Details of Drug Off-Target (DOT)

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

• DOT Name: Signal peptidase complex subunit 2 (SPCS2)
• Synonyms: Microsomal signal peptidase 25 kDa subunit; SPase 25 kDa subunit
• Gene Name: SPCS2
• UniProt ID: SPCS2_HUMAN
• PDB ID: 7P2P; 7P2Q
• Pfam ID: PF06703
• Sequence:
  MAAAAVQGGRSGGSGGCSGAGGASNCGTGSGRSGLLDKWKIDDKPVKIDKWDGSAVKNSL
  DDSAKKVLLEKYKYVENFGLIDGRLTICTISCFFAIVALIWDYMHPFPESKPVLALCVIS
  YFVMMGILTIYTSYKEKSIFLVAHRKDPTGMDPDDIWQLSSSLKRFDDKYTLKLTFISGR
  TKQQREAEFTKSIAKFFDHSGTLVMDAYEPEISRLHDSLAIERKIK
• Function: Component of the signal peptidase complex (SPC) which catalyzes the cleavage of N-terminal signal sequences from nascent proteins as they are translocated into the lumen of the endoplasmic reticulum. Enhances the enzymatic activity of SPC and facilitates the interactions between different components of the translocation site.
• KEGG Pathway: Protein export (hsa03060)
• Reactome Pathway:
  Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) (R-HSA-381771)
  Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) (R-HSA-400511)
  Synthesis, secretion, and deacylation of Ghrelin (R-HSA-422085)
  SRP-dependent cotranslational protein targeting to membrane (R-HSA-1799339)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Signal peptidase complex subunit 2 (SPCS2).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Signal peptidase complex subunit 2 (SPCS2).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Signal peptidase complex subunit 2 (SPCS2).	[3]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Signal peptidase complex subunit 2 (SPCS2).	[4]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Signal peptidase complex subunit 2 (SPCS2).	[5]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Signal peptidase complex subunit 2 (SPCS2).	[6]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Signal peptidase complex subunit 2 (SPCS2).	[4]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Signal peptidase complex subunit 2 (SPCS2).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Signal peptidase complex subunit 2 (SPCS2).	[8]

References

• [1] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [4] 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.
• [5] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [6] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [7] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.