Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4K90WD)

DOT Name Transcription termination factor 1 (TTF1)
Synonyms TTF-1; RNA polymerase I termination factor; Transcription termination factor I; TTF-I
Gene Name TTF1
Related Disease
Advanced cancer ( )
Lung neoplasm ( )
Prostate cancer ( )
Prostate carcinoma ( )
Adenoma ( )
Brain neoplasm ( )
Breast cancer ( )
Breast carcinoma ( )
Carcinoid tumor ( )
Carcinoma ( )
Congenital hypothyroidism ( )
Hepatocellular carcinoma ( )
Hypothyroidism ( )
Lung adenocarcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Lung squamous cell carcinoma ( )
Malignant soft tissue neoplasm ( )
Medullary thyroid gland carcinoma ( )
Mesothelioma ( )
Metastatic malignant neoplasm ( )
Metastatic sarcoma ( )
Neuroendocrine neoplasm ( )
Non-small-cell lung cancer ( )
Ovarian neoplasm ( )
Pneumonia ( )
Pneumonitis ( )
Prostate neoplasm ( )
Respiratory failure ( )
Sarcoma ( )
Small-cell lung cancer ( )
Thyroid gland carcinoma ( )
Thyroid gland undifferentiated (anaplastic) carcinoma ( )
Thyroid tumor ( )
Trichohepatoenteric syndrome ( )
Triple negative breast cancer ( )
Wilms tumor ( )
Colorectal carcinoma ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Hereditary progressive chorea without dementia ( )
Neuroendocrine cancer ( )
Squamous cell carcinoma ( )
Thyroid cancer ( )
UniProt ID
TTF1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF13921
Sequence
MEGESSRFEIHTPVSDKKKKKCSIHKERPQKHSHEIFRDSSLVNEQSQITRRKKRKKDFQ
HLISSPLKKSRICDETANATSTLKKRKKRRYSALEVDEEAGVTVVLVDKENINNTPKHFR
KDVDVVCVDMSIEQKLPRKPKTDKFQVLAKSHAHKSEALHSKVREKKNKKHQRKAASWES
QRARDTLPQSESHQEESWLSVGPGGEITELPASAHKNKSKKKKKKSSNREYETLAMPEGS
QAGREAGTDMQESQPTVGLDDETPQLLGPTHKKKSKKKKKKKSNHQEFEALAMPEGSQVG
SEVGADMQESRPAVGLHGETAGIPAPAYKNKSKKKKKKSNHQEFEAVAMPESLESAYPEG
SQVGSEVGTVEGSTALKGFKESNSTKKKSKKRKLTSVKRARVSGDDFSVPSKNSESTLFD
SVEGDGAMMEEGVKSRPRQKKTQACLASKHVQEAPRLEPANEEHNVETAEDSEIRYLSAD
SGDADDSDADLGSAVKQLQEFIPNIKDRATSTIKRMYRDDLERFKEFKAQGVAIKFGKFS
VKENKQLEKNVEDFLALTGIESADKLLYTDRYPEEKSVITNLKRRYSFRLHIGRNIARPW
KLIYYRAKKMFDVNNYKGRYSEGDTEKLKMYHSLLGNDWKTIGEMVARSSLSVALKFSQI
SSQRNRGAWSKSETRKLIKAVEEVILKKMSPQELKEVDSKLQENPESCLSIVREKLYKGI
SWVEVEAKVQTRNWMQCKSKWTEILTKRMTNGRRIYYGMNALRAKVSLIERLYEINVEDT
NEIDWEDLASAIGDVPPSYVQTKFSRLKAVYVPFWQKKTFPEIIDYLYETTLPLLKEKLE
KMMEKKGTKIQTPAAPKQVFPFRDIFYYEDDSEGEDIEKESEGQAPCMAHACNSSTLGGQ
GRWII
Function
Multifunctional nucleolar protein that terminates ribosomal gene transcription, mediates replication fork arrest and regulates RNA polymerase I transcription on chromatin. Plays a dual role in rDNA regulation, being involved in both activation and silencing of rDNA transcription. Interaction with BAZ2A/TIP5 recovers DNA-binding activity.
