Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPAH75C)

DOT Name Histone-lysine N-methyltransferase SMYD1 (SMYD1)
Synonyms EC 2.1.1.354; SET and MYND domain-containing protein 1
Gene Name SMYD1
Related Disease
Cardiac failure ( )
Congestive heart failure ( )
Rhabdomyosarcoma ( )
Breast carcinoma ( )
Hypertrophic cardiomyopathy ( )
UniProt ID
SMYD1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.1.1.354
Pfam ID
PF00856 ; PF01753
Sequence
MTIGRMENVEVFTAEGKGRGLKATKEFWAADIIFAERAYSAVVFDSLVNFVCHTCFKRQE
KLHRCGQCKFAHYCDRTCQKDAWLNHKNECSAIKRYGKVPNENIRLAARIMWRVEREGTG
LTEGCLVSVDDLQNHVEHFGEEEQKDLRVDVDTFLQYWPPQSQQFSMQYISHIFGVINCN
GFTLSDQRGLQAVGVGIFPNLGLVNHDCWPNCTVIFNNGNHEAVKSMFHTQMRIELRALG
KISEGEELTVSYIDFLNVSEERKRQLKKQYYFDCTCEHCQKKLKDDLFLGVKDNPKPSQE
VVKEMIQFSKDTLEKIDKARSEGLYHEVVKLCRECLEKQEPVFADTNIYMLRMLSIVSEV
LSYLQAFEEASFYARRMVDGYMKLYHPNNAQLGMAVMRAGLTNWHAGNIEVGHGMICKAY
AILLVTHGPSHPITKDLEAMRVQTEMELRMFRQNEFMYYKMREAALNNQPMQVMAEPSNE
PSPALFHKKQ
Function
Methylates histone H3 at 'Lys-4' (H3K4me), seems able to perform both mono-, di-, and trimethylation. Acts as a transcriptional repressor. Essential for cardiomyocyte differentiation and cardiac morphogenesis.
Tissue Specificity Expression seems mostly restricted to heart and skeletal muscle.
KEGG Pathway
Lysine degradation (hsa00310 )
Metabolic pathways (hsa01100 )
Reactome Pathway
Cardiogenesis (R-HSA-9733709 )
BioCyc Pathway
MetaCyc:ENSG00000115593-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cardiac failure DISDC067 Strong Genetic Variation [1]
Congestive heart failure DIS32MEA Strong Genetic Variation [1]
Rhabdomyosarcoma DISNR7MS moderate Biomarker [2]
Breast carcinoma DIS2UE88 Limited Altered Expression [3]
Hypertrophic cardiomyopathy DISQG2AI Limited Autosomal dominant [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 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 Histone-lysine N-methyltransferase SMYD1 (SMYD1). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Histone-lysine N-methyltransferase SMYD1 (SMYD1). [6]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Histone-lysine N-methyltransferase SMYD1 (SMYD1). [7]
Folic acid DMEMBJC Approved Folic acid increases the expression of Histone-lysine N-methyltransferase SMYD1 (SMYD1). [8]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Histone-lysine N-methyltransferase SMYD1 (SMYD1). [10]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Histone-lysine N-methyltransferase SMYD1 (SMYD1). [11]
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⏷ Show the Full List of 6 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 increases the methylation of Histone-lysine N-methyltransferase SMYD1 (SMYD1). [9]
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References

1 Heart Transplantation from Biventricular Support in Infant with Novel SMYD1 Mutation.Pediatr Cardiol. 2019 Dec;40(8):1745-1747. doi: 10.1007/s00246-019-02139-7. Epub 2019 Jul 5.
2 SMYD1 and G6PD modulation are critical events for miR-206-mediated differentiation of rhabdomyosarcoma.Cell Cycle. 2015;14(9):1389-402. doi: 10.1080/15384101.2015.1005993.
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 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
5 Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
6 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.
7 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
8 Neuronal and cardiac toxicity of pharmacological compounds identified through transcriptomic analysis of human pluripotent stem cell-derived embryoid bodies. Toxicol Appl Pharmacol. 2021 Dec 15;433:115792. doi: 10.1016/j.taap.2021.115792. Epub 2021 Nov 3.
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 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.
11 Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.