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Center for Computational Systems Medicine
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Kinase Fusion Gene Summary

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Kinase Fusion Gene Sample Information

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Kinase Fusion ORF Analysis

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Kinase Fusion Amino Acid Sequences

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Multiple Sequence Alignment of All Fusion Protein Isoforms

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Kinase Fusion Protein Functional Features

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Kinase Fusion Protein Structures

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Comparison of Fusion Protein Isoforms

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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB

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pLDDT Scores and Difference Analysis of pLDDT Scores Between the Active Sites (Best) and Non-Active Sites.

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Ramachandran Plot of Kinase Fusion Protein Structure

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Potential Active Site Information

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Virtual Screening Results

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Kinase-Substrate Information

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Related Drugs with This Kinase Fusion Protein

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Related Disease with This Kinase Fusion Protein

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Clinical Trials of the Found Drugs/Small Molecules

Kinase Fusion Gene:VRK2_IVNS1ABP

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: VRK2_IVNS1ABP
KinaseFusionDB ID: KFG7089
FusionGDB2.0 ID: KFG7089
HgeneTgene
Gene symbol

VRK2

IVNS1ABP

Gene ID

7444

10625

Gene nameVRK serine/threonine kinase 2influenza virus NS1A binding protein
Synonyms-ARA3|FLARA3|HSPC068|IMD70|KLHL39|ND1|NS-1|NS1-BP|NS1BP
Cytomap

2p16.1

1q25.3

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein kinase VRK2vaccinia related kinase 2vaccinia virus B1R-related kinase 2influenza virus NS1A-binding proteinNCX downstream gene 1NS1-binding proteinaryl hydrocarbon receptor-associated 3aryl hydrocarbon receptor-associated protein 3kelch-like family member 39kelch-like protein 39
Modification date2024040320240407
UniProtAcc

Q86Y07

Q9Y6Y0

Ensembl transtripts involved in fusion geneENST idsENST00000435505, ENST00000417641, 
ENST00000478687, ENST00000412104, 
ENST00000340157, ENST00000440705, 
ENST00000367498, ENST00000459929, 
ENST00000392007, ENST00000367497, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: VRK2 [Title/Abstract] AND IVNS1ABP [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)
check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneVRK2

GO:0046777

protein autophosphorylation

14645249|16704422


check buttonKinase Fusion gene breakpoints across VRK2 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check buttonKinase Fusion gene breakpoints across IVNS1ABP (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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Kinase Fusion Gene Sample Information

check buttonKinase Fusion gene information.
check button Kinase Fusion gene information from four resources (ChiTars 5.0, ChimerDB 4.0, COSMIC, and CCLE)
* 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.
SourceSampleHgeneHchrHbpTgeneTchrTbp
CCLECCLF_PEDS_0001_TVRK2chr2

58316858

IVNS1ABPchr1

185274775



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Kinase Fusion ORF Analysis


check buttonKinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB.
HenstTenstHgeneHchrHbpTgeneTchrTbpSeq length
(transcript)
Seq length
(amino acids)

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Kinase Fusion Amino Acid Sequences


check button For individual full-length fusion transcript sequence from KinaseFusionDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.
>Henst_Tenst_Hgene_Hchr_Hbp_Tgene_Tchr_Tbp_length(fusion AA)_AAseq

Multiple Sequence Alignment of All Fusion Protein Isoforms



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Kinase 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/chr2:/chr1:)
- 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
VRK2

