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Fusion Protein:HUWE1-FOXO4 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: HUWE1-FOXO4 | FusionPDB ID: 38108 | FusionGDB2.0 ID: 38108 | Hgene | Tgene | Gene symbol | HUWE1 | FOXO4 | Gene ID | 10075 | 4303 |
| Gene name | HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1 | forkhead box O4 | |
| Synonyms | ARF-BP1|HECTH9|HSPC272|Ib772|LASU1|MRXST|MULE|URE-B1|UREB1 | AFX|AFX1|MLLT7 | |
| Cytomap | Xp11.22 | Xq13.1 | |
| Type of gene | protein-coding | protein-coding | |
| Description | E3 ubiquitin-protein ligase HUWE1ARF-binding protein 1BJ-HCC-24 tumor antigenHECT domain protein LASU1HECT, UBA and WWE domain containing 1, E3 ubiquitin protein ligaseHECT-type E3 ubiquitin transferase HUWE1Mcl-1 ubiquitin ligase E3URE-binding pro | forkhead box protein O4fork head domain transcription factor AFX1myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 7 | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | Q7Z6Z7 | P98177 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000262854, ENST00000342160, ENST00000218328, ENST00000474288, | ENST00000341558, ENST00000466874, ENST00000374259, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 17 X 22 X 7=2618 | 4 X 4 X 3=48 |
| # samples | 22 | 4 | |
| ** MAII score | log2(22/2618*10)=-3.57288966842058 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(4/48*10)=-0.263034405833794 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: HUWE1 [Title/Abstract] AND FOXO4 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | HUWE1(53585932)-FOXO4(70321927), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | HUWE1-FOXO4 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. HUWE1-FOXO4 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. HUWE1-FOXO4 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. HUWE1-FOXO4 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. HUWE1-FOXO4 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF. HUWE1-FOXO4 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. HUWE1-FOXO4 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF. HUWE1-FOXO4 seems lost the major protein functional domain in Tgene partner, which is a transcription factor due to the frame-shifted ORF. HUWE1-FOXO4 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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 | HUWE1 | GO:0000209 | protein polyubiquitination | 15989957 |
| Hgene | HUWE1 | GO:0006513 | protein monoubiquitination | 19713937 |
| Hgene | HUWE1 | GO:0016574 | histone ubiquitination | 15767685 |
| Hgene | HUWE1 | GO:0031398 | positive regulation of protein ubiquitination | 20534529 |
| Hgene | HUWE1 | GO:0098779 | positive regulation of mitophagy in response to mitochondrial depolarization | 30217973 |
| Tgene | FOXO4 | GO:0006355 | regulation of transcription, DNA-templated | 15126506 |
| Tgene | FOXO4 | GO:0007050 | cell cycle arrest | 10783894 |
