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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:MAPKAPK3_SLC5A6

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: MAPKAPK3_SLC5A6
KinaseFusionDB ID: KFG3599
FusionGDB2.0 ID: KFG3599
HgeneTgene
Gene symbol

MAPKAPK3

SLC5A6

Gene ID

7867

8884

Gene nameMAPK activated protein kinase 3solute carrier family 5 member 6
Synonyms3PK|MAPKAP-K3|MAPKAP3|MAPKAPK-3|MDPT3|MK-3|MK3COMNB|NERIB|SMVT|SMVTD|hSMVT
Cytomap

3p21.2

2p23.3

Type of geneprotein-codingprotein-coding
DescriptionMAP kinase-activated protein kinase 3MAPKAP kinase 3chromosome 3p kinasemitogen-activated protein kinase-activated protein kinase 3sodium-dependent multivitamin transporterNa(+)-dependent multivitamin transporterNa+-dependent multivitamin transportersolute carrier family 5 (sodium-dependent vitamin transporter), member 6solute carrier family 5 (sodium/multivitamin and iodide cotr
Modification date2024040320240403
UniProtAcc

Q16644

Q9Y289

Ensembl transtripts involved in fusion geneENST idsENST00000446044, ENST00000497283, 
ENST00000357955, 
ENST00000310574, 
ENST00000408041, ENST00000461319, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: MAPKAPK3 [Title/Abstract] AND SLC5A6 [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
HgeneMAPKAPK3

GO:0018105

peptidyl-serine phosphorylation

15850461

HgeneMAPKAPK3

GO:0034097

response to cytokine

8774846

TgeneSLC5A6

GO:0015878

biotin transport

10329687|15561972|19211916|20980265

TgeneSLC5A6

GO:0015887

pantothenate transmembrane transport

10329687

TgeneSLC5A6

GO:1904200

iodide transmembrane transport

20980265

TgeneSLC5A6

GO:1905135

biotin import across plasma membrane

21570947|22015582


check buttonKinase Fusion gene breakpoints across MAPKAPK3 (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 SLC5A6 (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
CCLESW1463MAPKAPK3chr3

50686152

SLC5A6chr2

27422742



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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/:/:)
- 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
MAPKAPK3

Q16644

SLC5A6

Q9Y289

FUNCTION: Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins, such as TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:15563468, ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20599781, ECO:0000269|PubMed:8626550, ECO:0000269|PubMed:8774846}.FUNCTION: Sodium-dependent multivitamin transporter that mediates the electrogenic transport of pantothenate, biotin, lipoate and iodide (PubMed:10329687, PubMed:15561972, PubMed:19211916, PubMed:21570947, PubMed:20980265, PubMed:22015582, PubMed:25971966, PubMed:25809983, PubMed:28052864, PubMed:27904971, PubMed:31754459). Functions as a Na(+)-coupled substrate symporter where the stoichiometry of Na(+):substrate is 2:1, creating an electrochemical Na(+) gradient used as driving force for substrate uptake (PubMed:10329687, PubMed:20980265). Required for biotin and pantothenate uptake in the intestine across the brush border membrane (PubMed:19211916). Plays a role in the maintenance of intestinal mucosa integrity, by providing the gut mucosa with biotin (By similarity). Contributes to the luminal uptake of biotin and pantothenate into the brain across the blood-brain barrier (PubMed:25809983). {ECO:0000250|UniProtKB:Q5U4D8, ECO:0000269|PubMed:10329687, ECO:0000269|PubMed:15561972, ECO:0000269|PubMed:19211916, ECO:0000269|PubMed:20980265, ECO:0000269|PubMed:21570947, ECO:0000269|PubMed:22015582, ECO:0000269|PubMed:25809983, ECO:0000269|PubMed:25971966, ECO:0000269|PubMed:27904971, ECO:0000269|PubMed:28052864, ECO:0000269|PubMed:31754459}.

