ERBB\|ERBB1\|HER1\|NISBD2\|PIG61\|mENA
	Cytomap	12q13.2	7p11.2
	Type of gene	protein-coding	protein-coding
	Description	receptor tyrosine-protein kinase erbB-3human epidermal growth factor receptor 3proto-oncogene-like protein c-ErbB-3tyrosine kinase-type cell surface receptor HER3v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3	epidermal growth factor receptoravian erythroblastic leukemia viral (v-erb-b) oncogene homologcell growth inhibiting protein 40cell proliferation-inducing protein 61epidermal growth factor receptor tyrosine kinase domainerb-b2 receptor tyrosine kinas
	Modification date	20200327	20200329
	UniProtAcc	P21860	P00533
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000267101, ENST00000415288, ENST00000450146, ENST00000553131, ENST00000549832, ENST00000411731,	ENST00000275493, ENST00000342916, ENST00000344576, ENST00000420316, ENST00000442591, ENST00000454757, ENST00000463948, ENST00000455089,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	16 X 18 X 11=3168	17 X 20 X 8=2720
	# samples	19	22
	** MAII score	log2(19/3168*10)=-4.05950101174866 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(22/2720*10)=-3.62803122261304 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: ERBB3 [Title/Abstract] AND EGFR [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	ERBB3(56492359)-EGFR(55266410), # samples:5 EGFR(55087058)-ERBB3(56492542), # samples:1
Anticipated loss of major functional domain due to fusion event.	EGFR-ERBB3 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. EGFR-ERBB3 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. ERBB3-EGFR 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. ERBB3-EGFR 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. ERBB3-EGFR 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. ERBB3-EGFR 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	ERBB3	GO:0007162	negative regulation of cell adhesion	7556068
Hgene	ERBB3	GO:0007165	signal transduction	10572067
Hgene	ERBB3	GO:0009968	negative regulation of signal transduction	11389077
Hgene	ERBB3	GO:0014065	phosphatidylinositol 3-kinase signaling	7556068
Hgene	ERBB3	GO:0042127	regulation of cell proliferation	11389077
Hgene	ERBB3	GO:0051048	negative regulation of secretion	10559227
Tgene	EGFR	GO:0001934	positive regulation of protein phosphorylation	20551055
Tgene	EGFR	GO:0007165	signal transduction	10572067
Tgene	EGFR	GO:0007166	cell surface receptor signaling pathway	7736574
Tgene	EGFR	GO:0007173	epidermal growth factor receptor signaling pathway	7736574\|12435727
Tgene	EGFR	GO:0008283	cell proliferation	17115032
Tgene	EGFR	GO:0008284	positive regulation of cell proliferation	7736574
Tgene	EGFR	GO:0010750	positive regulation of nitric oxide mediated signal transduction	12828935
Tgene	EGFR	GO:0018108	peptidyl-tyrosine phosphorylation	22732145
Tgene	EGFR	GO:0030307	positive regulation of cell growth	15467833
Tgene	EGFR	GO:0042177	negative regulation of protein catabolic process	17115032
Tgene	EGFR	GO:0042327	positive regulation of phosphorylation	15082764
Tgene	EGFR	GO:0043406	positive regulation of MAP kinase activity	10572067
Tgene	EGFR	GO:0045739	positive regulation of DNA repair	17115032
Tgene	EGFR	GO:0045740	positive regulation of DNA replication	17115032
Tgene	EGFR	GO:0045944	positive regulation of transcription by RNA polymerase II	20551055
Tgene	EGFR	GO:0050679	positive regulation of epithelial cell proliferation	10572067
Tgene	EGFR	GO:0050999	regulation of nitric-oxide synthase activity	12828935
Tgene	EGFR	GO:0070141	response to UV-A	18483258
Tgene	EGFR	GO:0070374	positive regulation of ERK1 and ERK2 cascade	20551055
Tgene	EGFR	GO:0071392	cellular response to estradiol stimulus	20551055
Tgene	EGFR	GO:1900020	positive regulation of protein kinase C activity	22732145
Tgene	EGFR	GO:1903078	positive regulation of protein localization to plasma membrane	22732145

Fusion gene breakpoints across ERBB3 (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 EGFR (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 Gene Sample Information

Fusion gene information from FusionGDB2.0.

Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* All genome coordinats were lifted-over on hg19.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.

Source	Disease	Sample	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
ChimerDB4	ESCA	TCGA-LN-A4A8	ERBB3	chr12	56492359	+	EGFR	chr7	55266410	+
ChimerDB4	ESCA	TCGA-Q9-A6FU	ERBB3	chr12	56492359	+	EGFR	chr7	55266410	+
ChimerDB4	ESCA	TCGA-VR-A8EY	ERBB3	chr12	56492359	+	EGFR	chr7	55266410	+
ChimerDB4	LGG	TCGA-DU-7292	ERBB3	chr12	56492359	+	EGFR	chr7	55266410	+
ChimerDB4	LGG	TCGA-HT-8104	ERBB3	chr12	56492359	+	EGFR	chr7	55266410	+

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Fusion ORF Analysis

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)

ENST00000267101

ERBB3

chr12

56492359

ENST00000455089

EGFR

chr7

55266410

4153

3132

440

3841

1133

ENST00000450146

ERBB3

chr12

56492359

ENST00000455089

EGFR

chr7

55266410

2088

1067

106

1776

556

ENST00000415288

ERBB3

chr12

56492359

ENST00000455089

EGFR

chr7

55266410

3756

2735

3444

1119

ENST00000553131

ERBB3

chr12

56492359

ENST00000455089

EGFR

chr7

55266410

2170

1149

482

1858

458

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
ENST00000267101	ENST00000455089	ERBB3	chr12	56492359	+	EGFR	chr7	55266410	+	0.001773078	0.99822694
ENST00000450146	ENST00000455089	ERBB3	chr12	56492359	+	EGFR	chr7	55266410	+	0.002794822	0.9972052
ENST00000415288	ENST00000455089	ERBB3	chr12	56492359	+	EGFR	chr7	55266410	+	0.000902222	0.9990978
ENST00000553131	ENST00000455089	ERBB3	chr12	56492359	+	EGFR	chr7	55266410	+	0.004832051	0.995168

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Fusion Amino Acid Sequences

For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.

>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

>27211_27211_1_ERBB3-EGFR_ERBB3_chr12_56492359_ENST00000267101_EGFR_chr7_55266410_ENST00000455089_length(amino acids)=1133AA_BP=47
MRANDALQVLGLLFSLARGSEVGNSQAVCPGTLNGLSVTGDAENQYQTLYKLYERCEVVMGNLEIVLTGHNADLSFLQWIREVTGYVLVA
MNEFSTLPLPNLRVVRGTQVYDGKFAIFVMLNYNTNSSHALRQLRLTQLTEILSGGVYIEKNDKLCHMDTIDWRDIVRDRDAEIVVKDNG
RSCPPCHEVCKGRCWGPGSEDCQTLTKTICAPQCNGHCFGPNPNQCCHDECAGGCSGPQDTDCFACRHFNDSGACVPRCPQPLVYNKLTF
QLEPNPHTKYQYGGVCVASCPHNFVVDQTSCVRACPPDKMEVDKNGLKMCEPCGGLCPKACEGTGSGSRFQTVDSSNIDGFVNCTKILGN
LDFLITGLNGDPWHKIPALDPEKLNVFRTVREITGYLNIQSWPPHMHNFSVFSNLTTIGGRSLYNRGFSLLIMKNLNVTSLGFRSLKEIS
AGRIYISANRQLCYHHSLNWTKVLRGPTEERLDIKHNRPRRDCVAEGKVCDPLCSSGGCWGPGPGQCLSCRNYSRGGVCVTHCNFLNGEP
REFAHEAECFSCHPECQPMEGTATCNGSGSDTCAQCAHFRDGPHCVSSCPHGVLGAKGPIYKYPDVQNECRPCHENCTQGCKGPELQDCL
GQTLVLIGKTHLTMALTVIAGLVVIFMMLGGTFLYWRGRRIQNKRAMRRYLERGESIEPLDPSEKANKVLARIFKETELRKLKVLGSGVF
GTVHKGVWIPEGESIKIPVCIKVIEDKSGRQSFQAVTDHMLAIGSLDHAHIVRLLGLCPGSSLQLVTQYLPLGSLLDHVRQHRGALGPQL
LLNWGVQIAKGMYYLEEHGMVHRNLAARNVLLKSPSQVQVADFGVADLLPPDDKQLLYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVT
VWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQGDERMHLPSPT
DSNFYRALMDEEDMDDVVDADEYLIPQQGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTEDSID

