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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:CTSC_JAK1

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: CTSC_JAK1
KinaseFusionDB ID: KFG1567
FusionGDB2.0 ID: KFG1567
HgeneTgene
Gene symbol

CTSC

JAK1

Gene ID

1075

3716

Gene namecathepsin CJanus kinase 1
SynonymsCPPI|DPP-I|DPP1|DPPI|HMS|JP|JPD|PALS|PDON1|PLSAIIDE|JAK1A|JAK1B|JTK3
Cytomap

11q14.2

1p31.3

Type of geneprotein-codingprotein-coding
Descriptiondipeptidyl peptidase 1cathepsin Jdipeptidyl transferasedipeptidyl-peptidase Ityrosine-protein kinase JAK1
Modification date2024041120240411
UniProtAcc

P53634

P23458

Ensembl transtripts involved in fusion geneENST idsENST00000227266, ENST00000393301, 
ENST00000524463, ENST00000529974, 
ENST00000342505, ENST00000465376, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: CTSC [Title/Abstract] AND JAK1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CTSC(88027212)-JAK1(65325893), # samples:3
check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneCTSC

GO:0006508

proteolysis

8811434

TgeneJAK1

GO:0007259

cell surface receptor signaling pathway via JAK-STAT

7657660|8232552|8272873

TgeneJAK1

GO:0035723

interleukin-15-mediated signaling pathway

7568001

TgeneJAK1

GO:0035771

interleukin-4-mediated signaling pathway

7929391

TgeneJAK1

GO:0038110

interleukin-2-mediated signaling pathway

7973659|11909529

TgeneJAK1

GO:0038113

interleukin-9-mediated signaling pathway

8756628

TgeneJAK1

GO:0038154

interleukin-11-mediated signaling pathway

8272872

TgeneJAK1

GO:0046677

response to antibiotic

16280321

TgeneJAK1

GO:0060333

type II interferon-mediated signaling pathway

8232552

TgeneJAK1

GO:0060337

type I interferon-mediated signaling pathway

7532278|8232552

TgeneJAK1

GO:0070102

interleukin-6-mediated signaling pathway

8272873

TgeneJAK1

GO:1900182

positive regulation of protein localization to nucleus

26479788


check buttonKinase Fusion gene breakpoints across CTSC (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 JAK1 (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-BQ-5878CTSCchr11

88027212

JAK1chr1

65325893



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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/:88027212/:65325893)
- 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
CTSC

P53634

JAK1

P23458

FUNCTION: Thiol protease (PubMed:1586157). Has dipeptidylpeptidase activity (PubMed:1586157). Active against a broad range of dipeptide substrates composed of both polar and hydrophobic amino acids (PubMed:1586157). Proline cannot occupy the P1 position and arginine cannot occupy the P2 position of the substrate (PubMed:1586157). Can act as both an exopeptidase and endopeptidase (PubMed:1586157). Activates serine proteases such as elastase, cathepsin G and granzymes A and B (PubMed:8428921). {ECO:0000269|PubMed:1586157, ECO:0000269|PubMed:8428921}.FUNCTION: Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway (PubMed:8232552, PubMed:7615558, PubMed:28111307, PubMed:32750333, PubMed:16239216). Kinase partner for the interleukin (IL)-2 receptor (PubMed:11909529) as well as interleukin (IL)-10 receptor (PubMed:12133952). Kinase partner for the type I interferon receptor IFNAR2 (PubMed:8232552, PubMed:7615558, PubMed:28111307, PubMed:32750333, PubMed:16239216). In response to interferon-binding to IFNAR1-IFNAR2 heterodimer, phosphorylates and activates its binding partner IFNAR2, creating docking sites for STAT proteins (PubMed:7759950). Directly phosphorylates STAT proteins but also activates STAT signaling through the transactivation of other JAK kinases associated with signaling receptors (PubMed:8232552, PubMed:16239216, PubMed:32750333). {ECO:0000269|PubMed:11909529, ECO:0000269|PubMed:12133952, ECO:0000269|PubMed:16239216, ECO:0000269|PubMed:28111307, ECO:0000269|PubMed:32750333, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:7657660, ECO:0000269|PubMed:8232552}.

