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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:MAP3K5_NKAIN2

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: MAP3K5_NKAIN2
KinaseFusionDB ID: KFG3430
FusionGDB2.0 ID: KFG3430
HgeneTgene
Gene symbol

MAP3K5

NKAIN2

Gene ID

4217

154215

Gene namemitogen-activated protein kinase kinase kinase 5sodium/potassium transporting ATPase interacting 2
SynonymsASK1|MAPKKK5|MEKK5FAM77B|NKAIP2|TCBA|TCBA1
Cytomap

6q23.3

6q22.31

Type of geneprotein-codingprotein-coding
Descriptionmitogen-activated protein kinase kinase kinase 5ASK-1MAP/ERK kinase kinase 5MAPK/ERK kinase kinase 5MEK kinase 5MEKK 5apoptosis signal-regulating kinase 1sodium/potassium-transporting ATPase subunit beta-1-interacting protein 2Na(+)/K(+)-transporting ATPase subunit beta-1-interacting protein 2Na+/K+ transporting ATPase interacting 2T-cell lymphoma breakpoint-associated target protein 1
Modification date2024040320240403
UniProtAcc

Q99683

Q5VXU1

Ensembl transtripts involved in fusion geneENST idsENST00000359015, ENST00000355845, 
ENST00000463140, 		ENST00000368416, 
ENST00000368417, ENST00000476571, 
ENST00000545433, ENST00000546092, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: MAP3K5 [Title/Abstract] AND NKAIN2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MAP3K5(137041588)-NKAIN2(125112485), # 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
HgeneMAP3K5

GO:0000165

MAPK cascade

17210579|21771788

HgeneMAP3K5

GO:0006468

protein phosphorylation

11096076|15983381

HgeneMAP3K5

GO:0007254

JNK cascade

11959862|21771788

HgeneMAP3K5

GO:0008631

intrinsic apoptotic signaling pathway in response to oxidative stress

21771788|26095851

HgeneMAP3K5

GO:0034198

cellular response to amino acid starvation

11096076

HgeneMAP3K5

GO:0043065

positive regulation of apoptotic process

21771788

HgeneMAP3K5

GO:0043280

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

20674765

HgeneMAP3K5

GO:0045860

positive regulation of protein kinase activity

11959862

HgeneMAP3K5

GO:0045893

positive regulation of DNA-templated transcription

11096076

HgeneMAP3K5

GO:0051403

stress-activated MAPK cascade

11096076

HgeneMAP3K5

GO:0070301

cellular response to hydrogen peroxide

20674765


check buttonKinase Fusion gene breakpoints across MAP3K5 (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 NKAIN2 (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-66-2759-01AMAP3K5chr6

137041588

NKAIN2chr6

125112485



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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/:137041588/:125112485)
- 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
MAP3K5

Q99683

NKAIN2

Q5VXU1

FUNCTION: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1). {ECO:0000269|PubMed:10411906, ECO:0000269|PubMed:10688666, ECO:0000269|PubMed:10849426, ECO:0000269|PubMed:11029458, ECO:0000269|PubMed:11154276, ECO:0000269|PubMed:11689443, ECO:0000269|PubMed:11920685, ECO:0000269|PubMed:14688258, ECO:0000269|PubMed:14749717, ECO:0000269|PubMed:15023544, ECO:0000269|PubMed:16129676, ECO:0000269|PubMed:17220297, ECO:0000269|PubMed:23102700, ECO:0000269|PubMed:26095851, ECO:0000269|PubMed:8940179, ECO:0000269|PubMed:8974401, ECO:0000269|PubMed:9564042, ECO:0000269|PubMed:9774977}.

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 MAP3K5_NKAIN2


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
MAP3K5Q99683humanSIAH1Q8IUQ4T74PKLtCCPtCRGPLGS
MAP3K5Q99683humanMAP3K5Q99683T838GINPCTEtFTGtLQYPkinase
MAP3K5Q99683humanSTRAPQ9Y3F4T175LWDHAtMtEVKsLNF
MAP3K5Q99683humanSIAH1Q8IUQ4T239RRLtWEAtPRSIHEGSina
MAP3K5Q99683humanSIAH1Q8IUQ4T70SNCRPKLtCCPtCRG
MAP3K5Q99683humanMAPK8P45983Y185tsFMMtPyVVtRYYRPkinase
MAP3K5Q99683humanMAP3K5Q99683T842CTEtFTGtLQYMAPEPkinase
MAP3K5Q99683humanZNF622Q969S3S314WCNEkGksFYStEAVzf-C2H2_2
MAP3K5Q99683humanMAPRE1Q15691S40TKIEQLCsGAAYCQFCH
MAP3K5Q99683humanPDPK1O15530S398SSssHsLsASDTGLP
MAP3K5Q99683humanCDKN1AP38936S98GGRRPGTsPALLQGT
MAP3K5Q99683humanSIAH1Q8IUQ4T235NGHRRRLtWEAtPRSSina
MAP3K5Q99683humanDAXXQ9UER7S176TNAENTAsQsPRTRG
MAP3K5Q99683humanMAP2K3P46734S218IsGyLVDsVAKtMDAPkinase
MAP3K5Q99683humanMAPK8P45983T183AGtsFMMtPyVVtRYPkinase
MAP3K5Q99683humanMAP2K6P52564S207IsGyLVDsVAKtIDAPkinase
MAP3K5Q99683humanMAPK14Q16539T180RHtDDEMtGyVAtRWPkinase
MAP3K5Q99683humanSTRAPQ9Y3F4S179AtMtEVKsLNFNMSV
MAP3K5Q99683humanZNF622Q969S3T318kGksFYStEAVQAHMzf-C2H2_2
MAP3K5Q99683humanDAXXQ9UER7S184QsPRTRGsRRQIQRL
MAP3K5Q99683humanMAPRE1Q15691T206QVNVLKLtVEDLEkE
MAP3K5Q99683humanMAPRE1Q15691T154NkPkkPLtssSAAPQ
MAP3K5Q99683humanMAP3K5Q99683T813GDNVLINtySGVLKIPkinase
MAP3K5Q99683humanMAP2K4P45985T261LVDsIAKtRDAGCRPPkinase
MAP3K5Q99683humanPDPK1O15530S394QVSSSSssHsLsASD
MAP3K5Q99683humanMAPK14Q16539Y182tDDEMtGyVAtRWYRPkinase
MAP3K5Q99683humanMAP3K5Q99683S966NEYLRsIsLPVPVLV


