Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWKZV4E)

• DOT Name: Small nuclear ribonucleoprotein Sm D1 (SNRPD1)
• Synonyms: Sm-D1; Sm-D autoantigen; snRNP core protein D1
• Gene Name: SNRPD1
• Related Disease:
  Autoimmune disease
  Hepatitis C virus infection
  Laryngeal carcinoma
  Nephritis
  Systemic lupus erythematosus
  Breast cancer
  Melanoma
  Sensorineural hearing loss disorder
  Alopecia
  Nephropathy
  Post-traumatic stress disorder
  Pulmonary arterial hypertension
  Ring dermoid of cornea
• UniProt ID: SMD1_HUMAN
• PDB ID: 1B34 ; 3CW1 ; 3JCR ; 3PGW ; 4F7U ; 4PJO ; 4V98 ; 4WZJ ; 5MQF ; 5O9Z ; 5XJC ; 5XJL ; 5XJQ ; 5XJR ; 5XJS ; 5XJT ; 5XJU ; 5YZG ; 5Z56 ; 5Z57 ; 5Z58 ; 6AH0 ; 6AHD ; 6FF7 ; 6ICZ ; 6ID0 ; 6ID1 ; 6QDV ; 6QW6 ; 6QX9 ; 6Y53 ; 6Y5Q ; 7A5P ; 7ABG ; 7ABI ; 7B0Y ; 7DVQ ; 7EVO ; 7QTT ; 7VPX ; 7W59 ; 7W5A ; 7W5B ; 8C6J ; 8CH6 ; 8HK1
• Pfam ID: PF01423
• Sequence:
  MKLVRFLMKLSHETVTIELKNGTQVHGTITGVDVSMNTHLKAVKMTLKNREPVQLETLSI
  RGNNIRYFILPDSLPLDTLLVDVEPKVKSKKREAVAGRGRGRGRGRGRGRGRGRGGPRR
• Function: Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. May act as a charged protein scaffold to promote snRNP assembly or strengthen snRNP-snRNP interactions through non-specific electrostatic contacts with RNA.
• KEGG Pathway:
  Spliceosome (hsa03040)
  Systemic lupus erythematosus (hsa05322)
• Reactome Pathway:
  mRNA Splicing - Major Pathway (R-HSA-72163)
  mRNA Splicing - Minor Pathway (R-HSA-72165)
  SARS-CoV-2 modulates host translation machinery (R-HSA-9754678)
  snRNP Assembly (R-HSA-191859)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Strong	Biomarker	[1]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[1]
Laryngeal carcinoma	DISNHCIV	Strong	Biomarker	[2]
Nephritis	DISQZQ70	Strong	Biomarker	[3]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	moderate	Biomarker	[5]
Melanoma	DIS1RRCY	moderate	Biomarker	[5]
Sensorineural hearing loss disorder	DISJV45Z	moderate	Biomarker	[6]
Alopecia	DIS37HU4	Limited	Biomarker	[7]
Nephropathy	DISXWP4P	Limited	Biomarker	[7]
Post-traumatic stress disorder	DISHL1EY	Limited	Genetic Variation	[8]
Pulmonary arterial hypertension	DISP8ZX5	Limited	Biomarker	[7]
Ring dermoid of cornea	DISI2QC5	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Small nuclear ribonucleoprotein Sm D1 (SNRPD1).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Small nuclear ribonucleoprotein Sm D1 (SNRPD1).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Small nuclear ribonucleoprotein Sm D1 (SNRPD1).	[11]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Small nuclear ribonucleoprotein Sm D1 (SNRPD1).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Small nuclear ribonucleoprotein Sm D1 (SNRPD1).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Small nuclear ribonucleoprotein Sm D1 (SNRPD1).	[14]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Small nuclear ribonucleoprotein Sm D1 (SNRPD1).	[15]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Small nuclear ribonucleoprotein Sm D1 (SNRPD1).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Small nuclear ribonucleoprotein Sm D1 (SNRPD1).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Small nuclear ribonucleoprotein Sm D1 (SNRPD1).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Small nuclear ribonucleoprotein Sm D1 (SNRPD1).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Small nuclear ribonucleoprotein Sm D1 (SNRPD1).	[19]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Small nuclear ribonucleoprotein Sm D1 (SNRPD1).	[20]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Small nuclear ribonucleoprotein Sm D1 (SNRPD1).	[21]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Small nuclear ribonucleoprotein Sm D1 (SNRPD1).	[22]

References

• [1] Hepatitis C virus nonstructural protein NS3 binds to Sm-D1, a small nuclear ribonucleoprotein associated with autoimmune disease.Microbiol Immunol. 2003;47(8):601-11. doi: 10.1111/j.1348-0421.2003.tb03423.x.
• [2] Expression, localization and clinical application of exogenous Smith proteins D1 in gene transfected HEp-2 cells.Int J Rheum Dis. 2013 Jun;16(3):303-9. doi: 10.1111/1756-185X.12000. Epub 2012 Oct 22.
• [3] Reactivities to the Sm autoantigenic complex and the synthetic SmD1-aa83-119 peptide in systemic lupus erythematosus and other autoimmune diseases.J Autoimmun. 2001 Dec;17(4):347-54. doi: 10.1006/jaut.2001.0545.
• [4] Clinical and serological associations of anti-ribosomal P0 protein antibodies in systemic lupus erythematosus.Clin Rheumatol. 2018 Mar;37(3):703-707. doi: 10.1007/s10067-017-3886-0. Epub 2017 Nov 18.
• [5] Targeting the deregulated spliceosome core machinery in cancer cells triggers mTOR blockade and autophagy.Cancer Res. 2013 Apr 1;73(7):2247-58. doi: 10.1158/0008-5472.CAN-12-2501. Epub 2013 Jan 28.
• [6] Overlap Syndrome with Rowell's Syndrome, Antiphospholipid Syndrome, Primary Sterility, and Sensorineural Hearing Loss: A Case Report, Brief Review, and Analysis of Cases of Rowell's Syndrome Reported from India and Abroad.Indian J Dermatol. 2018 Sep-Oct;63(5):418-423. doi: 10.4103/ijd.IJD_437_17.
• [7] Anti-SmD1 antibodies are associated with renal disorder, seizures, and pulmonary arterial hypertension in Chinese patients with active SLE.Sci Rep. 2017 Aug 8;7(1):7617. doi: 10.1038/s41598-017-08099-3.
• [8] Psychosocial interventions for post-traumatic stress disorder in refugees and asylum seekers resettled in high-income countries: Systematic review and meta-analysis.PLoS One. 2017 Feb 2;12(2):e0171030. doi: 10.1371/journal.pone.0171030. eCollection 2017.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] 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.
• [12] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [13] 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.
• [14] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [15] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [16] Benzo[a]pyrene increases the Nrf2 content by downregulating the Keap1 message. Toxicol Sci. 2010 Aug;116(2):549-61.
• [17] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [18] 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.
• [19] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [21] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [22] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.