Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9JAL80)

• DOT Name: Chymotrypsin-like elastase family member 3A (CELA3A)
• Synonyms: EC 3.4.21.70; Elastase IIIA; Elastase-3A; Protease E
• Gene Name: CELA3A
• Related Disease:
  Cystic fibrosis
  Exocrine pancreatic insufficiency
  Irritable bowel syndrome
  Neoplasm
  Non-insulin dependent diabetes
  Type-1/2 diabetes
  Type-1 diabetes
  Chronic pancreatitis
  Nephropathy
• UniProt ID: CEL3A_HUMAN
• EC Number: 3.4.21.70
• Pfam ID: PF00089
• Sequence:
  MMLRLLSSLLLVAVASGYGPPSSHSSSRVVHGEDAVPYSWPWQVSLQYEKSGSFYHTCGG
  SLIAPDWVVTAGHCISRDLTYQVVLGEYNLAVKEGPEQVIPINSEELFVHPLWNRSCVAC
  GNDIALIKLSRSAQLGDAVQLASLPPAGDILPNKTPCYITGWGRLYTNGPLPDKLQQARL
  PVVDYKHCSRWNWWGSTVKKTMVCAGGYIRSGCNGDSGGPLNCPTEDGGWQVHGVTSFVS
  AFGCNFIWKPTVFTRVSAFIDWIEETIASH
• Function: Efficient protease with alanine specificity but only little elastolytic activity.
• KEGG Pathway:
  Pancreatic secretion (hsa04972)
  Protein digestion and absorption (hsa04974)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[1]
Exocrine pancreatic insufficiency	DISCZYU2	Strong	Biomarker	[2]
Irritable bowel syndrome	DIS27206	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[5]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[6]
Type-1 diabetes	DIS7HLUB	Disputed	Altered Expression	[7]
Chronic pancreatitis	DISBUOMJ	Limited	Biomarker	[8]
Nephropathy	DISXWP4P	Limited	Biomarker	[6]

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 Chymotrypsin-like elastase family member 3A (CELA3A).	[9]

References

• [1] Use of monoclonal faecal elastase-1 concentration for pancreatic status assessment in cystic fibrosis patients.J Pediatr (Rio J). 2011 Mar-Apr;87(2):157-62. doi: 10.2223/JPED.2075.
• [2] The ageing pancreas: a systematic review of the evidence and analysis of the consequences.J Intern Med. 2018 May;283(5):446-460. doi: 10.1111/joim.12745. Epub 2018 Mar 23.
• [3] Protease signaling through protease activated receptor 1 mediate nerve activation by mucosal supernatants from irritable bowel syndrome but not from ulcerative colitis patients.PLoS One. 2018 Mar 12;13(3):e0193943. doi: 10.1371/journal.pone.0193943. eCollection 2018.
• [4] Serum Elastase 1 Level as a Risk Factor for Postoperative Recurrence in Patients with Well-Differentiated Pancreatic Neuroendocrine Neoplasms.Ann Surg Oncol. 2018 Oct;25(11):3358-3364. doi: 10.1245/s10434-018-6675-3. Epub 2018 Jul 27.
• [5] Nutritional markers in patients with diabetes and pancreatic exocrine failure.Acta Diabetol. 2019 Jun;56(6):651-658. doi: 10.1007/s00592-019-01294-w. Epub 2019 Feb 10.
• [6] Exocrine pancreatic dysfunction is common in hepatocyte nuclear factor 1-associated renal disease and can be symptomatic.Clin Kidney J. 2018 Aug;11(4):453-458. doi: 10.1093/ckj/sfx150. Epub 2018 Jan 30.
• [7] Pancreas size and exocrine function is decreased in young children with recent-onset Type 1 diabetes.Diabet Med. 2020 Aug;37(8):1340-1343. doi: 10.1111/dme.13987. Epub 2019 Jun 17.
• [8] Genetic Analysis of Human Chymotrypsin-Like Elastases 3A and 3B (CELA3A and CELA3B) to Assess the Role of Complex Formation between Proelastases and Procarboxypeptidases in Chronic Pancreatitis.Int J Mol Sci. 2016 Dec 20;17(12):2148. doi: 10.3390/ijms17122148.
• [9] 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.