Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCRXC6B)

DOT Name General transcription factor IIH subunit 1 (GTF2H1)
Synonyms Basic transcription factor 2 62 kDa subunit; BTF2 p62; General transcription factor IIH polypeptide 1; TFIIH basal transcription factor complex p62 subunit
Gene Name GTF2H1
Related Disease
Melanoma ( )
Adenocarcinoma ( )
Adult glioblastoma ( )
Advanced cancer ( )
Amyloidosis ( )
Amyotrophic lateral sclerosis ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Breast cancer ( )
Breast carcinoma ( )
Chronic obstructive pulmonary disease ( )
Colorectal carcinoma ( )
Endometriosis ( )
Epithelial ovarian cancer ( )
Fatty liver disease ( )
Gastric cancer ( )
Glioblastoma multiforme ( )
Glioma ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
Inclusion body myositis ( )
Lung cancer ( )
Lung carcinoma ( )
Motor neurone disease ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
Obesity ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Parkinson disease ( )
Polymyositis ( )
Prostate carcinoma ( )
Rheumatoid arthritis ( )
Skin cancer ( )
Stomach cancer ( )
Type-1/2 diabetes ( )
Xeroderma pigmentosum group D ( )
Head-neck squamous cell carcinoma ( )
Paget's disease ( )
B-cell neoplasm ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Clear cell renal carcinoma ( )
Cockayne syndrome ( )
Liver cancer ( )
Prostate cancer ( )
Renal cell carcinoma ( )
Squamous cell carcinoma ( )
Trichothiodystrophy ( )
UniProt ID
TF2H1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1PFJ ; 2DII ; 2RNR ; 2RUK ; 2RVB ; 5GOW ; 5XV8 ; 6NMI ; 6O9L ; 6O9M ; 7AD8 ; 7BUL ; 7DTI ; 7EGB ; 7EGC ; 7ENA ; 7ENC ; 7LBM ; 7NVR ; 7NVW ; 7NVX ; 7NVY ; 7NVZ ; 7NW0 ; 8BVW ; 8BYQ ; 8EBS ; 8EBT ; 8EBU ; 8EBV ; 8EBW ; 8EBX ; 8EBY ; 8GXQ ; 8GXS ; 8WAK ; 8WAL ; 8WAN ; 8WAO ; 8WAP ; 8WAQ ; 8WAR ; 8WAS
Pfam ID
PF03909 ; PF08567
Sequence
MATSSEEVLLIVKKVRQKKQDGALYLMAERIAWAPEGKDRFTISHMYADIKCQKISPEGK
AKIQLQLVLHAGDTTNFHFSNESTAVKERDAVKDLLQQLLPKFKRKANKELEEKNRMLQE
DPVLFQLYKDLVVSQVISAEEFWANRLNVNATDSSSTSNHKQDVGISAAFLADVRPQTDG
CNGLRYNLTSDIIESIFRTYPAVKMKYAENVPHNMTEKEFWTRFFQSHYFHRDRLNTGSK
DLFAECAKIDEKGLKTMVSLGVKNPLLDLTALEDKPLDEGYGISSVPSASNSKSIKENSN
AAIIKRFNHHSAMVLAAGLRKQEAQNEQTSEPSNMDGNSGDADCFQPAVKRAKLQESIEY
EDLGKNNSVKTIALNLKKSDRYYHGPTPIQSLQYATSQDIINSFQSIRQEMEAYTPKLTQ
VLSSSAASSTITALSPGGALMQGGTQQAINQMVPNDIQSELKHLYVAVGELLRHFWSCFP
VNTPFLEEKVVKMKSNLERFQVTKLCPFQEKIRRQYLSTNLVSHIEEMLQTAYNKLHTWQ
SRRLMKKT
Function
Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription.
KEGG Pathway
Basal transcription factors (hsa03022 )
Nucleotide excision repair (hsa03420 )
Viral carcinogenesis (hsa05203 )
Reactome Pathway
Formation of the Early Elongation Complex (R-HSA-113418 )
Formation of HIV elongation complex in the absence of HIV Tat (R-HSA-167152 )
Formation of the HIV-1 Early Elongation Complex (R-HSA-167158 )
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection (R-HSA-167160 )
HIV Transcription Initiation (R-HSA-167161 )
RNA Polymerase II HIV Promoter Escape (R-HSA-167162 )
Transcription of the HIV genome (R-HSA-167172 )
Formation of HIV-1 elongation complex containing HIV-1 Tat (R-HSA-167200 )
Tat-mediated elongation of the HIV-1 transcript (R-HSA-167246 )
NoRC negatively regulates rRNA expression (R-HSA-427413 )
Formation of Incision Complex in GG-NER (R-HSA-5696395 )
Dual Incision in GG-NER (R-HSA-5696400 )
RNA Polymerase II Pre-transcription Events (R-HSA-674695 )
Formation of TC-NER Pre-Incision Complex (R-HSA-6781823 )
Transcription-Coupled Nucleotide Excision Repair (TC-NER) (R-HSA-6781827 )
Dual incision in TC-NER (R-HSA-6782135 )
Gap-filling DNA repair synthesis and ligation in TC-NER (R-HSA-6782210 )
TP53 Regulates Transcription of DNA Repair Genes (R-HSA-6796648 )
mRNA Capping (R-HSA-72086 )
RNA Polymerase I Transcription Initiation (R-HSA-73762 )
RNA Polymerase I Promoter Escape (R-HSA-73772 )
RNA Polymerase II Promoter Escape (R-HSA-73776 )
RNA Polymerase II Transcription Pre-Initiation And Promoter Opening (R-HSA-73779 )
RNA Polymerase I Transcription Termination (R-HSA-73863 )
RNA Polymerase II Transcription Initiation (R-HSA-75953 )
RNA Polymerase II Transcription Elongation (R-HSA-75955 )
RNA Polymerase II Transcription Initiation And Promoter Clearance (R-HSA-76042 )
RNA Pol II CTD phosphorylation and interaction with CE (R-HSA-77075 )
Formation of RNA Pol II elongation complex (R-HSA-112382 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Melanoma DIS1RRCY Definitive Altered Expression [1]
Adenocarcinoma DIS3IHTY Strong Biomarker [2]
Adult glioblastoma DISVP4LU Strong Altered Expression [3]
Advanced cancer DISAT1Z9 Strong Biomarker [4]
Amyloidosis DISHTAI2 Strong Altered Expression [5]
Amyotrophic lateral sclerosis DISF7HVM Strong Genetic Variation [6]
Arteriosclerosis DISK5QGC Strong Biomarker [7]
Atherosclerosis DISMN9J3 Strong Biomarker [7]
Breast cancer DIS7DPX1 Strong Biomarker [8]
Breast carcinoma DIS2UE88 Strong Biomarker [8]
Chronic obstructive pulmonary disease DISQCIRF Strong Altered Expression [9]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [4]
Endometriosis DISX1AG8 Strong Altered Expression [10]
Epithelial ovarian cancer DIS56MH2 Strong Genetic Variation [11]
Fatty liver disease DIS485QZ Strong Biomarker [12]
Gastric cancer DISXGOUK Strong Altered Expression [13]
Glioblastoma multiforme DISK8246 Strong Biomarker [3]
Glioma DIS5RPEH Strong Biomarker [14]
Hepatitis C virus infection DISQ0M8R Strong Altered Expression [15]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [4]
Inclusion body myositis DISZXXG5 Strong Biomarker [16]
Lung cancer DISCM4YA Strong Altered Expression [4]
Lung carcinoma DISTR26C Strong Altered Expression [4]
Motor neurone disease DISUHWUI Strong Biomarker [17]
Neoplasm DISZKGEW Strong Biomarker [18]
Non-insulin dependent diabetes DISK1O5Z Strong Altered Expression [19]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [20]
Obesity DIS47Y1K Strong Biomarker [7]
Ovarian cancer DISZJHAP Strong Genetic Variation [11]
Ovarian neoplasm DISEAFTY Strong Genetic Variation [11]
Parkinson disease DISQVHKL Strong Biomarker [21]
Polymyositis DIS5DHFP Strong Biomarker [22]
Prostate carcinoma DISMJPLE Strong Biomarker [23]
Rheumatoid arthritis DISTSB4J Strong Altered Expression [24]
Skin cancer DISTM18U Strong Altered Expression [25]
Stomach cancer DISKIJSX Strong Altered Expression [13]
Type-1/2 diabetes DISIUHAP Strong Altered Expression [26]
Xeroderma pigmentosum group D DISFFE93 Strong Biomarker [27]
Head-neck squamous cell carcinoma DISF7P24 moderate Altered Expression [28]
Paget's disease DISO3MC0 Disputed Biomarker [29]
B-cell neoplasm DISVY326 Limited Biomarker [30]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Limited Altered Expression [4]
Clear cell renal carcinoma DISBXRFJ Limited Altered Expression [31]
Cockayne syndrome DISW6GL2 Limited Biomarker [32]
Liver cancer DISDE4BI Limited Altered Expression [4]
Prostate cancer DISF190Y Limited Biomarker [23]
Renal cell carcinoma DISQZ2X8 Limited Altered Expression [31]
Squamous cell carcinoma DISQVIFL Limited Altered Expression [33]
Trichothiodystrophy DISOMQD2 Limited Altered Expression [34]
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⏷ Show the Full List of 49 Disease(s)
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 General transcription factor IIH subunit 1 (GTF2H1). [35]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of General transcription factor IIH subunit 1 (GTF2H1). [41]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of General transcription factor IIH subunit 1 (GTF2H1). [42]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of General transcription factor IIH subunit 1 (GTF2H1). [44]
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8 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 General transcription factor IIH subunit 1 (GTF2H1). [36]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of General transcription factor IIH subunit 1 (GTF2H1). [37]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of General transcription factor IIH subunit 1 (GTF2H1). [38]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of General transcription factor IIH subunit 1 (GTF2H1). [39]
Zidovudine DM4KI7O Approved Zidovudine increases the expression of General transcription factor IIH subunit 1 (GTF2H1). [40]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of General transcription factor IIH subunit 1 (GTF2H1). [43]
geraniol DMS3CBD Investigative geraniol increases the expression of General transcription factor IIH subunit 1 (GTF2H1). [45]
Manganese DMKT129 Investigative Manganese decreases the expression of General transcription factor IIH subunit 1 (GTF2H1). [46]
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⏷ Show the Full List of 8 Drug(s)

References

1 Lineage-specific control of TFIIH by MITF determines transcriptional homeostasis and DNA repair.Oncogene. 2019 May;38(19):3616-3635. doi: 10.1038/s41388-018-0661-x. Epub 2019 Jan 16.
2 Prognostic Significance of LC3B and p62/SQSTM1 Expression in Gastric Adenocarcinoma.Anticancer Res. 2019 Dec;39(12):6711-6722. doi: 10.21873/anticanres.13886.
3 HMGB1-Induced p62 Overexpression Promotes Snail-Mediated Epithelial-Mesenchymal Transition in Glioblastoma Cells via the Degradation of GSK-3.Theranostics. 2019 Mar 16;9(7):1909-1922. doi: 10.7150/thno.30578. eCollection 2019.
4 p62 functions as an oncogene in colorectal cancer through inhibiting apoptosis and promoting cell proliferation by interacting with the vitamin D receptor.Cell Prolif. 2019 May;52(3):e12585. doi: 10.1111/cpr.12585. Epub 2019 Feb 22.
5 Orientin Improves Cognition by Enhancing Autophagosome Clearance in an Alzheimer's Mouse Model.J Mol Neurosci. 2019 Oct;69(2):246-253. doi: 10.1007/s12031-019-01353-5. Epub 2019 Jun 26.
6 An FTLD-associated SQSTM1 variant impacts Nrf2 and NF-B signalling and is associated with reduced phosphorylation of p62.Mol Cell Neurosci. 2019 Jul;98:32-45. doi: 10.1016/j.mcn.2019.04.001. Epub 2019 Apr 4.
7 p62/SQSTM1 and Selective Autophagy in Cardiometabolic Diseases.Antioxid Redox Signal. 2019 Aug 20;31(6):458-471. doi: 10.1089/ars.2018.7649. Epub 2019 Feb 11.
8 IL-1 induces p62/SQSTM1 and autophagy in ER(+) /PR(+) BCa cell lines concomitant with ER and PR repression, conferring an ER(-) /PR(-) BCa-like phenotype.J Cell Biochem. 2019 Feb;120(2):1477-1491. doi: 10.1002/jcb.27340. Epub 2018 Oct 15.
9 Augmentation of S-Nitrosoglutathione Controls Cigarette Smoke-Induced Inflammatory-Oxidative Stress and Chronic Obstructive Pulmonary Disease-Emphysema Pathogenesis by Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function.Antioxid Redox Signal. 2017 Sep 1;27(7):433-451. doi: 10.1089/ars.2016.6895. Epub 2017 Feb 7.
10 NLRC5 and autophagy combined as possible predictors in patients with endometriosis.Fertil Steril. 2018 Oct;110(5):949-956. doi: 10.1016/j.fertnstert.2018.06.028.
11 Expression and role of autophagy-associated p62 (SQSTM1) in multidrug resistant ovarian cancer.Gynecol Oncol. 2018 Jul;150(1):143-150. doi: 10.1016/j.ygyno.2018.04.557. Epub 2018 Apr 24.
12 Celecoxib alleviates nonalcoholic fatty liver disease by restoring autophagic flux.Sci Rep. 2018 Mar 7;8(1):4108. doi: 10.1038/s41598-018-22339-0.
13 SP1 reduces autophagic flux through activating p62 in gastric cancer cells.Mol Med Rep. 2018 Mar;17(3):4633-4638. doi: 10.3892/mmr.2018.8400. Epub 2018 Jan 9.
14 Nrf2 and SQSTM1/p62 jointly contribute to mesenchymal transition and invasion in glioblastoma.Oncogene. 2019 Dec;38(50):7473-7490. doi: 10.1038/s41388-019-0956-6. Epub 2019 Aug 23.
15 Hepatitis C virus core or NS3/4A protein expression preconditions hepatocytes against oxidative stress and endoplasmic reticulum stress.Redox Rep. 2019 Dec;24(1):17-26. doi: 10.1080/13510002.2019.1596431.
16 Association between TDP-43 and mitochondria in inclusion body myositis.Lab Invest. 2019 Jul;99(7):1041-1048. doi: 10.1038/s41374-019-0233-x. Epub 2019 Feb 11.
17 Accumulation of dipeptide repeat proteins predates that of TDP-43 in frontotemporal lobar degeneration associated with hexanucleotide repeat expansions in C9ORF72 gene.Neuropathol Appl Neurobiol. 2015 Aug;41(5):601-12. doi: 10.1111/nan.12178. Epub 2015 Apr 30.
18 Listeria-based hepatocellular carcinoma vaccine facilitates anti-PD-1 therapy by regulating macrophage polarization.Oncogene. 2020 Feb;39(7):1429-1444. doi: 10.1038/s41388-019-1072-3. Epub 2019 Oct 28.
19 The Mitochondrial Antioxidant SS-31 Modulates Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy in Type 2 Diabetes.J Clin Med. 2019 Aug 28;8(9):1322. doi: 10.3390/jcm8091322.
20 AZD9291 promotes autophagy and inhibits PI3K/Akt pathway in NSCLC cancer cells. J Cell Biochem. 2019 Jan;120(1):756-767. doi: 10.1002/jcb.27434. Epub 2018 Aug 26.
21 The central regulator p62 between ubiquitin proteasome system and autophagy and its role in the mitophagy and Parkinson's disease.BMB Rep. 2020 Jan;53(1):56-63. doi: 10.5483/BMBRep.2020.53.1.283.
22 Sporadic inclusion body myositis: Diagnostic value of p62 immunostaining.Med Clin (Barc). 2019 Dec 13;153(11):437-440. doi: 10.1016/j.medcli.2019.04.022. Epub 2019 Jun 26.
23 Adipocyte p62/SQSTM1 Suppresses Tumorigenesis through Opposite Regulations of Metabolism in Adipose Tissue and Tumor.Cancer Cell. 2018 Apr 9;33(4):770-784.e6. doi: 10.1016/j.ccell.2018.03.001.
24 Arsenic Trioxide in Synergy with Vitamin D Rescues the Defective VDR-PPAR- Functional Module of Autophagy in Rheumatoid Arthritis.PPAR Res. 2019 May 7;2019:6403504. doi: 10.1155/2019/6403504. eCollection 2019.
25 Autophagy Controls CSL/RBPJ Stability through a p62/SQSTM1-Dependent Mechanism.Cell Rep. 2018 Sep 18;24(12):3108-3114.e4. doi: 10.1016/j.celrep.2018.08.043.
26 Nicotinate-curcumin ameliorates cognitive impairment in diabetic rats by rescuing autophagic flux in CA1 hippocampus.CNS Neurosci Ther. 2019 Apr;25(4):430-441. doi: 10.1111/cns.13059. Epub 2018 Sep 9.
27 MMXD, a TFIIH-independent XPD-MMS19 protein complex involved in chromosome segregation.Mol Cell. 2010 Aug 27;39(4):632-40. doi: 10.1016/j.molcel.2010.07.029.
28 PWP1 Mediates Nutrient-Dependent Growth Control through Nucleolar Regulation of Ribosomal Gene Expression.Dev Cell. 2017 Oct 23;43(2):240-252.e5. doi: 10.1016/j.devcel.2017.09.022.
29 p62/sequestosome 1 deficiency accelerates osteoclastogenesis in vitro and leads to Paget's disease-like bone phenotypes in mice.J Biol Chem. 2018 Jun 15;293(24):9530-9541. doi: 10.1074/jbc.RA118.002449. Epub 2018 Mar 19.
30 Long Noncoding RNA KCNQ1OT1 Promotes the Progression of Non-Small Cell Lung Cancer via Regulating miR-204-5p/ATG3 Axis.Onco Targets Ther. 2019 Dec 10;12:10787-10797. doi: 10.2147/OTT.S226044. eCollection 2019.
31 Discovery of a novel 2,5-dihydroxycinnamic acid-based 5-lipoxygenase inhibitor that induces apoptosis and may impair autophagic flux in RCC4 renal cancer cells.Eur J Med Chem. 2019 Oct 1;179:347-357. doi: 10.1016/j.ejmech.2019.06.060. Epub 2019 Jun 23.
32 Transcription preinitiation complex structure and dynamics provide insight into genetic diseases.Nat Struct Mol Biol. 2019 Jun;26(6):397-406. doi: 10.1038/s41594-019-0220-3. Epub 2019 May 20.
33 Investigation of cancer-associated fibroblasts and p62 expression in oral cancer before and after chemotherapy.J Craniomaxillofac Surg. 2018 Apr;46(4):605-610. doi: 10.1016/j.jcms.2017.12.016. Epub 2018 Jan 12.
34 Small molecule-based targeting of TTD-A dimerization to control TFIIH transcriptional activity represents a potential strategy for anticancer therapy.J Biol Chem. 2018 Sep 28;293(39):14974-14988. doi: 10.1074/jbc.RA118.003444. Epub 2018 Aug 1.
35 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.
36 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.
37 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
38 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.
39 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
40 XPC is essential for nucleotide excision repair of zidovudine-induced DNA damage in human hepatoma cells. Toxicol Appl Pharmacol. 2011 Mar 1;251(2):155-62. doi: 10.1016/j.taap.2010.12.009. Epub 2010 Dec 28.
41 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.
42 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.
43 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.
44 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.
45 Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
46 Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.