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
MAP3K5IDDescription0.00e+00
MAP3K5GO:0090398cellular senescence1.84e-10
MAP3K5GO:0051403stress-activated MAPK cascade1.84e-10
MAP3K5GO:0031098stress-activated protein kinase signaling cascade1.84e-10
MAP3K5GO:0097193intrinsic apoptotic signaling pathway6.26e-06
MAP3K5GO:0033674positive regulation of kinase activity6.26e-06
MAP3K5GO:0038066p38MAPK cascade6.26e-06
MAP3K5GO:0007254JNK cascade6.26e-06
MAP3K5GO:0008631intrinsic apoptotic signaling pathway in response to oxidative stress7.85e-06
MAP3K5GO:0051770positive regulation of nitric-oxide synthase biosynthetic process1.26e-05
MAP3K5GO:0051347positive regulation of transferase activity1.29e-05
MAP3K5GO:0051767nitric-oxide synthase biosynthetic process1.92e-05
MAP3K5GO:0051769regulation of nitric-oxide synthase biosynthetic process1.92e-05
MAP3K5GO:0045860positive regulation of protein kinase activity5.14e-05
MAP3K5GO:0034198cellular response to amino acid starvation2.97e-04
MAP3K5GO:1990928response to amino acid starvation3.29e-04
MAP3K5GO:0002931response to ischemia4.93e-04
MAP3K5GO:0043410positive regulation of MAPK cascade4.99e-04
MAP3K5GO:0046330positive regulation of JNK cascade1.13e-03
MAP3K5GO:0071493cellular response to UV-B1.13e-03
MAP3K5GO:0010657muscle cell apoptotic process1.13e-03
MAP3K5GO:0051402neuron apoptotic process1.13e-03
MAP3K5GO:0035331negative regulation of hippo signaling1.23e-03
MAP3K5GO:0071214cellular response to abiotic stimulus2.01e-03
MAP3K5GO:0104004cellular response to environmental stimulus2.01e-03
MAP3K5GO:0071496cellular response to external stimulus2.20e-03
MAP3K5GO:0032874positive regulation of stress-activated MAPK cascade2.20e-03
MAP3K5GO:0070304positive regulation of stress-activated protein kinase signaling cascade2.23e-03
MAP3K5GO:0046328regulation of JNK cascade2.42e-03
MAP3K5GO:0010224response to UV-B2.42e-03
MAP3K5GO:0036480neuron intrinsic apoptotic signaling pathway in response to oxidative stress2.42e-03
MAP3K5GO:0038095Fc-epsilon receptor signaling pathway3.27e-03
MAP3K5GO:0071322cellular response to carbohydrate stimulus3.27e-03
MAP3K5GO:0009411response to UV3.27e-03
MAP3K5GO:0035330regulation of hippo signaling3.27e-03
MAP3K5GO:0034614cellular response to reactive oxygen species3.27e-03
MAP3K5GO:0046685response to arsenic-containing substance4.75e-03
MAP3K5GO:0009267cellular response to starvation4.82e-03
MAP3K5GO:0032872regulation of stress-activated MAPK cascade5.23e-03
MAP3K5GO:0042770signal transduction in response to DNA damage5.23e-03
MAP3K5GO:0070302regulation of stress-activated protein kinase signaling cascade5.23e-03
MAP3K5GO:0031667response to nutrient levels5.33e-03
MAP3K5GO:0071276cellular response to cadmium ion5.33e-03
MAP3K5GO:0002764immune response-regulating signaling pathway5.33e-03
MAP3K5GO:0031281positive regulation of cyclase activity5.79e-03
MAP3K5GO:0000302response to reactive oxygen species5.90e-03
MAP3K5GO:0009612response to mechanical stimulus6.46e-03
MAP3K5GO:0045663positive regulation of myoblast differentiation6.59e-03
MAP3K5GO:0042594response to starvation6.62e-03
MAP3K5GO:0035329hippo signaling6.62e-03

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Related Drugs to MAP3K5_NKAIN2


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 MAP3K5-NKAIN2 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 MAP3K5_NKAIN2


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