Q86Y07

IVNS1ABP

Q9Y6Y0

FUNCTION: Serine/threonine kinase that regulates several signal transduction pathways (PubMed:16704422, PubMed:14645249, PubMed:16495336, PubMed:17709393, PubMed:18617507, PubMed:18286207, PubMed:20679487). Isoform 1 modulates the stress response to hypoxia and cytokines, such as interleukin-1 beta (IL1B) and this is dependent on its interaction with MAPK8IP1, which assembles mitogen-activated protein kinase (MAPK) complexes (PubMed:17709393). Inhibition of signal transmission mediated by the assembly of MAPK8IP1-MAPK complexes reduces JNK phosphorylation and JUN-dependent transcription (PubMed:18286207). Phosphorylates 'Thr-18' of p53/TP53, histone H3, and may also phosphorylate MAPK8IP1 (PubMed:16704422). Phosphorylates BANF1 and disrupts its ability to bind DNA and reduces its binding to LEM domain-containing proteins (PubMed:16495336). Down-regulates the transactivation of transcription induced by ERBB2, HRAS, BRAF, and MEK1 (PubMed:20679487). Blocks the phosphorylation of ERK in response to ERBB2 and HRAS (PubMed:20679487). Can also phosphorylate the following substrates that are commonly used to establish in vitro kinase activity: casein, MBP and histone H2B, but it is not sure that this is physiologically relevant (PubMed:14645249). {ECO:0000269|PubMed:14645249, ECO:0000269|PubMed:16495336, ECO:0000269|PubMed:16704422, ECO:0000269|PubMed:17709393, ECO:0000269|PubMed:18286207, ECO:0000269|PubMed:18617507, ECO:0000269|PubMed:20679487}.; FUNCTION: [Isoform 2]: Phosphorylates 'Thr-18' of p53/TP53, as well as histone H3. Reduces p53/TP53 ubiquitination by MDM2, promotes p53/TP53 acetylation by EP300 and thereby increases p53/TP53 stability and activity. {ECO:0000269|PubMed:16704422}.FUNCTION: Involved in many cell functions, including pre-mRNA splicing, the aryl hydrocarbon receptor (AHR) pathway, F-actin organization and protein ubiquitination. Plays a role in the dynamic organization of the actin skeleton as a stabilizer of actin filaments by association with F-actin through Kelch repeats (By similarity). Protects cells from cell death induced by actin destabilization (By similarity). Functions as modifier of the AHR/Aryl hydrocarbon receptor pathway increasing the concentration of AHR available to activate transcription (PubMed:16582008). In addition, functions as a negative regulator of BCR(KLHL20) E3 ubiquitin ligase complex to prevent ubiquitin-mediated proteolysis of PML and DAPK1, two tumor suppressors (PubMed:25619834). Inhibits pre-mRNA splicing (in vitro) (PubMed:9696811). {ECO:0000250|UniProtKB:Q920Q8, ECO:0000269|PubMed:16582008, ECO:0000269|PubMed:25619834, ECO:0000269|PubMed:9696811}.; FUNCTION: (Microbial infection) Involved in the alternative splicing of influenza A virus M1 mRNA through interaction with HNRNPK, thereby facilitating the generation of viral M2 protein. {ECO:0000269|PubMed:23825951, ECO:0000269|PubMed:9696811}.

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.

check button - Retained domain in the 5'-partner of fusion protein (protein functional feature from UniProt).
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote


check button - Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt).
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote


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Kinase-Substrate Information of VRK2_IVNS1ABP


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
VRK2Q86Y07humanCOILP38432S184NEEAKRKsPKKKEKCCoilin_N
VRK2Q86Y07humanGAPDHP04406S151LkIIsNAsCttNCLA
VRK2Q86Y07humanUSP25Q9UHP3T680QPLVGIEtLPPDLRD
VRK2Q86Y07humanUSP25Q9UHP3S745PEyLEQPsRSDFSKH
VRK2Q86Y07humanBANF1O75531S4____MttsQkHRDFVBAF
VRK2Q86Y07humanDTNBP1Q96EV8S299RAKPPsSssTCtDSADysbindin
VRK2Q86Y07humanBANF1O75531T3_____MttsQkHRDFBAF
VRK2Q86Y07humanPLK1P53350T210YDGERKktLCGtPNyPkinase
VRK2Q86Y07humanUSP25Q9UHP3T727QkLRESEtSVTTAQA
VRK2Q86Y07humanIKBKBO14920S177AkELDQGsLCtsFVGPkinase
VRK2Q86Y07humanBANF1O75531T2______MttsQkHRDBAF
VRK2Q86Y07humanIKBKBO14920S181DQGsLCtsFVGTLQyPkinase
VRK2Q86Y07humanDTNBP1Q96EV8S297ELRAKPPsSssTCtDDysbindin


check button Biological Network Integration of This Kinase and Substrates
(GeneMANIA website)

