Details of Drug Off-Target (DOT)

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

• DOT Name: Retroelement silencing factor 1 (RESF1)
• Gene Name: RESF1
• Related Disease:
  Testicular germ cell tumor
  Melanoma
• UniProt ID: RESF1_HUMAN
• Pfam ID: PF15395
• Sequence:
  MNWNEKPKSATLPPLYPKSQPPFLHQSLINQITTTSQSSFSYPGSNQEACMYPGNSNPIS
  QPLLNIQNYPQQISVSDMHNGTVVASHTSVERITYANVNGPKQLTHNLQMSSGVTQNVWL
  NSPMRNPVHSHIGATVSHQTDFGANVPNMPALQSQLITSDTYSMQMQMIPSNSTRLPVAY
  QGNQGLNQSFSEQQVDWTQQCISKGLTYPDYRPPPKLYRYSPQSFLPDSTIQKQNFIPHT
  SLQVKNSQLLNSVLTLPSRQTSAVPSQQYATQTDKRPPPPPYNCRYGSQPLQSTQHITKH
  LSMEVPQSREMLSSEIRTSFQQQWQNPNENVSTIGNFTNLKVNTNSKQPFNSPIRSSVDG
  VQTLAQTNEEKIMDSCNPTSNQVLDTSVAKEKLVRDIKTLVEIKQKFSELARKIKINKDL
  LMAAGCIKMTNTSYSEPAQNSKLSLKQTAKIQSGPQITPVMPENAERQTPTVVESAETNK
  TQCMLNSDIQEVNCRRFNQVDSVLPNPVYSEKRPMPDSSHDVKVLTSKTSAVEMTQAVLN
  TQLSSENVTKVEQNSPAVCETISVPKSMSTEEYKSKIQNENMLLLALLSQARKTQKTVLK
  DANQTIQDSKPDSCEMNPNTQMTGNQLNLKNMETPSTSNVSGRVLDNSFCSGQESSTKGM
  PAKSDSSCSMEVLATCLSLWKKQPSDTAKEKECDKLRTNTTAVGISKPANIHVKSPCSVV
  GNSNSQNKISNPSQQTALSMVMHNYESSGINITKGTELQIAVVSPLVLSEVKTLSVKGIT
  PAVLPETVYPVIKEGSVCSLQNQLAENAKATAALKVDVSGPVASTATSTKIFPLTQKEKQ
  NESTNGNSEVTPNVNQGKHNKLESAIHSPMNDQQISQESRNSTVVSSDTLQIDNICSLVE
  GDTSYNSQIAKIFSSLPLKMVEPQKPSLPNQQGIGSREPEKQLDNTTENKDFGFQKDKPV
  QCTDVSHKICDQSKSEPPLESSFNNLETNRVILEKSSLEHATEKSTANDTCSSAAIQEDI
  YPQEIDASSNYTPQDPARNEIHSDKAPVLYLHDQLSELLKEFPYGIEAVNTREGSVGQQT
  TYQTSEDQTADKTSSDSKDPADQIQITILSSEQMKEIFPEQDDQPYVVDKLAEPQKEEPI
  TEVVSQCDLQAPAAGQSRDSVILDSEKDDIHCCALGWLSMVYEGVPQCQCNSIKNSSSEE
  EKQKEQCSPLDTNSCKQGERTSDRDVTVVQFKSLVNNPKTPPDGKSHFPELQDDSRKDTP
  KTKHKSLPRTEQELVAGQFSSKCDKLNPLQNHKRKKLRFHEVTFHSSNKMTASYEQASQE
  TRQKKHVTQNSRPLKTKTAFLPNKDVYKKHSSLGQSLSPEKIKLKLKSVSFKQKRKLDQG
  NVLDMEVKKKKHDKQEQKGSVGATFKLGDSLSNPNERAIVKEKMVSNTKSVDTKASSSKF
  SRILTPKEYLQRQKHKEALSNKASKKICVKNVPCDSEHMRPSKLAVQVESCGKSNEKHSS
  GVQTSKESLNGLTSHGKNLKIHHSQESKTYNILRNVKEKVGGKQPDKIWIDKTKLDKLTN
  ISNEAQFSQMPPQVKDQKKLYLNRVGFKCTERESISLTKLESSPRKLHKDKRQENKHKTF
  LPVKGNTEKSNMLEFKLCPDILLKNTNSVEERKDVKPHPRKEQAPLQVSGIKSTKEDWLK
  FVATKKRTQKDSQERDNVNSRLSKRSFSADGFEMLQNPVKDSKEMFQTYKQMYLEKRSRS
  LGSSPVK
• Function: Plays a role in the regulation of imprinted gene expression, regulates repressive epigenetic modifications associated with SETDB1. Required for the recruitment or accumulation of SETDB1 to the endogenous retroviruses (ERVs) and maintenance of repressive chromatin configuration, contributing to a subset of the SETDB1-dependent ERV silencing in embryonic stem cells.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Testicular germ cell tumor	DIS5RN24	Strong	Genetic Variation	[1]
Melanoma	DIS1RRCY	moderate	Biomarker	[2]

10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Retroelement silencing factor 1 (RESF1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Retroelement silencing factor 1 (RESF1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Retroelement silencing factor 1 (RESF1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Retroelement silencing factor 1 (RESF1).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Retroelement silencing factor 1 (RESF1).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Retroelement silencing factor 1 (RESF1).	[8]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Retroelement silencing factor 1 (RESF1).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Retroelement silencing factor 1 (RESF1).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Retroelement silencing factor 1 (RESF1).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Retroelement silencing factor 1 (RESF1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Retroelement silencing factor 1 (RESF1).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Retroelement silencing factor 1 (RESF1).	[12]

References

• [1] Identification of 19 new risk loci and potential regulatory mechanisms influencing susceptibility to testicular germ cell tumor.Nat Genet. 2017 Jul;49(7):1133-1140. doi: 10.1038/ng.3896. Epub 2017 Jun 12.
• [2] Altered peptide ligands revisited: vaccine design through chemically modified HLA-A2-restricted T cell epitopes.J Immunol. 2014 Nov 15;193(10):4803-13. doi: 10.4049/jimmunol.1400800. Epub 2014 Oct 13.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [12] 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.
• [13] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.