Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8EB87R)

• DOT Name: Sex comb on midleg-like protein 2 (SCML2)
• Gene Name: SCML2
• Related Disease:
  Medulloblastoma
  Neoplasm
  Neuroendocrine neoplasm
• UniProt ID: SCML2_HUMAN
• PDB ID: 1OI1; 2BIV; 2MEM; 2VYT; 4EDU
• Pfam ID: PF02820 ; PF17208 ; PF00536 ; PF12140
• Sequence:
  MGQTVNEDSMDVKKENQEKTPQSSTSSVQRDDFHWEEYLKETGSISAPSECFRQSQIPPV
  NDFKVGMKLEARDPRNATSVCIATVIGITGARLRLRLDGSDNRNDFWRLVDSPDIQPVGT
  CEKEGDLLQPPLGYQMNTSSWPMFLLKTLNGSEMASATLFKKEPPKPPLNNFKVGMKLEA
  IDKKNPYLICPATIGDVKGDEVHITFDGWSGAFDYWCKYDSRDIFPAGWCRLTGDVLQPP
  GTSVPIVKNIAKTESSPSEASQHSMQSPQKTTLILPTQQVRRSSRIKPPGPTAVPKRSSS
  VKNITPRKKGPNSGKKEKPLPVICSTSAASLKSLTRDRGMLYKDVASGPCKIVMSTVCVY
  VNKHGNFGPHLDPKRIQQLPDHFGPGPVNVVLRRIVQACVDCALETKTVFGYLKPDNRGG
  EVITASFDGETHSIQLPPVNSASFALRFLENFCHSLQCDNLLSSQPFSSSRGHTHSSAEH
  DKNQSAKEDVTERQSTKRSPQQTVPYVVPLSPKLPKTKEYASEGEPLFAGGSAIPKEENL
  SEDSKSSSLNSGNYLNPACRNPMYIHTSVSQDFSRSVPGTTSSPLVGDISPKSSPHEVKF
  QMQRKSEAPSYIAVPDPSVLKQGFSKDPSTWSVDEVIQFMKHTDPQISGPLADLFRQHEI
  DGKALFLLKSDVMMKYMGLKLGPALKLCYYIEKLKEGKYS
• Function: Putative Polycomb group (PcG) protein. PcG proteins act by forming multiprotein complexes, which are required to maintain the transcriptionally repressive state of homeotic genes throughout development.
• Tissue Specificity: Highly expressed in placenta, thymus and testis. Detected at lower levels in brain, liver, skeletal muscle, pancreas and ovary.
• KEGG Pathway: Polycomb repressive complex (hsa03083)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Medulloblastoma	DISZD2ZL	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Limited	Altered Expression	[2]
Neuroendocrine neoplasm	DISNPLOO	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Sex comb on midleg-like protein 2 (SCML2).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Sex comb on midleg-like protein 2 (SCML2).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Sex comb on midleg-like protein 2 (SCML2).	[11]

8 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 Sex comb on midleg-like protein 2 (SCML2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Sex comb on midleg-like protein 2 (SCML2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Sex comb on midleg-like protein 2 (SCML2).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Sex comb on midleg-like protein 2 (SCML2).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Sex comb on midleg-like protein 2 (SCML2).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Sex comb on midleg-like protein 2 (SCML2).	[7]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Sex comb on midleg-like protein 2 (SCML2).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Sex comb on midleg-like protein 2 (SCML2).	[10]

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] Sex comb on midleg like-2 is a novel specific marker for the diagnosis of gastroenteropancreatic neuroendocrine tumors.Exp Ther Med. 2017 Aug;14(2):1749-1755. doi: 10.3892/etm.2017.4677. Epub 2017 Jun 26.
• [3] 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.
• [4] 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.
• [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] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [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] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.