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Center for Computational Systems Medicine
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Fusion Gene Summary

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Fusion Gene ORF analysis

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Fusion Genomic Features

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Fusion Protein Features

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Fusion Gene Sequence

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Fusion Gene PPI analysis

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Related Drugs

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Related Diseases

Fusion gene:MAP3K5-UBE3D (FusionGDB2 ID:51335)

Fusion Gene Summary for MAP3K5-UBE3D

check button Fusion gene summary
Fusion gene informationFusion gene name: MAP3K5-UBE3D
Fusion gene ID: 51335
HgeneTgene
Gene symbol

MAP3K5

UBE3D

Gene ID

4217

90025

Gene namemitogen-activated protein kinase kinase kinase 5ubiquitin protein ligase E3D
SynonymsASK1|MAPKKK5|MEKK5C6orf157|H10BH|UBE2CBP|YJR141W
Cytomap

6q23.3

6q14.1

Type of geneprotein-codingprotein-coding
Descriptionmitogen-activated protein kinase kinase kinase 5ASK-1MAP/ERK kinase kinase 5MAPK/ERK kinase kinase 5MEK kinase 5MEKK 5apoptosis signal-regulating kinase 1E3 ubiquitin-protein ligase E3DHECT-type E3 ubiquitin transferase E3DUBCH10 binding protein with a hect-like domainubcH10-binding protein with a HECT-like domainubiquitin-conjugating enzyme E2C-binding protein
Modification date2020032720200313
UniProtAcc

Q99683

.
Ensembl transtripts involved in fusion geneENST00000355845, ENST00000359015, 
ENST00000463140, 
ENST00000369745, 
ENST00000503942, ENST00000369747, 
Fusion gene scores* DoF score14 X 11 X 10=15403 X 3 X 3=27
# samples 166
** MAII scorelog2(16/1540*10)=-3.2667865406949
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/27*10)=1.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Context

PubMed: MAP3K5 [Title/Abstract] AND UBE3D [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointMAP3K5(136901438)-UBE3D(83667169), # samples:2
Anticipated loss of major functional domain due to fusion event.MAP3K5-UBE3D seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
MAP3K5-UBE3D seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
MAP3K5-UBE3D seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF.
MAP3K5-UBE3D seems lost the major protein functional domain in Tgene partner, which is a essential gene 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
HgeneMAP3K5

GO:0000165

MAPK cascade

17210579|21771788

HgeneMAP3K5

GO:0000186

activation of MAPKK activity

11959862

HgeneMAP3K5

GO:0006468

protein phosphorylation

11096076|15983381

HgeneMAP3K5

GO:0007254

JNK cascade

21771788

HgeneMAP3K5

GO:0008631

intrinsic apoptotic signaling pathway in response to oxidative stress

21771788

HgeneMAP3K5

GO:0034198

cellular response to amino acid starvation

11096076

HgeneMAP3K5

GO:0043065

positive regulation of apoptotic process

21771788

HgeneMAP3K5

GO:0043280

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

20674765

HgeneMAP3K5

GO:0045893

positive regulation of transcription, DNA-templated

11096076

HgeneMAP3K5

GO:0051403

stress-activated MAPK cascade

11096076

HgeneMAP3K5

GO:0070301

cellular response to hydrogen peroxide

20674765

TgeneUBE3D

GO:0000209

protein polyubiquitination

15749827

TgeneUBE3D

GO:0006513

protein monoubiquitination

15749827

TgeneUBE3D

GO:0051865

protein autoubiquitination

15749827


check buttonFusion gene breakpoints across MAP3K5 (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 UBE3D (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

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-LN-A49MMAP3K5chr6

136901438

-UBE3Dchr6

83667169

-


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Fusion Gene ORF analysis for MAP3K5-UBE3D

check button Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
5CDS-intronENST00000355845ENST00000369745MAP3K5chr6

136901438

-UBE3Dchr6

83667169

-
5CDS-intronENST00000355845ENST00000503942MAP3K5chr6

136901438

-UBE3Dchr6

83667169

-
5CDS-intronENST00000359015ENST00000369745MAP3K5chr6

136901438

-UBE3Dchr6

83667169

-
5CDS-intronENST00000359015ENST00000503942MAP3K5chr6

136901438

-UBE3Dchr6

83667169

-
Frame-shiftENST00000359015ENST00000369747MAP3K5chr6

136901438

-UBE3Dchr6

83667169

-
In-frameENST00000355845ENST00000369747MAP3K5chr6

136901438

-UBE3Dchr6

83667169

-
intron-3CDSENST00000463140ENST00000369747MAP3K5chr6

136901438

-UBE3Dchr6

83667169

-
intron-intronENST00000463140ENST00000369745MAP3K5chr6

136901438

-UBE3Dchr6

83667169

-
intron-intronENST00000463140ENST00000503942MAP3K5chr6

136901438

-UBE3Dchr6

83667169

-

check buttonORFfinder result based on the fusion transcript sequence of in-frame fusion genes.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000355845MAP3K5chr6136901438-ENST00000369747UBE3Dchr683667169-264218585041901465

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
ENST00000355845ENST00000369747MAP3K5chr6136901438-UBE3Dchr683667169-0.0004876990.9995123

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Fusion Genomic Features for MAP3K5-UBE3D


check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page.
genomic feature

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page.

