Details of Drug Off-Target (DOT)

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

• DOT Name: Butyrophilin subfamily 2 member A2 (BTN2A2)
• Gene Name: BTN2A2
• Related Disease:
  Cockayne syndrome
  Schizophrenia
  Xeroderma pigmentosum
  Nervous system inflammation
• UniProt ID: BT2A2_HUMAN
• PDB ID: 8IH4
• Pfam ID: PF13765 ; PF00622 ; PF07686
• Sequence:
  MEPAAALHFSLPASLLLLLLLLLLSLCALVSAQFTVVGPANPILAMVGENTTLRCHLSPE
  KNAEDMEVRWFRSQFSPAVFVYKGGRERTEEQMEEYRGRITFVSKDINRGSVALVIHNVT
  AQENGIYRCYFQEGRSYDEAILRLVVAGLGSKPLIEIKAQEDGSIWLECISGGWYPEPLT
  VWRDPYGEVVPALKEVSIADADGLFMVTTAVIIRDKYVRNVSCSVNNTLLGQEKETVIFI
  PESFMPSASPWMVALAVILTASPWMVSMTVILAVFIIFMAVSICCIKKLQREKKILSGEK
  KVEQEEKEIAQQLQEELRWRRTFLHAADVVLDPDTAHPELFLSEDRRSVRRGPYRQRVPD
  NPERFDSQPCVLGWESFASGKHYWEVEVENVMVWTVGVCRHSVERKGEVLLIPQNGFWTL
  EMFGNQYRALSSPERILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSAFTVPV
  RPFFRLGSDDSPIFICPALTGASGVMVPEEGLKLHRVGTHQSL
• Function: Inhibits the proliferation of CD4 and CD8 T-cells activated by anti-CD3 antibodies, T-cell metabolism and IL2 and IFNG secretion.
• Tissue Specificity: Highly expressed in brain, bone marrow, small intestine, muscle, spleen and pancreas. Moderate expression was seen in lung, liver and kidney.
• Reactome Pathway: Butyrophilin (BTN) family interactions (R-HSA-8851680)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cockayne syndrome	DISW6GL2	Strong	Genetic Variation	[1]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[2]
Xeroderma pigmentosum	DISQ9H19	Strong	Genetic Variation	[1]
Nervous system inflammation	DISB3X5A	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Butyrophilin subfamily 2 member A2 (BTN2A2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Butyrophilin subfamily 2 member A2 (BTN2A2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Butyrophilin subfamily 2 member A2 (BTN2A2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Butyrophilin subfamily 2 member A2 (BTN2A2).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Butyrophilin subfamily 2 member A2 (BTN2A2).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Butyrophilin subfamily 2 member A2 (BTN2A2).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Butyrophilin subfamily 2 member A2 (BTN2A2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Butyrophilin subfamily 2 member A2 (BTN2A2).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Butyrophilin subfamily 2 member A2 (BTN2A2).	[12]

References

• [1] DNA repair helicase: a component of BTF2 (TFIIH) basic transcription factor.Science. 1993 Apr 2;260(5104):58-63. doi: 10.1126/science.8465201.
• [2] Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.Mol Autism. 2017 May 22;8:21. doi: 10.1186/s13229-017-0137-9. eCollection 2017.
• [3] Btn2a2, a T cell immunomodulatory molecule coregulated with MHC class II genes.J Exp Med. 2016 Feb 8;213(2):177-87. doi: 10.1084/jem.20150435. Epub 2016 Jan 25.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] 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.
• [10] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [11] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.