Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5LJOWM)

DOT Name Transcription termination factor 2 (TTF2)
Synonyms EC 3.6.4.-; Lodestar homolog; RNA polymerase II termination factor; Transcription release factor 2; F2; HuF2
Gene Name TTF2
Related Disease
Athyreosis ( )
Cleft lip ( )
Cleft palate ( )
Congenital hypothyroidism ( )
Isolated cleft lip ( )
Isolated cleft palate ( )
Pancreatic cancer ( )
Thyroid cancer ( )
Thyroid gland carcinoma ( )
Thyroid tumor ( )
Thyroid gland papillary carcinoma ( )
UniProt ID
TTF2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
3.6.4.-
Pfam ID
PF00271 ; PF00176 ; PF06839
Sequence
MEEVRCPEHGTFCFLKTGVRDGPNKGKSFYVCRADTCSFVRATDIPVSHCLLHEDFVVEL
QGLLLPQDKKEYRLFFRCIRSKAEGKRWCGSIPWQDPDSKEHSVSNKSQHASETFHHSSN
WLRNPFKVLDKNQEPALWKQLIKGEGEEKKADKKQREKGDQLFDQKKEQKPEMMEKDLSS
GLVPKKKQSVVQEKKQEEGAEIQCEAETGGTHKRDFSEIKSQQCQGNELTRPSASSQEKS
SGKSQDVQRESEPLREKVTQLLPQNVHSHNSISKPQKGGPLNKEYTNWEAKETKAKDGPS
IQATQKSLPQGHFQERPETHSVPAPGGPAAQAAPAAPGLSLGEGREAATSSDDEEEDDVV
FVSSKPGSPLLFDSTLDLETKENLQFPDRSVQRKVSPASGVSKKVEPSDPVARRVYLTTQ
LKQKKSTLASVNIQALPDKGQKLIKQIQELEEVLSGLTLSPEQGTNEKSNSQVPQQSHFT
KTTTGPPHLVPPQPLPRRGTQPVGSLELKSACQVTAGGSSQCYRGHTNQDHVHAVWKITS
EAIGQLHRSLESCPGETVVAEDPAGLKVPLLLHQKQALAWLLWRESQKPQGGILADDMGL
GKTLTMIALILTQKNQEKKEEKEKSTALTWLSKDDSCDFTSHGTLIICPASLIHHWKNEV
EKRVNSNKLRVYLYHGPNRDSRARVLSTYDIVITTYSLVAKEIPTNKQEAEIPGANLNVE
GTSTPLLRIAWARIILDEAHNVKNPRVQTSIAVCKLQACARWAVTGTPIQNNLLDMYSLL
KFLRCSPFDEFNLWRSQVDNGSKKGGERLSILTKSLLLRRTKDQLDSTGRPLVILPQRKF
QLHHLKLSEDEETVYNVFFARSRSALQSYLKRHESRGNQSGRSPNNPFSRVALEFGSEEP
RHSEAADSPRSSTVHILSQLLRLRQCCCHLSLLKSALDPMELKGEGLVLSLEEQLSALTL
SELRDSEPSSTVSLNGTFFKMELFEGMRESTKISSLLAELEAIQRNSASQKSVIVSQWTN
MLKVVALHLKKHGLTYATIDGSVNPKQRMDLVEAFNHSRGPQVMLISLLAGGVGLNLTGG
NHLFLLDMHWNPSLEDQACDRIYRVGQQKDVVIHRFVCEGTVEEKILQLQEKKKDLAKQV
LSGSGESVTKLTLADLRVLFGI
Function
DsDNA-dependent ATPase which acts as a transcription termination factor by coupling ATP hydrolysis with removal of RNA polymerase II from the DNA template. May contribute to mitotic transcription repression. May also be involved in pre-mRNA splicing.
KEGG Pathway
Thyroid hormone synthesis (hsa04918 )

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Athyreosis DISBHHCU Strong Genetic Variation [1]
Cleft lip DISV3XW6 Strong Genetic Variation [2]
Cleft palate DIS6G5TF Strong Genetic Variation [2]
Congenital hypothyroidism DISL5XVU Strong Biomarker [3]
Isolated cleft lip DIS2O2JV Strong Genetic Variation [2]
Isolated cleft palate DISV80CD Strong Genetic Variation [2]
Pancreatic cancer DISJC981 Strong Biomarker [4]
Thyroid cancer DIS3VLDH Strong Biomarker [5]
Thyroid gland carcinoma DISMNGZ0 Strong Biomarker [5]
Thyroid tumor DISLVKMD Strong Biomarker [5]
Thyroid gland papillary carcinoma DIS48YMM moderate Genetic Variation [6]
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⏷ Show the Full List of 11 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Methotrexate DM2TEOL Approved Transcription termination factor 2 (TTF2) affects the response to substance of Methotrexate. [21]
Vinblastine DM5TVS3 Approved Transcription termination factor 2 (TTF2) affects the response to substance of Vinblastine. [21]
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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 Transcription termination factor 2 (TTF2). [7]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Transcription termination factor 2 (TTF2). [19]
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12 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 Transcription termination factor 2 (TTF2). [8]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Transcription termination factor 2 (TTF2). [9]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Transcription termination factor 2 (TTF2). [10]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Transcription termination factor 2 (TTF2). [11]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Transcription termination factor 2 (TTF2). [12]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Transcription termination factor 2 (TTF2). [13]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Transcription termination factor 2 (TTF2). [14]
Progesterone DMUY35B Approved Progesterone increases the expression of Transcription termination factor 2 (TTF2). [15]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Transcription termination factor 2 (TTF2). [16]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Transcription termination factor 2 (TTF2). [17]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Transcription termination factor 2 (TTF2). [18]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Transcription termination factor 2 (TTF2). [20]
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⏷ Show the Full List of 12 Drug(s)

References

1 A novel loss-of-function mutation in TTF-2 is associated with congenital hypothyroidism, thyroid agenesis and cleft palate. Hum Mol Genet. 2002 Aug 15;11(17):2051-9. doi: 10.1093/hmg/11.17.2051.
2 Genetic analysis of TTF-2 gene in children with congenital hypothyroidism and cleft palate, congenital hypothyroidism, or isolated cleft palate.Thyroid. 2004 Aug;14(8):584-8. doi: 10.1089/1050725041692864.
3 Genetics of congenital hypothyroidism. J Med Genet. 2005 May;42(5):379-89. doi: 10.1136/jmg.2004.024158.
4 EGFR pathway biomarkers in erlotinib-treated patients with advanced pancreatic cancer: translational results from the randomised, crossover phase 3 trial AIO-PK0104.Br J Cancer. 2013 Feb 5;108(2):469-76. doi: 10.1038/bjc.2012.495. Epub 2012 Nov 20.
5 Transcriptional activation of the thyroglobulin promoter directing suicide gene expression by thyroid transcription factor-1 in thyroid cancer cells.Cancer Res. 2001 May 1;61(9):3640-6.
6 Replication and Meta-Analysis of Common Gene Mutations in TTF1 and TTF2 with Papillary Thyroid Cancer.Medicine (Baltimore). 2015 Sep;94(36):e1246. doi: 10.1097/MD.0000000000001246.
7 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.
8 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.
9 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
10 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
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 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
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 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
15 Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
16 Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
17 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
18 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
19 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.
20 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.
21 Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.