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Center for Computational Systems Medicine level2
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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 Structure

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pLDDT scores

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Ramachandran Plot of Fusion Protein Structure

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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:SIK2-PIR

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SIK2-PIR
FusionPDB ID: 81856
FusionGDB2.0 ID: 81856
HgeneTgene
Gene symbol

SIK2

PIR

Gene ID

23235

8544

Gene namesalt inducible kinase 2pirin
SynonymsLOH11CR1I|QIK|SIK-2|SNF1LK2-
Cytomap

11q23.1

Xp22.2

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein kinase SIK2SNF1-like kinase 2qin-induced kinasesalt-inducible protein kinase 2salt-inducible serine/threonine kinase 2serine/threonine-protein kinase SNF1-like kinase 2pirinpirin (iron-binding nuclear protein)probable quercetin 2,3-dioxygenase PIRprobable quercetinase
Modification date2020031320200313
UniProtAcc.

PIR

Ensembl transtripts involved in fusion geneENST idsENST00000304987, ENST00000533868, 
ENST00000476381, ENST00000380420, 
ENST00000380421, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 7 X 10=9103 X 4 X 3=36
# samples 133
** MAII scorelog2(13/910*10)=-2.8073549220576
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/36*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: SIK2 [Title/Abstract] AND PIR [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SIK2(111583099)-PIR(15477863), # samples:3
Anticipated loss of major functional domain due to fusion event.SIK2-PIR 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.
SIK2-PIR 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)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneSIK2

GO:0006468

protein phosphorylation

14976552

HgeneSIK2

GO:0035556

intracellular signal transduction

14976552

HgeneSIK2

GO:0046777

protein autophosphorylation

18348280


check buttonFusion gene breakpoints across SIK2 (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 PIR (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
ChimerDB4PRADTCGA-G9-6361-01ASIK2chr11

111583099

-PIRchrX

15477863

-
ChimerDB4PRADTCGA-G9-6361-01ASIK2chr11

111583099

+PIRchrX

15477863

-
ChimerDB4PRADTCGA-G9-6361SIK2chr11

111583099

+PIRchrX

15477863

-


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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)
ENST00000304987SIK2chr11111583099+ENST00000380420PIRchrX15477863-23281439352122695
ENST00000304987SIK2chr11111583099+ENST00000380421PIRchrX15477863-23281439352122695

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
ENST00000304987ENST00000380420SIK2chr11111583099+PIRchrX15477863-0.0019724390.9980275
ENST00000304987ENST00000380421SIK2chr11111583099+PIRchrX15477863-0.0019724390.9980275

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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

>81856_81856_1_SIK2-PIR_SIK2_chr11_111583099_ENST00000304987_PIR_chrX_15477863_ENST00000380420_length(amino acids)=695AA_BP=467
MGPGEREGRSEGAKEQAERPSPKPSRAANPPARPRSCPPCLAAGPSMVMADGPRHLQRGPVRVGFYDIEGTLGKGNFAVVKLGRHRITKT
EVAIKIIDKSQLDAVNLEKIYREVQIMKMLDHPHIIKLYQVMETKSMLYLVTEYAKNGEIFDYLANHGRLNESEARRKFWQILSAVDYCH
GRKIVHRDLKAENLLLDNNMNIKIADFGFGNFFKSGELLATWCGSPPYAAPEVFEGQQYEGPQLDIWSMGVVLYVLVCGALPFDGPTLPI
LRQRVLEGRFRIPYFMSEDCEHLIRRMLVLDPSKRLTIAQIKEHKWMLIEVPVQRPVLYPQEQENEPSIGEFNEQVLRLMHSLGIDQQKT
IESLQNKSYNHFAAIYFLLVERLKSHRSSFPVEQRLDGRQRRPSTIAEQTVAKAQTVGLPVTMHSPNMRLLRSALLPQASNVEAFSFPAS
GCQAEAAFMEEECVDTPKVSYLLEGGSMAHEDFCGHTGKMNPGDLQWMTAGRGILHAEMPCSEEPAHGLQLWVNLRSSEKMVEPQYQELK
SEEIPKPSKDGVTVAVISGEALGIKSKVYTRTPTLYLDFKLDPGAKHSQPIPKGWTSFIYTISGDVYIGPDDAQQKIEPHHTAVLGEGDS

