General Information of Drug Off-Target (DOT) (ID: OTG47JQE)

DOT Name Deoxynucleotidyltransferase terminal-interacting protein 2 (DNTTIP2)
Synonyms Estrogen receptor-binding protein; LPTS-interacting protein 2; LPTS-RP2; Terminal deoxynucleotidyltransferase-interacting factor 2; TdIF2; TdT-interacting factor 2
Gene Name DNTTIP2
UniProt ID
TDIF2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7MQ8; 7MQ9; 7MQA
Pfam ID
PF08698
Sequence
MVVTRSARAKASIQAASAESSGQKSFAANGIQAHPESSTGSDARTTAESQTTGKQSLIPR
TPKARKRKSRTTGSLPKGTEPSTDGETSEAESNYSVSEHHDTILRVTRRRQILIACSPVS
SVRKKPKVTPTKESYTEEIVSEAESHVSGISRIVLPTEKTTGARRSKAKSLTDPSQESHT
EAISDAETSSSDISFSGIATRRTRSMQRKLKAQTEKKDSKIVPGNEKQIVGTPVNSEDSD
TRQTSHLQARSLSEINKPNFYNNDFDDDFSHRSSENILTVHEQANVESLKETKQNCKDLD
EDANGITDEGKEINEKSSQLKNLSELQDTSLQQLVSQRHSTPQNKNAVSVHSNLNSEAVM
KSLTQTFATVEVGRWNNNKKSPIKASDLTKFGDCGGSDDEEESTVISVSEDMNSEGNVDF
ECDTKLYTSAPNTSQGKDNSVLLVLSSDESQQSENSENEEDTLCFVENSGQRESLSGDTG
SLSCDNALFVIDTTPGMSADKNFYLEEEDKASEVAIEEEKEEEEDEKSEEDSSDHDENED
EFSDEEDFLNSTKAKLLKLTSSSIDPGLSIKQLGGLYINFNADKLQSNKRTLTQIKEKKK
NELLQKAVITPDFEKNHCVPPYSESKYQLQKKRRKERQKTAGDGWFGMKAPEMTNELKND
LKALKMRASMDPKRFYKKNDRDGFPKYFQIGTIVDNPADFYHSRIPKKQRKRTIVEELLA
DSEFRRYNRRKYSEIMAEKAANAAGKKFRKKKKFRN
Function
Regulates the transcriptional activity of DNTT and ESR1. May function as a chromatin remodeling protein. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.
Tissue Specificity Widely expressed with higher levels in testis.

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 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 Deoxynucleotidyltransferase terminal-interacting protein 2 (DNTTIP2). [1]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Deoxynucleotidyltransferase terminal-interacting protein 2 (DNTTIP2). [9]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Deoxynucleotidyltransferase terminal-interacting protein 2 (DNTTIP2). [10]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Deoxynucleotidyltransferase terminal-interacting protein 2 (DNTTIP2). [10]
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11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Deoxynucleotidyltransferase terminal-interacting protein 2 (DNTTIP2). [2]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Deoxynucleotidyltransferase terminal-interacting protein 2 (DNTTIP2). [3]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Deoxynucleotidyltransferase terminal-interacting protein 2 (DNTTIP2). [4]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Deoxynucleotidyltransferase terminal-interacting protein 2 (DNTTIP2). [5]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Deoxynucleotidyltransferase terminal-interacting protein 2 (DNTTIP2). [6]
Quercetin DM3NC4M Approved Quercetin increases the expression of Deoxynucleotidyltransferase terminal-interacting protein 2 (DNTTIP2). [7]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Deoxynucleotidyltransferase terminal-interacting protein 2 (DNTTIP2). [8]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Deoxynucleotidyltransferase terminal-interacting protein 2 (DNTTIP2). [2]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Deoxynucleotidyltransferase terminal-interacting protein 2 (DNTTIP2). [11]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of Deoxynucleotidyltransferase terminal-interacting protein 2 (DNTTIP2). [12]
KOJIC ACID DMP84CS Investigative KOJIC ACID decreases the expression of Deoxynucleotidyltransferase terminal-interacting protein 2 (DNTTIP2). [13]
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⏷ Show the Full List of 11 Drug(s)

References

1 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.
2 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
3 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.
4 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
5 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.
6 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
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 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
9 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.
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 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
12 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
13 Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.