Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5QAGJ4)

• DOT Name: Three prime repair exonuclease 2 (TREX2)
• Synonyms: EC 3.1.11.2; 3'-5' exonuclease TREX2
• Gene Name: TREX2
• Related Disease:
  Colorectal carcinoma
  Laryngeal carcinoma
  Prostate neoplasm
  Psoriasis
  Systemic lupus erythematosus
  Squamous cell carcinoma
• UniProt ID: TREX2_HUMAN
• PDB ID: 1Y97
• EC Number: 3.1.11.2
• Sequence:
  MSEAPRAETFVFLDLEATGLPSVEPEIAELSLFAVHRSSLENPEHDESGALVLPRVLDKL
  TLCMCPERPFTAKASEITGLSSEGLARCRKAGFDGAVVRTLQAFLSRQAGPICLVAHNGF
  DYDFPLLCAELRRLGARLPRDTVCLDTLPALRGLDRAHSHGTRARGRQGYSLGSLFHRYF
  RAEPSAAHSAEGDVHTLLLIFLHRAAELLAWADEQARGWAHIEPMYLPPDDPSLEA
• Function: Exonuclease with a preference for double-stranded DNA with mismatched 3' termini. May play a role in DNA repair.
• Tissue Specificity: Detected in heart, breast, prostate, skeletal muscle, testis, uterus, bone marrow, colon, small intestine, stomach and thymus.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[1]
Laryngeal carcinoma	DISNHCIV	Strong	Posttranslational Modification	[1]
Prostate neoplasm	DISHDKGQ	Strong	Genetic Variation	[2]
Psoriasis	DIS59VMN	Strong	Altered Expression	[3]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[4]
Squamous cell carcinoma	DISQVIFL	moderate	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Three prime repair exonuclease 2 (TREX2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Three prime repair exonuclease 2 (TREX2).	[7]

References

• [1] DNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer.Clin Epigenetics. 2019 May 3;11(1):67. doi: 10.1186/s13148-019-0666-5.
• [2] Sequence variants in the 3'-->5' deoxyribonuclease TREX2: identification in a genetic screen and effects on catalysis by the recombinant proteins.Adv Enzyme Regul. 2004;44:37-49. doi: 10.1016/j.advenzreg.2003.11.010.
• [3] Structural insights into the duplex DNA processing of TREX2.Nucleic Acids Res. 2018 Dec 14;46(22):12166-12176. doi: 10.1093/nar/gky970.
• [4] TREX1 polymorphisms associated with autoantibodies in patients with systemic lupus erythematosus.Rheumatol Int. 2008 Jun;28(8):783-9. doi: 10.1007/s00296-007-0509-0. Epub 2007 Dec 19.
• [5] Multifaceted role of TREX2 in the skin defense against UV-induced skin carcinogenesis.Oncotarget. 2015 Sep 8;6(26):22375-96. doi: 10.18632/oncotarget.4296.
• [6] 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.
• [7] 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.