UTHEALTH HOME    ABOUT SBMI    A-Z    WEBMAIL    INSIDE THE UNIVERSITY
FusionGDB Logo

Home

Download

Statistics

Examples

Help

Contact

Terms of Use

Center for Computational Systems Medicine level1
leaf

Fusion Gene Summary

leaf

Fusion Gene Sample Information

leaf

Fusion ORF Analysis

leaf

Fusion Amino Acid Sequences

leaf

Fusion Protein Functional Features

leaf

Fusion Protein-Protein Interaction

leaf

Related drugs with this fusion protein

leaf

Related disease with this fusion protein

Fusion Protein:HSP90AB1-MKL2

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: HSP90AB1-MKL2
FusionPDB ID: 37802
FusionGDB2.0 ID: 37802
HgeneTgene
Gene symbol

HSP90AB1

MKL2

Gene ID

3326

57496

Gene nameheat shock protein 90 alpha family class B member 1myocardin related transcription factor B
SynonymsD6S182|HSP84|HSP90B|HSPC2|HSPCBMKL2|MRTF-B|NPD001
Cytomap

6p21.1

16p13.12

Type of geneprotein-codingprotein-coding
Descriptionheat 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 1myocardin-related transcription factor BCTA-276F8.1MKL and myocardin family member 2MKL/myocardin like 2MKL/myocardin-like protein 2MKL1/myocardin like 2megakaryoblastic leukemia 2
Modification date2020032720200313
UniProtAcc

P08238

.
Ensembl transtripts involved in fusion geneENST idsENST00000353801, ENST00000371554, 
ENST00000371646, 
ENST00000341243, 
ENST00000572567, ENST00000573051, 
ENST00000575537, ENST00000571589, 
ENST00000574045, ENST00000318282, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score20 X 20 X 7=280010 X 10 X 6=600
# samples 2210
** MAII scorelog2(22/2800*10)=-3.66985139830767
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/600*10)=-2.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: HSP90AB1 [Title/Abstract] AND MKL2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)HSP90AB1(44220004)-MKL2(14354765), # samples:1
Anticipated loss of major functional domain due to fusion event.HSP90AB1-MKL2 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-MKL2 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-MKL2 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-MKL2 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-MKL2 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
HSP90AB1-MKL2 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target 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)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneHSP90AB1

GO:0007004

telomere maintenance via telomerase

10197982

HgeneHSP90AB1

GO:0030511

positive regulation of transforming growth factor beta receptor signaling pathway

24613385

HgeneHSP90AB1

GO:0031396

regulation of protein ubiquitination

16809764

HgeneHSP90AB1

GO:0032435

negative regulation of proteasomal ubiquitin-dependent protein catabolic process

24613385

HgeneHSP90AB1

GO:0032516

positive regulation of phosphoprotein phosphatase activity

26593036

HgeneHSP90AB1

GO:0051131

chaperone-mediated protein complex assembly

10811660

HgeneHSP90AB1

GO:0051973

positive regulation of telomerase activity

10197982

HgeneHSP90AB1

GO:1901389

negative regulation of transforming growth factor beta activation

20599762

HgeneHSP90AB1

GO:1905323

telomerase holoenzyme complex assembly

10197982

HgeneHSP90AB1

GO:2000010

positive regulation of protein localization to cell surface

23431407

TgeneMKL2

GO:0045844

positive regulation of striated muscle tissue development

14565952

TgeneMKL2

GO:0045944

positive regulation of transcription by RNA polymerase II

14565952


check buttonFusion 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.
all structure

check buttonFusion gene breakpoints across MKL2 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


Top

Fusion Gene Sample Information

check buttonFusion gene information from FusionGDB2.0.
check button 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.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4ESCATCGA-L5-A88THSP90AB1chr6

44220004

+MKL2chr16

14354765

+


Top

Fusion ORF Analysis


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000353801HSP90AB1chr644220004+ENST00000318282MKL2chr1614354765+771718531221870582
ENST00000371646HSP90AB1chr644220004+ENST00000318282MKL2chr1614354765+77041840731857594
ENST00000371554HSP90AB1chr644220004+ENST00000318282MKL2chr1614354765+780919452141962582

check buttonDeepORF 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.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000353801ENST00000318282HSP90AB1chr644220004+MKL2chr1614354765+0.0003937150.9996063
ENST00000371646ENST00000318282HSP90AB1chr644220004+MKL2chr1614354765+0.0003979790.999602
ENST00000371554ENST00000318282HSP90AB1chr644220004+MKL2chr1614354765+0.0003649080.9996351