| Tgene | FOXO4 | GO:0008285 | negative regulation of cell proliferation | 10783894 |
| Tgene | FOXO4 | GO:0008286 | insulin receptor signaling pathway | 10217147 |
| Tgene | FOXO4 | GO:0016525 | negative regulation of angiogenesis | 12761217 |
| Tgene | FOXO4 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 11689711|15905404 |
| Tgene | FOXO4 | GO:0051151 | negative regulation of smooth muscle cell differentiation | 16054032 |
| Tgene | FOXO4 | GO:0070317 | negative regulation of G0 to G1 transition | 10783894 |
| Tgene | FOXO4 | GO:0071158 | positive regulation of cell cycle arrest | 15905404 |
| Fusion gene breakpoints across HUWE1 (5'-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 breakpoints across FOXO4 (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 | STAD | TCGA-D7-6818-01A | HUWE1 | chrX | 53585932 | - | FOXO4 | chrX | 70321927 | + |
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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) |
| ENST00000262854 | HUWE1 | chrX | 53585932 | - | ENST00000374259 | FOXO4 | chrX | 70321927 | + | 9866 | 8407 | 387 | 8414 | 2675 |
| 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 |
| ENST00000262854 | ENST00000374259 | HUWE1 | chrX | 53585932 | - | FOXO4 | chrX | 70321927 | + | 0.00315906 | 0.99684095 |
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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 >38108_38108_1_HUWE1-FOXO4_HUWE1_chrX_53585932_ENST00000262854_FOXO4_chrX_70321927_ENST00000374259_length(amino acids)=2675AA_BP= MKIEIMKVDRTKLKKTPTEAPADCRALIDKLKVCNDEQLLLELQQIKTWNIGKCELYHWVDLLDRFDGILADAGQTVENMSWMLVCDRPE REQLKMLLLAVLNFTALLIEYSFSRHLYSSIEHLTTLLASSDMQVVLAVLNLLYVFSKRSNYITRLGSDKRTPLLTRLQHLAESWGGKEN GFGLAECCRDLHMMKYPPSATTLHFEFYADPGAEVKIEKRTTSNTLHYIHIEQLDKISESPSEIMESLTKMYSIPKDKQMLLFTHIRLAH GFSNHRKRLQAVQARLHAISILVYSNALQESANSILYNGLIEELVDVLQITDKQLMEIKAASLRTLTSIVHLERTPKLSSIIDCTGTASY HGFLPVLVRNCIQAMIDPSMDPYPHQFATALFSFLYHLASYDAGGEALVSCGMMEALLKVIKFLGDEQDQITFVTRAVRVVDLITNLDMA AFQSHSGLSIFIYRLEHEVDLCRKECPFVIKPKIQRPNTTQEGEEMETDMDGVQCIPQRAALLKSMLNFLKKAIQDPAFSDGIRHVMDGS LPTSLKHIISNAEYYGPSLFLLATEVVTVFVFQEPSLLSSLQDNGLTDVMLHALLIKDVPATREVLGSLPNVFSALCLNARGLQSFVQCQ PFERLFKVLLSPDYLPAMRRRRSSDPLGDTASNLGSAVDELMRHQPTLKTDATTAIIKLLEEICNLGRDPKYICQKPSIQKADGTATAPP PRSNHAAEEASSEDEEEEEVQAMQSFNSTQQNETEPNQQVVGTEERIPIPLMDYILNVMKFVESILSNNTTDDHCQEFVNQKGLLPLVTI LGLPNLPIDFPTSAACQAVAGVCKSILTLSHEPKVLQEGLLQLDSILSSLEPLHRPIESPGGSVLLRELACAGNVADATLSAQATPLLHA LTAAHAYIMMFVHTCRVGQSEIRSISVNQWGSQLGLSVLSKLSQLYCSLVWESTVLLSLCTPNSLPSGCEFGQADMQKLVPKDEKAGTTQ GGKRSDGEQDGAAGSMDASTQGLLEGIGLDGDTLAPMETDEPTASDSKGKSKITPAMAARIKQIKPLLSASSRLGRALAELFGLLVKLCV GSPVRQRRSHHAASTTTAPTPAARSTASALTKLLTKGLSWQPPPYTPTPRFRLTFFICSVGFTSPMLFDERKYPYHLMLQKFLCSGGHNA LFETFNWALSMGGKVPVSEGLEHSDLPDGTGEFLDAWLMLVEKMVNPTTVLESPHSLPAKLPGGVQNFPQFSALRFLVVTQKAAFTCIKN LWNRKPLKVYGGRMAESMLAILCHILRGEPVIRERLSKEKEGSRGEEDTGQEEGGSRREPQVNQQQLQQLMDMGFTREHAMEALLNTSTM EQATEYLLTHPPPIMGGVVRDLSMSEEDQMMRAIAMSLGQDIPMDQRAESPEEVACRKEEEERKAREKQEEEEAKCLEKFQDADPLEQDE