Details of Drug Off-Target (DOT)

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

• DOT Name: Threonine synthase-like 2 (THNSL2)
• Synonyms: TSH2; EC 4.2.3.-; Secreted osteoclastogenic factor of activated T-cells; SOFAT
• Gene Name: THNSL2
• Related Disease:
  Periodontitis
  Rheumatoid arthritis
• UniProt ID: THNS2_HUMAN
• EC Number: 4.2.3.-
• Pfam ID: PF00291 ; PF14821
• Sequence:
  MWYVSTRGVAPRVNFEGALFSGYAPDGGLFMPEELPQLDRGTLCQWSTLSYPGLVKELCA
  LFIGSELLPKDELNDLIDRAFSRFRHREVVHLSRLRNGLNVLELWHGVTYAFKDLSLSCT
  TQFLQYFLEKREKHVTVVVGTSGDTGSAAIESVQGAKNMDIIVLLPKGHCTKIQELQMTT
  VLKQNVHVFGVEGNSDELDEPIKTVFADVAFVKKHNLMSLNSINWSRVLVQMAHHFFAYF
  QCTPSLDTHPLPLVEVVVPTGAAGNLAAGYIAQKIGLPIRLVVAVNRNDIIHRTVQQGDF
  SLSEAVKSTLASAMDIQVPYNMERVFWLLSGSDSQVTRALMEQFERTQSVNLPKELHSKL
  SEAVTSVSVSDEAITQTMGRCWDENQYLLCPHSAVAVNYHYQQIDRQQPSTPRCCLAPAS
  AAKFPEAVLAAGLTPETPAEIVALEHKETRCTLMRRGDNWMLMLRDTIEDLSRQWRSHAL
  NTSQ
• Function: [Isoform 1]: Acts as a catabolic phospho-lyase on both gamma- and beta-phosphorylated substrates. Degrades O-phospho-threonine (PThr) to alpha-ketobutyrate, ammonia and phosphate; [Isoform SOFAT]: Potent inducer of osteoblastic production of IL6. May act to exacerbate inflammation and/or bone turnover under inflammatory conditions.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Periodontitis	DISI9JOI	Strong	Altered Expression	[1]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[2]

7 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 Threonine synthase-like 2 (THNSL2).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Threonine synthase-like 2 (THNSL2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Threonine synthase-like 2 (THNSL2).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Threonine synthase-like 2 (THNSL2).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Threonine synthase-like 2 (THNSL2).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Threonine synthase-like 2 (THNSL2).	[6]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Threonine synthase-like 2 (THNSL2).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Threonine synthase-like 2 (THNSL2).	[5]

References

• [1] Secreted osteoclastogenic factor of activated T cells (SOFAT), a novel osteoclast activator, in chronic periodontitis.Hum Immunol. 2013 Jul;74(7):861-6. doi: 10.1016/j.humimm.2013.04.013. Epub 2013 Apr 22.
• [2] A novel T cell cytokine, secreted osteoclastogenic factor of activated T cells, induces osteoclast formation in a RANKL-independent manner.Arthritis Rheum. 2009 Nov;60(11):3324-35. doi: 10.1002/art.24877.
• [3] 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.
• [4] 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.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S. Toxicol In Vitro. 2015 Aug;29(5):1060-9.
• [7] Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009 Sep 15;239(3):273-83.