Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9Y2Z9B)

• DOT Name: Neuroendocrine convertase 2 (PCSK2)
• Synonyms: NEC 2; EC 3.4.21.94; KEX2-like endoprotease 2; Prohormone convertase 2; Proprotein convertase 2; PC2
• Gene Name: PCSK2
• UniProt ID: NEC2_HUMAN
• EC Number: 3.4.21.94
• Pfam ID: PF01483 ; PF00082 ; PF16470
• Sequence:
  MKGGCVSQWKAAAGFLFCVMVFASAERPVFTNHFLVELHKGGEDKARQVAAEHGFGVRKL
  PFAEGLYHFYHNGLAKAKRRRSLHHKQQLERDPRVKMALQQEGFDRKKRGYRDINEIDIN
  MNDPLFTKQWYLINTGQADGTPGLDLNVAEAWELGYTGKGVTIGIMDDGIDYLHPDLASN
  YNAEASYDFSSNDPYPYPRYTDDWFNSHGTRCAGEVSAAANNNICGVGVAYNSKVAGIRM
  LDQPFMTDIIEASSISHMPQLIDIYSASWGPTDNGKTVDGPRELTLQAMADGVNKGRGGK
  GSIYVWASGDGGSYDDCNCDGYASSMWTISINSAINDGRTALYDESCSSTLASTFSNGRK
  RNPEAGVATTDLYGNCTLRHSGTSAAAPEAAGVFALALEANLGLTWRDMQHLTVLTSKRN
  QLHDEVHQWRRNGVGLEFNHLFGYGVLDAGAMVKMAKDWKTVPERFHCVGGSVQDPEKIP
  STGKLVLTLTTDACEGKENFVRYLEHVQAVITVNATRRGDLNINMTSPMGTKSILLSRRP
  RDDDSKVGFDKWPFMTTHTWGEDARGTWTLELGFVGSAPQKGVLKEWTLMLHGTQSAPYI
  DQVVRDYQSKLAMSKKEELEEELDEAVERSLKSILNKN
• Function: Serine endopeptidase which is involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Responsible for the release of glucagon from proglucagon in pancreatic A cells.
• Reactome Pathway: Insulin processing (R-HSA-264876)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Neuroendocrine convertase 2 (PCSK2).	[1]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Neuroendocrine convertase 2 (PCSK2).	[2]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Neuroendocrine convertase 2 (PCSK2).	[3]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Neuroendocrine convertase 2 (PCSK2).	[4]
Liothyronine	DM6IR3P	Approved	Liothyronine decreases the expression of Neuroendocrine convertase 2 (PCSK2).	[4]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Neuroendocrine convertase 2 (PCSK2).	[5]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Neuroendocrine convertase 2 (PCSK2).	[8]

2 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 Neuroendocrine convertase 2 (PCSK2).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Neuroendocrine convertase 2 (PCSK2).	[7]

References

• [1] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [2] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [3] Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse. Pharmacogenomics J. 2003;3(1):27-40.
• [4] Regulation of regional expression in rat brain PC2 by thyroid hormone/characterization of novel negative thyroid hormone response elements in the PC2 promoter. Am J Physiol Endocrinol Metab. 2005 Jan;288(1):E236-45. doi: 10.1152/ajpendo.00144.2004.
• [5] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [6] 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.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [8] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.