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Fusion Protein Features for MAP3K5-UBE3D


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/chr6:136901438/chr6:83667169)
- 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
MAP3K5

Q99683

.
FUNCTION: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1). {ECO:0000269|PubMed:10411906, ECO:0000269|PubMed:10688666, ECO:0000269|PubMed:10849426, ECO:0000269|PubMed:11029458, ECO:0000269|PubMed:11154276, ECO:0000269|PubMed:11689443, ECO:0000269|PubMed:11920685, ECO:0000269|PubMed:12697749, ECO:0000269|PubMed:14688258, ECO:0000269|PubMed:14749717, ECO:0000269|PubMed:15023544, ECO:0000269|PubMed:16129676, ECO:0000269|PubMed:17220297, ECO:0000269|PubMed:23102700, ECO:0000269|PubMed:26095851, ECO:0000269|PubMed:8940179, ECO:0000269|PubMed:8974401, ECO:0000269|PubMed:9564042, ECO:0000269|PubMed:9774977}.FUNCTION: Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP (By similarity). {ECO:0000250}.

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.
- In-frame and retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneMAP3K5chr6:136901438chr6:83667169ENST00000359015-2530680_93811721375.0DomainProtein kinase
HgeneMAP3K5chr6:136901438chr6:83667169ENST00000359015-2530686_69411721375.0Nucleotide bindingATP
TgeneUBE3Dchr6:136901438chr6:83667169ENST00000369747710353_389336390.0RegionNote=HECT-like

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneMAP3K5chr6:136901438chr6:83667169ENST00000359015-25301245_128511721375.0Coiled coilOntology_term=ECO:0000255


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Fusion Gene Sequence for MAP3K5-UBE3D