Top

Fusion Amino Acid Sequences


check button 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

>37802_37802_1_HSP90AB1-MKL2_HSP90AB1_chr6_44220004_ENST00000353801_MKL2_chr16_14354765_ENST00000318282_length(amino acids)=582AA_BP=
MPEEVHHGEEEVETFAFQAEIAQLMSLIINTFYSNKEIFLRELISNASDALDKIRYESLTDPSKLDSGKELKIDIIPNPQERTLTLVDTG
IGMTKADLINNLGTIAKSGTKAFMEALQAGADISMIGQFGVGFYSAYLVAEKVVVITKHNDDEQYAWESSAGGSFTVRADHGEPIGRGTK
VILHLKEDQTEYLEERRVKEVVKKHSQFIGYPITLYLEKEREKEISDDEAEEEKGEKEEEDKDDEEKPKIEDVGSDEEDDSGKDKKKKTK
KIKEKYIDQEELNKTKPIWTRNPDDITQEEYGEFYKSLTNDWEDHLAVKHFSVEGQLEFRALLFIPRRAPFDLFENKKKKNNIKLYVRRV
FIMDSCDELIPEYLNFIRGVVDSEDLPLNISREMLQQSKILKVIRKNIVKKCLELFSELAEDKENYKKFYEAFSKNLKLGIHEDSTNRRR
LSELLRYHTSQSGDEMTSLSEYVSRMKETQKSIYYITGESKEQVANSAFVERVRKRGFEVVYMTEPIDEYCVQQLKEFDGKSLVSVTKEG

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

>37802_37802_2_HSP90AB1-MKL2_HSP90AB1_chr6_44220004_ENST00000371554_MKL2_chr16_14354765_ENST00000318282_length(amino acids)=582AA_BP=
MPEEVHHGEEEVETFAFQAEIAQLMSLIINTFYSNKEIFLRELISNASDALDKIRYESLTDPSKLDSGKELKIDIIPNPQERTLTLVDTG
IGMTKADLINNLGTIAKSGTKAFMEALQAGADISMIGQFGVGFYSAYLVAEKVVVITKHNDDEQYAWESSAGGSFTVRADHGEPIGRGTK
VILHLKEDQTEYLEERRVKEVVKKHSQFIGYPITLYLEKEREKEISDDEAEEEKGEKEEEDKDDEEKPKIEDVGSDEEDDSGKDKKKKTK
KIKEKYIDQEELNKTKPIWTRNPDDITQEEYGEFYKSLTNDWEDHLAVKHFSVEGQLEFRALLFIPRRAPFDLFENKKKKNNIKLYVRRV
FIMDSCDELIPEYLNFIRGVVDSEDLPLNISREMLQQSKILKVIRKNIVKKCLELFSELAEDKENYKKFYEAFSKNLKLGIHEDSTNRRR
LSELLRYHTSQSGDEMTSLSEYVSRMKETQKSIYYITGESKEQVANSAFVERVRKRGFEVVYMTEPIDEYCVQQLKEFDGKSLVSVTKEG

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

>37802_37802_3_HSP90AB1-MKL2_HSP90AB1_chr6_44220004_ENST00000371646_MKL2_chr16_14354765_ENST00000318282_length(amino acids)=594AA_BP=
MLTITYNPFLFKMPEEVHHGEEEVETFAFQAEIAQLMSLIINTFYSNKEIFLRELISNASDALDKIRYESLTDPSKLDSGKELKIDIIPN
PQERTLTLVDTGIGMTKADLINNLGTIAKSGTKAFMEALQAGADISMIGQFGVGFYSAYLVAEKVVVITKHNDDEQYAWESSAGGSFTVR
ADHGEPIGRGTKVILHLKEDQTEYLEERRVKEVVKKHSQFIGYPITLYLEKEREKEISDDEAEEEKGEKEEEDKDDEEKPKIEDVGSDEE
DDSGKDKKKKTKKIKEKYIDQEELNKTKPIWTRNPDDITQEEYGEFYKSLTNDWEDHLAVKHFSVEGQLEFRALLFIPRRAPFDLFENKK
KKNNIKLYVRRVFIMDSCDELIPEYLNFIRGVVDSEDLPLNISREMLQQSKILKVIRKNIVKKCLELFSELAEDKENYKKFYEAFSKNLK
LGIHEDSTNRRRLSELLRYHTSQSGDEMTSLSEYVSRMKETQKSIYYITGESKEQVANSAFVERVRKRGFEVVYMTEPIDEYCVQQLKEF

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

Top

Fusion Protein Functional Features


check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr6:44220004/chr16:14354765)
- 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.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
HSP90AB1

P08238

.
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}.FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.

