Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5S0DV4)

• DOT Name: Structural maintenance of chromosomes protein 2 (SMC2)
• Synonyms: SMC protein 2; SMC-2; Chromosome-associated protein E; hCAP-E; XCAP-E homolog
• Gene Name: SMC2
• UniProt ID: SMC2_HUMAN
• PDB ID: 4U4P
• Pfam ID: PF06470 ; PF02463
• Sequence:
  MHIKSIILEGFKSYAQRTEVNGFDPLFNAITGLNGSGKSNILDSICFLLGISNLSQVRAS
  NLQDLVYKNGQAGITKASVSITFDNSDKKQSPLGFEVHDEITVTRQVVIGGRNKYLINGV
  NANNTRVQDLFCSVGLNVNNPHFLIMQGRITKVLNMKPPEILSMIEEAAGTRMYEYKKIA
  AQKTIEKKEAKLKEIKTILEEEITPTIQKLKEERSSYLEYQKVMREIEHLSRLYIAYQFL
  LAEDTKVRSAEELKEMQDKVIKLQEELSENDKKIKALNHEIEELEKRKDKETGGILRSLE
  DALAEAQRVNTKSQSAFDLKKKNLACEESKRKELEKNMVEDSKTLAAKEKEVKKITDGLH
  ALQEASNKDAEALAAAQQHFNAVSAGLSSNEDGAEATLAGQMMACKNDISKAQTEAKQAQ
  MKLKHAQQELKNKQAEVKKMDSGYRKDQEALEAVKRLKEKLEAEMKKLNYEENKEESLLE
  KRRQLSRDIGRLKETYEALLARFPNLRFAYKDPEKNWNRNCVKGLVASLISVKDTSATTA
  LELVAGERLYNVVVDTEVTGKKLLERGELKRRYTIIPLNKISARCIAPETLRVAQNLVGP
  DNVHVALSLVEYKPELQKAMEFVFGTTFVCDNMDNAKKVAFDKRIMTRTVTLGGDVFDPH
  GTLSGGARSQAASILTKFQELKDVQDELRIKENELRALEEELAGLKNTAEKYRQLKQQWE
  MKTEEADLLQTKLQQSSYHKQQEELDALKKTIEESEETLKNTKEIQRKAEEKYEVLENKM
  KNAEAERERELKDAQKKLDCAKTKADASSKKMKEKQQEVEAITLELEELKREHTSYKQQL
  EAVNEAIKSYESQIEVMAAEVAKNKESVNKAQEEVTKQKEVITAQDTVIKAKYAEVAKHK
  EQNNDSQLKIKELDHNISKHKREAEDGAAKVSKMLKDYDWINAERHLFGQPNSAYDFKTN
  NPKEAGQRLQKLQEMKEKLGRNVNMRAMNVLTEAEERYNDLMKKKRIVENDKSKILTTIE
  DLDQKKNQALNIAWQKVNKDFGSIFSTLLPGANAMLAPPEGQTVLDGLEFKVALGNTWKE
  NLTELSGGQRSLVALSLILSMLLFKPAPIYILDEVDAALDLSHTQNIGQMLRTHFTHSQF
  IVVSLKEGMFNNANVLFKTKFVDGVSTVARFTQCQNGKISKEAKSKAKPPKGAHVEV
• Function: Central component of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases.
• Reactome Pathway:
  Condensation of Prometaphase Chromosomes (R-HSA-2514853)
  Condensation of Prophase Chromosomes (R-HSA-2299718)

Molecular Interaction Atlas (MIA) of This DOT

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Structural maintenance of chromosomes protein 2 (SMC2).	[1]

22 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 Structural maintenance of chromosomes protein 2 (SMC2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[10]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[11]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[12]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[13]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[14]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[15]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[16]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[17]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[7]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Structural maintenance of chromosomes protein 2 (SMC2).	[20]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] 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.
• [3] 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.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 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.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] 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.
• [10] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [11] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [12] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [13] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [14] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [15] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [16] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [17] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [18] Gene expression changes in human prostate carcinoma cells exposed to genotoxic and nongenotoxic aryl hydrocarbon receptor ligands. Toxicol Lett. 2011 Oct 10;206(2):178-88.
• [19] 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.
• [20] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.