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 CTSC_JAK1


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
JAK1P23458humanSIRT1Q96EB6Y280FRSRDGIyARLAVDFSIR2
JAK1P23458humanEIF2AK3Q9NZJ5Y585NDIkNSGyISRYLTD
JAK1P23458humanSTAT5AP42229Y694LAkAVDGyVkPQIkQ
JAK1P23458humanRIPK1Q13546Y384kLQDEANyHLyGsRM
JAK1P23458humanSNX8Q9Y5X2Y126MLLHkFPyRMVPALPPX
JAK1P23458humanMAP3K5Q99683Y718IPERDSRySQPLHEEPkinase
JAK1P23458humanH3C1P68431Y41GVkkPHryrPGtVALHistone
JAK1P23458humanEIF2AK3Q9NZJ5Y619NKVDDCNyAIkRIRLPkinase
JAK1P23458humanSIRT1Q96EB6Y301QAMFDIEyFRKDPRPSIR2
JAK1P23458humanSNX8Q9Y5X2Y95LFLKHVEyEVSSQRF
JAK1P23458humanCD274Q9NZQ7Y112KLQDAGVyRCMISYGV-set
JAK1P23458humanSTAT1P42224Y701DGPkGtGyIktELIs


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
JAK1IDDescription0.00e+00
JAK1GO:0042542response to hydrogen peroxide7.47e-05
JAK1GO:0001819positive regulation of cytokine production3.40e-04
JAK1GO:0000302response to reactive oxygen species3.40e-04
JAK1GO:0043124negative regulation of canonical NF-kappaB signal transduction3.40e-04
JAK1GO:0071356cellular response to tumor necrosis factor3.96e-04
JAK1GO:0070059intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress3.96e-04
JAK1GO:0070301cellular response to hydrogen peroxide3.96e-04
JAK1GO:0034612response to tumor necrosis factor4.05e-04
JAK1GO:0062197cellular response to chemical stress8.02e-04
JAK1GO:0043280positive regulation of cysteine-type endopeptidase activity involved in apoptotic process1.27e-03
JAK1GO:0071887leukocyte apoptotic process1.50e-03
JAK1GO:0006979response to oxidative stress1.50e-03
JAK1GO:2001056positive regulation of cysteine-type endopeptidase activity1.53e-03
JAK1GO:0030099myeloid cell differentiation1.71e-03
JAK1GO:0034614cellular response to reactive oxygen species2.20e-03
JAK1GO:0010950positive regulation of endopeptidase activity2.20e-03
JAK1GO:0043281regulation of cysteine-type endopeptidase activity involved in apoptotic process2.31e-03
JAK1GO:0031667response to nutrient levels2.31e-03
JAK1GO:0010952positive regulation of peptidase activity2.39e-03
JAK1GO:0009267cellular response to starvation2.61e-03
JAK1GO:0001936regulation of endothelial cell proliferation2.61e-03
JAK1GO:2000108positive regulation of leukocyte apoptotic process2.70e-03
JAK1GO:2000116regulation of cysteine-type endopeptidase activity2.97e-03
JAK1GO:0001935endothelial cell proliferation3.16e-03
JAK1GO:1902235regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway3.32e-03
JAK1GO:0042594response to starvation3.65e-03
JAK1GO:0002573myeloid leukocyte differentiation4.40e-03
JAK1GO:0031669cellular response to nutrient levels5.15e-03
JAK1GO:0034599cellular response to oxidative stress5.21e-03
JAK1GO:0043122regulation of canonical NF-kappaB signal transduction5.52e-03
JAK1GO:0034976response to endoplasmic reticulum stress5.52e-03
JAK1GO:0042149cellular response to glucose starvation5.74e-03
JAK1GO:0051402neuron apoptotic process5.74e-03
JAK1GO:0034198cellular response to amino acid starvation5.74e-03
JAK1GO:0031668cellular response to extracellular stimulus5.74e-03
JAK1GO:0052548regulation of endopeptidase activity6.00e-03
JAK1GO:1990928response to amino acid starvation6.05e-03
JAK1GO:0007249canonical NF-kappaB signal transduction6.41e-03
JAK1GO:0070231T cell apoptotic process6.58e-03
JAK1GO:0071375cellular response to peptide hormone stimulus6.58e-03
JAK1GO:0052547regulation of peptidase activity6.58e-03
JAK1GO:0097300programmed necrotic cell death6.58e-03
JAK1GO:0097193intrinsic apoptotic signaling pathway6.79e-03
JAK1GO:0008631intrinsic apoptotic signaling pathway in response to oxidative stress6.92e-03
JAK1GO:0030225macrophage differentiation6.99e-03
JAK1GO:0071496cellular response to external stimulus8.05e-03
JAK1GO:0045862positive regulation of proteolysis8.15e-03
JAK1GO:0043536positive regulation of blood vessel endothelial cell migration9.23e-03
JAK1GO:1901653cellular response to peptide9.49e-03

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Related Drugs to CTSC_JAK1


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 CTSC-JAK1 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 CTSC_JAK1


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