Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4N1C7O)

• DOT Name: Dipeptidase 3 (DPEP3)
• Gene Name: DPEP3
• UniProt ID: DPEP3_HUMAN
• PDB ID: 6VGO; 6VGR
• Pfam ID: PF01244
• Sequence:
  MQPTGREGSRALSRRYLRRLLLLLLLLLLRQPVTRAETTPGAPRALSTLGSPSLFTTPGV
  PSALTTPGLTTPGTPKTLDLRGRAQALMRSFPLVDGHNDLPQVLRQRYKNVLQDVNLRNF
  SHGQTSLDRLRDGLVGAQFWSASVSCQSQDQTAVRLALEQIDLIHRMCASYSELELVTSA
  EGLNSSQKLACLIGVEGGHSLDSSLSVLRSFYVLGVRYLTLTFTCSTPWAESSTKFRHHM
  YTNVSGLTSFGEKVVEELNRLGMMIDLSYASDTLIRRVLEVSQAPVIFSHSAARAVCDNL
  LNVPDDILQLLKKNGGIVMVTLSMGVLQCNLLANVSTVADHFDHIRAVIGSEFIGIGGNY
  DGTGRFPQGLEDVSTYPVLIEELLSRSWSEEELQGVLRGNLLRVFRQVEKVREESRAQSP
  VEAEFPYGQLSTSCHSHLVPQNGHQATHLEVTKQPTNRVPWRSSNASPYLVPGLVAAATI
  PTFTQWLC
• Function: Lacks dipeptidase activity and is unable to hydrolyze cystinyl-bis-glycine, leukotriene D4 and the beta-lactam antibiotic imipenem. The absence of activity may be due to the inability of asparagine (instead of aspartate found in DPEP1/2) at position 359 to function as the acid/base catalyst and activate the nucleophilic water/hydroxide. A tyrosine (instead of histidine) at position 269 reduces affinity for the beta zinc and may cause substrate steric hindrance.
• Reactome Pathway:
  Aflatoxin activation and detoxification (R-HSA-5423646)
  LTC4-CYSLTR mediated IL4 production (R-HSA-9664535)
  Synthesis of Leukotrienes (LT) and Eoxins (EX) (R-HSA-2142691)

Molecular Interaction Atlas (MIA) of This DOT

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 Dipeptidase 3 (DPEP3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Dipeptidase 3 (DPEP3).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Dipeptidase 3 (DPEP3).	[2]

References

• [1] 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.
• [2] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [3] 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.