KEGG Pathway
Thyroid hormone synthesis (hsa04918 )
Reactome Pathway
NoRC negatively regulates rRNA expression (R-HSA-427413 )
Surfactant metabolism (R-HSA-5683826 )
RNA Polymerase I Transcription Initiation (R-HSA-73762 )
RNA Polymerase I Transcription Termination (R-HSA-73863 )
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression (R-HSA-427389 )

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Definitive Biomarker [1]
Lung neoplasm DISVARNB Definitive Altered Expression [2]
Prostate cancer DISF190Y Definitive Biomarker [3]
Prostate carcinoma DISMJPLE Definitive Biomarker [3]
Adenoma DIS78ZEV Strong Altered Expression [4]
Brain neoplasm DISY3EKS Strong Altered Expression [5]
Breast cancer DIS7DPX1 Strong Altered Expression [6]
Breast carcinoma DIS2UE88 Strong Altered Expression [6]
Carcinoid tumor DISMNRDC Strong Altered Expression [7]
Carcinoma DISH9F1N Strong Altered Expression [8]
Congenital hypothyroidism DISL5XVU Strong Genetic Variation [9]
Hepatocellular carcinoma DIS0J828 Strong Posttranslational Modification [10]
Hypothyroidism DISR0H6D Strong Biomarker [11]
Lung adenocarcinoma DISD51WR Strong Altered Expression [8]
Lung cancer DISCM4YA Strong Biomarker [12]
Lung carcinoma DISTR26C Strong Biomarker [12]
Lung squamous cell carcinoma DISXPIBD Strong Biomarker [13]
Malignant soft tissue neoplasm DISTC6NO Strong Biomarker [14]
Medullary thyroid gland carcinoma DISHBL3K Strong Biomarker [15]
Mesothelioma DISKWK9M Strong Biomarker [16]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [17]
Metastatic sarcoma DISKYC7V Strong Altered Expression [18]
Neuroendocrine neoplasm DISNPLOO Strong Biomarker [19]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [20]
Ovarian neoplasm DISEAFTY Strong Altered Expression [21]
Pneumonia DIS8EF3M Strong Biomarker [22]
Pneumonitis DIS88E0K Strong Biomarker [22]
Prostate neoplasm DISHDKGQ Strong Altered Expression [23]
Respiratory failure DISVMYJO Strong Genetic Variation [9]
Sarcoma DISZDG3U Strong Biomarker [14]
Small-cell lung cancer DISK3LZD Strong Biomarker [20]
Thyroid gland carcinoma DISMNGZ0 Strong Altered Expression [8]
Thyroid gland undifferentiated (anaplastic) carcinoma DISYBB1W Strong Altered Expression [24]
Thyroid tumor DISLVKMD Strong Altered Expression [8]
Trichohepatoenteric syndrome DISL3ODF Strong Genetic Variation [25]
Triple negative breast cancer DISAMG6N Strong Biomarker [26]
Wilms tumor DISB6T16 Strong Biomarker [27]
Colorectal carcinoma DIS5PYL0 moderate Genetic Variation [28]
Endometrial cancer DISW0LMR Limited Biomarker [29]
Endometrial carcinoma DISXR5CY Limited Biomarker [29]
Hereditary progressive chorea without dementia DISW33PR Limited Genetic Variation [30]
Neuroendocrine cancer DISVGJET Limited Biomarker [31]
Squamous cell carcinoma DISQVIFL Limited Altered Expression [32]
Thyroid cancer DIS3VLDH Limited Altered Expression [33]
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⏷ Show the Full List of 44 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Transcription termination factor 1 (TTF1). [34]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of Transcription termination factor 1 (TTF1). [41]
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6 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 1 (TTF1). [35]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Transcription termination factor 1 (TTF1). [36]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Transcription termination factor 1 (TTF1). [37]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of Transcription termination factor 1 (TTF1). [38]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Transcription termination factor 1 (TTF1). [39]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Transcription termination factor 1 (TTF1). [40]
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⏷ Show the Full List of 6 Drug(s)

References

1 Thyroid transcription factor 1 enhances cellular statin sensitivity via perturbing cholesterol metabolism.Oncogene. 2018 Jun;37(24):3290-3300. doi: 10.1038/s41388-018-0174-7. Epub 2018 Mar 19.
2 Correlation between molecular analysis, diagnosis according to the 2015 WHO classification of unresected lung tumours and TTF1 expression in small biopsies and cytology specimens from 344 non-small cell lung carcinoma patients.Pathology. 2017 Oct;49(6):604-610. doi: 10.1016/j.pathol.2017.07.002. Epub 2017 Aug 12.
3 Identifying cancer origin using circulating tumor cells.Cancer Biol Ther. 2016 Apr 2;17(4):430-8. doi: 10.1080/15384047.2016.1141839.
4 Mst1/2 kinases restrain transformation in a novel transgenic model of Ras driven non-small cell lung cancer.Oncogene. 2020 Jan;39(5):1152-1164. doi: 10.1038/s41388-019-1031-z. Epub 2019 Sep 30.
5 Thyroid transcription factor-1 in primary CNS tumors.Appl Immunohistochem Mol Morphol. 2011 Oct;19(5):437-43. doi: 10.1097/PAI.0b013e31820e6baf.
6 GCDFP-15 positive and TTF-1 negative primary lung neoplasms: a tissue microarray study of 381 primary lung tumors.Appl Immunohistochem Mol Morphol. 2009 Dec;17(6):505-11. doi: 10.1097/PAI.0b013e3181a8e809.
7 Immunohistochemical Characterization of the Origins of Metastatic Well-differentiated Neuroendocrine Tumors to the Liver.Am J Surg Pathol. 2017 Jul;41(7):915-922. doi: 10.1097/PAS.0000000000000876.
8 Napsin A Expression in Subtypes of Thyroid Tumors: Comparison with Lung Adenocarcinomas.Endocr Pathol. 2020 Mar;31(1):39-45. doi: 10.1007/s12022-019-09600-6.
9 Respiratory insufficiency in a newborn with congenital hypothyroidism due to a new mutation of TTF-1/NKX2.1 gene.Pediatr Pulmonol. 2014 Mar;49(3):E42-4. doi: 10.1002/ppul.22788. Epub 2013 Sep 2.
10 TTF1NP induces protective autophagy during apoptosis by inhibiting the Akt/mTOR pathway and activating JNK in human liver cancer cells.Oncol Rep. 2018 Mar;39(3):1423-1431. doi: 10.3892/or.2018.6196. Epub 2018 Jan 5.
11 High-resolution computed tomography findings of thyroid transcription factor 1 deficiency (NKX2-1 mutations).Pediatr Radiol. 2019 Jun;49(7):869-875. doi: 10.1007/s00247-019-04388-3. Epub 2019 Mar 30.
12 Immunohistochemical profiles in primary lung cancers and epithelial pulmonary metastases.Hum Pathol. 2019 Feb;84:221-230. doi: 10.1016/j.humpath.2018.10.009. Epub 2018 Oct 31.
13 Combined Immunohistochemistry after Mass Spectrometry Imaging for Superior Spatial Information.Proteomics Clin Appl. 2019 Jan;13(1):e1800035. doi: 10.1002/prca.201800035. Epub 2018 Aug 21.
14 SMARCA4-deficient thoracic sarcoma: a distinctive clinicopathological entity with undifferentiated rhabdoid morphology and aggressive behavior.Mod Pathol. 2017 Oct;30(10):1422-1432. doi: 10.1038/modpathol.2017.61. Epub 2017 Jun 23.
15 Expression of Tenascin C, EGFR, E-Cadherin, and TTF-1 in Medullary Thyroid Carcinoma and the Correlation with RET Mutation Status.Int J Mol Sci. 2016 Jul 9;17(7):1093. doi: 10.3390/ijms17071093.
16 Biomarkers in the diagnosis of pleural diseases: a 2018 update.Ther Adv Respir Dis. 2018 Jan-Dec;12:1753466618808660. doi: 10.1177/1753466618808660.
17 Occludin is a direct target of thyroid transcription factor-1 (TTF-1/NKX2-1).J Biol Chem. 2012 Aug 17;287(34):28790-801. doi: 10.1074/jbc.M112.367987. Epub 2012 Jul 2.
18 TTF-1-positive Metastatic Endometrioid Carcinoma: A Case Report and Review of Literature of a Potential Diagnostic Pitfall.Appl Immunohistochem Mol Morphol. 2020 Jan;28(1):e6-e9. doi: 10.1097/PAI.0000000000000539.
