Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI67SR2)

• DOT Name: U1 small nuclear ribonucleoprotein C (SNRPC)
• Synonyms: U1 snRNP C; U1-C; U1C
• Gene Name: SNRPC
• Related Disease: Systemic lupus erythematosus
• UniProt ID: RU1C_HUMAN
• PDB ID: 2VRD; 3CW1; 4PJO; 6ELD; 6QX9; 7VPX
• Pfam ID: PF06220
• Sequence:
  MPKFYCDYCDTYLTHDSPSVRKTHCSGRKHKENVKDYYQKWMEEQAQSLIDKTTAAFQQG
  KIPPTPFSAPPPAGAMIPPPPSLPGPPRPGMMPAPHMGGPPMMPMMGPPPPGMMPVGPAP
  GMRPPMGGHMPMMPGPPMMRPPARPMMVPTRPGMTRPDR
• Function: Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5' splice-site and the subsequent assembly of the spliceosome. SNRPC/U1-C is directly involved in initial 5' splice-site recognition for both constitutive and regulated alternative splicing. The interaction with the 5' splice-site seems to precede base-pairing between the pre-mRNA and the U1 snRNA. Stimulates commitment or early (E) complex formation by stabilizing the base pairing of the 5' end of the U1 snRNA and the 5' splice-site region.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[1]

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 U1 small nuclear ribonucleoprotein C (SNRPC).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of U1 small nuclear ribonucleoprotein C (SNRPC).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of U1 small nuclear ribonucleoprotein C (SNRPC).	[4]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of U1 small nuclear ribonucleoprotein C (SNRPC).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of U1 small nuclear ribonucleoprotein C (SNRPC).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of U1 small nuclear ribonucleoprotein C (SNRPC).	[6]

References

• [1] Immunoscreening of phage-displayed cDNA-encoded polypeptides identifies B cell targets in autoimmune disease.Biochem Biophys Res Commun. 2002 Oct 18;298(1):169-77. doi: 10.1016/s0006-291x(02)02421-x.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] 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.
• [4] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [5] Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
• [6] 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.
• [7] 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.