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Center for Computational Systems Medicine level1
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Fusion Gene Summary

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Fusion Gene Sample Information

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Fusion ORF Analysis

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Fusion Amino Acid Sequences

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Fusion Protein Functional Features

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Fusion Protein-Protein Interaction

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Related drugs with this fusion protein

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Related disease with this fusion protein

Fusion Protein:ISG15-IFITM1

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ISG15-IFITM1
FusionPDB ID: 40301
FusionGDB2.0 ID: 40301
HgeneTgene
Gene symbol

ISG15

IFITM1

Gene ID

9636

8519

Gene nameISG15 ubiquitin like modifierinterferon induced transmembrane protein 1
SynonymsG1P2|IFI15|IMD38|IP17|UCRP|hUCRP9-27|CD225|DSPA2a|IFI17|LEU13
Cytomap

1p36.33

11p15.5

Type of geneprotein-codingprotein-coding
Descriptionubiquitin-like protein ISG15interferon, alpha-inducible protein (clone IFI-15K)interferon-induced 17-kDa/15-kDa proteininterferon-stimulated protein, 15 kDaubiquitin cross-reactive proteininterferon-induced transmembrane protein 1dispanin subfamily A member 2ainterferon-induced protein 17interferon-inducible protein 9-27leu-13 antigen
Modification date2020031320200313
UniProtAcc

P05161

A6NMD0

Ensembl transtripts involved in fusion geneENST idsENST00000379389, ENST00000525554, 
ENST00000408968, ENST00000528780, 
ENST00000328221, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score2 X 1 X 1=27 X 8 X 5=280
# samples 18
** MAII scorelog2(1/2*10)=2.32192809488736log2(8/280*10)=-1.8073549220576
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: ISG15 [Title/Abstract] AND IFITM1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ISG15(949543)-IFITM1(314961), # samples:1
Anticipated loss of major functional domain due to fusion event.ISG15-IFITM1 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.
ISG15-IFITM1 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.
ISG15-IFITM1 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.
ISG15-IFITM1 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.
ISG15-IFITM1 seems lost the major protein functional domain in Hgene 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)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneISG15

GO:0007229

integrin-mediated signaling pathway

29100055

HgeneISG15

GO:0031397

negative regulation of protein ubiquitination

18305167

HgeneISG15

GO:0032020

ISG15-protein conjugation

16122702|21543490

HgeneISG15

GO:0034340

response to type I interferon

22859821

HgeneISG15

GO:0072608

interleukin-10 secretion

29100055

HgeneISG15

GO:0072643

interferon-gamma secretion

29100055

TgeneIFITM1

GO:0009615

response to virus

21253575|22479637

TgeneIFITM1

GO:0034341

response to interferon-gamma

21253575

TgeneIFITM1

GO:0035455

response to interferon-alpha

22479637

TgeneIFITM1

GO:0035456

response to interferon-beta

21253575

TgeneIFITM1

GO:0045071

negative regulation of viral genome replication

21253575

TgeneIFITM1

GO:0046597

negative regulation of viral entry into host cell

21253575|23358889


check buttonFusion gene breakpoints across ISG15 (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 IFITM1 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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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
ChimerDB4UCECTCGA-EY-A1GR-01AISG15chr1

949543

+IFITM1chr11

314961

+


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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)
ENST00000379389ISG15chr1949543+ENST00000328221IFITM1chr11314961+81053122468148

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
ENST00000379389ENST00000328221ISG15chr1949543+IFITM1chr11314961+0.198417860.80158216

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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

>40301_40301_1_ISG15-IFITM1_ISG15_chr1_949543_ENST00000379389_IFITM1_chr11_314961_ENST00000328221_length(amino acids)=148AA_BP=
MTCVPQAYNRAGAACRSRRLRGSELIFASTGACAVAHSPQPTAMSQGLGPGSTVLLVVDKCDEPLSILVRNNKGRSSTYEVRLTQTVAHL

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

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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/chr1:949543/chr11:314961)
- 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
ISG15