--------------------------------------------------------------

>27211_27211_2_ERBB3-EGFR_ERBB3_chr12_56492359_ENST00000415288_EGFR_chr7_55266410_ENST00000455089_length(amino acids)=1119AA_BP=33
MKKEIFSPSHSWNVCPGTLNGLSVTGDAENQYQTLYKLYERCEVVMGNLEIVLTGHNADLSFLQWIREVTGYVLVAMNEFSTLPLPNLRV
VRGTQVYDGKFAIFVMLNYNTNSSHALRQLRLTQLTEILSGGVYIEKNDKLCHMDTIDWRDIVRDRDAEIVVKDNGRSCPPCHEVCKGRC
WGPGSEDCQTLTKTICAPQCNGHCFGPNPNQCCHDECAGGCSGPQDTDCFACRHFNDSGACVPRCPQPLVYNKLTFQLEPNPHTKYQYGG
VCVASCPHNFVVDQTSCVRACPPDKMEVDKNGLKMCEPCGGLCPKACEGTGSGSRFQTVDSSNIDGFVNCTKILGNLDFLITGLNGDPWH
KIPALDPEKLNVFRTVREITGYLNIQSWPPHMHNFSVFSNLTTIGGRSLYNRGFSLLIMKNLNVTSLGFRSLKEISAGRIYISANRQLCY
HHSLNWTKVLRGPTEERLDIKHNRPRRDCVAEGKVCDPLCSSGGCWGPGPGQCLSCRNYSRGGVCVTHCNFLNGEPREFAHEAECFSCHP
ECQPMEGTATCNGSGSDTCAQCAHFRDGPHCVSSCPHGVLGAKGPIYKYPDVQNECRPCHENCTQGCKGPELQDCLGQTLVLIGKTHLTM
ALTVIAGLVVIFMMLGGTFLYWRGRRIQNKRAMRRYLERGESIEPLDPSEKANKVLARIFKETELRKLKVLGSGVFGTVHKGVWIPEGES
IKIPVCIKVIEDKSGRQSFQAVTDHMLAIGSLDHAHIVRLLGLCPGSSLQLVTQYLPLGSLLDHVRQHRGALGPQLLLNWGVQIAKGMYY
LEEHGMVHRNLAARNVLLKSPSQVQVADFGVADLLPPDDKQLLYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVTVWELMTFGSKPYDG
IPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSNFYRALMDEEDM
DDVVDADEYLIPQQGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTEDSIDDTFLPVPGEWLVWK

--------------------------------------------------------------

>27211_27211_3_ERBB3-EGFR_ERBB3_chr12_56492359_ENST00000450146_EGFR_chr7_55266410_ENST00000455089_length(amino acids)=556AA_BP=122
MGSLHPLRSHEGERRSAGAKGPIYKYPDVQNECRPCHENCTQGCKGPELQDCLGQTLVLIGKTHLTMALTVIAGLVVIFMMLGGTFLYWR
GRRIQNKRAMRRYLERGESIEPLDPSEKANKVLARIFKETELRKLKVLGSGVFGTVHKGVWIPEGESIKIPVCIKVIEDKSGRQSFQAVT
DHMLAIGSLDHAHIVRLLGLCPGSSLQLVTQYLPLGSLLDHVRQHRGALGPQLLLNWGVQIAKGMYYLEEHGMVHRNLAARNVLLKSPSQ
VQVADFGVADLLPPDDKQLLYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICT
IDVYMIMVKCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSNFYRALMDEEDMDDVVDADEYLIPQQGFFSSPSTS
RTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTEDSIDDTFLPVPGEWLVWKQSCSSTSSTHSAAASLQCPSQVL