check button For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.
>51335_51335_1_MAP3K5-UBE3D_MAP3K5_chr6_136901438_ENST00000355845_UBE3D_chr6_83667169_ENST00000369747_length(transcript)=2642nt_BP=1858nt
GGTACCTCAAGTCTATTGTAGAGACAATTTTAATATATAAGCATTTTGTGAAACTGACCACAGAACAGCCTGTGGCCAAGCAAGAACTTG
TGGACTTTTGGATGGATTTCCTGGTCGAGGCCACAAAGACAGATGTTACTGTGGTTAGGTTTCCAGTATTAATATTAGAACCAACCAAAA
TCTATCAACCTTCTTATTTGTCTATCAACAATGAAGTTGAGGAAAAGACAATCTCTATTTGGCACGTGCTTCCTGATGACAAGAAAGGTA
TACATGAGTGGAATTTTAGTGCCTCTTCTGTCAGGGGAGTGAGTATTTCTAAATTTGAAGAAAGATGCTGCTTTCTTTATGTGCTTCACA
ATTCTGATGATTTCCAAATCTATTTCTGTACAGAACTTCATTGTAAAAAGTTTTTTGAGATGGTGAACACCATTACCGAAGAGAAGGGGA
GAAGCACAGAGGAAGGAGACTGTGAAAGTGACTTGCTGGAGATACTCTCAGCCCCTGCATGAAGAAATAGCATTGCATAAACACCTGAAG
CACAAAAATATTGTCCAGTATCTGGGCTCTTTCAGTGAGAATGGTTTCATTAAAATCTTCATGGAGCAGGTCCCTGGAGGAAGTCTTTCT
GCTCTCCTTCGTTCCAAATGGGGTCCATTAAAAGACAATGAGCAAACAATTGGCTTTTATACAAAGCAAATACTGGAAGGATTAAAATAT
CTCCATGACAATCAGATAGTTCACCGGGACATAAAGGGTGACAATGTGTTGATTAATACCTACAGTGGTGTTCTCAAGATCTCTGACTTC
GGAACATCAAAGAGGCTTGCTGGCATAAACCCCTGTACTGAAACTTTTACTGGTACCCTCCAGTATATGGCACCAGAAATAATAGATAAA
GGACCAAGAGGCTACGGAAAAGCAGCAGACATCTGGTCTCTGGGCTGTACAATCATTGAAATGGCCACAGGAAAACCCCCATTTTATGAA
CTGGGAGAACCACAAGCAGCTATGTTCAAGGTGGGAATGTTTAAAGTCCACCCTGAGATCCCAGAGTCCATGTCTGCAGAGGCCAAGGCA
TTCATACTGAAATGTTTTGAACCAGATCCTGACAAGAGAGCCTGTGCTAACGACTTGCTTGTTGATGAGTTTTTAAAAGTTTCAAGCAAA
AAGAAAAAGACACAACCTAAGCTTTCAGCTCTTTCAGCTGGATCAAATGAATATCTCAGGAGTATATCCTTGCCGGTACCTGTGCTGGTG
GAGGACACCAGCAGCAGCAGTGAGTACGGCTCAGTTTCACCCGACACGGAGTTGAAAGTGGACCCCTTCTCTTTCAAAACAAGAGCCAAG
TCCTGCGGAGAAAGAGATGTCAAGGGAATTCGGACACTCTTTTTGGGCATTCCAGATGAGAATTTTGAAGATCACAGTGCTCCTCCTTCC
CCTGAAGAAAAAGATTCTGGATTCTTCATGCTGAGGAAGGACAGTGAGAGGCGAGCTACCCTTCACAGGATCCTGACGGAAGACCAAGAC
AAAATTGTGAGAAACCTAATGGAATCTTTAGCTCAGGGGGCTGAAGAACCGAAACTAAAATGGGAACACATCACAACCCTCATTGCAAGC
CTCAGAGAATTTGTGAGATCCACTGACCGAAAAATCATAGCCACCACACTGTCAAAGCTGAAACTGGAGCTGGACTTCGACAGCCATGGC
ATTAGCCAAGTCCAGGTGGTACTCTTTGGTTTTCAAGATGCTGTCAATAAAGTTCTTCGGAATCATAACATCAAGCCGCACTGGATGTTT
GCCTTAGACAGTATCATTCGGAAGGCGGTACAGACAGCCATTACCATCCTGGTTCCAGACTTGTCAGCTTGTGGGAAAGTGACATCAGCG
TCCACCCGCTAACCCTGCCCTCTGCAACCTGCTTGGAGCTGCTGTTGATATTGTCAAAGAGTAATGCCAATCTGCCTTCATCCCTTCGCC
GTGTGAATTCCTTTCAGGTGGCCTTTTTGAAGATGTAACTATTAGAGCTGGGCATTCTCCTCCCCCGGCAGACAGCTCTCAAGCAGGAGC
ACACCGAGGCCAGCAGTCAGCTCAGGAGGCATCAATTACAAAGACAAGAACCAGAGCTATGGGATAAGAGCATTGCATTGAAGTTTTAAG
TTTACTTGTTTGCATGTATTCTCTAAGAGAAGAGTTAACTTTAGATCTTTGAAAACCCAGGACTGTGAAGAAAGTCATAGTAGCAGGTTG
AGGCAAGTGTAGAAGTTACATCTCTATTTCCCACAGAGAGGAATATTCACATATGTGCAGTGTCAGCACCACCTGGAAGGTTATTACCTA
ATGGAGATCCATCTGTCCTGTGTGGAATCCAGTGAGGAATTTTATTGGTGGAACTGAATGTTAACTGCTGTAAATCCTAGGAAATAAACT
TTTAAAGAGTTTCTCAGGATGATTTAAAACAAATTTTAAAAAAGAAAAGTAGAAAACATTTTATACTTTATTCAGAGGAGATGCTCAATA
GATGTTTGTTGAATGAATGATTATCAAATTAAAGGATTTCCTATTTATGCAAATCTGCATGTTTCTTTTGTTATTTCCTTTACCATACAT

>51335_51335_1_MAP3K5-UBE3D_MAP3K5_chr6_136901438_ENST00000355845_UBE3D_chr6_83667169_ENST00000369747_length(amino acids)=465AA_BP=449
MHEEIALHKHLKHKNIVQYLGSFSENGFIKIFMEQVPGGSLSALLRSKWGPLKDNEQTIGFYTKQILEGLKYLHDNQIVHRDIKGDNVLI
NTYSGVLKISDFGTSKRLAGINPCTETFTGTLQYMAPEIIDKGPRGYGKAADIWSLGCTIIEMATGKPPFYELGEPQAAMFKVGMFKVHP
EIPESMSAEAKAFILKCFEPDPDKRACANDLLVDEFLKVSSKKKKTQPKLSALSAGSNEYLRSISLPVPVLVEDTSSSSEYGSVSPDTEL
KVDPFSFKTRAKSCGERDVKGIRTLFLGIPDENFEDHSAPPSPEEKDSGFFMLRKDSERRATLHRILTEDQDKIVRNLMESLAQGAEEPK
LKWEHITTLIASLREFVRSTDRKIIATTLSKLKLELDFDSHGISQVQVVLFGFQDAVNKVLRNHNIKPHWMFALDSIIRKAVQTAITILV

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

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Fusion Gene PPI Analysis for MAP3K5-UBE3D


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 (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with
HgeneMAP3K5chr6:136901438chr6:83667169ENST00000359015-2530649_13741172.33333333333331375.0PPIA/CYPA
TgeneUBE3Dchr6:136901438chr6:83667169ENST00000369747710235_257336.6666666666667390.0UBE2C


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs for MAP3K5-UBE3D


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status

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Related Diseases for MAP3K5-UBE3D


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