Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVR8V1L)

• DOT Name: Dipeptidase 1 (DPEP1)
• Synonyms: EC 3.4.13.19; Beta-lactamase; EC 3.5.2.6; Dehydropeptidase-I; Microsomal dipeptidase; Renal dipeptidase; hRDP
• Gene Name: DPEP1
• UniProt ID: DPEP1_HUMAN
• PDB ID: 1ITQ; 1ITU
• EC Number: 3.4.13.19; 3.5.2.6
• Pfam ID: PF01244
• Sequence:
  MWSGWWLWPLVAVCTADFFRDEAERIMRDSPVIDGHNDLPWQLLDMFNNRLQDERANLTT
  LAGTHTNIPKLRAGFVGGQFWSVYTPCDTQNKDAVRRTLEQMDVVHRMCRMYPETFLYVT
  SSAGIRQAFREGKVASLIGVEGGHSIDSSLGVLRALYQLGMRYLTLTHSCNTPWADNWLV
  DTGDSEPQSQGLSPFGQRVVKELNRLGVLIDLAHVSVATMKATLQLSRAPVIFSHSSAYS
  VCASRRNVPDDVLRLVKQTDSLVMVNFYNNYISCTNKANLSQVADHLDHIKEVAGARAVG
  FGGDFDGVPRVPEGLEDVSKYPDLIAELLRRNWTEAEVKGALADNLLRVFEAVEQASNLT
  QAPEEEPIPLDQLGGSCRTHYGYSSGASSLHRHWGLLLASLAPLVLCLSLL
• Function: Hydrolyzes a wide range of dipeptides including the conversion of leukotriene D4 to leukotriene E4. Hydrolyzes cystinyl-bis-glycine (cys-bis-gly) formed during glutathione degradation. Possesses also beta lactamase activity and can hydrolyze the beta-lactam antibiotic imipenem ; Independently of its dipeptidase activity, acts as an adhesion receptor for neutrophil recruitment from bloodstream into inflamed lungs and liver.
• Tissue Specificity: Expressed in lung and kidneys.
• 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)
• BioCyc Pathway: MetaCyc:HS00367-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 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 1 (DPEP1).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Dipeptidase 1 (DPEP1).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Dipeptidase 1 (DPEP1).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Dipeptidase 1 (DPEP1).	[4]
Cilastatin	DME2H5T	Approved	Cilastatin decreases the activity of Dipeptidase 1 (DPEP1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Dipeptidase 1 (DPEP1).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Dipeptidase 1 (DPEP1).	[6]

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] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data. Nat Genet. 2019 Feb;51(2):230-236.
• [6] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.