Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY8QG2J)

• DOT Name: Chymotrypsin-like elastase family member 2A (CELA2A)
• Synonyms: EC 3.4.21.71; Elastase-2A
• Gene Name: CELA2A
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  High blood pressure
  Abdominal obesity-metabolic syndrome 4
  Post-traumatic stress disorder
• UniProt ID: CEL2A_HUMAN
• EC Number: 3.4.21.71
• Pfam ID: PF00089
• Sequence:
  MIRTLLLSTLVAGALSCGDPTYPPYVTRVVGGEEARPNSWPWQVSLQYSSNGKWYHTCGG
  SLIANSWVLTAAHCISSSRTYRVGLGRHNLYVAESGSLAVSVSKIVVHKDWNSNQISKGN
  DIALLKLANPVSLTDKIQLACLPPAGTILPNNYPCYVTGWGRLQTNGAVPDVLQQGRLLV
  VDYATCSSSAWWGSSVKTSMICAGGDGVISSCNGDSGGPLNCQASDGRWQVHGIVSFGSR
  LGCNYYHKPSVFTRVSNYIDWINSVIANN
• Function: Elastase that enhances insulin signaling and might have a physiologic role in cellular glucose metabolism. Circulates in plasma and reduces platelet hyperactivation, triggers both insulin secretion and degradation, and increases insulin sensitivity.
• Tissue Specificity: Expressed in pancreas. Not detected in keratinocytes . Detected in exocrine secretions of the pancreas (at protein level). Also expressed in a small fraction of cells in pancreatic islets, adrenal cortex, intestinal glands and colonic lymphoid follicles (at protein level) . Detected in plasma .
• KEGG Pathway:
  Pancreatic secretion (hsa04972)
  Protein digestion and absorption (hsa04974)
• Reactome Pathway: Formation of the cornified envelope (R-HSA-6809371)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[1]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[1]
High blood pressure	DISY2OHH	Strong	Biomarker	[2]
Abdominal obesity-metabolic syndrome 4	DIST311R	Limited	Unknown	[1]
Post-traumatic stress disorder	DISHL1EY	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Chymotrypsin-like elastase family member 2A (CELA2A).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Chymotrypsin-like elastase family member 2A (CELA2A).	[6]
Phenytoin	DMNOKBV	Approved	Phenytoin decreases the expression of Chymotrypsin-like elastase family member 2A (CELA2A).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Chymotrypsin-like elastase family member 2A (CELA2A).	[5]

References

• [1] CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation. Nat Genet. 2019 Aug;51(8):1233-1243. doi: 10.1038/s41588-019-0470-3. Epub 2019 Jul 29.
• [2] Angiotensin-converting enzyme inhibition augments the expression of rat elastase-2, an angiotensin II-forming enzyme.Am J Physiol Heart Circ Physiol. 2011 Aug;301(2):H565-70. doi: 10.1152/ajpheart.00534.2010. Epub 2011 May 20.
• [3] Incentivizing attendance to prolonged exposure for PTSD with opioid use disorder patients: A randomized controlled trial.J Consult Clin Psychol. 2017 Jul;85(7):689-701. doi: 10.1037/ccp0000208. Epub 2017 Apr 17.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [7] Role of phenytoin in wound healing: microarray analysis of early transcriptional responses in human dermal fibroblasts. Biochem Biophys Res Commun. 2004 Feb 13;314(3):661-6. doi: 10.1016/j.bbrc.2003.12.146.