Details of Drug Off-Target (DOT)

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

• DOT Name: snRNA-activating protein complex subunit 3 (SNAPC3)
• Synonyms: SNAPc subunit 3; Proximal sequence element-binding transcription factor subunit beta; PSE-binding factor subunit beta; PTF subunit beta; Small nuclear RNA-activating complex polypeptide 3; snRNA-activating protein complex 50 kDa subunit; SNAPc 50 kDa subunit
• Gene Name: SNAPC3
• UniProt ID: SNPC3_HUMAN
• PDB ID: 7XUR; 7ZWC; 7ZWD; 7ZX7; 7ZX8; 7ZXE; 8ITY; 8IUE; 8IUH
• Pfam ID: PF12251
• Sequence:
  MAEGSRGGPTCSGVGGRQDPVSGSGGCNFPEYELPELNTRAFHVGAFGELWRGRLRGAGD
  LSLREPPASALPGSQAADSDREDAAVARDLDCSLEAAAELRAVCGLDKLKCLEDGEDPEV
  IPENTDLVTLGVRKRFLEHREETITIDRACRQETFVYEMESHAIGKKPENSADMIEEGEL
  ILSVNILYPVIFHKHKEHKPYQTMLVLGSQKLTQLRDSIRCVSDLQIGGEFSNTPDQAPE
  HISKDLYKSAFFYFEGTFYNDKRYPECRDLSRTIIEWSESHDRGYGKFQTARMEDFTFND
  LCIKLGFPYLYCHQGDCEHVIVITDIRLVHHDDCLDRTLYPLLIKKHWLWTRKCFVCKMY
  TARWVTNNDSFAPEDPCFFCDVCFRMLHYDSEGNKLGEFLAYPYVDPGTFN
• Function: Part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes. Binds to the proximal sequence element (PSE), a non-TATA-box basal promoter element common to these 2 types of genes. Recruits TBP and BRF2 to the U6 snRNA TATA box.
• Reactome Pathway:
  RNA Polymerase III Abortive And Retractive Initiation (R-HSA-749476)
  RNA Polymerase III Transcription Initiation From Type 3 Promoter (R-HSA-76071)
  RNA polymerase II transcribes snRNA genes (R-HSA-6807505)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	snRNA-activating protein complex subunit 3 (SNAPC3) increases the response to substance of Cisplatin.	[11]

9 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 snRNA-activating protein complex subunit 3 (SNAPC3).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of snRNA-activating protein complex subunit 3 (SNAPC3).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of snRNA-activating protein complex subunit 3 (SNAPC3).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of snRNA-activating protein complex subunit 3 (SNAPC3).	[4]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of snRNA-activating protein complex subunit 3 (SNAPC3).	[5]
DTI-015	DMXZRW0	Approved	DTI-015 increases the expression of snRNA-activating protein complex subunit 3 (SNAPC3).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of snRNA-activating protein complex subunit 3 (SNAPC3).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of snRNA-activating protein complex subunit 3 (SNAPC3).	[9]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of snRNA-activating protein complex subunit 3 (SNAPC3).	[10]

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 decreases the methylation of snRNA-activating protein complex subunit 3 (SNAPC3).	[8]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [3] 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.
• [4] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [5] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [6] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] 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.
• [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] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [11] Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.