Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH56TIH)

• DOT Name: NHP2-like protein 1 (SNU13)
• Synonyms: High mobility group-like nuclear protein 2 homolog 1; OTK27; SNU13 homolog; hSNU13; U4/U6.U5 small nuclear ribonucleoprotein SNU13; U4/U6.U5 tri-snRNP 15.5 kDa protein
• Gene Name: SNU13
• Related Disease:
  Lung cancer
  Lung carcinoma
  Bipolar disorder
  Fanconi anemia complementation group A
  Fanconi's anemia
  Prediabetes syndrome
  Pseudohypoparathyroidism
• UniProt ID: NH2L1_HUMAN
• PDB ID: 1E7K; 2JNB; 2OZB; 3JCR; 3SIU; 3SIV; 5O9Z; 6AH0; 6AHD; 6QW6; 6QX9; 7MQ8; 7MQ9; 7MQA
• Pfam ID: PF01248
• Sequence:
  MTEADVNPKAYPLADAHLTKKLLDLVQQSCNYKQLRKGANEATKTLNRGISEFIVMAADA
  EPLEIILHLPLLCEDKNVPYVFVRSKQALGRACGVSRPVIACSVTIKEGSQLKQQIQSIQ
  QSIERLLV
• Function: Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Involved in pre-mRNA splicing as component of the spliceosome. Binds to the 5'-stem-loop of U4 snRNA and thereby contributes to spliceosome assembly. The protein undergoes a conformational change upon RNA-binding.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  Ribosome biogenesis in eukaryotes (hsa03008)
  Spliceosome (hsa03040)
• Reactome Pathway:
  Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)
  mRNA Splicing - Major Pathway (R-HSA-72163)
  rRNA modification in the nucleus and cytosol (R-HSA-6790901)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Lung carcinoma	DISTR26C	Strong	Biomarker	[1]
Bipolar disorder	DISAM7J2	Limited	Genetic Variation	[2]
Fanconi anemia complementation group A	DIS8PZLI	Limited	Biomarker	[3]
Fanconi's anemia	DISGW6Q8	Limited	Biomarker	[3]
Prediabetes syndrome	DISH2I53	Limited	Biomarker	[4]
Pseudohypoparathyroidism	DIS183OJ	Limited	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of NHP2-like protein 1 (SNU13).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of NHP2-like protein 1 (SNU13).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of NHP2-like protein 1 (SNU13).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of NHP2-like protein 1 (SNU13).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of NHP2-like protein 1 (SNU13).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of NHP2-like protein 1 (SNU13).	[9]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of NHP2-like protein 1 (SNU13).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of NHP2-like protein 1 (SNU13).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of NHP2-like protein 1 (SNU13).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of NHP2-like protein 1 (SNU13).	[14]
PP-242	DM2348V	Investigative	PP-242 increases the expression of NHP2-like protein 1 (SNU13).	[15]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of NHP2-like protein 1 (SNU13).	[11]

References

• [1] Brucea javanica oil emulsion alleviates cachexia induced by Lewis lung cancer cells in mice.J Drug Target. 2018 Mar;26(3):222-230. doi: 10.1080/1061186X.2017.1354003. Epub 2017 Jul 18.
• [2] Genome-wide DNA methylation analysis of patients with imprinting disorders identifies differentially methylated regions associated with novel candidate imprinted genes.J Med Genet. 2014 Apr;51(4):229-38. doi: 10.1136/jmedgenet-2013-102116. Epub 2014 Feb 5.
• [3] Parallel genome-wide screens identify synthetic viable interactions between the BLM helicase complex and Fanconi anemia.Nat Commun. 2017 Nov 1;8(1):1238. doi: 10.1038/s41467-017-01439-x.
• [4] Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity.Molecules. 2018 Jun 19;23(6):1483. doi: 10.3390/molecules23061483.
• [5] 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.
• [6] 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.
• [7] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [8] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [9] 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.
• [10] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [11] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [12] 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.
• [13] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.