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Fusion Protein:HSP90AB1-MYH11

Fusion Gene and Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: HSP90AB1-MYH11
	FusionPDB ID: 37804
	FusionGDB2.0 ID: 37804
		Hgene	Tgene
	Gene symbol	HSP90AB1	MYH11
	Gene ID	3326	4629
	Gene name	heat shock protein 90 alpha family class B member 1	myosin heavy chain 11
	Synonyms	D6S182\|HSP84\|HSP90B\|HSPC2\|HSPCB	AAT4\|FAA4\|SMHC\|SMMHC
	Cytomap	6p21.1	16p13.11
	Type of gene	protein-coding	protein-coding
	Description	heat shock protein HSP 90-betaHSP90-betaheat shock 84 kDaheat shock 90kD protein 1, betaheat shock protein 90 kDaheat shock protein 90kDa alpha (cytosolic), class B member 1heat shock protein 90kDa alpha family class B member 1	myosin-11epididymis secretory sperm binding proteinmyosin heavy chain, smooth muscle isoformmyosin, heavy chain 11, smooth musclemyosin, heavy polypeptide 11, smooth muscle
	Modification date	20200327	20200322
	UniProtAcc	P08238 Main function of 5'-partner protein: FUNCTION: Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:16478993, PubMed:19696785). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:27295069, PubMed:26991466). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. They first alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery (PubMed:18239673). Main chaperone involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription (PubMed:20353823). Involved in the translocation into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269\|PubMed:16478993, ECO:0000269\|PubMed:18239673, ECO:0000269\|PubMed:19696785, ECO:0000269\|PubMed:20353823, ECO:0000269\|PubMed:24613385, ECO:0000269\|PubMed:32272059, ECO:0000303\|PubMed:25973397, ECO:0000303\|PubMed:26991466, ECO:0000303\|PubMed:27295069}.	P35749 Main function of 5'-partner protein: FUNCTION: Muscle contraction.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000353801, ENST00000371554, ENST00000371646,	ENST00000573908, ENST00000300036, ENST00000396324, ENST00000452625, ENST00000576790,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	20 X 20 X 7=2800	44 X 55 X 10=24200
	# samples	22	62
	** MAII score	log2(22/2800*10)=-3.66985139830767 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(62/24200*10)=-5.28659502177508 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Fusion gene context	PubMed: HSP90AB1 [Title/Abstract] AND MYH11 [Title/Abstract] AND fusion [Title/Abstract]
Fusion neoantigen context	PubMed: HSP90AB1 [Title/Abstract] AND MYH11 [Title/Abstract] AND neoantigen [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	HSP90AB1(44218074)-MYH11(15815477), # samples:1
Anticipated loss of major functional domain due to fusion event.	HSP90AB1-MYH11 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. HSP90AB1-MYH11 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. HSP90AB1-MYH11 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. HSP90AB1-MYH11 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	HSP90AB1	GO:0007004	telomere maintenance via telomerase	10197982
Hgene	HSP90AB1	GO:0030511	positive regulation of transforming growth factor beta receptor signaling pathway	24613385
Hgene	HSP90AB1	GO:0031396	regulation of protein ubiquitination	16809764
Hgene	HSP90AB1	GO:0032435	negative regulation of proteasomal ubiquitin-dependent protein catabolic process	24613385
Hgene	HSP90AB1	GO:0032516	positive regulation of phosphoprotein phosphatase activity	26593036
Hgene	HSP90AB1	GO:0051131	chaperone-mediated protein complex assembly	10811660
Hgene	HSP90AB1	GO:0051973	positive regulation of telomerase activity	10197982
Hgene	HSP90AB1	GO:1901389	negative regulation of transforming growth factor beta activation	20599762
Hgene	HSP90AB1	GO:1905323	telomerase holoenzyme complex assembly	10197982
Hgene	HSP90AB1	GO:2000010	positive regulation of protein localization to cell surface	23431407

