Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYOYP14)

• DOT Name: Carboxypeptidase N subunit 2 (CPN2)
• Synonyms: Carboxypeptidase N 83 kDa chain; Carboxypeptidase N large subunit; Carboxypeptidase N polypeptide 2; Carboxypeptidase N regulatory subunit
• Gene Name: CPN2
• Related Disease:
  Neoplasm
  Coronary heart disease
  Leiomyoma
  Uterine fibroids
  Anorexia nervosa cachexia
  Obesity
• UniProt ID: CPN2_HUMAN
• Pfam ID: PF13855
• Sequence:
  MLPGAWLLWTSLLLLARPAQPCPMGCDCFVQEVFCSDEELATVPLDIPPYTKNIIFVETS
  FTTLETRAFGSNPNLTKVVFLNTQLCQFRPDAFGGLPRLEDLEVTGSSFLNLSTNIFSNL
  TSLGKLTLNFNMLEALPEGLFQHLAALESLHLQGNQLQALPRRLFQPLTHLKTLNLAQNL
  LAQLPEELFHPLTSLQTLKLSNNALSGLPQGVFGKLGSLQELFLDSNNISELPPQVFSQL
  FCLERLWLQRNAITHLPLSIFASLGNLTFLSLQWNMLRVLPAGLFAHTPCLVGLSLTHNQ
  LETVAEGTFAHLSNLRSLMLSYNAITHLPAGIFRDLEELVKLYLGSNNLTALHPALFQNL
  SKLELLSLSKNQLTTLPEGIFDTNYNLFNLALHGNPWQCDCHLAYLFNWLQQYTDRLLNI
  QTYCAGPAYLKGQVVPALNEKQLVCPVTRDHLGFQVTWPDESKAGGSWDLAVQERAARSQ
  CTYSNPEGTVVLACDQAQCRWLNVQLSPQQGSLGLQYNASQEWDLRSSCGSLRLTVSIEA
  RAAGP
• Function: The 83 kDa subunit binds and stabilizes the catalytic subunit at 37 degrees Celsius and keeps it in circulation. Under some circumstances it may be an allosteric modifier of the catalytic subunit.
• Reactome Pathway: Regulation of Complement cascade (R-HSA-977606)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Coronary heart disease	DIS5OIP1	Strong	Biomarker	[2]
Leiomyoma	DISLDDFN	Strong	Biomarker	[3]
Uterine fibroids	DISBZRMJ	Strong	Biomarker	[3]
Anorexia nervosa cachexia	DISFO5RQ	moderate	Altered Expression	[4]
Obesity	DIS47Y1K	moderate	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Carboxypeptidase N subunit 2 (CPN2).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Carboxypeptidase N subunit 2 (CPN2).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Carboxypeptidase N subunit 2 (CPN2).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Carboxypeptidase N subunit 2 (CPN2).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Carboxypeptidase N subunit 2 (CPN2).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Carboxypeptidase N subunit 2 (CPN2).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Carboxypeptidase N subunit 2 (CPN2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Carboxypeptidase N subunit 2 (CPN2).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Carboxypeptidase N subunit 2 (CPN2).	[13]

References

• [1] Acyl-CoA-Binding Protein Drives Glioblastoma Tumorigenesis by Sustaining Fatty Acid Oxidation.Cell Metab. 2019 Aug 6;30(2):274-289.e5. doi: 10.1016/j.cmet.2019.04.004. Epub 2019 May 2.
• [2] Myocardial Injury Is Distinguished from Stable Angina by a Set of Candidate Plasma Biomarkers Identified Using iTRAQ/MRM-Based Approach.J Proteome Res. 2018 Jan 5;17(1):499-515. doi: 10.1021/acs.jproteome.7b00651. Epub 2017 Nov 7.
• [3] Expression of the energy substrate transporters in uterine fibroids.Prostaglandins Other Lipid Mediat. 2016 Mar;123:9-15. doi: 10.1016/j.prostaglandins.2016.02.002. Epub 2016 Feb 27.
• [4] Acyl-CoA-Binding Protein Is a Lipogenic Factor that Triggers Food Intake and Obesity.Cell Metab. 2019 Oct 1;30(4):754-767.e9. doi: 10.1016/j.cmet.2019.07.010. Epub 2019 Aug 15.
• [5] 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.
• [6] 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.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] 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.
• [12] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [13] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.