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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:DYNLT1_MAP2K4

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: DYNLT1_MAP2K4
KinaseFusionDB ID: KFG1770
FusionGDB2.0 ID: KFG1770
HgeneTgene
Gene symbol

DYNLT1

MAP2K4

Gene ID

6993

6416

Gene namedynein light chain Tctex-type 1mitogen-activated protein kinase kinase 4
SynonymsCW-1|TCTEL1|TCTEX1|tctex-1JNKK|JNKK1|MAPKK4|MEK4|MKK4|PRKMK4|SAPKK-1|SAPKK1|SEK1|SERK1|SKK1
Cytomap

6q25.3

17p12

Type of geneprotein-codingprotein-coding
Descriptiondynein light chain Tctex-type 1T-complex testis-specific protein 1 homologt-complex-associated-testis-expressed 1-like 1dual specificity mitogen-activated protein kinase kinase 4JNK-activated kinase 1JNK-activating kinase 1MAP kinase kinase 4MAPK/ERK kinase 4MAPKK 4MEK 4SAPK/ERK kinase 1c-Jun N-terminal kinase kinase 1c-Jun NH2-terminal kinase kinase 1stress-acti
Modification date2024030520240403
UniProtAcc

P63172

P45985

Ensembl transtripts involved in fusion geneENST idsENST00000367085, ENST00000367089, 
ENST00000367088, 
ENST00000353533, 
ENST00000415385, ENST00000581941, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: DYNLT1 [Title/Abstract] AND MAP2K4 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DYNLT1(159058888)-MAP2K4(12018920), # samples:1
DYNLT1(159065714)-MAP2K4(12018848), # 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

check buttonKinase Fusion gene breakpoints across DYNLT1 (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 MAP2K4 (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
ChiTaRS5.0FN110717DYNLT1chr6

159065714

MAP2K4chr17

12018848

ChimerDB4TCGA-S9-A6U1-01ADYNLT1chr6

159058888

MAP2K4chr17

12018920



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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/:159058888/:12018920)
- 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
DYNLT1

P63172

MAP2K4

P45985

FUNCTION: Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Binds to transport cargos and is involved in apical cargo transport such as rhodopsin-bearing vesicles in polarized epithelia. May also be a accessory component of axonemal dynein.; FUNCTION: Plays a role in neuronal morphogenesis; the function is independent of cytoplasmic dynein and seems to be coupled to regulation of the actin cytoskeleton by enhancing Rac1 activity. The function in neurogenesis may be regulated by association with a G-protein beta-gamma dimer. May function as a receptor-independent activator of heterotrimeric G-protein signaling; the activation appears to be independent of a nucleotide exchange. Plays a role in regulating neurogenesis; inhibits the genesis of neurons from precursor cells during cortical development presumably by antagonizing ARHGEF2. Involved in the regulation of mitotic spindle orientation (By similarity). Unrelated to the role in retrograde microtubule-associated movement may play a role in the dimerization of cytoplasmic proteins/domains such as for ACVR2B. Binds to the cytoplasmic domain of ACVR2B and, in vitro, inhibits ACVR2B signaling (PubMed:27502274). {ECO:0000250, ECO:0000269|PubMed:27502274}.; FUNCTION: (Microbial infection) Is involved in intracellular targeting of D-type retrovirus gag polyproteins to the cytoplasmic assembly site. {ECO:0000269|PubMed:18647839}.FUNCTION: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to pro-inflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14. {ECO:0000269|PubMed:7716521}.

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 DYNLT1_MAP2K4


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
MAP2K4P45985humanMAPK8P45983-2Y185TSFMMtPyVVTRYYRPkinase
MAP2K4P45985humanMAPK9P45984Y185tNFMMtPyVVtRYYRPkinase
MAP2K4P45985humanMAPK8P45983Y185tsFMMtPyVVtRYYRPkinase
MAP2K4P45985humanRXRAP19793Y249VEPKTETyVEANMGL
MAP2K4P45985humanMAPK10P53779Y223tsFMMtPyVVtRYYRPkinase
MAP2K4P45985humanMAP2K4P45985S257ISGQLVDsIAKtRDAPkinase
MAP2K4P45985humanMAPK8P45983-3T228GGVLFPGtDHIDQWNPkinase
MAP2K4P45985humanMAPK8P45983-3S377GVIRGQPsPLAQVQQ
MAP2K4P45985humanMAPK10P53779-2Y223TSFMMtPyVVTRYYRPkinase
MAP2K4P45985humanMAPK8P45983T183AGtsFMMtPyVVtRYPkinase
MAP2K4P45985humanMAPK8P45983-3T183AGTSFMMtPyVVTRYPkinase
MAP2K4P45985humanMAPK14Q16539T180RHtDDEMtGyVAtRWPkinase
MAP2K4P45985humanMAPK8P45983-3S284DVLFPADsEHNKLKAPkinase
MAP2K4P45985humanMAPK8P45983-3Y185TSFMMtPyVVTRYYRPkinase
MAP2K4P45985humanMAP2K4P45985T261LVDsIAKtRDAGCRPPkinase
MAP2K4P45985humanMAPK14Q16539Y182tDDEMtGyVAtRWYRPkinase