--------------------------------------------------------------

>27211_27211_4_ERBB3-EGFR_ERBB3_chr12_56492359_ENST00000553131_EGFR_chr7_55266410_ENST00000455089_length(amino acids)=458AA_BP=24
MSNSFPFAPQSIEPLDPSEKANKVLARIFKETELRKLKVLGSGVFGTVHKGVWIPEGESIKIPVCIKVIEDKSGRQSFQAVTDHMLAIGS
LDHAHIVRLLGLCPGSSLQLVTQYLPLGSLLDHVRQHRGALGPQLLLNWGVQIAKGMYYLEEHGMVHRNLAARNVLLKSPSQVQVADFGV
ADLLPPDDKQLLYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMV
KCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSNFYRALMDEEDMDDVVDADEYLIPQQGFFSSPSTSRTPLLSSL
SATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTEDSIDDTFLPVPGEWLVWKQSCSSTSSTHSAAASLQCPSQVLPPASPEGE

--------------------------------------------------------------

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Fusion Protein Functional Features

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr12:56492359/chr7:55266410)
- 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.

Main function of each fusion partner protein. (from UniProt)

Hgene	Tgene
ERBB3 P21860	EGFR P00533
FUNCTION: Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. Binds to neuregulin-1 (NRG1) and is activated by it; ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase (PubMed:20682778). May also be activated by CSPG5 (PubMed:15358134). Involved in the regulation of myeloid cell differentiation (PubMed:27416908). {ECO:0000269\|PubMed:15358134, ECO:0000269\|PubMed:20682778, ECO:0000269\|PubMed:27416908}.	FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:2790960, PubMed:10805725, PubMed:27153536). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975, PubMed:15611079, PubMed:12297049, PubMed:27153536, PubMed:20837704, PubMed:17909029). Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules (PubMed:27153536). May also activate the NF-kappa-B signaling cascade (PubMed:11116146). Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling (PubMed:11602604). Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589). Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (PubMed:20462955). Plays a role in enhancing learning and memory performance (By similarity). {ECO:0000250\|UniProtKB:Q01279, ECO:0000269\|PubMed:10805725, ECO:0000269\|PubMed:11116146, ECO:0000269\|PubMed:11483589, ECO:0000269\|PubMed:11602604, ECO:0000269\|PubMed:12297049, ECO:0000269\|PubMed:12297050, ECO:0000269\|PubMed:12620237, ECO:0000269\|PubMed:12873986, ECO:0000269\|PubMed:15374980, ECO:0000269\|PubMed:15590694, ECO:0000269\|PubMed:15611079, ECO:0000269\|PubMed:17115032, ECO:0000269\|PubMed:17909029, ECO:0000269\|PubMed:19560417, ECO:0000269\|PubMed:20462955, ECO:0000269\|PubMed:20837704, ECO:0000269\|PubMed:21258366, ECO:0000269\|PubMed:27153536, ECO:0000269\|PubMed:2790960, ECO:0000269\|PubMed:7679104, ECO:0000269\|PubMed:8144591, ECO:0000269\|PubMed:9419975}.; FUNCTION: Isoform 2 may act as an antagonist of EGF action.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269\|PubMed:21516087}.

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, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at
download page
* Minus value of BPloci means that the break pointn is located before the CDS.

