Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4JCT4K)

• DOT Name: piRNA biogenesis protein EXD1 (EXD1)
• Synonyms: Exonuclease 3'-5' domain-containing protein 1; Exonuclease 3'-5' domain-like-containing protein 1; Inactive exonuclease EXD1
• Gene Name: EXD1
• Related Disease: Asthma
• UniProt ID: EXD1_HUMAN
• Pfam ID: PF01612
• Sequence:
  MEDSEFLAYVELLDEVEQGSVRAKASSVSLHAERTWMEKMKVEDLNVCEPASPAPEAPAT
  SLLNDLKYSPSEEEEVTYTVINQFQQKFGAAILHIKKQNVLSVAAEGANVCRHGKLCWLQ
  VATNCRVYLFDIFLLGSRAFHNGLQMILEDKRILKVIHDCRWLSDCLSHQYGILLNNVFD
  TQVADVLQFSMETGGYLPNCITTLQESLIKHLQVAPKYLSFLEKRQKLIQENPEVWFIRP
  VSPSLLKILALEATYLLPLRLALLDEMMSDLTTLVDGYLNTYREGSADRLGGTEPTCMEL
  PEELLQLKDFQKQRREKAAREYRVNAQGLLIRTVLQPKKLVTETAGKEEKVKGFLFGKNF
  RIDKAPSFTSQDFHGDVNLLKEESLNKQATNPQHLPPTEEGETSEDSSNKLICTKSKGSE
  DQRITQKEHFMTPKHEFQASLSLKEETEQLLMVENKEDLKCTKQAVSMSSFPQETRVSPS
  DTFYPIRKTVVSTLPPCPALEKIDSWISPFLNLP
• Function: RNA-binding component of the PET complex, a multiprotein complex required for the processing of piRNAs during spermatogenesis. The piRNA metabolic process mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposable elements, preventing their mobilization, which is essential for the germline integrity. The PET complex is required during the secondary piRNAs metabolic process for the PIWIL2 slicing-triggered loading of PIWIL4 piRNAs. In the PET complex, EXD1 probably acts as an RNA adapter. EXD1 is an inactive exonuclease.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Limited	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of piRNA biogenesis protein EXD1 (EXD1).	[2]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of piRNA biogenesis protein EXD1 (EXD1).	[3]

References

• [1] A genome-wide cross-trait analysis from UK Biobank highlights the shared genetic architecture of asthma and allergic diseases.Nat Genet. 2018 Jun;50(6):857-864. doi: 10.1038/s41588-018-0121-0. Epub 2018 May 21.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.