Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3UJ4ZU)

• DOT Name: Small nuclear ribonucleoprotein-associated proteins B and B' (SNRPB)
• Synonyms: snRNP-B; Sm protein B/B'; Sm-B/B'; SmB/B'
• Gene Name: SNRPB
• Related Disease:
  Advanced cancer
  Cerebrocostomandibular syndrome
  Cone-rod dystrophy
  Cone-rod dystrophy 2
  Focal segmental glomerulosclerosis
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Lupus
  Malignant mesothelioma
  Non-small-cell lung cancer
  Retinitis pigmentosa
  Systemic lupus erythematosus
  Acrofacial dysostosis
  Adult glioblastoma
  Glioblastoma multiforme
  Nager acrofacial dysostosis
• UniProt ID: RSMB_HUMAN
• PDB ID: 1D3B ; 3CW1 ; 3JCR ; 3PGW ; 4PJO ; 4WZJ ; 5MQF ; 5O9Z ; 5XJC ; 5YZG ; 5Z56 ; 5Z57 ; 5Z58 ; 6AH0 ; 6FF7 ; 6ICZ ; 6ID0 ; 6ID1 ; 6QDV ; 6QW6 ; 6QX9 ; 6V4X ; 6Y53 ; 6Y5Q ; 7A5P ; 7ABG ; 7ABI ; 7DVQ ; 7EVO ; 7QTT ; 7VPX ; 7W59 ; 7W5A ; 7W5B ; 8C6J ; 8CH6 ; 8HK1
• Pfam ID: PF01423
• Sequence:
  MTVGKSSKMLQHIDYRMRCILQDGRIFIGTFKAFDKHMNLILCDCDEFRKIKPKNSKQAE
  REEKRVLGLVLLRGENLVSMTVEGPPPKDTGIARVPLAGAAGGPGIGRAAGRGIPAGVPM
  PQAPAGLAGPVRGVGGPSQQVMTPQGRGTVAAAAAAATASIAGAPTQYPPGRGGPPPPMG
  RGAPPPGMMGPPPGMRPPMGPPMGIPPGRGTPMGMPPPGMRPPPPGMRGPPPPGMRPPRP
• 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. As part of the U7 snRNP it is involved in histone pre-mRNA 3'-end processing.
• KEGG Pathway:
  Spliceosome (hsa03040)
  Systemic lupus erythematosus (hsa05322)
• Reactome Pathway:
  snRNP Assembly (R-HSA-191859)
  mRNA Splicing - Major Pathway (R-HSA-72163)
  mRNA Splicing - Minor Pathway (R-HSA-72165)
  RNA Polymerase II Transcription Termination (R-HSA-73856)
  SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs (R-HSA-77588)
  SARS-CoV-2 modulates host translation machinery (R-HSA-9754678)
  SLBP independent Processing of Histone Pre-mRNAs (R-HSA-111367)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Cerebrocostomandibular syndrome	DIS7SW2F	Strong	Autosomal dominant	[2]
Cone-rod dystrophy	DISY9RWN	Strong	Genetic Variation	[3]
Cone-rod dystrophy 2	DISX2RWY	Strong	Biomarker	[4]
Focal segmental glomerulosclerosis	DISJNHH0	Strong	Biomarker	[5]
Gastric cancer	DISXGOUK	Strong	Biomarker	[6]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[6]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[6]
Lupus	DISOKJWA	Strong	Altered Expression	[7]
Malignant mesothelioma	DISTHJGH	Strong	Biomarker	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[9]
Retinitis pigmentosa	DISCGPY8	Strong	Biomarker	[3]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[7]
Acrofacial dysostosis	DISNBM5T	moderate	Biomarker	[10]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[11]
Glioblastoma multiforme	DISK8246	moderate	Altered Expression	[11]
Nager acrofacial dysostosis	DIS9WQOT	moderate	Altered Expression	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Small nuclear ribonucleoprotein-associated proteins B and B' (SNRPB).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Small nuclear ribonucleoprotein-associated proteins B and B' (SNRPB).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Small nuclear ribonucleoprotein-associated proteins B and B' (SNRPB).	[14]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Small nuclear ribonucleoprotein-associated proteins B and B' (SNRPB).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Small nuclear ribonucleoprotein-associated proteins B and B' (SNRPB).	[16]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Small nuclear ribonucleoprotein-associated proteins B and B' (SNRPB).	[17]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Small nuclear ribonucleoprotein-associated proteins B and B' (SNRPB).	[18]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Small nuclear ribonucleoprotein-associated proteins B and B' (SNRPB).	[19]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Small nuclear ribonucleoprotein-associated proteins B and B' (SNRPB).	[20]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Small nuclear ribonucleoprotein-associated proteins B and B' (SNRPB).	[21]
Selenium	DM25CGV	Approved	Selenium increases the expression of Small nuclear ribonucleoprotein-associated proteins B and B' (SNRPB).	[22]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Small nuclear ribonucleoprotein-associated proteins B and B' (SNRPB).	[23]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Small nuclear ribonucleoprotein-associated proteins B and B' (SNRPB).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Small nuclear ribonucleoprotein-associated proteins B and B' (SNRPB).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Small nuclear ribonucleoprotein-associated proteins B and B' (SNRPB).	[26]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Small nuclear ribonucleoprotein-associated proteins B and B' (SNRPB).	[15]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Small nuclear ribonucleoprotein-associated proteins B and B' (SNRPB).	[27]