- Retained protein feature among the 13 regional features.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000267101

715_723

897.3333333333334

1343.0

Nucleotide binding

Note=ATP

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000267101

788_790

897.3333333333334

1343.0

Nucleotide binding

Note=ATP

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000267101

834_839

897.3333333333334

1343.0

Nucleotide binding

Note=ATP

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000415288

715_723

838.3333333333334

1284.0

Nucleotide binding

Note=ATP

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000415288

788_790

838.3333333333334

1284.0

Nucleotide binding

Note=ATP

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000415288

834_839

838.3333333333334

1284.0

Nucleotide binding

Note=ATP

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000267101

20_643

897.3333333333334

1343.0

Topological domain

Extracellular

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000415288

20_643

838.3333333333334

1284.0

Topological domain

Extracellular

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000267101

644_664

897.3333333333334

1343.0

Transmembrane

Helical

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000415288

644_664

838.3333333333334

1284.0

Transmembrane

Helical

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000342916

712_979

629.0

Domain

Protein kinase

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000344576

712_979

706.0

Domain

Protein kinase

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000420316

712_979

406.0

Domain

Protein kinase

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000342916

718_726

629.0

Nucleotide binding

ATP

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000342916

790_791

629.0

Nucleotide binding

ATP

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000344576

718_726

706.0

Nucleotide binding

ATP

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000344576

790_791

706.0

Nucleotide binding

ATP

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000420316

718_726

406.0

Nucleotide binding

ATP

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000420316

790_791

406.0

Nucleotide binding

ATP

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000342916

688_704

629.0

Region

Note=Important for dimerization%2C phosphorylation and activation

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000344576

688_704

706.0

Region

Note=Important for dimerization%2C phosphorylation and activation

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000420316

688_704

406.0

Region

Note=Important for dimerization%2C phosphorylation and activation

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000342916

390_600

629.0

Repeat

Note=Approximate

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000342916

75_300

629.0

Repeat

Note=Approximate

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000344576

390_600

706.0

Repeat

Note=Approximate

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000344576

75_300

706.0

Repeat

Note=Approximate

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000420316

390_600

406.0

Repeat

Note=Approximate

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000420316

75_300

406.0

Repeat

Note=Approximate

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000342916

25_645

629.0

Topological domain

Extracellular

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000342916

669_1210

629.0

Topological domain

Cytoplasmic

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000344576

25_645

706.0

Topological domain

Extracellular

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000344576

669_1210

706.0

Topological domain

Cytoplasmic

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000420316

25_645

406.0

Topological domain

Extracellular

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000420316

669_1210

406.0

Topological domain

Cytoplasmic

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000342916

646_668

629.0

Transmembrane

Helical

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000344576

646_668

706.0

Transmembrane

Helical

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000420316

646_668

406.0

Transmembrane

Helical

- Not-retained protein feature among the 13 regional features.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000267101