P05161

IFITM1

A6NMD0

FUNCTION: Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated protein. ISGylation involves a cascade of enzymatic reactions involving E1, E2, and E3 enzymes which catalyze the conjugation of ISG15 to a lysine residue in the target protein. Its target proteins include IFIT1, MX1/MxA, PPM1B, UBE2L6, UBA7, CHMP5, CHMP2A, CHMP4B and CHMP6. Can also isgylate: EIF2AK2/PKR which results in its activation, DDX58/RIG-I which inhibits its function in antiviral signaling response, EIF4E2 which enhances its cap structure-binding activity and translation-inhibition activity, UBE2N and UBE2E1 which negatively regulates their activity, IRF3 which inhibits its ubiquitination and degradation and FLNB which prevents its ability to interact with the upstream activators of the JNK cascade thereby inhibiting IFNA-induced JNK signaling. Exhibits antiviral activity towards both DNA and RNA viruses, including influenza A, HIV-1 and Ebola virus. Restricts HIV-1 and ebola virus via disruption of viral budding. Inhibits the ubiquitination of HIV-1 Gag and host TSG101 and disrupts their interaction, thereby preventing assembly and release of virions from infected cells. Inhibits Ebola virus budding mediated by the VP40 protein by disrupting ubiquitin ligase activity of NEDD4 and its ability to ubiquitinate VP40. ISGylates influenza A virus NS1 protein which causes a loss of function of the protein and the inhibition of virus replication. The secreted form of ISG15 can: induce natural killer cell proliferation, act as a chemotactic factor for neutrophils and act as a IFN-gamma-inducing cytokine playing an essential role in antimycobacterial immunity. The secreted form acts through the integrin ITGAL/ITGB2 receptor to initiate activation of SRC family tyrosine kinases including LYN, HCK and FGR which leads to secretion of IFNG and IL10; the interaction is mediated by ITGAL (PubMed:29100055). {ECO:0000269|PubMed:1373138, ECO:0000269|PubMed:16009940, ECO:0000269|PubMed:16112642, ECO:0000269|PubMed:16428300, ECO:0000269|PubMed:16434471, ECO:0000269|PubMed:16872604, ECO:0000269|PubMed:18305167, ECO:0000269|PubMed:19270716, ECO:0000269|PubMed:19357168, ECO:0000269|PubMed:2005397, ECO:0000269|PubMed:20133869, ECO:0000269|PubMed:20308324, ECO:0000269|PubMed:20639253, ECO:0000269|PubMed:21543490, ECO:0000269|PubMed:22693631, ECO:0000269|PubMed:22859821, ECO:0000269|PubMed:23229543, ECO:0000269|PubMed:29100055, ECO:0000269|PubMed:7526157, ECO:0000269|PubMed:8550581}.

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
TgeneIFITM1chr1:949543chr11:314961ENST000003282210337_570126.0IntramembraneHelical
TgeneIFITM1chr1:949543chr11:314961ENST000004089680237_570126.0IntramembraneHelical
TgeneIFITM1chr1:949543chr11:314961ENST000005287800337_570126.0IntramembraneHelical
TgeneIFITM1chr1:949543chr11:314961ENST0000032822103108_1250126.0Topological domainExtracellular
TgeneIFITM1chr1:949543chr11:314961ENST00000328221031_360126.0Topological domainCytoplasmic
TgeneIFITM1chr1:949543chr11:314961ENST000003282210358_860126.0Topological domainCytoplasmic
TgeneIFITM1chr1:949543chr11:314961ENST0000040896802108_1250126.0Topological domainExtracellular
TgeneIFITM1chr1:949543chr11:314961ENST00000408968021_360126.0Topological domainCytoplasmic
TgeneIFITM1chr1:949543chr11:314961ENST000004089680258_860126.0Topological domainCytoplasmic
TgeneIFITM1chr1:949543chr11:314961ENST0000052878003108_1250126.0Topological domainExtracellular
TgeneIFITM1chr1:949543chr11:314961ENST00000528780031_360126.0Topological domainCytoplasmic
TgeneIFITM1chr1:949543chr11:314961ENST000005287800358_860126.0Topological domainCytoplasmic
TgeneIFITM1chr1:949543chr11:314961ENST000003282210387_1070126.0TransmembraneHelical
TgeneIFITM1chr1:949543chr11:314961ENST000004089680287_1070126.0TransmembraneHelical
TgeneIFITM1chr1:949543chr11:314961ENST000005287800387_1070126.0TransmembraneHelical

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneISG15chr1:949543chr11:314961ENST00000379389+122_780166.0DomainUbiquitin-like 1
HgeneISG15chr1:949543chr11:314961ENST00000379389+1279_1570166.0DomainUbiquitin-like 2
HgeneISG15chr1:949543chr11:314961ENST00000379389+12152_1570166.0MotifNote=LRLRGG
HgeneISG15chr1:949543chr11:314961ENST00000379389+12153_1570166.0RegionInvolved in the ligation of specific target proteins


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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
ISG15
IFITM1


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


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Related Drugs to ISG15-IFITM1


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

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Related Diseases to ISG15-IFITM1


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