Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS93BTX)

DOT Name Mitogen-activated protein kinase kinase kinase 13 (MAP3K13)
Synonyms EC 2.7.11.25; Leucine zipper-bearing kinase; Mixed lineage kinase; MLK
Gene Name MAP3K13
Related Disease
Breast cancer ( )
Breast carcinoma ( )
Cardiac failure ( )
Congestive heart failure ( )
Hepatocellular carcinoma ( )
Parkinson disease ( )
Advanced cancer ( )
Head and neck cancer ( )
Head and neck carcinoma ( )
Head-neck squamous cell carcinoma ( )
Melanoma ( )
Neoplasm ( )
UniProt ID
M3K13_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.7.11.25
Pfam ID
PF07714
Sequence
MANFQEHLSCSSSPHLPFSESKTFNGLQDELTAMGNHPSPKLLEDQQEKGMVRTELIESV
HSPVTTTVLTSVSEDSRDQFENSVLQLREHDESETAVSQGNSNTVDGESTSGTEDIKIQF
SRSGSGSGGFLEGLFGCLRPVWNIIGKAYSTDYKLQQQDTWEVPFEEISELQWLGSGAQG
AVFLGKFRAEEVAIKKVREQNETDIKHLRKLKHPNIIAFKGVCTQAPCYCIIMEYCAHGQ
LYEVLRAGRKITPRLLVDWSTGIASGMNYLHLHKIIHRDLKSPNVLVTHTDAVKISDFGT
SKELSDKSTKMSFAGTVAWMAPEVIRNEPVSEKVDIWSFGVVLWELLTGEIPYKDVDSSA
IIWGVGSNSLHLPVPSTCPDGFKILMKQTWQSKPRNRPSFRQTLMHLDIASADVLATPQE
TYFKSQAEWREEVKKHFEKIKSEGTCIHRLDEELIRRRREELRHALDIREHYERKLERAN
NLYMELSAIMLQLEMREKELIKREQAVEKKYPGTYKRHPVRPIIHPNAMEKLMKRKGVPH
KSGMQTKRPDLLRSEGIPTTEVAPTASPLSGSPKMSTSSSKSRYRSKPRHRRGNSRGSHS
DFAAILKNQPAQENSPHPTYLHQAQSQYPSLHHHNSLQQQYQQPPPAMSQSHHPRLNMHG
QDIATCANNLRYFGPAAALRSPLSNHAQRQLPGSSPDLISTAMAADCWRSSEPDKGQAGP
WGCCQADAYDPCLQCRPEQYGSLDIPSAEPVGRSPDLSKSPAHNPLLENAQSSEKTEENE
FSGCRSESSLGTSHLGTPPALPRKTRPLQKSGDDSSEEEEGEVDSEVEFPRRQRPHRCIS
SCQSYSTFSSENFSVSDGEEGNTSDHSNSPDELADKLEDRLAEKLDDLLSQTPEIPIDIS
SHSDGLSDKECAVRRVKTQMSLGKLCVEERGYENPMQFEESDCDSSDGECSDATVRTNKH
YSSATW
Function
Activates the JUN N-terminal pathway through activation of the MAP kinase kinase MAP2K7. Acts synergistically with PRDX3 to regulate the activation of NF-kappa-B in the cytosol. This activation is kinase-dependent and involves activating the IKK complex, the IKBKB-containing complex that phosphorylates inhibitors of NF-kappa-B.
Tissue Specificity Expressed in the adult brain, liver, placenta and pancreas, with expression strongest in the pancreas.
KEGG Pathway
MAPK sig.ling pathway (hsa04010 )

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast cancer DIS7DPX1 Strong Biomarker [1]
Breast carcinoma DIS2UE88 Strong Biomarker [1]
Cardiac failure DISDC067 Strong Biomarker [2]
Congestive heart failure DIS32MEA Strong Biomarker [2]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [3]
Parkinson disease DISQVHKL Strong Biomarker [4]
Advanced cancer DISAT1Z9 moderate Altered Expression [5]
Head and neck cancer DISBPSQZ Limited Biomarker [5]
Head and neck carcinoma DISOU1DS Limited Biomarker [5]
Head-neck squamous cell carcinoma DISF7P24 Limited Biomarker [5]
Melanoma DIS1RRCY Limited Biomarker [1]
Neoplasm DISZKGEW Limited Biomarker [3]
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⏷ Show the Full List of 12 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Mitogen-activated protein kinase kinase kinase 13 (MAP3K13). [6]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Mitogen-activated protein kinase kinase kinase 13 (MAP3K13). [7]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Mitogen-activated protein kinase kinase kinase 13 (MAP3K13). [8]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Mitogen-activated protein kinase kinase kinase 13 (MAP3K13). [9]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Mitogen-activated protein kinase kinase kinase 13 (MAP3K13). [10]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Mitogen-activated protein kinase kinase kinase 13 (MAP3K13). [11]
Sertraline DM0FB1J Approved Sertraline increases the expression of Mitogen-activated protein kinase kinase kinase 13 (MAP3K13). [12]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Mitogen-activated protein kinase kinase kinase 13 (MAP3K13). [14]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of Mitogen-activated protein kinase kinase kinase 13 (MAP3K13). [15]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Mitogen-activated protein kinase kinase kinase 13 (MAP3K13). [16]
Glyphosate DM0AFY7 Investigative Glyphosate decreases the expression of Mitogen-activated protein kinase kinase kinase 13 (MAP3K13). [17]
Resorcinol DMM37C0 Investigative Resorcinol decreases the expression of Mitogen-activated protein kinase kinase kinase 13 (MAP3K13). [18]
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⏷ Show the Full List of 12 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Mitogen-activated protein kinase kinase kinase 13 (MAP3K13). [13]
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References

1 Pro-necrotic molecules impact local immunosurveillance in human breast cancer.Oncoimmunology. 2017 Apr 17;6(4):e1299302. doi: 10.1080/2162402X.2017.1299302. eCollection 2017.
2 Tissue distribution and functional expression of a cDNA encoding a novel mixed lineage kinase.J Mol Cell Cardiol. 2001 Sep;33(9):1739-50. doi: 10.1006/jmcc.2001.1437.
3 The MAP3K13-TRIM25-FBXW7 axis affects c-Myc protein stability and tumor development.Cell Death Differ. 2020 Feb;27(2):420-433. doi: 10.1038/s41418-019-0363-0. Epub 2019 Jun 11.
4 Levodopa activates apoptosis signaling kinase 1 (ASK1) and promotes apoptosis in a neuronal model: implications for the treatment of Parkinson's disease. Chem Res Toxicol. 2011 Oct 17;24(10):1644-52. doi: 10.1021/tx200082h. Epub 2011 Aug 22.
5 Survival of Head and Neck Cancer Cells Relies upon LZK Kinase-Mediated Stabilization of Mutant p53.Cancer Res. 2017 Sep 15;77(18):4961-4972. doi: 10.1158/0008-5472.CAN-17-0267. Epub 2017 Jul 31.
6 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
7 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
8 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
9 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
10 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
11 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
12 Sertraline induces endoplasmic reticulum stress in hepatic cells. Toxicology. 2014 Aug 1;322:78-88. doi: 10.1016/j.tox.2014.05.007. Epub 2014 May 24.
13 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
14 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
15 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
16 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
17 Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.
18 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.