Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKXIFI6)

• DOT Name: Carboxypeptidase N catalytic chain (CPN1)
• Synonyms: CPN; EC 3.4.17.3; Anaphylatoxin inactivator; Arginine carboxypeptidase; Carboxypeptidase N polypeptide 1; Carboxypeptidase N small subunit; Kininase-1; Lysine carboxypeptidase; Plasma carboxypeptidase B; Serum carboxypeptidase N; SCPN
• Gene Name: CPN1
• Related Disease: Carboxypeptidase N deficiency
• UniProt ID: CBPN_HUMAN
• PDB ID: 2NSM
• EC Number: 3.4.17.3
• Pfam ID: PF13620 ; PF00246
• Sequence:
  MSDLLSVFLHLLLLFKLVAPVTFRHHRYDDLVRTLYKVQNECPGITRVYSIGRSVEGRHL
  YVLEFSDHPGIHEPLEPEVKYVGNMHGNEALGRELMLQLSEFLCEEFRNRNQRIVQLIQD
  TRIHILPSMNPDGYEVAAAQGPNKPGYLVGRNNANGVDLNRNFPDLNTYIYYNEKYGGPN
  HHLPLPDNWKSQVEPETRAVIRWMHSFNFVLSANLHGGAVVANYPYDKSFEHRVRGVRRT
  ASTPTPDDKLFQKLAKVYSYAHGWMFQGWNCGDYFPDGITNGASWYSLSKGMQDFNYLHT
  NCFEITLELSCDKFPPEEELQREWLGNREALIQFLEQVHQGIKGMVLDENYNNLANAVIS
  VSGINHDVTSGDHGDYFRLLLPGIYTVSATAPGYDPETVTVTVGPAEPTLVNFHLKRSIP
  QVSPVRRAPSRRHGVRAKVQPQARKKEMEMRQLQRGPA
• Function: Protects the body from potent vasoactive and inflammatory peptides containing C-terminal Arg or Lys (such as kinins or anaphylatoxins) which are released into the circulation.
• Tissue Specificity: Synthesized in the liver and secreted in plasma.
• Reactome Pathway: Regulation of Complement cascade (R-HSA-977606)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carboxypeptidase N deficiency	DISYA73V	Limited	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Carboxypeptidase N catalytic chain (CPN1).	[2]

7 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 Carboxypeptidase N catalytic chain (CPN1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Carboxypeptidase N catalytic chain (CPN1).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Carboxypeptidase N catalytic chain (CPN1).	[5]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Carboxypeptidase N catalytic chain (CPN1).	[6]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Carboxypeptidase N catalytic chain (CPN1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Carboxypeptidase N catalytic chain (CPN1).	[7]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Carboxypeptidase N catalytic chain (CPN1).	[8]

References

• [1] Targeted disruption of the gene encoding the murine small subunit of carboxypeptidase N (CPN1) causes susceptibility to C5a anaphylatoxin-mediated shock. J Immunol. 2009 May 15;182(10):6533-9. doi: 10.4049/jimmunol.0804207.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [7] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [8] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.