Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR3TNTJ)

• DOT Name: Steroid receptor-associated and regulated protein (SRARP)
• Synonyms: Estrogen receptor-related factor; ER-related factor; Steroid receptor-regulated protein
• Gene Name: SRARP
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Estrogen-receptor positive breast cancer
  Neoplasm
• UniProt ID: SRARP_HUMAN
• Pfam ID: PF15547
• Sequence:
  MAPSEDPRDWRANLKGTIRETGLETSSGGKLAGHQKTVPTAHLTFVIDCTHGKQLSLAAT
  ASPPQAPSPNRGLVTPPMKTYIVFCGENWPHLTRVTPMGGGCLAQARATLPLCRGSVASA
  SFPVSPLCPQEVPEAKGKPVKAAPVRSSTWGTVKDSLKALSSCVCGQAD
• Function: May regulate the transcriptional function of androgen and estrogen receptors.
• Tissue Specificity: Expressed in breast tumors with a higher expression level in estrogen receptor-positive cancers .

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Posttranslational Modification	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[3]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	moderate	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Steroid receptor-associated and regulated protein (SRARP).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Steroid receptor-associated and regulated protein (SRARP).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Steroid receptor-associated and regulated protein (SRARP).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Steroid receptor-associated and regulated protein (SRARP).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Steroid receptor-associated and regulated protein (SRARP).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Steroid receptor-associated and regulated protein (SRARP).	[12]

2 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 decreases the methylation of Steroid receptor-associated and regulated protein (SRARP).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Steroid receptor-associated and regulated protein (SRARP).	[10]

References

• [1] SRARP and HSPB7 are epigenetically regulated gene pairs that function as tumor suppressors and predict clinical outcome in malignancies.Mol Oncol. 2018 May;12(5):724-755. doi: 10.1002/1878-0261.12195. Epub 2018 Apr 16.
• [2] ERRF sensitizes ERBB2-positive breast cancer cells to lapatinib treatment likely by attenuating MCL1 and ERBB2 expression.Oncotarget. 2017 May 30;8(22):36054-36066. doi: 10.18632/oncotarget.16425.
• [3] C1orf64 is a novel androgen receptor target gene and coregulator that interacts with 14-3-3 protein in breast cancer.Oncotarget. 2017 May 11;8(34):57907-57933. doi: 10.18632/oncotarget.17826. eCollection 2017 Aug 22.
• [4] Role of ERRF, a novel ER-related nuclear factor, in the growth control of ER-positive human breast cancer cells.Am J Pathol. 2012 Mar;180(3):1189-1201. doi: 10.1016/j.ajpath.2011.11.025.
• [5] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] 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.
• [11] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.