Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA7UQF1)

DOT Name Transcriptional-regulating factor 1 (TRERF1)
Synonyms Breast cancer anti-estrogen resistance 2; Transcriptional-regulating protein 132; Zinc finger protein rapa; Zinc finger transcription factor TReP-132
Gene Name TRERF1
Related Disease
Autism spectrum disorder ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Colon cancer ( )
Colon carcinoma ( )
Depression ( )
Endometriosis ( )
Non-alcoholic fatty liver disease ( )
Non-small-cell lung cancer ( )
Complex neurodevelopmental disorder ( )
Neoplasm ( )
UniProt ID
TREF1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF01448 ; PF13912
Sequence
MGDQQLYKTNHVAHGSENLFYQQPPLGVHSGLNHNYGNAVTGGGMDAPQASPISPHFPQD
TRDGLGLPVGSKNLGQMDTSRQGGWGSHAGPGNHVQLRGNLANSNMMWGAPAQAEPTDGY
QYTYSQASEIRTQKLTSGVLHKLDSFTQVFANQNLRIQVNNMAQVLHTQSAVMDGAPDSA
LRQLLSQKPMEPPAPAIPSRYQQVPQQPHPGFTGGLSKPALQVGQHPTQGHLYYDYQQPL
AQVPVQGGQPLQAPQMLSQHMQQMQQHQYYPPQQQQQAGQQRISMQEIQTQPQQIRPSQP
QPPPQQQQPQQLQLQQRQGSMQIPQYYQPQPMMQHLQEQQQQQMHLQPPSYHRDPHQYTP
EQAHTVQLIPLGSMSQYYYQEPQQPYSHPLYQQSHLSQHQQREDSQLKTYSSDRQAQAML
SSHGDLGPPDTGMGDPASSDLTRVSSTLPHRPLLSPSGIHLNNMGPQHQQLSPSAMWPQM
HLPDGRAQPGSPESSGQPKGAFGEQFDAKNKLTCSICLKEFKNLPALNGHMRSHGGMRAS
PNLKQEEGEKVLPPQPQPPLPPPPPPPPPPQLPPEAESLTPMVMPVSVPVKLLPPKPSSQ
GFTNSTVAAPSARDKPASSMSDDEMPVLEIPRKHQPSVPKAEEPLKTVQEKKKFRHRPEP
LFIPPPPSYNPNPAASYSGATLYQSQLRSPRVLGDHLLLDPTHELPPYTPPPMLSPVRQG
SGLFSNVLISGHGPGAHPQLPLTPLTPTPRVLLCRSNSIDGSNVTVTPGPGEQTVDVEPR
INIGLRFQAEIPELQDISALAQDTHKATLVWKPWPELENHDLQQRVENLLNLCCSSALPG
GGTNSEFALHSLFEAKGDVMVALEMLLLRKPVRLKCHPLANYHYAGSDKWTSLERKLFNK
ALATYSKDFIFVQKMVKSKTVAQCVEYYYTWKKIMRLGRKHRTRLAEIIDDCVTSEEEEE
LEEEEEEDPEEDRKSTKEEESEVPKSPEPPPVPVLAPTEGPPLQALGQPSGSFICEMPNC
GAVFSSRQALNGHARIHGGTNQVTKARGAIPSGKQKPGGTQSGYCSVKSSPSHSTTSGET
DPTTIFPCKECGKVFFKIKSRNAHMKTHRQQEEQQRQKAQKAAFAAEMAATIERTTGPVG
APGLLPLDQLSLIKPIKDVDILDDDVVQQLGGVMEEAEVVDTDLLLDDQDSVLLQGDAEL
Function Binds DNA and activates transcription of CYP11A1. Interaction with CREBBP and EP300 results in a synergistic transcriptional activation of CYP11A1.
Tissue Specificity
Highest expression was seen in thymus, testis and adrenal cortex, expressed also in the adrenal medulla, thyroid, and stomach. Highly expressed in steroidogenic JEG-3 and MCF-7 cells, low expression was seen in non-steroidogenic Hep-G2 and HEK293 cells.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autism spectrum disorder DISXK8NV Strong Biomarker [1]
Breast cancer DIS7DPX1 Strong Biomarker [2]
Breast carcinoma DIS2UE88 Strong Biomarker [2]
Breast neoplasm DISNGJLM Strong Biomarker [2]
Colon cancer DISVC52G Strong Biomarker [3]
Colon carcinoma DISJYKUO Strong Biomarker [3]
Depression DIS3XJ69 Strong Altered Expression [4]
Endometriosis DISX1AG8 Strong Biomarker [5]
Non-alcoholic fatty liver disease DISDG1NL Strong Biomarker [6]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [7]
Complex neurodevelopmental disorder DISB9AFI Limited Autosomal recessive [8]
Neoplasm DISZKGEW Limited Biomarker [9]
------------------------------------------------------------------------------------
⏷ Show the Full List of 12 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Afimoxifene DMFORDT Phase 2 Transcriptional-regulating factor 1 (TRERF1) decreases the response to substance of Afimoxifene. [27]
------------------------------------------------------------------------------------
13 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 Transcriptional-regulating factor 1 (TRERF1). [10]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Transcriptional-regulating factor 1 (TRERF1). [11]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Transcriptional-regulating factor 1 (TRERF1). [12]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Transcriptional-regulating factor 1 (TRERF1). [13]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Transcriptional-regulating factor 1 (TRERF1). [14]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Transcriptional-regulating factor 1 (TRERF1). [15]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Transcriptional-regulating factor 1 (TRERF1). [16]
Folic acid DMEMBJC Approved Folic acid decreases the expression of Transcriptional-regulating factor 1 (TRERF1). [17]
Melphalan DMOLNHF Approved Melphalan decreases the expression of Transcriptional-regulating factor 1 (TRERF1). [18]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate increases the expression of Transcriptional-regulating factor 1 (TRERF1). [19]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Transcriptional-regulating factor 1 (TRERF1). [21]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Transcriptional-regulating factor 1 (TRERF1). [24]
Coumestrol DM40TBU Investigative Coumestrol decreases the expression of Transcriptional-regulating factor 1 (TRERF1). [26]
------------------------------------------------------------------------------------
⏷ Show the Full List of 13 Drug(s)
4 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 affects the methylation of Transcriptional-regulating factor 1 (TRERF1). [20]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Transcriptional-regulating factor 1 (TRERF1). [22]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Transcriptional-regulating factor 1 (TRERF1). [23]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of Transcriptional-regulating factor 1 (TRERF1). [25]
------------------------------------------------------------------------------------

