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Fusion Protein:MED24-ERBB2

Fusion Gene and Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: MED24-ERBB2
	FusionPDB ID: 52711
	FusionGDB2.0 ID: 52711
		Hgene	Tgene
	Gene symbol	MED24	ERBB2
	Gene ID	9862	2064
	Gene name	mediator complex subunit 24	erb-b2 receptor tyrosine kinase 2
	Synonyms	ARC100\|CRSP100\|CRSP4\|DRIP100\|MED5\|THRAP4\|TRAP100	CD340\|HER-2\|HER-2/neu\|HER2\|MLN 19\|NEU\|NGL\|TKR1
	Cytomap	17q21.1	17q12
	Type of gene	protein-coding	protein-coding
	Description	mediator of RNA polymerase II transcription subunit 24CRSP complex subunit 4activator-recruited cofactor 100 kDa componentcofactor required for Sp1 transcriptional activation subunit 4cofactor required for Sp1 transcriptional activation, subunit 4, 10	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
	Modification date	20200313	20200329
	UniProtAcc	O75448 Main function of 5'-partner protein: FUNCTION: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. {ECO:0000269\|PubMed:12218053, ECO:0000269\|PubMed:16595664}.	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	ENST00000356271, ENST00000394126, ENST00000394127, ENST00000394128, ENST00000501516, ENST00000479829,	ENST00000269571, ENST00000445658, ENST00000540042, ENST00000540147, ENST00000578199, ENST00000584450, ENST00000584888, ENST00000406381, ENST00000541774, ENST00000584601,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	21 X 18 X 9=3402	34 X 40 X 10=13600
	# samples	26	43
	** MAII score	log2(26/3402*10)=-3.70979961263493 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(43/13600*10)=-4.9831261814356 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Fusion gene context	PubMed: MED24 [Title/Abstract] AND ERBB2 [Title/Abstract] AND fusion [Title/Abstract]
Fusion neoantigen context	PubMed: MED24 [Title/Abstract] AND ERBB2 [Title/Abstract] AND neoantigen [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	MED24(38188901)-ERBB2(37868574), # samples:1 MED24(38185078)-ERBB2(37865570), # samples:1
Anticipated loss of major functional domain due to fusion event.	MED24-ERBB2 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. MED24-ERBB2 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. MED24-ERBB2 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. MED24-ERBB2 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. MED24-ERBB2 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF. MED24-ERBB2 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. MED24-ERBB2 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF. MED24-ERBB2 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. MED24-ERBB2 seems lost the major protein functional domain in Tgene partner, which is a kinase due to the frame-shifted 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	MED24	GO:0006367	transcription initiation from RNA polymerase II promoter	12218053
Hgene	MED24	GO:0045893	positive regulation of transcription, DNA-templated	10198638
Tgene	ERBB2	GO:0007165	signal transduction	10572067
Tgene	ERBB2	GO:0007166	cell surface receptor signaling pathway	9685399
Tgene	ERBB2	GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway	7514177
Tgene	ERBB2	GO:0014065	phosphatidylinositol 3-kinase signaling	7556068
Tgene	ERBB2	GO:0018108	peptidyl-tyrosine phosphorylation	12000754
Tgene	ERBB2	GO:0032886	regulation of microtubule-based process	20937854
Tgene	ERBB2	GO:0035556	intracellular signal transduction	19372587
Tgene	ERBB2	GO:0042060	wound healing	12646923
Tgene	ERBB2	GO:0043406	positive regulation of MAP kinase activity	10572067
Tgene	ERBB2	GO:0045785	positive regulation of cell adhesion	7556068
Tgene	ERBB2	GO:0046777	protein autophosphorylation	7556068
Tgene	ERBB2	GO:0050679	positive regulation of epithelial cell proliferation	10572067
Tgene	ERBB2	GO:0071363	cellular response to growth factor stimulus	20010870
Tgene	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/chr17:38188901/chr17:37868574)
- 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 MED24 (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 ERBB2 (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)
ENST00000356271	MED24	chr17	38188901	-	ENST00000584601	ERBB2	chr17	37868574	+	4045	981	992	3727	911
ENST00000356271	MED24	chr17	38188901	-	ENST00000406381	ERBB2	chr17	37868574	+	4346	981	992	3727	911
ENST00000356271	MED24	chr17	38188901	-	ENST00000541774	ERBB2	chr17	37868574	+	4346	981	992	3727	911
ENST00000356271	MED24	chr17	38188901	-	ENST00000445658	ERBB2	chr17	37868574	+	3763	981	992	3727	911
ENST00000356271	MED24	chr17	38188901	-	ENST00000540147	ERBB2	chr17	37868574	+	4346	981	992	3727	911
ENST00000356271	MED24	chr17	38188901	-	ENST00000584450	ERBB2	chr17	37868574	+	3475	981	992	3127	711
ENST00000356271	MED24	chr17	38188901	-	ENST00000269571	ERBB2	chr17	37868574	+	4346	981	992	3727	911
ENST00000356271	MED24	chr17	38188901	-	ENST00000578199	ERBB2	chr17	37868574	+	2035	981	60	1019	319
ENST00000356271	MED24	chr17	38188901	-	ENST00000540042	ERBB2	chr17	37868574	+	2031	981	60	1019	319
ENST00000394128	MED24	chr17	38188901	-	ENST00000584601	ERBB2	chr17	37868574	+	4082	1018	1029	3764	911
ENST00000394128	MED24	chr17	38188901	-	ENST00000406381	ERBB2	chr17	37868574	+	4383	1018	1029	3764	911
ENST00000394128	MED24	chr17	38188901	-	ENST00000541774	ERBB2	chr17	37868574	+	4383	1018	1029	3764	911
ENST00000394128	MED24	chr17	38188901	-	ENST00000445658	ERBB2	chr17	37868574	+	3800	1018	1029	3764	911
ENST00000394128	MED24	chr17	38188901	-	ENST00000540147	ERBB2	chr17	37868574	+	4383	1018	1029	3764	911
ENST00000394128	MED24	chr17	38188901	-	ENST00000584450	ERBB2	chr17	37868574	+	3512	1018	1029	3164	711
ENST00000394128	MED24	chr17	38188901	-	ENST00000269571	ERBB2	chr17	37868574	+	4383	1018	1029	3764	911
ENST00000394128	MED24	chr17	38188901	-	ENST00000578199	ERBB2	chr17	37868574	+	2072	1018	58	1056	332
ENST00000394128	MED24	chr17	38188901	-	ENST00000540042	ERBB2	chr17	37868574	+	2068	1018	58	1056	332
ENST00000394127	MED24	chr17	38185078	-	ENST00000584601	ERBB2	chr17	37865570	+	5120	1474	1479	4802	1107
ENST00000394127	MED24	chr17	38185078	-	ENST00000406381	ERBB2	chr17	37865570	+	5421	1474	1479	4802	1107
ENST00000394127	MED24	chr17	38185078	-	ENST00000541774	ERBB2	chr17	37865570	+	5421	1474	1479	4802	1107