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
MAP2K4IDDescription0.00e+00
MAP2K4GO:0038095Fc-epsilon receptor signaling pathway7.81e-09
MAP2K4GO:0090398cellular senescence7.81e-09
MAP2K4GO:0038093Fc receptor signaling pathway1.47e-07
MAP2K4GO:0051403stress-activated MAPK cascade1.55e-07
MAP2K4GO:0031098stress-activated protein kinase signaling cascade1.55e-07
MAP2K4GO:0007254JNK cascade5.64e-06
MAP2K4GO:0002768immune response-regulating cell surface receptor signaling pathway9.85e-05
MAP2K4GO:0042752regulation of circadian rhythm2.26e-04
MAP2K4GO:0002764immune response-regulating signaling pathway3.32e-04
MAP2K4GO:0034614cellular response to reactive oxygen species4.46e-04
MAP2K4GO:0007623circadian rhythm8.76e-04
MAP2K4GO:0000302response to reactive oxygen species8.76e-04
MAP2K4GO:0009612response to mechanical stimulus9.06e-04
MAP2K4GO:0034599cellular response to oxidative stress1.44e-03
MAP2K4GO:0071276cellular response to cadmium ion1.59e-03
MAP2K4GO:0031281positive regulation of cyclase activity1.65e-03
MAP2K4GO:0018105peptidyl-serine phosphorylation1.75e-03
MAP2K4GO:0048511rhythmic process1.75e-03
MAP2K4GO:0018209peptidyl-serine modification1.85e-03
MAP2K4GO:0062197cellular response to chemical stress1.85e-03
MAP2K4GO:0009416response to light stimulus1.85e-03
MAP2K4GO:0071214cellular response to abiotic stimulus1.96e-03
MAP2K4GO:0104004cellular response to environmental stimulus1.96e-03
MAP2K4GO:0071496cellular response to external stimulus2.04e-03
MAP2K4GO:0031279regulation of cyclase activity2.04e-03
MAP2K4GO:0046686response to cadmium ion2.34e-03
MAP2K4GO:0006979response to oxidative stress2.84e-03
MAP2K4GO:0071260cellular response to mechanical stimulus3.24e-03
MAP2K4GO:0009314response to radiation3.24e-03
MAP2K4GO:0002534cytokine production involved in inflammatory response3.71e-03
MAP2K4GO:1900015regulation of cytokine production involved in inflammatory response3.71e-03
MAP2K4GO:0055017cardiac muscle tissue growth4.34e-03
MAP2K4GO:0031667response to nutrient levels4.37e-03
MAP2K4GO:0060419heart growth4.85e-03
MAP2K4GO:0002532production of molecular mediator involved in inflammatory response5.62e-03
MAP2K4GO:0030278regulation of ossification7.12e-03
MAP2K4GO:0009411response to UV1.09e-02
MAP2K4GO:0090316positive regulation of intracellular protein transport1.15e-02
MAP2K4GO:0035265organ growth1.40e-02
MAP2K4GO:0031334positive regulation of protein-containing complex assembly1.67e-02
MAP2K4GO:0071248cellular response to metal ion1.67e-02
MAP2K4GO:0032388positive regulation of intracellular transport1.67e-02
MAP2K4GO:0033157regulation of intracellular protein transport2.01e-02
MAP2K4GO:0071222cellular response to lipopolysaccharide2.01e-02
MAP2K4GO:0071241cellular response to inorganic substance2.02e-02
MAP2K4GO:0071219cellular response to molecule of bacterial origin2.15e-02
MAP2K4GO:0048738cardiac muscle tissue development2.24e-02
MAP2K4GO:0031669cellular response to nutrient levels2.26e-02
MAP2K4GO:0014706striated muscle tissue development2.42e-02

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Related Drugs to DYNLT1_MAP2K4


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 DYNLT1-MAP2K4 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 DYNLT1_MAP2K4


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