Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT06L834)

• DOT Name: Signal peptidase complex catalytic subunit SEC11A (SEC11A)
• Synonyms: EC 3.4.21.89; Endopeptidase SP18; Microsomal signal peptidase 18 kDa subunit; SPase 18 kDa subunit; SEC11 homolog A; SEC11-like protein 1; SPC18
• Gene Name: SEC11A
• Related Disease:
  Bipolar disorder
  Colorectal carcinoma
  Gastric cancer
  Major depressive disorder
  Neoplasm
  Stomach cancer
  Bladder cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: SC11A_HUMAN
• PDB ID: 7P2P
• EC Number: 3.4.21.89
• Pfam ID: PF00717
• Sequence:
  MLSLDFLDDVRRMNKRQLYYQVLNFGMIVSSALMIWKGLMVITGSESPIVVVLSGSMEPA
  FHRGDLLFLTNRVEDPIRVGEIVVFRIEGREIPIVHRVLKIHEKQNGHIKFLTKGDNNAV
  DDRGLYKQGQHWLEKKDVVGRARGFVPYIGIVTILMNDYPKFKYAVLFLLGLFVLVHRE
• 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

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Gastric cancer	DISXGOUK	Strong	Biomarker	[3]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Stomach cancer	DISKIJSX	Strong	Biomarker	[3]
Bladder cancer	DISUHNM0	moderate	Altered Expression	[4]
Urinary bladder cancer	DISDV4T7	moderate	Altered Expression	[4]
Urinary bladder neoplasm	DIS7HACE	moderate	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Signal peptidase complex catalytic subunit SEC11A (SEC11A).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Signal peptidase complex catalytic subunit SEC11A (SEC11A).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Signal peptidase complex catalytic subunit SEC11A (SEC11A).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Signal peptidase complex catalytic subunit SEC11A (SEC11A).	[8]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Signal peptidase complex catalytic subunit SEC11A (SEC11A).	[9]

References

• [1] Exploratory genome-wide association analysis of response to ketamine and a polygenic analysis of response to scopolamine in depression.Transl Psychiatry. 2018 Dec 14;8(1):280. doi: 10.1038/s41398-018-0311-7.
• [2] Clinicopathological significance of SPC18 in colorectal cancer: SPC18 participates in tumor progression.Cancer Sci. 2017 Jan;108(1):143-150. doi: 10.1111/cas.13121.
• [3] Signal peptidase complex 18, encoded by SEC11A, contributes to progression via TGF- secretion in gastric cancer.Oncogene. 2014 Jul 24;33(30):3918-26. doi: 10.1038/onc.2013.364. Epub 2013 Sep 2.
• [4] SEC11A Expression Is Associated with Basal-Like Bladder Cancer and Predicts Patient Survival.Pathobiology. 2019;86(4):208-216. doi: 10.1159/000497206. Epub 2019 Jun 4.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] 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.
• [7] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [8] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [9] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.