Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYIG6TP)

• DOT Name: SERTA domain-containing protein 2 (SERTAD2)
• Synonyms: Transcriptional regulator interacting with the PHD-bromodomain 2; TRIP-Br2
• Gene Name: SERTAD2
• Related Disease:
  Advanced cancer
  Hepatocellular carcinoma
  Neoplasm
• UniProt ID: SRTD2_HUMAN
• Pfam ID: PF06031
• Sequence:
  MLGKGGKRKFDEHEDGLEGKIVSPCDGPSKVSYTLQRQTIFNISLMKLYNHRPLTEPSLQ
  KTVLINNMLRRIQEELKQEGSLRPMFTPSSQPTTEPSDSYREAPPAFSHLASPSSHPCDL
  GSTTPLEACLTPASLLEDDDDTFCTSQAMQPTAPTKLSPPALLPEKDSFSSALDEIEELC
  PTSTSTEAATAATDSVKGTSSEAGTQKLDGPQESRADDSKLMDSLPGNFEITTSTGFLTD
  LTLDDILFADIDTSMYDFDPCTSSSGTASKMAPVSADDLLKTLAPYSSQPVTPSQPFKMD
  LTELDHIMEVLVGS
• Function: Acts at E2F-responsive promoters as coregulator to integrate signals provided by PHD- and/or bromodomain-containing transcription factors. May act as coactivator as well as corepressor of E2F1-TFDP1 and E2F4-TFDP1 complexes on E2F consensus binding sites, which would activate or inhibit E2F-target genes expression. Modulates fat storage by down-regulating the expression of key genes involved in adipocyte lipolysis, thermogenesis and oxidative metabolism.
• Tissue Specificity: Expressed in adipose tissue.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]

2 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 SERTA domain-containing protein 2 (SERTAD2).	[2]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of SERTA domain-containing protein 2 (SERTAD2).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of SERTA domain-containing protein 2 (SERTAD2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of SERTA domain-containing protein 2 (SERTAD2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of SERTA domain-containing protein 2 (SERTAD2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of SERTA domain-containing protein 2 (SERTAD2).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of SERTA domain-containing protein 2 (SERTAD2).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of SERTA domain-containing protein 2 (SERTAD2).	[8]
Selenium	DM25CGV	Approved	Selenium decreases the expression of SERTA domain-containing protein 2 (SERTAD2).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of SERTA domain-containing protein 2 (SERTAD2).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of SERTA domain-containing protein 2 (SERTAD2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of SERTA domain-containing protein 2 (SERTAD2).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of SERTA domain-containing protein 2 (SERTAD2).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of SERTA domain-containing protein 2 (SERTAD2).	[14]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide increases the expression of SERTA domain-containing protein 2 (SERTAD2).	[15]

References

• [1] TRIP-Br2 promotes oncogenesis in nude mice and is frequently overexpressed in multiple human tumors.J Transl Med. 2009 Jan 20;7:8. doi: 10.1186/1479-5876-7-8.
• [2] 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.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Changes in gene expression profiles of multiple myeloma cells induced by arsenic trioxide (ATO): possible mechanisms to explain ATO resistance in vivo. Br J Haematol. 2005 Mar;128(5):636-44.
• [9] 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.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] 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.
• [14] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [15] Comparative analysis of AhR-mediated TCDD-elicited gene expression in human liver adult stem cells. Toxicol Sci. 2009 Nov;112(1):229-44.