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 Small nuclear ribonucleoprotein-associated proteins B and B' (SNRPB).	[24]

References

• [1] Analysis of the relationship between coexpression domains and chromatin 3D organization.PLoS Comput Biol. 2017 Sep 13;13(9):e1005708. doi: 10.1371/journal.pcbi.1005708. eCollection 2017 Sep.
• [2] Differential host range of viruses of feline leukemia-sarcoma complex. Virology. 1975 Apr;64(2):438-46. doi: 10.1016/0042-6822(75)90121-x.
• [3] The Spectrum of Structural and Functional Abnormalities in Female Carriers of Pathogenic Variants in the RPGR Gene.Invest Ophthalmol Vis Sci. 2018 Aug 1;59(10):4123-4133. doi: 10.1167/iovs.17-23453.
• [4] Novel compound heterozygous mutation in the POC1B gene underlie peripheral cone dystrophy in a Chinese family.Ophthalmic Genet. 2018 Jun;39(3):300-306. doi: 10.1080/13816810.2018.1430239. Epub 2018 Jan 29.
• [5] Dietary intake of cod protein beneficially affects concentrations of urinary markers of kidney function and results in lower urinary loss of amino acids in obese Zucker fa/fa rats.Br J Nutr. 2018 Oct;120(7):740-750. doi: 10.1017/S0007114518002076. Epub 2018 Aug 29.
• [6] A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients.PLoS One. 2011 Feb 18;6(2):e16694. doi: 10.1371/journal.pone.0016694.
• [7] Lupus autoantibodies recognize the product of an alternative open reading frame of SmB/B'.Biochem Biophys Res Commun. 2001 Aug 3;285(5):1206-12. doi: 10.1006/bbrc.2001.5302.
• [8] Assessing the completeness and correctness of the registration of malignant mesothelioma in Belgium.Lung Cancer. 2018 Aug;122:38-43. doi: 10.1016/j.lungcan.2018.05.018. Epub 2018 May 21.
• [9] SNRPB promotes the tumorigenic potential of NSCLC in part by regulating RAB26.Cell Death Dis. 2019 Sep 11;10(9):667. doi: 10.1038/s41419-019-1929-y.
• [10] A review of craniofacial disorders caused by spliceosomal defects.Clin Genet. 2015 Nov;88(5):405-15. doi: 10.1111/cge.12596. Epub 2015 May 1.
• [11] Functional genomics analyses of RNA-binding proteins reveal the splicing regulator SNRPB as an oncogenic candidate in glioblastoma.Genome Biol. 2016 Jun 10;17(1):125. doi: 10.1186/s13059-016-0990-4.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [13] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [14] Systematic transcriptome-based comparison of cellular adaptive stress response activation networks in hepatic stem cell-derived progeny and primary human hepatocytes. Toxicol In Vitro. 2021 Jun;73:105107. doi: 10.1016/j.tiv.2021.105107. Epub 2021 Feb 3.
• [15] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [16] 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.
• [17] 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.
• [18] Endoplasmic reticulum stress contributes to arsenic trioxide-induced intrinsic apoptosis in human umbilical and bone marrow mesenchymal stem cells. Environ Toxicol. 2016 Mar;31(3):314-28.
• [19] Inhibition of fatty acid synthase expression by 1alpha,25-dihydroxyvitamin D3 in prostate cancer cells. J Steroid Biochem Mol Biol. 2003 May;85(1):1-8. doi: 10.1016/s0960-0760(03)00142-0.
• [20] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [21] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [22] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [23] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [24] 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.
• [25] 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.
• [26] 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.
• [27] 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.