Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4CQTCM)

• DOT Name: Signal recognition particle 9 kDa protein (SRP9)
• Synonyms: SRP9
• Gene Name: SRP9
• Related Disease:
  Colonic neoplasm
  Asthma
  Hepatocellular carcinoma
• UniProt ID: SRP09_HUMAN
• PDB ID: 1E8O; 1E8S; 1RY1; 4UYJ; 4UYK; 5AOX; 7NFX
• Pfam ID: PF05486
• Sequence:
  MPQYQTWEEFSRAAEKLYLADPMKARVVLKYRHSDGNLCVKVTDDLVCLVYKTDQAQDVK
  KIEKFHSQLMRLMVAKEARNVTMETE
• Function: Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). SRP9 together with SRP14 and the Alu portion of the SRP RNA, constitutes the elongation arrest domain of SRP. The complex of SRP9 and SRP14 is required for SRP RNA binding.
• KEGG Pathway: Protein export (hsa03060)
• Reactome Pathway: SRP-dependent cotranslational protein targeting to membrane (R-HSA-1799339)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[1]
Asthma	DISW9QNS	moderate	Genetic Variation	[2]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	Signal recognition particle 9 kDa protein (SRP9) affects the binding of 4-hydroxy-2-nonenal.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Signal recognition particle 9 kDa protein (SRP9).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Signal recognition particle 9 kDa protein (SRP9).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Signal recognition particle 9 kDa protein (SRP9).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Signal recognition particle 9 kDa protein (SRP9).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Signal recognition particle 9 kDa protein (SRP9).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Signal recognition particle 9 kDa protein (SRP9).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Signal recognition particle 9 kDa protein (SRP9).	[11]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Signal recognition particle 9 kDa protein (SRP9).	[12]

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 recognition particle 9 kDa protein (SRP9).	[10]

References

• [1] Proteomic expression analysis of surgical human colorectal cancer tissues: up-regulation of PSB7, PRDX1, and SRP9 and hypoxic adaptation in cancer.J Proteome Res. 2008 Jul;7(7):2959-72. doi: 10.1021/pr8000892. Epub 2008 Jun 13.
• [2] Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.Nat Genet. 2011 Jul 31;43(9):887-92. doi: 10.1038/ng.888.
• [3] Scutellaria barbata polysaccharides inhibit tumor growth and affect the serum proteomic profiling of hepatoma H22bearing mice.Mol Med Rep. 2019 Mar;19(3):2254-2262. doi: 10.3892/mmr.2019.9862. Epub 2019 Jan 15.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Expression Profiling of Human Pluripotent Stem Cell-Derived Cardiomyocytes Exposed to Doxorubicin-Integration and Visualization of Multi-Omics Data. Toxicol Sci. 2018 May 1;163(1):182-195. doi: 10.1093/toxsci/kfy012.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [12] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [13] Site-specific protein adducts of 4-hydroxy-2(E)-nonenal in human THP-1 monocytic cells: protein carbonylation is diminished by ascorbic acid. Chem Res Toxicol. 2010 Jan;23(1):37-47. doi: 10.1021/tx9002462.