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
ENST00000356271	ENST00000584601	MED24	chr17	38188901	-	ERBB2	chr17	37868574	+	0.006543724	0.9934563
ENST00000356271	ENST00000406381	MED24	chr17	38188901	-	ERBB2	chr17	37868574	+	0.004708974	0.995291
ENST00000356271	ENST00000541774	MED24	chr17	38188901	-	ERBB2	chr17	37868574	+	0.004708974	0.995291
ENST00000356271	ENST00000445658	MED24	chr17	38188901	-	ERBB2	chr17	37868574	+	0.00693583	0.9930642
ENST00000356271	ENST00000540147	MED24	chr17	38188901	-	ERBB2	chr17	37868574	+	0.004708974	0.995291
ENST00000356271	ENST00000584450	MED24	chr17	38188901	-	ERBB2	chr17	37868574	+	0.018613847	0.9813861
ENST00000356271	ENST00000269571	MED24	chr17	38188901	-	ERBB2	chr17	37868574	+	0.004708974	0.995291
ENST00000356271	ENST00000578199	MED24	chr17	38188901	-	ERBB2	chr17	37868574	+	0.050301667	0.94969827
ENST00000356271	ENST00000540042	MED24	chr17	38188901	-	ERBB2	chr17	37868574	+	0.051356867	0.9486431
ENST00000394128	ENST00000584601	MED24	chr17	38188901	-	ERBB2	chr17	37868574	+	0.006219683	0.9937803
ENST00000394128	ENST00000406381	MED24	chr17	38188901	-	ERBB2	chr17	37868574	+	0.00453286	0.99546707
ENST00000394128	ENST00000541774	MED24	chr17	38188901	-	ERBB2	chr17	37868574	+	0.00453286	0.99546707
ENST00000394128	ENST00000445658	MED24	chr17	38188901	-	ERBB2	chr17	37868574	+	0.00657859	0.9934214
ENST00000394128	ENST00000540147	MED24	chr17	38188901	-	ERBB2	chr17	37868574	+	0.00453286	0.99546707
ENST00000394128	ENST00000584450	MED24	chr17	38188901	-	ERBB2	chr17	37868574	+	0.01705661	0.9829434
ENST00000394128	ENST00000269571	MED24	chr17	38188901	-	ERBB2	chr17	37868574	+	0.00453286	0.99546707
ENST00000394128	ENST00000578199	MED24	chr17	38188901	-	ERBB2	chr17	37868574	+	0.057326313	0.9426737
ENST00000394128	ENST00000540042	MED24	chr17	38188901	-	ERBB2	chr17	37868574	+	0.05824936	0.94175065
ENST00000394127	ENST00000584601	MED24	chr17	38185078	-	ERBB2	chr17	37865570	+	0.010891314	0.9891087
ENST00000394127	ENST00000406381	MED24	chr17	38185078	-	ERBB2	chr17	37865570	+	0.008162095	0.9918379
ENST00000394127	ENST00000541774	MED24	chr17	38185078	-	ERBB2	chr17	37865570	+	0.008162095	0.9918379

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 MED24-ERBB2

+/-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 MED24-ERBB2 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 MED24-ERBB2 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 MED24-ERBB2

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 MED24-ERBB2

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 MED24-ERBB2

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 MED24-ERBB2

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 MED24-ERBB2

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

Tgene

ERBB2

chr17:38185078

chr17:37865570

ENST00000269571

653_675

1256.0

Transmembrane

Helical

Tgene

ERBB2

chr17:38185078

chr17:37865570

ENST00000541774

653_675

1241.0

Transmembrane

Helical

Tgene

ERBB2

chr17:38188901

chr17:37868574

ENST00000269571

653_675

1256.0

Transmembrane

Helical

Tgene

ERBB2

chr17:38188901

chr17:37868574

ENST00000541774

653_675

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 MED24-ERBB2

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 MED24-ERBB2

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)