check button Enriched GO biological processes of the phosphorylation target genes of the kinase
KinaseGOIDGO termP.adjust
VRK2IDDescription0.00e+00
VRK2GO:0043086negative regulation of catalytic activity9.49e-05
VRK2GO:0051348negative regulation of transferase activity1.28e-02
VRK2GO:0071763nuclear membrane organization1.52e-02
VRK2GO:0006998nuclear envelope organization1.52e-02
VRK2GO:0031647regulation of protein stability1.52e-02
VRK2GO:0045936negative regulation of phosphate metabolic process1.68e-02
VRK2GO:0010563negative regulation of phosphorus metabolic process1.68e-02
VRK2GO:0031400negative regulation of protein modification process2.28e-02
VRK2GO:0032479regulation of type I interferon production3.92e-02
VRK2GO:0032606type I interferon production3.92e-02
VRK2GO:0006997nucleus organization4.87e-02
VRK2GO:0006469negative regulation of protein kinase activity5.90e-02
VRK2GO:0033673negative regulation of kinase activity5.90e-02
VRK2GO:0043123positive regulation of canonical NF-kappaB signal transduction5.90e-02
VRK2GO:0061136regulation of proteasomal protein catabolic process5.90e-02
VRK2GO:0051346negative regulation of hydrolase activity5.90e-02
VRK2GO:0045861negative regulation of proteolysis5.90e-02
VRK2GO:1903050regulation of proteolysis involved in protein catabolic process5.90e-02
VRK2GO:0007084mitotic nuclear membrane reassembly5.90e-02
VRK2GO:0051081nuclear membrane disassembly5.90e-02
VRK2GO:0101024mitotic nuclear membrane organization5.90e-02
VRK2GO:0043122regulation of canonical NF-kappaB signal transduction5.90e-02
VRK2GO:0014049positive regulation of glutamate secretion5.90e-02
VRK2GO:0030397membrane disassembly5.90e-02
VRK2GO:0035666TRIF-dependent toll-like receptor signaling pathway5.90e-02
VRK2GO:0060159regulation of dopamine receptor signaling pathway5.90e-02
VRK2GO:0072697protein localization to cell cortex5.90e-02
VRK2GO:0140014mitotic nuclear division5.90e-02
VRK2GO:0015074DNA integration5.90e-02
VRK2GO:0061000negative regulation of dendritic spine development5.90e-02
VRK2GO:0090435protein localization to nuclear envelope5.90e-02
VRK2GO:0018105peptidyl-serine phosphorylation5.90e-02
VRK2GO:0007249canonical NF-kappaB signal transduction5.90e-02
VRK2GO:0001933negative regulation of protein phosphorylation5.90e-02
VRK2GO:0018209peptidyl-serine modification5.90e-02
VRK2GO:0048308organelle inheritance5.90e-02
VRK2GO:0048313Golgi inheritance5.90e-02
VRK2GO:0002756MyD88-independent toll-like receptor signaling pathway5.90e-02
VRK2GO:0017014protein nitrosylation5.90e-02
VRK2GO:0018119peptidyl-cysteine S-nitrosylation5.90e-02
VRK2GO:0042326negative regulation of phosphorylation5.90e-02
VRK2GO:0001956positive regulation of neurotransmitter secretion5.90e-02
VRK2GO:1901550regulation of endothelial cell development5.90e-02
VRK2GO:1903140regulation of establishment of endothelial barrier5.90e-02
VRK2GO:0048490anterograde synaptic vesicle transport5.90e-02
VRK2GO:0099514synaptic vesicle cytoskeletal transport5.90e-02
VRK2GO:0099517synaptic vesicle transport along microtubule5.90e-02
VRK2GO:1904666regulation of ubiquitin protein ligase activity5.90e-02
VRK2GO:1990778protein localization to cell periphery5.90e-02

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Related Drugs to VRK2_IVNS1ABP


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

check button Distribution of the number of studies mentioning VRK2-IVNS1ABP and kinase inhibitors the PubMed Abstract (04-01-2024)

Fusion gene - drug pair 1Fusion gene - drug pair 2PMIDPublication dateDOIStudy title

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Related Diseases to VRK2_IVNS1ABP


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

check button Related diseases from the literature mentioned this fusion gene and drug.
(PubMed, 04-01-2024)
MeSH IDMeSH term

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


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Clinical Trials of the Found Drugs/Small Molecules


check button Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024)

check button Clinical Trials from clinicaltrials.gov (06-17-2024)

Fusion GeneKinase InhibitorNCT IDStudy StatusPhasesDisease# EnrolmentDate