709_966

897.3333333333334

1343.0

Domain

Protein kinase

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000411731

709_966

184.0

Domain

Protein kinase

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000415288

709_966

838.3333333333334

1284.0

Domain

Protein kinase

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000450146

709_966

254.33333333333334

700.0

Domain

Protein kinase

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000411731

715_723

184.0

Nucleotide binding

Note=ATP

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000411731

788_790

184.0

Nucleotide binding

Note=ATP

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000411731

834_839

184.0

Nucleotide binding

Note=ATP

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000450146

715_723

254.33333333333334

700.0

Nucleotide binding

Note=ATP

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000450146

788_790

254.33333333333334

700.0

Nucleotide binding

Note=ATP

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000450146

834_839

254.33333333333334

700.0

Nucleotide binding

Note=ATP

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000267101

665_1342

897.3333333333334

1343.0

Topological domain

Cytoplasmic

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000411731

20_643

184.0

Topological domain

Extracellular

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000411731

665_1342

184.0

Topological domain

Cytoplasmic

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000415288

665_1342

838.3333333333334

1284.0

Topological domain

Cytoplasmic

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000450146

20_643

254.33333333333334

700.0

Topological domain

Extracellular

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000450146

665_1342

254.33333333333334

700.0

Topological domain

Cytoplasmic

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000411731

644_664

184.0

Transmembrane

Helical

Hgene

ERBB3

chr12:56492359

chr7:55266410

ENST00000450146

644_664

254.33333333333334

700.0

Transmembrane

Helical

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000275493

712_979

900.3333333333334

1211.0

Domain

Protein kinase

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000275493

718_726

900.3333333333334

1211.0

Nucleotide binding

ATP

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000275493

790_791

900.3333333333334

1211.0

Nucleotide binding

ATP

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000275493

688_704

900.3333333333334

1211.0

Region

Note=Important for dimerization%2C phosphorylation and activation

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000275493

390_600

900.3333333333334

1211.0

Repeat

Note=Approximate

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000275493

75_300

900.3333333333334

1211.0

Repeat

Note=Approximate

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000275493

25_645

900.3333333333334

1211.0

Topological domain

Extracellular

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000275493

669_1210

900.3333333333334

1211.0

Topological domain

Cytoplasmic

Tgene

EGFR

chr12:56492359

chr7:55266410

ENST00000275493

646_668

900.3333333333334

1211.0

Transmembrane

Helical

Top

Fusion Protein Structures

PDB and CIF files of the predicted fusion proteins
* Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.

Fusion protein PDB link (fusion AA seq ID in FusionPDB)	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	AA seq	Len(AA seq)
PDB file >>>1879_ERBB3_56492359_EGFR_55266410_ranked_0.pdb	ERBB3	56492359	56492359	ENST00000455089	EGFR	chr7	55266410	+	MRANDALQVLGLLFSLARGSEVGNSQAVCPGTLNGLSVTGDAENQYQTLYKLYERCEVVMGNLEIVLTGHNADLSFLQWIREVTGYVLVA MNEFSTLPLPNLRVVRGTQVYDGKFAIFVMLNYNTNSSHALRQLRLTQLTEILSGGVYIEKNDKLCHMDTIDWRDIVRDRDAEIVVKDNG RSCPPCHEVCKGRCWGPGSEDCQTLTKTICAPQCNGHCFGPNPNQCCHDECAGGCSGPQDTDCFACRHFNDSGACVPRCPQPLVYNKLTF QLEPNPHTKYQYGGVCVASCPHNFVVDQTSCVRACPPDKMEVDKNGLKMCEPCGGLCPKACEGTGSGSRFQTVDSSNIDGFVNCTKILGN LDFLITGLNGDPWHKIPALDPEKLNVFRTVREITGYLNIQSWPPHMHNFSVFSNLTTIGGRSLYNRGFSLLIMKNLNVTSLGFRSLKEIS AGRIYISANRQLCYHHSLNWTKVLRGPTEERLDIKHNRPRRDCVAEGKVCDPLCSSGGCWGPGPGQCLSCRNYSRGGVCVTHCNFLNGEP REFAHEAECFSCHPECQPMEGTATCNGSGSDTCAQCAHFRDGPHCVSSCPHGVLGAKGPIYKYPDVQNECRPCHENCTQGCKGPELQDCL GQTLVLIGKTHLTMALTVIAGLVVIFMMLGGTFLYWRGRRIQNKRAMRRYLERGESIEPLDPSEKANKVLARIFKETELRKLKVLGSGVF GTVHKGVWIPEGESIKIPVCIKVIEDKSGRQSFQAVTDHMLAIGSLDHAHIVRLLGLCPGSSLQLVTQYLPLGSLLDHVRQHRGALGPQL LLNWGVQIAKGMYYLEEHGMVHRNLAARNVLLKSPSQVQVADFGVADLLPPDDKQLLYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVT VWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQGDERMHLPSPT DSNFYRALMDEEDMDDVVDADEYLIPQQGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTEDSID	1133

Top

pLDDT score distribution

pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

ERBB3_pLDDT.png

EGFR_pLDDT.png

pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

Top

Ramachandran Plot of Fusion Protein Structure

Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.

Fusion AA seq ID in FusionPDB and their Ramachandran plots

Top

Fusion Protein-Protein Interaction

Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in
ChiPPI page.

Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160)

Gene

PPI interactors

Protein-protein interactors based on sequence similarity (STRING)

Gene	STRING network
ERBB3
EGFR

- Retained interactions in fusion protein (protein functional feature from UniProt).

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Still interaction with

- Lost interactions due to fusion (protein functional feature from UniProt).

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

Top

Related Drugs to ERBB3-EGFR

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

Hgene

Tgene

Drug

Source

PMID

Top

Related Diseases to ERBB3-EGFR

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