Details of Drug Off-Target (DOT)

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

• DOT Name: Survival of motor neuron-related-splicing factor 30 (SMNDC1)
• Synonyms: 30 kDa splicing factor SMNrp; SMN-related protein; Survival motor neuron domain-containing protein 1
• Gene Name: SMNDC1
• Related Disease:
  Skin neoplasm
  Spinal muscular atrophy
• UniProt ID: SPF30_HUMAN
• PDB ID: 4A4F; 4A4H; 8POI
• Pfam ID: PF06003
• Sequence:
  MSEDLAKQLASYKAQLQQVEAALSGNGENEDLLKLKKDLQEVIELTKDLLSTQPSETLAS
  SDSFASTQPTHSWKVGDKCMAVWSEDGQCYEAEIEEIDEENGTAAITFAGYGNAEVTPLL
  NLKPVEEGRKAKEDSGNKPMSKKEMIAQQREYKKKKALKKAQRIKELEQEREDQKVKWQQ
  FNNRAYSKNKKGQVKRSIFASPESVTGKVGVGTCGIADKPMTQYQDTSKYNVRHLMPQ
• Function: Involved in spliceosome assembly.
• Tissue Specificity: Detected at intermediate levels in skeletal muscle, and at low levels in heart and pancreas.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Skin neoplasm	DIS16DDV	Strong	Biomarker	[1]
Spinal muscular atrophy	DISTLKOB	Strong	Biomarker	[2]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Survival of motor neuron-related-splicing factor 30 (SMNDC1).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Survival of motor neuron-related-splicing factor 30 (SMNDC1).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Survival of motor neuron-related-splicing factor 30 (SMNDC1).	[11]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Survival of motor neuron-related-splicing factor 30 (SMNDC1).	[11]

8 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 Survival of motor neuron-related-splicing factor 30 (SMNDC1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Survival of motor neuron-related-splicing factor 30 (SMNDC1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Survival of motor neuron-related-splicing factor 30 (SMNDC1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Survival of motor neuron-related-splicing factor 30 (SMNDC1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Survival of motor neuron-related-splicing factor 30 (SMNDC1).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Survival of motor neuron-related-splicing factor 30 (SMNDC1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Survival of motor neuron-related-splicing factor 30 (SMNDC1).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Survival of motor neuron-related-splicing factor 30 (SMNDC1).	[13]

References

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• [2] Fungal Smn and Spf30 homologues are mainly present in filamentous fungi and genomes with many introns: implications for spinal muscular atrophy.Gene. 2012 Jan 10;491(2):135-41. doi: 10.1016/j.gene.2011.10.006. Epub 2011 Oct 13.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] 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.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [12] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.