Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEGT4GI)

• DOT Name: Protein TESPA1 (TESPA1)
• Synonyms: Thymocyte-expressed positive selection-associated protein 1
• Gene Name: TESPA1
• Related Disease:
  Ankylosing spondylitis
  Asthma
  Rheumatoid arthritis
• UniProt ID: TESP1_HUMAN
• Pfam ID: PF14722
• Sequence:
  MEASVLSPTSWEKRRAWLRQSRNWQTQVLEEEAAAALQDVPDPEPSSLDDVFQEGNPINK
  IEDWLQDCGYSEEGFSEEAGQFIYNGFCSHGTSFEDDLTLGAEATLLAANGKLFSRSFLE
  TARPCQLLDLGCSLASSSMTGGTNKTSSSISEILDKVQEDAEDVLFSLGFGQEDHKDTSR
  IPARFFTTPSQAKGIDFQLFLKSQVRRIEMEDPCLMLASRFKQVQTLAVTADAFFCLYSY
  VSKTPVQKFTPSHMFWNCNHPTDVPSIRILSREPEPQSPRDRLRKAISKMCLYTCPRDRP
  PPPHNTPKRNSLDQVVLEVMDKVKEEKQFLQQDSDLGQFSQEDPVPPAEGKKLPTSPYPC
  VFCCEEETQQRMSTVLAPSQTLDSNPKVPCCTHSLPIEDPQWSTDPAQIRRELCSLPATN
  TETHPAKDETFWKRKSRARKSLFQKNLMGRKVKSLDLSITQQKWKQSVDRPELRRSLSQQ
  PQDTFDLEEVQSNSEEEQSQSRWPSRPRHPHHHQTFAGKDS
• Function: Required for the development and maturation of T-cells, its function being essential for the late stages of thymocyte development. Plays a role in T-cell antigen receptor (TCR)-mediated activation of the ERK and NFAT signaling pathways, possibly by serving as a scaffolding protein that promotes the assembly of the LAT signalosome in thymocytes. May play a role in the regulation of inositol 1,4,5-trisphosphate receptor-mediated Ca(2+) release and mitochondrial Ca(2+) uptake via the mitochondria-associated endoplasmic reticulum membrane (MAM) compartment.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[1]
Asthma	DISW9QNS	Limited	Genetic Variation	[2]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Protein TESPA1 (TESPA1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein TESPA1 (TESPA1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Protein TESPA1 (TESPA1).	[5]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein TESPA1 (TESPA1).	[7]

References

• [1] Lack of association between TESPA1 gene polymorphisms (rs1801876, rs2171497, rs4758994, and rs997173) and ankylosing spondylitis in a Chinese population.Inflammation. 2014 Dec;37(6):2040-6. doi: 10.1007/s10753-014-9936-8.
• [2] Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct.Am J Hum Genet. 2019 Apr 4;104(4):665-684. doi: 10.1016/j.ajhg.2019.02.022. Epub 2019 Mar 28.
• [3] Tespa1 is associated with susceptibility but not severity of rheumatoid arthritis in the Zhejiang Han population in China.Clin Rheumatol. 2015 Apr;34(4):665-71. doi: 10.1007/s10067-015-2900-7. Epub 2015 Mar 4.
• [4] Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
• [5] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [6] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [7] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.