Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOK8M0V)

• DOT Name: Mast cell carboxypeptidase A (CPA3)
• Synonyms: MC-CPA; EC 3.4.17.1; Carboxypeptidase A3
• Gene Name: CPA3
• Related Disease:
  Coronary atherosclerosis
  Coronary heart disease
  Eosinophilic esophagitis
  Lung adenocarcinoma
  Mastocytosis
  Myocardial infarction
  Nasal polyp
  Asthma
  Melanoma
• UniProt ID: CBPA3_HUMAN
• EC Number: 3.4.17.1
• Pfam ID: PF00246 ; PF02244
• Sequence:
  MRLILPVGLIATTLAIAPVRFDREKVFRVKPQDEKQADIIKDLAKTNELDFWYPGATHHV
  AANMMVDFRVSEKESQAIQSALDQNKMHYEILIHDLQEEIEKQFDVKEDIPGRHSYAKYN
  NWEKIVAWTEKMMDKYPEMVSRIKIGSTVEDNPLYVLKIGEKNERRKAIFTDCGIHAREW
  VSPAFCQWFVYQATKTYGRNKIMTKLLDRMNFYILPVFNVDGYIWSWTKNRMWRKNRSKN
  QNSKCIGTDLNRNFNASWNSIPNTNDPCADNYRGSAPESEKETKAVTNFIRSHLNEIKVY
  ITFHSYSQMLLFPYGYTSKLPPNHEDLAKVAKIGTDVLSTRYETRYIYGPIESTIYPISG
  SSLDWAYDLGIKHTFAFELRDKGKFGFLLPESRIKPTCRETMLAVKFIAKYILKHTS
• KEGG Pathway:
  Renin-angiotensin system (hsa04614)
  Pancreatic secretion (hsa04972)
  Protein digestion and absorption (hsa04974)
• Reactome Pathway: Metabolism of Angiotensinogen to Angiotensins (R-HSA-2022377)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[1]
Coronary heart disease	DIS5OIP1	Strong	Biomarker	[1]
Eosinophilic esophagitis	DISR8WSB	Strong	Altered Expression	[2]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[3]
Mastocytosis	DIS1TEE0	Strong	Biomarker	[4]
Myocardial infarction	DIS655KI	Strong	Biomarker	[1]
Nasal polyp	DISLP3XE	Strong	Altered Expression	[5]
Asthma	DISW9QNS	Limited	Biomarker	[6]
Melanoma	DIS1RRCY	Limited	Altered Expression	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Mast cell carboxypeptidase A (CPA3).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Mast cell carboxypeptidase A (CPA3).	[9]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Mast cell carboxypeptidase A (CPA3).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Mast cell carboxypeptidase A (CPA3).	[11]

References

• [1] Mast cell derived carboxypeptidase A3 is decreased among patients with advanced coronary artery disease.Cardiol J. 2019;26(6):680-686. doi: 10.5603/CJ.a2018.0018. Epub 2018 Mar 7.
• [2] A Distinct Esophageal mRNA Pattern Identifies Eosinophilic Esophagitis Patients With Food Impactions.Front Immunol. 2018 Nov 5;9:2059. doi: 10.3389/fimmu.2018.02059. eCollection 2018.
• [3] Interleukin-1 provided by KIT-competent mast cells is required for KRAS-mutant lung adenocarcinoma.Oncoimmunology. 2019 Apr 11;8(7):1593802. doi: 10.1080/2162402X.2019.1593802. eCollection 2019.
• [4] Involvement of mast cells in eosinophilic esophagitis.J Allergy Clin Immunol. 2010 Jul;126(1):140-9. doi: 10.1016/j.jaci.2010.04.009. Epub 2010 Jun 9.
• [5] Glandular mast cells with distinct phenotype are highly elevated in chronic rhinosinusitis with nasal polyps.J Allergy Clin Immunol. 2012 Aug;130(2):410-20.e5. doi: 10.1016/j.jaci.2012.02.046. Epub 2012 Apr 24.
• [6] A sputum 6-gene signature predicts future exacerbations of poorly controlled asthma.J Allergy Clin Immunol. 2019 Jul;144(1):51-60.e11. doi: 10.1016/j.jaci.2018.12.1020. Epub 2019 Jan 22.
• [7] The combined action of mast cell chymase, tryptase and carboxypeptidase A3 protects against melanoma colonization of the lung.Oncotarget. 2017 Apr 11;8(15):25066-25079. doi: 10.18632/oncotarget.15339.
• [8] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [9] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [10] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [11] 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.