check buttonRetention 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.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
TgeneMKL2chr6:44220004chr16:14354765ENST0000057305109545_6010379.0Coiled coilOntology_term=ECO:0000255
TgeneMKL2chr6:44220004chr16:14354765ENST0000057305109671_7870379.0Compositional biasNote=Gln-rich
TgeneMKL2chr6:44220004chr16:14354765ENST0000057305109389_4230379.0DomainSAP
TgeneMKL2chr6:44220004chr16:14354765ENST0000057305109128_1530379.0RepeatNote=RPEL 3
TgeneMKL2chr6:44220004chr16:14354765ENST000005730510940_650379.0RepeatNote=RPEL 1
TgeneMKL2chr6:44220004chr16:14354765ENST000005730510984_1090379.0RepeatNote=RPEL 2

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneHSP90AB1chr6:44220004chr16:14354765ENST00000353801+1012720_724577.0725.0MotifNote=TPR repeat-binding
HgeneHSP90AB1chr6:44220004chr16:14354765ENST00000371554+1012720_724577.0725.0MotifNote=TPR repeat-binding
HgeneHSP90AB1chr6:44220004chr16:14354765ENST00000371646+1012720_724577.0725.0MotifNote=TPR repeat-binding
TgeneMKL2chr6:44220004chr16:14354765ENST000003182821416545_601871.33333333333341050.0Coiled coilOntology_term=ECO:0000255
TgeneMKL2chr6:44220004chr16:14354765ENST000003412431315545_601910.33333333333341089.0Coiled coilOntology_term=ECO:0000255
TgeneMKL2chr6:44220004chr16:14354765ENST000005740451517545_601871.33333333333341050.0Coiled coilOntology_term=ECO:0000255
TgeneMKL2chr6:44220004chr16:14354765ENST000003182821416671_787871.33333333333341050.0Compositional biasNote=Gln-rich
TgeneMKL2chr6:44220004chr16:14354765ENST000003412431315671_787910.33333333333341089.0Compositional biasNote=Gln-rich
TgeneMKL2chr6:44220004chr16:14354765ENST000005740451517671_787871.33333333333341050.0Compositional biasNote=Gln-rich
TgeneMKL2chr6:44220004chr16:14354765ENST000003182821416389_423871.33333333333341050.0DomainSAP
TgeneMKL2chr6:44220004chr16:14354765ENST000003412431315389_423910.33333333333341089.0DomainSAP
TgeneMKL2chr6:44220004chr16:14354765ENST000005740451517389_423871.33333333333341050.0DomainSAP
TgeneMKL2chr6:44220004chr16:14354765ENST000003182821416128_153871.33333333333341050.0RepeatNote=RPEL 3
TgeneMKL2chr6:44220004chr16:14354765ENST00000318282141640_65871.33333333333341050.0RepeatNote=RPEL 1
TgeneMKL2chr6:44220004chr16:14354765ENST00000318282141684_109871.33333333333341050.0RepeatNote=RPEL 2
TgeneMKL2chr6:44220004chr16:14354765ENST000003412431315128_153910.33333333333341089.0RepeatNote=RPEL 3
TgeneMKL2chr6:44220004chr16:14354765ENST00000341243131540_65910.33333333333341089.0RepeatNote=RPEL 1
TgeneMKL2chr6:44220004chr16:14354765ENST00000341243131584_109910.33333333333341089.0RepeatNote=RPEL 2
TgeneMKL2chr6:44220004chr16:14354765ENST000005740451517128_153871.33333333333341050.0RepeatNote=RPEL 3
TgeneMKL2chr6:44220004chr16:14354765ENST00000574045151740_65871.33333333333341050.0RepeatNote=RPEL 1
TgeneMKL2chr6:44220004chr16:14354765ENST00000574045151784_109871.33333333333341050.0RepeatNote=RPEL 2


Top

Fusion Protein-Protein Interaction


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


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


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
HSP90AB1
MKL2


check button - Retained interactions in fusion protein (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost interactions due to fusion (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with
HgeneHSP90AB1chr6:44220004chr16:14354765ENST00000353801+1012620_723577.0725.0NR1D1
HgeneHSP90AB1chr6:44220004chr16:14354765ENST00000371554+1012620_723577.0725.0NR1D1
HgeneHSP90AB1chr6:44220004chr16:14354765ENST00000371646+1012620_723577.0725.0NR1D1
HgeneHSP90AB1chr6:44220004chr16:14354765ENST00000353801+1012264_608577.0725.0NR3C1
HgeneHSP90AB1chr6:44220004chr16:14354765ENST00000371554+1012264_608577.0725.0NR3C1
HgeneHSP90AB1chr6:44220004chr16:14354765ENST00000371646+1012264_608577.0725.0NR3C1


Top

Related Drugs to HSP90AB1-MKL2


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

Top

Related Diseases to HSP90AB1-MKL2


check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource