Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6C0S52)

• DOT Name: TATA-box-binding protein (TBP)
• Synonyms: TATA sequence-binding protein; TATA-binding factor; TATA-box factor; Transcription initiation factor TFIID TBP subunit
• Gene Name: TBP
• Related Disease:
  Bladder cancer
  Choreatic disease
  Spinocerebellar ataxia type 17
  Urinary bladder cancer
  Urinary bladder neoplasm
  Acute myelogenous leukaemia
  Adenoma
  Advanced cancer
  Alzheimer disease
  Arthritis
  Breast cancer
  Cerebellar ataxia
  Cervical cancer
  Cervical carcinoma
  Clear cell renal carcinoma
  Dementia
  Depression
  Drug dependence
  Head-neck squamous cell carcinoma
  Hepatitis B virus infection
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Hereditary spherocytosis
  Inflammatory bowel disease
  Kidney neoplasm
  Neoplasm
  Neuroblastoma
  Non-small-cell lung cancer
  Rhabdomyosarcoma
  Schizophrenia
  Spinocerebellar ataxia
  Spinocerebellar ataxia type 3
  Type-1 diabetes
  Type-1/2 diabetes
  Vitiligo
  Melanoma
  Nasopharyngeal carcinoma
  Parkinsonian disorder
  Prostate carcinoma
  Adenocarcinoma
  Autoimmune disease
  Cardiac arrest
  Classic Hodgkin lymphoma
  Dentatorubral-pallidoluysian atrophy
  Dystonia
  Huntington disease
  Intellectual disability
  Nervous system disease
  Prostate cancer
• UniProt ID: TBP_HUMAN
• PDB ID: 1C9B ; 1CDW ; 1JFI ; 1NVP ; 1TGH ; 4ROC ; 4ROD ; 4ROE ; 5FUR ; 5IY6 ; 5IY7 ; 5IY8 ; 5IY9 ; 5IYA ; 5IYB ; 5IYC ; 5IYD ; 5N9G ; 6MZD ; 6MZL ; 6MZM ; 6O9L ; 7EDX ; 7EG7 ; 7EG8 ; 7EG9 ; 7EGA ; 7EGB ; 7EGC ; 7EGD ; 7EGE ; 7EGF ; 7EGI ; 7EGJ ; 7ENA ; 7ENC ; 7LBM ; 7NVR ; 7NVS ; 7NVT ; 7NVU ; 7NVY ; 7NVZ ; 7NW0 ; 7ZWC ; 7ZWD ; 7ZX7 ; 7ZX8 ; 7ZXE ; 8BVW ; 8BYQ ; 8BZ1 ; 8GXQ ; 8GXS ; 8ITY ; 8IUE ; 8IUH ; 8WAK ; 8WAL ; 8WAN ; 8WAO ; 8WAP ; 8WAQ ; 8WAR ; 8WAS
• Pfam ID: PF00352
• Sequence:
  MDQNNSLPPYAQGLASPQGAMTPGIPIFSPMMPYGTGLTPQPIQNTNSLSILEEQQRQQQ
  QQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQAVAAAAVQQSTSQQATQGTSGQAPQ
  LFHSQTLTTAPLPGTTPLYPSPMTPMTPITPATPASESSGIVPQLQNIVSTVNLGCKLDL
  KTIALRARNAEYNPKRFAAVIMRIREPRTTALIFSSGKMVCTGAKSEEQSRLAARKYARV
  VQKLGFPAKFLDFKIQNMVGSCDVKFPIRLEGLVLTHQQFSSYEPELFPGLIYRMIKPRI
  VLLIFVSGKVVLTGAKVRAEIYEAFENIYPILKGFRKTT
• Function: The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. The TFIID complex structure can be divided into 3 modules TFIID-A, TFIID-B, and TFIID-C. TBP forms the TFIID-A module together with TAF3 and TAF5. TBP is a general transcription factor that functions at the core of the TFIID complex. During assembly of the core PIC on the promoter, as part of TFIID, TBP binds to and also bends promoter DNA, irrespective of whether the promoter contains a TATA box. Component of a BRF2-containing transcription factor complex that regulates transcription mediated by RNA polymerase III. Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1 with the rDNA promoter. SL1 is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA.
• Tissue Specificity: Widely expressed, with levels highest in the testis and ovary.
• KEGG Pathway:
  Basal transcription factors (hsa03022)
  Huntington disease (hsa05016)
  Spinocerebellar ataxia (hsa05017)
  Human papillomavirus infection (hsa05165)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway:
  RNA Polymerase II HIV Promoter Escape (R-HSA-167162)
  Transcription of the HIV genome (R-HSA-167172)
  SIRT1 negatively regulates rRNA expression (R-HSA-427359)
  NoRC negatively regulates rRNA expression (R-HSA-427413)
  B-WICH complex positively regulates rRNA expression (R-HSA-5250924)
  RNA Polymerase II Pre-transcription Events (R-HSA-674695)
  Regulation of TP53 Activity through Phosphorylation (R-HSA-6804756)
  RNA polymerase II transcribes snRNA genes (R-HSA-6807505)
  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 III Abortive And Retractive Initiation (R-HSA-749476)