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 MAPKAPK3_SLC5A6


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
MAPKAPK3Q16644humanTAB3Q8N5C8S506HKYQRsSsSGSDDyA
MAPKAPK3Q16644humanBECN1Q14457S90IPPARMMstEsANsF
MAPKAPK3Q16644humanHSPB1P04792S82RALsRQLssGVsEIr


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
MAPKAPK3IDDescription0.00e+00
MAPKAPK3GO:0010506regulation of autophagy1.63e-03
MAPKAPK3GO:0010507negative regulation of autophagy8.31e-03
MAPKAPK3GO:2001242regulation of intrinsic apoptotic signaling pathway2.22e-02
MAPKAPK3GO:0031330negative regulation of cellular catabolic process2.22e-02
MAPKAPK3GO:0043122regulation of canonical NF-kappaB signal transduction2.80e-02
MAPKAPK3GO:0007249canonical NF-kappaB signal transduction2.80e-02
MAPKAPK3GO:0097193intrinsic apoptotic signaling pathway2.80e-02
MAPKAPK3GO:0009895negative regulation of catabolic process2.80e-02
MAPKAPK3GO:2001233regulation of apoptotic signaling pathway2.80e-02
MAPKAPK3GO:0009615response to virus2.80e-02
MAPKAPK3GO:0051987positive regulation of attachment of spindle microtubules to kinetochore2.80e-02
MAPKAPK3GO:1905383protein localization to presynapse2.80e-02
MAPKAPK3GO:0006995cellular response to nitrogen starvation2.80e-02
MAPKAPK3GO:0043562cellular response to nitrogen levels2.80e-02
MAPKAPK3GO:1905671regulation of lysosome organization2.80e-02
MAPKAPK3GO:0090235regulation of metaphase plate congression2.80e-02
MAPKAPK3GO:1902902negative regulation of autophagosome assembly2.80e-02
MAPKAPK3GO:0098840protein transport along microtubule2.80e-02
MAPKAPK3GO:0099118microtubule-based protein transport2.80e-02
MAPKAPK3GO:0043652engulfment of apoptotic cell2.80e-02
MAPKAPK3GO:2001028positive regulation of endothelial cell chemotaxis2.80e-02
MAPKAPK3GO:0035821modulation of process of another organism3.05e-02
MAPKAPK3GO:2000786positive regulation of autophagosome assembly3.05e-02
MAPKAPK3GO:0010288response to lead ion3.05e-02
MAPKAPK3GO:0051315attachment of mitotic spindle microtubules to kinetochore3.05e-02
MAPKAPK3GO:0051988regulation of attachment of spindle microtubules to kinetochore3.05e-02
MAPKAPK3GO:0098780response to mitochondrial depolarisation3.05e-02
MAPKAPK3GO:0036092phosphatidylinositol-3-phosphate biosynthetic process3.08e-02
MAPKAPK3GO:0044090positive regulation of vacuole organization3.14e-02
MAPKAPK3GO:2001026regulation of endothelial cell chemotaxis3.14e-02
MAPKAPK3GO:0071280cellular response to copper ion3.21e-02
MAPKAPK3GO:0042026protein refolding3.21e-02
MAPKAPK3GO:0051984positive regulation of chromosome segregation3.21e-02
MAPKAPK3GO:0032801receptor catabolic process3.23e-02
MAPKAPK3GO:0010039response to iron ion3.32e-02
MAPKAPK3GO:0035767endothelial cell chemotaxis3.32e-02
MAPKAPK3GO:0016242negative regulation of macroautophagy3.32e-02
MAPKAPK3GO:0006622protein targeting to lysosome3.32e-02
MAPKAPK3GO:1902176negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway3.32e-02
MAPKAPK3GO:0010613positive regulation of cardiac muscle hypertrophy3.32e-02
MAPKAPK3GO:0014742positive regulation of muscle hypertrophy3.32e-02
MAPKAPK3GO:0045324late endosome to vacuole transport3.32e-02
MAPKAPK3GO:0046688response to copper ion3.32e-02
MAPKAPK3GO:0000423mitophagy3.32e-02
MAPKAPK3GO:0071364cellular response to epidermal growth factor stimulus3.32e-02
MAPKAPK3GO:0045022early endosome to late endosome transport3.32e-02
MAPKAPK3GO:0070849response to epidermal growth factor3.32e-02
MAPKAPK3GO:1902116negative regulation of organelle assembly3.32e-02
MAPKAPK3GO:1902175regulation of oxidative stress-induced intrinsic apoptotic signaling pathway3.32e-02

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Related Drugs to MAPKAPK3_SLC5A6


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 MAPKAPK3-SLC5A6 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 MAPKAPK3_SLC5A6


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