Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP3WS0U)

• DOT Name: Signal peptidase complex catalytic subunit SEC11C (SEC11C)
• Synonyms: EC 3.4.21.89; Microsomal signal peptidase 21 kDa subunit; SPase 21 kDa subunit; SEC11 homolog C; SEC11-like protein 3; SPC21
• Gene Name: SEC11C
• Related Disease:
  Matthew-Wood syndrome
  Neoplasm
• UniProt ID: SC11C_HUMAN
• PDB ID: 7P2Q
• EC Number: 3.4.21.89
• Pfam ID: PF00717
• Sequence:
  MVRAGAVGAHLPASGLDIFGDLKKMNKRQLYYQVLNFAMIVSSALMIWKGLIVLTGSESP
  IVVVLSGSMEPAFHRGDLLFLTNFREDPIRAGEIVVFKVEGRDIPIVHRVIKVHEKDNGD
  IKFLTKGDNNEVDDRGLYKEGQNWLEKKDVVGRARGFLPYVGMVTIIMNDYPKFKYALLA
  VMGAYVLLKRES
• Function: Catalytic 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. Specifically cleaves N-terminal signal peptides that contain a hydrophobic alpha-helix (h-region) shorter than 18-20 amino acids.
• 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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Matthew-Wood syndrome	DISA7HR7	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Signal peptidase complex catalytic subunit SEC11C (SEC11C).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Signal peptidase complex catalytic subunit SEC11C (SEC11C).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Signal peptidase complex catalytic subunit SEC11C (SEC11C).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Signal peptidase complex catalytic subunit SEC11C (SEC11C).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Signal peptidase complex catalytic subunit SEC11C (SEC11C).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Signal peptidase complex catalytic subunit SEC11C (SEC11C).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Signal peptidase complex catalytic subunit SEC11C (SEC11C).	[8]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Signal peptidase complex catalytic subunit SEC11C (SEC11C).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Signal peptidase complex catalytic subunit SEC11C (SEC11C).	[11]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Signal peptidase complex catalytic subunit SEC11C (SEC11C).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Signal peptidase complex catalytic subunit SEC11C (SEC11C).	[13]

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 Signal peptidase complex catalytic subunit SEC11C (SEC11C).	[10]

References

• [1] Identification of genetic alterations in pancreatic cancer by the combined use of tissue microdissection and array-based comparative genomic hybridisation.Br J Cancer. 2007 Jan 29;96(2):373-82. doi: 10.1038/sj.bjc.6603563.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [12] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.