LHTFTDTMLPGCFHLLDELPDTVYRVCDLIMTAIKRNGADYRDMILKQVVNQVWEAADVLIKAALPLTTSDTKTVSEWISQMATLPQASN LATRILLLTLLFEELKLPCAWVVESSGILNVLIKLLEVVQPCLQAAKEQKEVQTPKWITPVLLLIDFYEKTAISSKRRAQMTKYLQSNSN NWRWFDDRSGRWCSYSASNNSTIDSAWKSGETSVRFTAGRRRYTVQFTTMVQVNEETGNRRPVMLTLLRVPRLNKNSKNSNGQELEKTLE ESKEMDIKRKENKGNDTPLALESTNTEKETSLEETKIGEILIQGLTEDMVTVLIRACVSMLGVPVDPDTLHATLRLCLRLTRDHKYAMMF AELKSTRMILNLTQSSGFNGFTPLVTLLLRHIIEDPCTLRHTMEKVVRSAATSGAGSTTSGVVSGSLGSREINYILRVLGPAACRNPDIF TEVANCCIRIALPAPRGSGTASDDEFENLRIKGPNAVQLVKTTPLKPSPLPVIPDTIKEVIYDMLNALAAYHAPEEADKSDPKPGVMTQE VGQLLQDMGDDVYQQYRSLTRQSSDFDTQSGFSINSQVFAADGASTETSASGTSQGEASTPEESRDGKKDKEGDRASEEGKQKGKGSKPL MPTSTILRLLAELVRSYVGIATLIANYSYTVGQSELIKEDCSVLAFVLDHLLPHTQNAEDKDTPALARLFLASLAAAGSGTDAQVALVNE VKAALGRALAMAESTEKHARLQAVMCIISTIMESCPSTSSFYSSATAKTQHNGMNNIIRLFLKKGLVNDLARVPHSLDLSSPNMANTVNA ALKPLETLSRIVNQPSSLFGSKSASSKNKSEQDAQGASQDSSSNQQDPGEPGEAEVQEEDHDVTQTEVADGDIMDGEAETDSVVIAGQPE VLSSQEMQVENELEDLIDELLERDGGSGNSTIIVSRSGEDESQEDVLMDEAPSNLSQASTLQANREDSMNILDPEDEEEHTQEEDSSGSN EDEDDSQDEEEEEEEDEEDDQEDDEGEEGDEDDDDDGSEMELDEDYPDMNASPLVRFERFDREDDLIIEFDNMFSSATDIPPSPGNIPTT HPLMVRHADHSSLTLGSGSSTTRLTQGIGRSQRTLRQLTANTGHTIHVHYPGNRQPNPPLILQRLLGPSAAADILQLSSSLPLQSRGRAR -------------------------------------------------------------- |
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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/chrX:53585932/chrX:70321927) - 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. |
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| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| HUWE1 | FOXO4 |
| FUNCTION: E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15989957, PubMed:19713937, PubMed:15567145, PubMed:15767685, PubMed:18488021, PubMed:17567951, PubMed:19037095, PubMed:20534529). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Binds to an upstream initiator-like sequence in the preprodynorphin gene. Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). {ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738}. | FUNCTION: Transcription factor involved in the regulation of the insulin signaling pathway. Binds to insulin-response elements (IREs) and can activate transcription of IGFBP1. Down-regulates expression of HIF1A and suppresses hypoxia-induced transcriptional activation of HIF1A-modulated genes. Also involved in negative regulation of the cell cycle. Involved in increased proteasome activity in embryonic stem cells (ESCs) by activating expression of PSMD11 in ESCs, leading to enhanced assembly of the 26S proteasome, followed by higher proteasome activity. {ECO:0000269|PubMed:10217147, ECO:0000269|PubMed:10783894, ECO:0000269|PubMed:12761217, ECO:0000269|PubMed:15126506, ECO:0000269|PubMed:16054032, ECO:0000269|PubMed:16964248, ECO:0000269|PubMed:20874444, ECO:0000269|PubMed:22972301}. |
| 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 * 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 | HUWE1 | chrX:53585932 | chrX:70321927 | ENST00000262854 | - | 58 | 84 | 2295_2469 | 2668.3333333333335 | 4375.0 | Compositional bias | Note=Glu-rich |
