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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:CHUK_HPSE2

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: CHUK_HPSE2
KinaseFusionDB ID: KFG1288
FusionGDB2.0 ID: KFG1288
HgeneTgene
Gene symbol

CHUK

HPSE2

Gene ID

1147

60495

Gene namecomponent of inhibitor of nuclear factor kappa B kinase complexheparanase 2 (inactive)
SynonymsBPS2|IKBKA|IKK-1|IKK-alpha|IKK1|IKKA|NFKBIKA|TCF16HPA2|HPR2|UFS|UFS1
Cytomap

10q24.31

10q24.2

Type of geneprotein-codingprotein-coding
Descriptioninhibitor of nuclear factor kappa-B kinase subunit alphaI-kappa-B kinase 1I-kappa-B kinase-alphaIKK-a kinaseIkB kinase alpha subunitNuclear factor NFkappaB inhibitor kinase alphaconserved helix-loop-helix ubiquitous kinasetranscription factor 16inactive heparanase-2heparanase 3heparanase-like protein
Modification date2024040720240403
UniProtAcc

O15111

Q8WWQ2

Ensembl transtripts involved in fusion geneENST idsENST00000370397, ENST00000590930, 
ENST00000370546, ENST00000370549, 
ENST00000370552, ENST00000404542, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: CHUK [Title/Abstract] AND HPSE2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CHUK(101979188)-HPSE2(100239866), # samples:1
check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneCHUK

GO:0006468

protein phosphorylation

20434986

HgeneCHUK

GO:0007249

canonical NF-kappaB signal transduction

9244310|9252186|9346484

HgeneCHUK

GO:0034142

toll-like receptor 4 signaling pathway

26189595

HgeneCHUK

GO:0038061

non-canonical NF-kappaB signal transduction

26189595

HgeneCHUK

GO:0045944

positive regulation of transcription by RNA polymerase II

23091055

HgeneCHUK

GO:0071356

cellular response to tumor necrosis factor

23091055


check buttonKinase Fusion gene breakpoints across CHUK (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 HPSE2 (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
ChimerDB4TCGA-G9-6362-11ACHUKchr10

101979188

HPSE2chr10

100239866



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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/:101979188/:100239866)
- 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
CHUK

O15111

HPSE2

Q8WWQ2

FUNCTION: Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses (PubMed:9244310, PubMed:9252186, PubMed:9346484, PubMed:18626576). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues (PubMed:9244310, PubMed:9252186, PubMed:9346484, PubMed:18626576, PubMed:35952808). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:9244310, PubMed:9252186, PubMed:9346484, PubMed:18626576). In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:9244310, PubMed:9252186, PubMed:9346484, PubMed:18626576). Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11) (PubMed:21765415). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes (PubMed:20501937). In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Participates also in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities (PubMed:17434128). Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP (PubMed:12789342). Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor (PubMed:15084260). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates AMBRA1 following mitophagy induction, promoting AMBRA1 interaction with ATG8 family proteins and its mitophagic activity (PubMed:30217973). {ECO:0000250|UniProtKB:Q60680, ECO:0000269|PubMed:12789342, ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:17434128, ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:20501937, ECO:0000269|PubMed:21765415, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35952808, ECO:0000269|PubMed:9244310, ECO:0000269|PubMed:9252186, ECO:0000269|PubMed:9346484, ECO:0000303|PubMed:18626576}.FUNCTION: Binds heparin and heparan sulfate with high affinity, but lacks heparanase activity. Inhibits HPSE, possibly by competing for its substrates (in vitro). {ECO:0000269|PubMed:20576607}.