References

1 Rapamycin modulated brain-derived neurotrophic factor and B-cell lymphoma 2 to mitigate autism spectrum disorder in rats.Neuropsychiatr Dis Treat. 2017 Mar 20;13:835-842. doi: 10.2147/NDT.S125088. eCollection 2017.
2 Relevance of breast cancer antiestrogen resistance genes in human breast cancer progression and tamoxifen resistance.J Clin Oncol. 2009 Feb 1;27(4):542-9. doi: 10.1200/JCO.2008.17.1462. Epub 2008 Dec 15.
3 An acellular tissue matrix-based drug carriers with dual chemo-agents for colon cancer growth suppression.Biomed Pharmacother. 2019 Sep;117:109048. doi: 10.1016/j.biopha.2019.109048. Epub 2019 Jun 8.
4 A pilot study of mindful walking training on physical activity and health outcomes among adults with inadequate activity.Complement Ther Med. 2019 Jun;44:116-122. doi: 10.1016/j.ctim.2019.03.009. Epub 2019 Mar 15.
5 Novel TRERF1 mutations in Chinese patients with ovarian endometriosis.Mol Med Rep. 2018 Apr;17(4):5435-5439. doi: 10.3892/mmr.2018.8510. Epub 2018 Jan 26.
6 Roles of Autophagy and Protein Kinase C-epsilon in Lipid Metabolism of Nonalcoholic Fatty Liver Cell Models.Arch Med Res. 2018 Aug;49(6):381-390. doi: 10.1016/j.arcmed.2018.11.006. Epub 2018 Dec 17.
7 Increased Inhibition Effect of Antrodin C from the Stout Camphor Medicinal Mushroom, Taiwanofungus camphoratus (Agaricomycetes), on A549 through Crosstalk between Apoptosis and Autophagy.Int J Med Mushrooms. 2019;21(6):595-610. doi: 10.1615/IntJMedMushrooms.2019025901.
8 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
9 Essential role of PDGFRalpha-p70S6K signaling in mesenchymal cells during therapeutic and tumor angiogenesis in vivo: role of PDGFRalpha during angiogenesis.Circ Res. 2004 May 14;94(9):1186-94. doi: 10.1161/01.RES.0000126925.66005.39. Epub 2004 Apr 1.
10 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
11 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.
12 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.
13 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.
14 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
15 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.
16 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
17 Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
18 Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
19 Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
20 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.
21 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
22 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.
23 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
24 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
25 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.
26 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
27 Functional identification of genes causing estrogen independence of human breast cancer cells. Breast Cancer Res Treat. 2009 Mar;114(1):23-30. doi: 10.1007/s10549-008-9969-5. Epub 2008 Mar 21.