Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT349CJ)

DOT Name SET and MYND domain-containing protein 4 (SMYD4)
Synonyms EC 2.1.1.-
Gene Name SMYD4
Related Disease
Medulloblastoma ( )
Breast cancer ( )
Neoplasm ( )
Breast carcinoma ( )
UniProt ID
SMYD4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.1.1.-
Pfam ID
PF00856 ; PF01753
Sequence
MDLPVDEWKSYLLQKWASLPTSVQVTISTAETLRDIFLHSSSLLQPEDELFLKRLSKGYL
VGKDSDAPLFYREEGNKKFQEKDYTGAAVLYSKGVSHSRPNTEDMSLCHANRSAALFHLG
QYETCLKDINRAQTHGYPERLQPKIMLRKAECLVALGRLQEASQTISDLERNFTATPALA
DVLPQTLQRNLHRLKMKMQEKDSLTESFPAALAKTLEDAALREENEQLSNASSSIGLCVD
PLKGRCLVATKDILPGELLVQEDAFVSVLNPGELPPPHHGLDSKWDTRVTNGDLYCHRCL
KHTLATVPCDGCSYAKYCSQECLQQAWELYHRTECPLGGLLLTLGVFCHIALRLTLLVGF
EDVRKIITKLCDKISNKDICLPESNNQVKTLNYGLGESEKNGNIVETPIPGCDINGKYEN
NYNAVFNLLPHTENHSPEHKFLCALCVSALCRQLEAASLQAIPTERIVNSSQLKAAVTPE
LCPDVTIWGVAMLRHMLQLQCNAQAMTTIQHTGPKGSIVTDSRQVRLATGIFPVISLLNH
SCSPNTSVSFISTVATIRASQRIRKGQEILHCYGPHKSRMGVAERQQKLRSQYFFDCACP
ACQTEAHRMAAGPRWEAFCCNSCGAPMQGDDVLRCGSRSCAESAVSRDHLVSRLQDLQQQ
VRVAQKLLRDGELERAVQRLSGCQRDAESFLWAEHAVVGEIADGLARACAALGDWQKSAT
HLQRSLYVVEVRHGPSSVEMGHELFKLAQIFFNGFAVPEALSTIQKAEEVLSLHCGPWDD
EIQELQKMKSCLLDLPPTPVGPAL
Function
Plays a critical role in cardiac development. Acts as a key epigenetic regulator of gene expression during cardiac development via its dual activities as a methyltransferase and negative regulator of HDAC1.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Medulloblastoma DISZD2ZL Definitive Biomarker [1]
Breast cancer DIS7DPX1 Strong Altered Expression [2]
Neoplasm DISZKGEW Strong Biomarker [3]
Breast carcinoma DIS2UE88 moderate Altered Expression [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of SET and MYND domain-containing protein 4 (SMYD4). [4]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of SET and MYND domain-containing protein 4 (SMYD4). [5]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of SET and MYND domain-containing protein 4 (SMYD4). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of SET and MYND domain-containing protein 4 (SMYD4). [7]
Estradiol DMUNTE3 Approved Estradiol increases the expression of SET and MYND domain-containing protein 4 (SMYD4). [8]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of SET and MYND domain-containing protein 4 (SMYD4). [10]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of SET and MYND domain-containing protein 4 (SMYD4). [11]
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⏷ Show the Full List of 7 Drug(s)
2 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 decreases the methylation of SET and MYND domain-containing protein 4 (SMYD4). [9]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the methylation of SET and MYND domain-containing protein 4 (SMYD4). [12]
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References

1 Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma.Nat Genet. 2009 Apr;41(4):465-72. doi: 10.1038/ng.336. Epub 2009 Mar 8.
2 miR-1307-3p Stimulates Breast Cancer Development and Progression by Targeting SMYD4.J Cancer. 2019 Jan 1;10(2):441-448. doi: 10.7150/jca.30041. eCollection 2019.
3 Expression patterns and the prognostic value of the SMYD family members in human breast carcinoma using integrative bioinformatics analysis.Oncol Lett. 2019 Apr;17(4):3851-3861. doi: 10.3892/ol.2019.10054. Epub 2019 Feb 19.
4 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
5 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.
6 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
7 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
8 Genome-Wide Analysis of Low Dose Bisphenol-A (BPA) Exposure in Human Prostate Cells. Curr Genomics. 2019 May;20(4):260-274. doi: 10.2174/1389202920666190603123040.
9 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.
10 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
11 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.
12 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.