19 Hypothalamic Vasopressin-Producing Tumors: Often Inappropriate Diuresis But Occasionally Cushing Disease.Am J Surg Pathol. 2019 Feb;43(2):251-260. doi: 10.1097/PAS.0000000000001185.
20 Comparative analysis of TTF-1 binding DNA regions in small-cell lung cancer and non-small-cell lung cancer.Mol Oncol. 2020 Feb;14(2):277-293. doi: 10.1002/1878-0261.12608. Epub 2019 Dec 15.
21 Overexpression of SMARCE1 is associated with CD8+ T-cell infiltration in early stage ovarian cancer.Int J Biochem Cell Biol. 2014 Aug;53:389-98. doi: 10.1016/j.biocel.2014.05.031. Epub 2014 May 29.
22 Airway epithelial transcription factor NK2 homeobox 1 inhibits mucous cell metaplasia and Th2 inflammation.Am J Respir Crit Care Med. 2011 Aug 15;184(4):421-9. doi: 10.1164/rccm.201101-0106OC.
23 Immunohistochemical study of the neural development transcription factors (TTF1, ASCL1 and BRN2) in neuroendocrine prostate tumours.Actas Urol Esp. 2017 Oct;41(8):529-534. doi: 10.1016/j.acuro.2016.11.009. Epub 2017 Mar 9.
24 Epigenetic Modifications in Thyroid Cancer Cells Restore NIS and Radio-Iodine Uptake and Promote Cell Death.J Clin Med. 2018 Mar 21;7(4):61. doi: 10.3390/jcm7040061.
25 Partial deficiency of thyroid transcription factor 1 produces predominantly neurological defects in humans and mice.J Clin Invest. 2002 Feb;109(4):469-73. doi: 10.1172/JCI14192.
26 SOX10, GATA3, GCDFP15, Androgen Receptor, and Mammaglobin for the Differential Diagnosis Between Triple-negative Breast Cancer and TTF1-negative Lung Adenocarcinoma.Am J Surg Pathol. 2019 Mar;43(3):293-302. doi: 10.1097/PAS.0000000000001216.
27 Cystic metastasis of prostate cancer: A case report.Medicine (Baltimore). 2018 Dec;97(50):e13697. doi: 10.1097/MD.0000000000013697.
28 Clinicopathological and molecular implications of aberrant thyroid transcription factor-1 expression in colorectal carcinomas: an immunohistochemical analysis of 1319 cases using three different antibody clones.Histopathology. 2018 Feb;72(3):423-432. doi: 10.1111/his.13398. Epub 2017 Dec 4.
29 Expressions and significances of TTF-1 and PTEN in early endometrial cancer.Eur Rev Med Pharmacol Sci. 2017 Jul;21(3 Suppl):20-26.
30 Functional characterization of two novel mutations in TTF-1/NKX2.1 homeodomain in patients with benign hereditary chorea.J Neurol Sci. 2016 Jan 15;360:78-83. doi: 10.1016/j.jns.2015.11.050. Epub 2015 Nov 27.
31 Differentiating Merkel cell carcinoma of lymph nodes without a detectable primary skin tumor from other metastatic neuroendocrine carcinomas: The ELECTHIP criteria.J Am Acad Dermatol. 2018 May;78(5):964-972.e3. doi: 10.1016/j.jaad.2017.11.037. Epub 2017 Nov 24.
32 Immunohistochemical characteristics of brain metastases and corresponding primary lung cancer.J BUON. 2019 Jul-Aug;24(4):1626-1637.
33 Correlation of 18F-FDG uptake and thyroid cancer stem cells.Q J Nucl Med Mol Imaging. 2020 Dec;64(4):393-399. doi: 10.23736/S1824-4785.18.03088-1. Epub 2018 Aug 28.
34 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.
35 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
36 Multifaceted suppression of aggressive behavior of thyroid carcinoma by all-trans retinoic acid induced re-differentiation. Mol Cell Endocrinol. 2012 Jan 2;348(1):260-9. doi: 10.1016/j.mce.2011.09.002. Epub 2011 Sep 6.
37 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
38 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.
39 Gene expression changes associated with altered growth and differentiation in benzo[a]pyrene or arsenic exposed normal human epidermal keratinocytes. J Appl Toxicol. 2008 May;28(4):491-508.
40 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
41 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.