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr6:44218074/chr16:15815477)
- 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 HSP90AB1 (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 MYH11 (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)
ENST00000353801	HSP90AB1	chr6	44218074	+	ENST00000396324	MYH11	chr16	15815477	-	3391	1032	2796	1906	296
ENST00000353801	HSP90AB1	chr6	44218074	+	ENST00000452625	MYH11	chr16	15815477	-	3430	1032	2835	1906	309
ENST00000353801	HSP90AB1	chr6	44218074	+	ENST00000576790	MYH11	chr16	15815477	-	2815	1032	2231	1173	352
ENST00000353801	HSP90AB1	chr6	44218074	+	ENST00000300036	MYH11	chr16	15815477	-	2572	1032	1988	918	356
ENST00000371646	HSP90AB1	chr6	44218074	+	ENST00000396324	MYH11	chr16	15815477	-	3378	1019	2783	1893	296
ENST00000371646	HSP90AB1	chr6	44218074	+	ENST00000452625	MYH11	chr16	15815477	-	3417	1019	2822	1893	309
ENST00000371646	HSP90AB1	chr6	44218074	+	ENST00000576790	MYH11	chr16	15815477	-	2802	1019	2218	1160	352
ENST00000371646	HSP90AB1	chr6	44218074	+	ENST00000300036	MYH11	chr16	15815477	-	2559	1019	1975	905	356
ENST00000371554	HSP90AB1	chr6	44218074	+	ENST00000396324	MYH11	chr16	15815477	-	3483	1124	2888	1998	296
ENST00000371554	HSP90AB1	chr6	44218074	+	ENST00000452625	MYH11	chr16	15815477	-	3522	1124	2927	1998	309
ENST00000371554	HSP90AB1	chr6	44218074	+	ENST00000576790	MYH11	chr16	15815477	-	2907	1124	2323	1265	352
ENST00000371554	HSP90AB1	chr6	44218074	+	ENST00000300036	MYH11	chr16	15815477	-	2664	1124	2080	1010	356

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
ENST00000353801	ENST00000396324	HSP90AB1	chr6	44218074	+	MYH11	chr16	15815477	-	0.004085081	0.9959149
ENST00000353801	ENST00000452625	HSP90AB1	chr6	44218074	+	MYH11	chr16	15815477	-	0.001415774	0.9985843
ENST00000353801	ENST00000576790	HSP90AB1	chr6	44218074	+	MYH11	chr16	15815477	-	0.001248787	0.99875116
ENST00000353801	ENST00000300036	HSP90AB1	chr6	44218074	+	MYH11	chr16	15815477	-	0.003294026	0.99670595
ENST00000371646	ENST00000396324	HSP90AB1	chr6	44218074	+	MYH11	chr16	15815477	-	0.004101263	0.99589866
ENST00000371646	ENST00000452625	HSP90AB1	chr6	44218074	+	MYH11	chr16	15815477	-	0.001440065	0.9985599
ENST00000371646	ENST00000576790	HSP90AB1	chr6	44218074	+	MYH11	chr16	15815477	-	0.00149371	0.99850625
ENST00000371646	ENST00000300036	HSP90AB1	chr6	44218074	+	MYH11	chr16	15815477	-	0.002904587	0.99709547
ENST00000371554	ENST00000396324	HSP90AB1	chr6	44218074	+	MYH11	chr16	15815477	-	0.003949659	0.9960503
ENST00000371554	ENST00000452625	HSP90AB1	chr6	44218074	+	MYH11	chr16	15815477	-	0.001294425	0.9987056
ENST00000371554	ENST00000576790	HSP90AB1	chr6	44218074	+	MYH11	chr16	15815477	-	0.001448386	0.99855155
ENST00000371554	ENST00000300036	HSP90AB1	chr6	44218074	+	MYH11	chr16	15815477	-	0.00282304	0.997177

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 HSP90AB1-MYH11

+/-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
HSP90AB1	chr6	44218074	MYH11	chr16	15815477	1019	36	GHLPALFESPSSEPSRQATGQLLCQF
HSP90AB1	chr6	44218074	MYH11	chr16	15815477	1032	36	GHLPALFESPSSEPSRQATGQLLCQF
HSP90AB1	chr6	44218074	MYH11	chr16	15815477	1124	36	GHLPALFESPSSEPSRQATGQLLCQF

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Potential FusionNeoAntigen Information of HSP90AB1-MYH11 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 HSP90AB1-MYH11 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 HSP90AB1-MYH11

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 HSP90AB1-MYH11

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 HSP90AB1-MYH11

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 HSP90AB1-MYH11

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 HSP90AB1-MYH11

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 HSP90AB1-MYH11

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 HSP90AB1-MYH11

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
Tgene	MYH11	C4707243	Familial thoracic aortic aneurysm and aortic dissection	10	CLINGEN;GENOMICS_ENGLAND
Tgene	MYH11	C0023467	Leukemia, Myelocytic, Acute	2	CTD_human
Tgene	MYH11	C0023479	Acute myelomonocytic leukemia	2	CTD_human;ORPHANET
Tgene	MYH11	C0026998	Acute Myeloid Leukemia, M1	2	CTD_human
Tgene	MYH11	C1851504	Aortic aneurysm, familial thoracic 4	2	CTD_human;GENOMICS_ENGLAND;UNIPROT
Tgene	MYH11	C1879321	Acute Myeloid Leukemia (AML-M2)	2	CTD_human
Tgene	MYH11	C1608393	Megacystis microcolon intestinal hypoperistalsis syndrome	1	GENOMICS_ENGLAND;ORPHANET

	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)