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 CHUK_HPSE2


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
CHUKO15111humanNCOA3Q9Y6Q9S857PPYNRAVsLDsPVsV
CHUKO15111humanMAP3K14Q99558S820PsKAsQSsRDTLSSG
CHUKO15111humanNFKB1P19838S923DELRDSDsVCDsGVE
CHUKO15111humanMTORP42345S1418AILEsLIsINNKLQQ
CHUKO15111humanFOXA2Q9Y261S107AGMGPHLsPSLsPLGForkhead_N
CHUKO15111humanATG16L1Q676U5S278PAGGLLDsITNIFGR
CHUKO15111humanCOPS5Q92905S201kPPDEGPsEyQtIPL
CHUKO15111humanCTNNB1P35222S37yLDsGIHsGATtTAP
CHUKO15111humanMTURNQ8N3F0S58GDNFHVWsESEDCLPDUF4581
CHUKO15111humanH3C1P68431S10tkQtArkstGGkAPrHistone
CHUKO15111humanCTNNB1P35222S45GATtTAPsLsGkGNP
CHUKO15111humanCREBBPQ92793S1382MkSRFVDsGEMsESFHAT_KAT11
CHUKO15111humanMTORP42345S1415PTPAILEsLIsINNK
CHUKO15111humanRELAQ04206S536sGDEDFSsIADMDFS
CHUKO15111humanELAVL1Q15717S304EAAMAIAsLNGYRLGRRM_1
CHUKO15111humanCCND1P24385T286EEVDLACtPtDVRDV
CHUKO15111humanBCL3P20749S454PsPAPGGs_______
CHUKO15111humanFOXA2Q9Y261S111PHLsPSLsPLGGQAAForkhead_N
CHUKO15111humanNFKB2Q00653S870kEDsAyGsQsVEQEA
CHUKO15111humanTAX1BP1Q86VP1-2S593NYKELKRsLENPAER
CHUKO15111humanMYCP01106S82PLsPsRRsGLCsPSyMyc_N
CHUKO15111humanCOPS5Q92905T205EGPsEyQtIPLNkIE
CHUKO15111humanNFKBIAP25963S32LLDDRHDsGLDsMkD
CHUKO15111humanFOXO3O43524S644GLDFNFDsLISTQNVFOXO-TAD
CHUKO15111humanRELQ04864S557SNTTVFVsQSDAFEG
CHUKO15111humanNFKB1P19838S927DSDsVCDsGVETsFR
CHUKO15111humanMYCP01106S86sRRsGLCsPSyVAVtMyc_N
CHUKO15111humanESR1P03372S118LHPPPQLsPFLQPHGOest_recep
CHUKO15111humanTRAF4Q9BUZ4S426kPGtWRGsLDEsSLG
CHUKO15111humanNFKBIAP25963S36RHDsGLDsMkDEEyE
CHUKO15111humanNFKB2Q00653S872DsAyGsQsVEQEAEK
CHUKO15111humanRELBQ01201S472DFFSGTVsLPGLEPPRelB_transactiv
CHUKO15111humanNFKB2Q00653S115sLVGkQCsELGICAVRHD_DNA_bind
CHUKO15111humanAMBRA1Q9C0C7S1043CRPEALNsGVEYYWD
CHUKO15111humanPPP1R1BQ9UD71T34MIrRRRPtPAMLFRLDARPP-32
CHUKO15111humanMAP3K14Q99558S817EKNPsKAsQSsRDTL
CHUKO15111humanNFKB2Q00653S99EVDLVtHsDPPRAHARHD_DNA_bind
CHUKO15111humanNCOR2Q9Y618S2407AkVSGRPsSRKAKsP
CHUKO15111humanCTNNB1P35222S33QQQsyLDsGIHsGAT
CHUKO15111humanBBC3Q9BXH1S10RARQEGSsPEPVEGLPUMA
CHUKO15111humanMAP3K14Q99558S814DDSEKNPsKAsQSsR
CHUKO15111humanCREBBPQ92793S1386FVDsGEMsESFPyRTHAT_KAT11
CHUKO15111humanTAX1BP1Q86VP1-2S624RPPVRVPsWGLEDNV
CHUKO15111humanNFKB2Q00653S123ELGICAVsVGPKDMTRHD_DNA_bind
CHUKO15111humanCTNNB1P35222T41GIHsGATtTAPsLsG
CHUKO15111humanNFKB1P19838S932CDsGVETsFRKLsFt
CHUKO15111humanNFKB2Q00653S108PPRAHAHsLVGkQCsRHD_DNA_bind
CHUKO15111humanNFKB2Q00653S866tAEVkEDsAyGsQsV