| Hgene | HUWE1 | chrX:53585932 | chrX:70321927 | ENST00000262854 | - | 58 | 84 | 2427_2490 | 2668.3333333333335 | 4375.0 | Compositional bias | Note=Asp-rich |
| Hgene | HUWE1 | chrX:53585932 | chrX:70321927 | ENST00000342160 | - | 57 | 83 | 2295_2469 | 2668.3333333333335 | 4375.0 | Compositional bias | Note=Glu-rich |
| Hgene | HUWE1 | chrX:53585932 | chrX:70321927 | ENST00000342160 | - | 57 | 83 | 2427_2490 | 2668.3333333333335 | 4375.0 | Compositional bias | Note=Asp-rich |
| Hgene | HUWE1 | chrX:53585932 | chrX:70321927 | ENST00000262854 | - | 58 | 84 | 1316_1355 | 2668.3333333333335 | 4375.0 | Domain | UBA |
| Hgene | HUWE1 | chrX:53585932 | chrX:70321927 | ENST00000262854 | - | 58 | 84 | 1370_1389 | 2668.3333333333335 | 4375.0 | Domain | UIM |
| Hgene | HUWE1 | chrX:53585932 | chrX:70321927 | ENST00000262854 | - | 58 | 84 | 1603_1680 | 2668.3333333333335 | 4375.0 | Domain | WWE |
| Hgene | HUWE1 | chrX:53585932 | chrX:70321927 | ENST00000342160 | - | 57 | 83 | 1316_1355 | 2668.3333333333335 | 4375.0 | Domain | UBA |
| Hgene | HUWE1 | chrX:53585932 | chrX:70321927 | ENST00000342160 | - | 57 | 83 | 1370_1389 | 2668.3333333333335 | 4375.0 | Domain | UIM |
| Hgene | HUWE1 | chrX:53585932 | chrX:70321927 | ENST00000342160 | - | 57 | 83 | 1603_1680 | 2668.3333333333335 | 4375.0 | Domain | WWE |
| - 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 | HUWE1 | chrX:53585932 | chrX:70321927 | ENST00000262854 | - | 58 | 84 | 3483_3550 | 2668.3333333333335 | 4375.0 | Compositional bias | Note=Thr-rich |
| Hgene | HUWE1 | chrX:53585932 | chrX:70321927 | ENST00000342160 | - | 57 | 83 | 3483_3550 | 2668.3333333333335 | 4375.0 | Compositional bias | Note=Thr-rich |
| Hgene | HUWE1 | chrX:53585932 | chrX:70321927 | ENST00000262854 | - | 58 | 84 | 4038_4374 | 2668.3333333333335 | 4375.0 | Domain | HECT |
| Hgene | HUWE1 | chrX:53585932 | chrX:70321927 | ENST00000342160 | - | 57 | 83 | 4038_4374 | 2668.3333333333335 | 4375.0 | Domain | HECT |
| Tgene | FOXO4 | chrX:53585932 | chrX:70321927 | ENST00000341558 | 2 | 4 | 100_188 | 448.3333333333333 | 451.0 | DNA binding | Fork-head | |
| Tgene | FOXO4 | chrX:53585932 | chrX:70321927 | ENST00000374259 | 1 | 3 | 100_188 | 503.3333333333333 | 506.0 | DNA binding | Fork-head |
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Fusion Protein-Protein Interaction |
| Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in |
| 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 |
| HUWE1 | |
| FOXO4 |  |
| - 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 |
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Related Drugs to HUWE1-FOXO4 |
| 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 HUWE1-FOXO4 |
| 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 | FOXO4 | C0025322 | Premature Menopause | 1 | GENOMICS_ENGLAND |
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