Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2M7VH6)

• DOT Name: SRA stem-loop-interacting RNA-binding protein, mitochondrial (SLIRP)
• Gene Name: SLIRP
• Related Disease:
  Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type
  Neoplasm
• UniProt ID: SLIRP_HUMAN
• PDB ID: 8ANY
• Pfam ID: PF00076
• Sequence:
  MAASAARGAAALRRSINQPVAFVRRIPWTAASSQLKEHFAQFGHVRRCILPFDKETGFHR
  GLGWVQFSSEEGLRNALQQENHIIDGVKVQVHTRRPKLPQTSDDEKKDF
• Function: RNA-binding protein that acts as a nuclear receptor corepressor. Probably acts by binding the SRA RNA, and repressing the SRA-mediated nuclear receptor coactivation. Binds the STR7 loop of SRA RNA. Also able to repress glucocorticoid (GR), androgen (AR), thyroid (TR) and VDR-mediated transactivation.
• Tissue Specificity: Ubiquitously expressed, with highest level in heart, liver, skeletal muscle and testis.
• Reactome Pathway: Mitochondrial RNA degradation (R-HSA-9836573)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	DISVZ0PJ	Definitive	Altered Expression	[1]
Neoplasm	DISZKGEW	Disputed	Altered Expression	[2]

7 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 SRA stem-loop-interacting RNA-binding protein, mitochondrial (SLIRP).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of SRA stem-loop-interacting RNA-binding protein, mitochondrial (SLIRP).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen affects the expression of SRA stem-loop-interacting RNA-binding protein, mitochondrial (SLIRP).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of SRA stem-loop-interacting RNA-binding protein, mitochondrial (SLIRP).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of SRA stem-loop-interacting RNA-binding protein, mitochondrial (SLIRP).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of SRA stem-loop-interacting RNA-binding protein, mitochondrial (SLIRP).	[8]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of SRA stem-loop-interacting RNA-binding protein, mitochondrial (SLIRP).	[9]

References

• [1] Tissue-specific responses to the LRPPRC founder mutation in French Canadian Leigh Syndrome.Hum Mol Genet. 2015 Jan 15;24(2):480-91. doi: 10.1093/hmg/ddu468. Epub 2014 Sep 11.
• [2] SLIRP, a small SRA binding protein, is a nuclear receptor corepressor.Mol Cell. 2006 Jun 9;22(5):657-68. doi: 10.1016/j.molcel.2006.05.024.
• [3] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [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] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [9] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.