Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV9RKSL)

• DOT Name: Transcriptional adapter 1 (TADA1)
• Synonyms: SPT3-associated factor 42; STAF42; Transcriptional adapter 1-like protein
• Gene Name: TADA1
• Related Disease:
  Malaria
  Acute lymphocytic leukaemia
  Arteriosclerosis
  Atherosclerosis
  Autism
  Childhood acute lymphoblastic leukemia
  Osteoarthritis
  Polycystic ovarian syndrome
  Rheumatoid arthritis
  Asthma
  Coronary heart disease
  Myotonic dystrophy type 1
  Non-insulin dependent diabetes
  Type-1/2 diabetes
• UniProt ID: TADA1_HUMAN
• PDB ID: 7KTR; 7KTS; 8H7G
• Pfam ID: PF12767
• Sequence:
  MATFVSELEAAKKNLSEALGDNVKQYWANLKLWFKQKISKEEFDLEAHRLLTQDNVHSHN
  DFLLAILTRCQILVSTPDGAGSLPWPGGSAAKPGKPKGKKKLSSVRQKFDHRFQPQNPLS
  GAQQFVAKDPQDDDDLKLCSHTMMLPTRGQLEGRMIVTAYEHGLDNVTEEAVSAVVYAVE
  NHLKDILTSVVSRRKAYRLRDGHFKYAFGSNVTPQPYLKNSVVAYNNLIESPPAFTAPCA
  GQNPASHPPPDDAEQQAALLLACSGDTLPASLPPVNMYDLFEALQVHREVIPTHTVYALN
  IERIITKLWHPNHEELQQDKVHRQRLAAKEGLLLC
• Function: Probably involved in transcriptional regulation.
• Reactome Pathway: HATs acetylate histones (R-HSA-3214847)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malaria	DISQ9Y50	Definitive	Genetic Variation	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[2]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[3]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[3]
Autism	DISV4V1Z	Strong	Genetic Variation	[4]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Biomarker	[2]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[5]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Genetic Variation	[6]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[7]
Asthma	DISW9QNS	Limited	Biomarker	[8]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[9]
Myotonic dystrophy type 1	DISJC0OX	Limited	Genetic Variation	[10]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[11]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[9]

1 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 Transcriptional adapter 1 (TADA1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcriptional adapter 1 (TADA1).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transcriptional adapter 1 (TADA1).	[14]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transcriptional adapter 1 (TADA1).	[15]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transcriptional adapter 1 (TADA1).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transcriptional adapter 1 (TADA1).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transcriptional adapter 1 (TADA1).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transcriptional adapter 1 (TADA1).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transcriptional adapter 1 (TADA1).	[19]

References

• [1] Further observations on associations between the ADA gene and past malaria morbidity in Sardinia.Am J Hum Biol. 2014 Sep-Oct;26(5):716-8. doi: 10.1002/ajhb.22580. Epub 2014 Jun 26.
• [2] Adenosine Deaminase 1 as a Biomarker for Diagnosis and Monitoring of Patients with Acute Lymphoblastic Leukemia.J Med Biochem. 2018 Apr 1;37(2):128-133. doi: 10.1515/jomb-2017-0042. eCollection 2018 Apr.
• [3] Inhibition of LPS-stimulated ecto-adenosine deaminase attenuates endothelial cell activation.J Mol Cell Cardiol. 2019 Mar;128:62-76. doi: 10.1016/j.yjmcc.2019.01.004. Epub 2019 Jan 11.
• [4] Adenosine deaminase alleles and autistic disorder: case-control and family-based association studies.Am J Med Genet. 2000 Dec 4;96(6):784-90.
• [5] Specific increase in enzymatic activity of adenosine deaminase 1 in rheumatoid synovial fibroblasts.Arthritis Rheum. 2003 Mar;48(3):668-74. doi: 10.1002/art.10956.
• [6] Association of G22A and A4223C ADA1 gene polymorphisms and ADA activity with PCOS.Syst Biol Reprod Med. 2016 Jun;62(3):213-22. doi: 10.3109/19396368.2016.1143055. Epub 2016 Mar 15.
• [7] A study of Adenosine-Deaminase genetic polymorphism in rheumatoid arthritis.Int J Immunopathol Pharmacol. 2010 Jul-Sep;23(3):791-5. doi: 10.1177/039463201002300313.
• [8] ADA polymorphisms and asthma: a study in the Chinese Han population.J Asthma. 2006 Apr;43(3):203-6. doi: 10.1080/02770900600566827.
• [9] The interaction of ACP1, ADA1, diabetes and gender in coronary artery disease.Am J Med Sci. 2010 Aug;340(2):103-8. doi: 10.1097/MAJ.0b013e3181e52c75.
• [10] A study of three polymorphic sites of the ADA gene in children with type 1 diabetes mellitus.J Pediatr Endocrinol Metab. 2010 Mar;23(3):283-90. doi: 10.1515/jpem.2010.23.3.283.
• [11] Type 2 diabetes and the genetics of signal transduction: a study of interaction between adenosine deaminase and acid phosphatase locus 1 polymorphisms.Metabolism. 2004 Aug;53(8):995-1001. doi: 10.1016/j.metabol.2004.03.006.
• [12] 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.
• [13] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] 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.
• [18] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.