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

>81856_81856_2_SIK2-PIR_SIK2_chr11_111583099_ENST00000304987_PIR_chrX_15477863_ENST00000380421_length(amino acids)=695AA_BP=467
MGPGEREGRSEGAKEQAERPSPKPSRAANPPARPRSCPPCLAAGPSMVMADGPRHLQRGPVRVGFYDIEGTLGKGNFAVVKLGRHRITKT
EVAIKIIDKSQLDAVNLEKIYREVQIMKMLDHPHIIKLYQVMETKSMLYLVTEYAKNGEIFDYLANHGRLNESEARRKFWQILSAVDYCH
GRKIVHRDLKAENLLLDNNMNIKIADFGFGNFFKSGELLATWCGSPPYAAPEVFEGQQYEGPQLDIWSMGVVLYVLVCGALPFDGPTLPI
LRQRVLEGRFRIPYFMSEDCEHLIRRMLVLDPSKRLTIAQIKEHKWMLIEVPVQRPVLYPQEQENEPSIGEFNEQVLRLMHSLGIDQQKT
IESLQNKSYNHFAAIYFLLVERLKSHRSSFPVEQRLDGRQRRPSTIAEQTVAKAQTVGLPVTMHSPNMRLLRSALLPQASNVEAFSFPAS
GCQAEAAFMEEECVDTPKVSYLLEGGSMAHEDFCGHTGKMNPGDLQWMTAGRGILHAEMPCSEEPAHGLQLWVNLRSSEKMVEPQYQELK
SEEIPKPSKDGVTVAVISGEALGIKSKVYTRTPTLYLDFKLDPGAKHSQPIPKGWTSFIYTISGDVYIGPDDAQQKIEPHHTAVLGEGDS

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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/chr11:111583099/chrX:15477863)
- 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
.PIR

PIR

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.714

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
HgeneSIK2chr11:111583099chrX:15477863ENST00000304987+91520_271422.0927.0DomainProtein kinase
HgeneSIK2chr11:111583099chrX:15477863ENST00000304987+915295_335422.0927.0DomainUBA
HgeneSIK2chr11:111583099chrX:15477863ENST00000304987+91526_34422.0927.0Nucleotide bindingATP

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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Fusion Protein Structures

check button PDB and CIF files of the predicted fusion proteins
* Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.
Fusion protein PDB link (fusion AA seq ID in FusionPDB)HgeneHchrHbpHstrandTgeneTchrTbpTstrandAA seqLen(AA seq)
PDB file >>>1426_SIK2_111583099_PIR_15477863_ranked_0.pdbSIK2111583099111583099ENST00000380421PIRchrX15477863-
MGPGEREGRSEGAKEQAERPSPKPSRAANPPARPRSCPPCLAAGPSMVMADGPRHLQRGPVRVGFYDIEGTLGKGNFAVVKLGRHRITKT
EVAIKIIDKSQLDAVNLEKIYREVQIMKMLDHPHIIKLYQVMETKSMLYLVTEYAKNGEIFDYLANHGRLNESEARRKFWQILSAVDYCH
GRKIVHRDLKAENLLLDNNMNIKIADFGFGNFFKSGELLATWCGSPPYAAPEVFEGQQYEGPQLDIWSMGVVLYVLVCGALPFDGPTLPI
LRQRVLEGRFRIPYFMSEDCEHLIRRMLVLDPSKRLTIAQIKEHKWMLIEVPVQRPVLYPQEQENEPSIGEFNEQVLRLMHSLGIDQQKT
IESLQNKSYNHFAAIYFLLVERLKSHRSSFPVEQRLDGRQRRPSTIAEQTVAKAQTVGLPVTMHSPNMRLLRSALLPQASNVEAFSFPAS
GCQAEAAFMEEECVDTPKVSYLLEGGSMAHEDFCGHTGKMNPGDLQWMTAGRGILHAEMPCSEEPAHGLQLWVNLRSSEKMVEPQYQELK
SEEIPKPSKDGVTVAVISGEALGIKSKVYTRTPTLYLDFKLDPGAKHSQPIPKGWTSFIYTISGDVYIGPDDAQQKIEPHHTAVLGEGDS
695


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pLDDT score distribution

check button pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
SIK2_pLDDT.png
all structure
all structure
PIR_pLDDT.png
all structure
all structure

check button pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
all structure


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Ramachandran Plot of Fusion Protein Structure


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.
Fusion AA seq ID in FusionPDB and their Ramachandran plots

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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
SIK2
PIR


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 SIK2-PIR


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 SIK2-PIR


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