Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXUMEL9)

• DOT Name: Transcriptional adapter 2-alpha (TADA2A)
• Synonyms: Transcriptional adapter 2-like; ADA2-like protein
• Gene Name: TADA2A
• Related Disease:
  Colon cancer
  Colon carcinoma
  Malaria
  Non-insulin dependent diabetes
  Obesity
  Vasculitis
  Coronary atherosclerosis
  Coronary heart disease
  Tetralogy of fallot
  Asthma
• UniProt ID: TAD2A_HUMAN
• PDB ID: 1X41
• Pfam ID: PF00249 ; PF04433
• Sequence:
  MDRLGPFSNDPSDKPPCRGCSSYLMEPYIKCAECGPPPFFLCLQCFTRGFEYKKHQSDHT
  YEIMTSDFPVLDPSWTAQEEMALLEAVMDCGFGNWQDVANQMCTKTKEECEKHYMKHFIN
  NPLFASTLLNLKQAEEAKTADTAIPFHSTDDPPRPTFDSLLSRDMAGYMPARADFIEEFD
  NYAEWDLRDIDFVEDDSDILHALKMAVVDIYHSRLKERQRRKKIIRDHGLINLRKFQLME
  RRYPKEVQDLYETMRRFARIVGPVEHDKFIESHALEFELRREIKRLQEYRTAGITNFCSA
  RTYDHLKKTREEERLKRTMLSEVLQYIQDSSACQQWLRRQADIDSGLSPSIPMASNSGRR
  SAPPLNLTGLPGTEKLNEKEKELCQMVRLVPGAYLEYKSALLNECNKQGGLRLAQARALI
  KIDVNKTRKIYDFLIREGYITKG
• Function: Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. Required for the function of some acidic activation domains, which activate transcription from a distant site. Binds double-stranded DNA. Binds dinucleosomes, probably at the linker region between neighboring nucleosomes. Plays a role in chromatin remodeling. May promote TP53/p53 'Lys-321' acetylation, leading to reduced TP53 stability and transcriptional activity. May also promote XRCC6 acetylation thus facilitating cell apoptosis in response to DNA damage.
• Tissue Specificity: Expressed in all tissues, but most abundantly in testis.
• Reactome Pathway:
  Formation of WDR5-containing histone-modifying complexes (R-HSA-9772755)
  HATs acetylate histones (R-HSA-3214847)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Biomarker	[1]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[1]
Malaria	DISQ9Y50	Strong	Genetic Variation	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[3]
Obesity	DIS47Y1K	Strong	Genetic Variation	[3]
Vasculitis	DISQRKDX	Strong	Biomarker	[4]
Coronary atherosclerosis	DISKNDYU	moderate	Genetic Variation	[5]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[5]
Tetralogy of fallot	DISMHFNW	moderate	Genetic Variation	[6]
Asthma	DISW9QNS	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Transcriptional adapter 2-alpha (TADA2A).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcriptional adapter 2-alpha (TADA2A).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcriptional adapter 2-alpha (TADA2A).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transcriptional adapter 2-alpha (TADA2A).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Transcriptional adapter 2-alpha (TADA2A).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transcriptional adapter 2-alpha (TADA2A).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transcriptional adapter 2-alpha (TADA2A).	[14]

References

• [1] A study of three polymorphic sites of ADA gene in colon cancer.Cancer Invest. 2010 Dec;28(10):989-92. doi: 10.3109/07357907.2010.483501. Epub 2010 Jun 30.
• [2] Adaptation to past malarial endemia and susceptibility to common diseases in modern populations: a study of adenosine deaminase and MN blood group genetic polymorphisms.Am J Phys Anthropol. 2005 Sep;128(1):194-8. doi: 10.1002/ajpa.20019.
• [3] Adenosine deaminase and body mass index in non-insulin-dependent diabetes mellitus.Metabolism. 1999 Aug;48(8):949-51. doi: 10.1016/s0026-0495(99)90187-7.
• [4] IL-17 receptor A and adenosine deaminase 2 deficiency in siblings with recurrent infections and chronic inflammation.J Allergy Clin Immunol. 2016 Apr;137(4):1189-1196.e2. doi: 10.1016/j.jaci.2015.07.053. Epub 2015 Nov 20.
• [5] ADA*2 allele of the adenosine deaminase gene may protect against coronary artery disease.Cardiology. 2007;108(4):275-81. doi: 10.1159/000099096. Epub 2007 Feb 8.
• [6] Oesophageal atresia with tracheoesophageal fistula and anal atresia in a patient with a de novo microduplication in 17q12.Eur J Med Genet. 2014 Jan;57(1):40-3. doi: 10.1016/j.ejmg.2013.10.007. Epub 2013 Nov 12.
• [7] ADA polymorphisms and asthma: a study in the Chinese Han population.J Asthma. 2006 Apr;43(3):203-6. doi: 10.1080/02770900600566827.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [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] 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.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.