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
CHUKIDDescription0.00e+00
CHUKGO:0007249canonical NF-kappaB signal transduction3.57e-10
CHUKGO:0038061non-canonical NF-kappaB signal transduction4.13e-10
CHUKGO:2000628regulation of miRNA metabolic process1.35e-06
CHUKGO:0140747regulation of ncRNA transcription1.35e-06
CHUKGO:0051090regulation of DNA-binding transcription factor activity1.35e-06
CHUKGO:0010586miRNA metabolic process2.26e-06
CHUKGO:0098781ncRNA transcription9.17e-06
CHUKGO:0035994response to muscle stretch9.28e-06
CHUKGO:1902893regulation of miRNA transcription9.29e-06
CHUKGO:0061614miRNA transcription9.29e-06
CHUKGO:0043433negative regulation of DNA-binding transcription factor activity1.98e-05
CHUKGO:0071496cellular response to external stimulus7.02e-05
CHUKGO:0045637regulation of myeloid cell differentiation7.02e-05
CHUKGO:1903706regulation of hemopoiesis2.14e-04
CHUKGO:0043122regulation of canonical NF-kappaB signal transduction2.16e-04
CHUKGO:2000630positive regulation of miRNA metabolic process2.16e-04
CHUKGO:0030099myeloid cell differentiation2.16e-04
CHUKGO:0009411response to UV2.31e-04
CHUKGO:0048511rhythmic process3.25e-04
CHUKGO:0030217T cell differentiation3.67e-04
CHUKGO:1903131mononuclear cell differentiation3.67e-04
CHUKGO:0009416response to light stimulus4.23e-04
CHUKGO:1902894negative regulation of miRNA transcription4.43e-04
CHUKGO:2000629negative regulation of miRNA metabolic process4.57e-04
CHUKGO:0032088negative regulation of NF-kappaB transcription factor activity4.57e-04
CHUKGO:0071214cellular response to abiotic stimulus4.57e-04
CHUKGO:0104004cellular response to environmental stimulus4.57e-04
CHUKGO:0009612response to mechanical stimulus7.68e-04
CHUKGO:0051403stress-activated MAPK cascade1.07e-03
CHUKGO:0032355response to estradiol1.15e-03
CHUKGO:0031098stress-activated protein kinase signaling cascade1.18e-03
CHUKGO:0031669cellular response to nutrient levels1.48e-03
CHUKGO:0009314response to radiation1.49e-03
CHUKGO:0030098lymphocyte differentiation1.49e-03
CHUKGO:0070741response to interleukin-61.64e-03
CHUKGO:0048732gland development1.69e-03
CHUKGO:0030879mammary gland development1.77e-03
CHUKGO:0042088T-helper 1 type immune response1.97e-03
CHUKGO:0031668cellular response to extracellular stimulus2.08e-03
CHUKGO:1902895positive regulation of miRNA transcription2.38e-03
CHUKGO:0031667response to nutrient levels2.75e-03
CHUKGO:0034504protein localization to nucleus3.07e-03
CHUKGO:0007254JNK cascade3.36e-03
CHUKGO:1902105regulation of leukocyte differentiation3.43e-03
CHUKGO:0022409positive regulation of cell-cell adhesion3.43e-03
CHUKGO:0034250positive regulation of amide metabolic process3.61e-03
CHUKGO:0033234negative regulation of protein sumoylation3.81e-03
CHUKGO:0019827stem cell population maintenance4.71e-03
CHUKGO:0032872regulation of stress-activated MAPK cascade4.91e-03

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Related Drugs to CHUK_HPSE2


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 CHUK-HPSE2 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 CHUK_HPSE2


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