Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTENP2YQ)

• DOT Name: U6 snRNA phosphodiesterase 1
• Synonyms: hUsb1; 3'-5' RNA exonuclease USB1; EC 4.6.1.-; Mutated in poikiloderma with neutropenia protein 1; Mutated in PN protein 1; hMpn1
• Gene Name: USB1
• Related Disease:
  Poikiloderma with neutropenia
  Dyskeratosis congenita
• UniProt ID: USB1_HUMAN
• PDB ID: 4H7W; 5V1M; 6D2Z; 6D30; 6D31
• EC Number: 4.6.1.-
• Pfam ID: PF09749
• Sequence:
  MSAAPLVGYSSSGSEDESEDGMRTRPGDGSHRRGQSPLPRQRFPVPDSVLNMFPGTEEGP
  EDDSTKHGGRVRTFPHERGNWATHVYVPYEAKEEFLDLLDVLLPHAQTYVPRLVRMKVFH
  LSLSQSVVLRHHWILPFVQALKARMTSFHRFFFTANQVKIYTNQEKTRTFIGLEVTSGHA
  QFLDLVSEVDRVMEEFNLTTFYQDPSFHLSLAWCVGDARLQLEGQCLQELQAIVDGFEDA
  EVLLRVHTEQVRCKSGNKFFSMPLK
• Function: 3'-5' RNA exonuclease that trims the 3' end of oligo(U) and oligo(A) tracts of the pre-U6 small nuclear RNA (snRNA) molecule, leading to the formation of a mature U6 snRNA 3' end-terminated with a 2',3'-cyclic phosphate. Participates in the U6 snRNA 3' end processing that prevents U6 snRNA degradation. In addition also removes uridines from the 3' end of U6atac snRNA and possibly the vault RNA VTRNA1-1.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Poikiloderma with neutropenia	DIS20E3L	Definitive	Autosomal recessive	[1]
Dyskeratosis congenita	DISSXV0K	Supportive	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of U6 snRNA phosphodiesterase 1.	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of U6 snRNA phosphodiesterase 1.	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of U6 snRNA phosphodiesterase 1.	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of U6 snRNA phosphodiesterase 1.	[6]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of U6 snRNA phosphodiesterase 1.	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of U6 snRNA phosphodiesterase 1.	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of U6 snRNA phosphodiesterase 1.	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of U6 snRNA phosphodiesterase 1.	[10]

References

• [1] Poikiloderma with neutropenia: beginning at the end. Blood. 2013 Feb 7;121(6):872-4. doi: 10.1182/blood-2012-12-471367.
• [2] Mutations in C16orf57 and normal-length telomeres unify a subset of patients with dyskeratosis congenita, poikiloderma with neutropenia and Rothmund-Thomson syndrome. Hum Mol Genet. 2010 Nov 15;19(22):4453-61. doi: 10.1093/hmg/ddq371. Epub 2010 Sep 3.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [8] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [9] 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.
• [10] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.