  RNA Polymerase II Transcription Initiation (R-HSA-75953)
  RNA Polymerase II Transcription Initiation And Promoter Clearance (R-HSA-76042)
  RNA Polymerase III Transcription Initiation From Type 1 Promoter (R-HSA-76061)
  RNA Polymerase III Transcription Initiation From Type 2 Promoter (R-HSA-76066)
  RNA Polymerase III Transcription Initiation From Type 3 Promoter (R-HSA-76071)
  Estrogen-dependent gene expression (R-HSA-9018519)
  HIV Transcription Initiation (R-HSA-167161)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Definitive	Biomarker	[1]
Choreatic disease	DISH8K3M	Definitive	Genetic Variation	[2]
Spinocerebellar ataxia type 17	DISJXO7P	Definitive	Autosomal dominant	[3]
Urinary bladder cancer	DISDV4T7	Definitive	Biomarker	[1]
Urinary bladder neoplasm	DIS7HACE	Definitive	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[4]
Adenoma	DIS78ZEV	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[7]
Arthritis	DIST1YEL	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[9]
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[10]
Cervical cancer	DISFSHPF	Strong	Biomarker	[6]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[6]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[11]
Dementia	DISXL1WY	Strong	Genetic Variation	[12]
Depression	DIS3XJ69	Strong	Genetic Variation	[13]
Drug dependence	DIS9IXRC	Strong	Biomarker	[14]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[15]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[16]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[17]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[18]
Hereditary spherocytosis	DISQYJP5	Strong	Genetic Variation	[19]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[20]
Kidney neoplasm	DISBNZTN	Strong	Altered Expression	[21]
Neoplasm	DISZKGEW	Strong	Biomarker	[22]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[23]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[24]
Rhabdomyosarcoma	DISNR7MS	Strong	Biomarker	[25]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[26]
Spinocerebellar ataxia	DISYMHUK	Strong	Biomarker	[27]
Spinocerebellar ataxia type 3	DISQBQID	Strong	Altered Expression	[28]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[29]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[30]
Vitiligo	DISR05SL	Strong	Biomarker	[31]
Melanoma	DIS1RRCY	moderate	Biomarker	[32]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Altered Expression	[33]
Parkinsonian disorder	DISHGY45	moderate	Genetic Variation	[34]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[35]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[36]
Autoimmune disease	DISORMTM	Limited	Genetic Variation	[29]
Cardiac arrest	DIS9DIA4	Limited	Genetic Variation	[37]
Classic Hodgkin lymphoma	DISV1LU6	Limited	Biomarker	[30]
Dentatorubral-pallidoluysian atrophy	DISHWE0K	Limited	Biomarker	[38]
Dystonia	DISJLFGW	Limited	Genetic Variation	[39]
Huntington disease	DISQPLA4	Limited	Biomarker	[38]
Intellectual disability	DISMBNXP	Limited	Biomarker	[40]
Nervous system disease	DISJ7GGT	Limited	Genetic Variation	[41]
Prostate cancer	DISF190Y	Limited	Biomarker	[35]

4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of TATA-box-binding protein (TBP).	[42]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of TATA-box-binding protein (TBP).	[44]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of TATA-box-binding protein (TBP).	[45]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of TATA-box-binding protein (TBP).	[47]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of TATA-box-binding protein (TBP).	[43]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide affects the methylation of TATA-box-binding protein (TBP).	[46]

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