Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAPN1NI)

• DOT Name: snRNA-activating protein complex subunit 1 (SNAPC1)
• Synonyms: SNAPc subunit 1; Proximal sequence element-binding transcription factor subunit gamma; PSE-binding factor subunit gamma; PTF subunit gamma; Small nuclear RNA-activating complex polypeptide 1; snRNA-activating protein complex 43 kDa subunit; SNAPc 43 kDa subunit
• Gene Name: SNAPC1
• Related Disease: Breast cancer
• UniProt ID: SNPC1_HUMAN
• PDB ID: 7XUR; 7ZWC; 7ZWD; 7ZX7; 7ZX8; 7ZXE; 8ITY; 8IUE; 8IUH
• Pfam ID: PF09808
• Sequence:
  MGTPPGLQTDCEALLSRFQETDSVRFEDFTELWRNMKFGTIFCGRMRNLEKNMFTKEALA
  LAWRYFLPPYTFQIRVGALYLLYGLYNTQLCQPKQKIRVALKDWDEVLKFQQDLVNAQHF
  DAAYIFRKLRLDRAFHFTAMPKLLSYRMKKKIHRAEVTEEFKDPSDRVMKLITSDVLEEM
  LNVHDHYQNMKHVISVDKSKPDKALSLIKDDFFDNIKNIVLEHQQWHKDRKNPSLKSKTN
  DGEEKMEGNSQETERCERAESLAKIKSKAFSVVIQASKSRRHRQVKLDSSDSDSASGQGQ
  VKATRKKEKKERLKPAGRKMSLRNKGNVQNIHKEDKPLSLSMPVITEEEENESLSGTEFT
  ASKKRRKH
• 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

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	snRNA-activating protein complex subunit 1 (SNAPC1) increases the response to substance of Paclitaxel.	[21]
Topotecan	DMP6G8T	Approved	snRNA-activating protein complex subunit 1 (SNAPC1) affects the response to substance of Topotecan.	[22]

19 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 snRNA-activating protein complex subunit 1 (SNAPC1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of snRNA-activating protein complex subunit 1 (SNAPC1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of snRNA-activating protein complex subunit 1 (SNAPC1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of snRNA-activating protein complex subunit 1 (SNAPC1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of snRNA-activating protein complex subunit 1 (SNAPC1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of snRNA-activating protein complex subunit 1 (SNAPC1).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of snRNA-activating protein complex subunit 1 (SNAPC1).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of snRNA-activating protein complex subunit 1 (SNAPC1).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of snRNA-activating protein complex subunit 1 (SNAPC1).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of snRNA-activating protein complex subunit 1 (SNAPC1).	[10]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of snRNA-activating protein complex subunit 1 (SNAPC1).	[11]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of snRNA-activating protein complex subunit 1 (SNAPC1).	[12]
DTI-015	DMXZRW0	Approved	DTI-015 increases the expression of snRNA-activating protein complex subunit 1 (SNAPC1).	[13]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of snRNA-activating protein complex subunit 1 (SNAPC1).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of snRNA-activating protein complex subunit 1 (SNAPC1).	[16]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of snRNA-activating protein complex subunit 1 (SNAPC1).	[17]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of snRNA-activating protein complex subunit 1 (SNAPC1).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of snRNA-activating protein complex subunit 1 (SNAPC1).	[19]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of snRNA-activating protein complex subunit 1 (SNAPC1).	[20]

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 1 (SNAPC1).	[15]

References

• [1] Discovery of over-expressed genes and genetic alterations in breast cancer cells using a combination of suppression subtractive hybridization, multiplex FISH and comparative genomic hybridization.Int J Oncol. 2002 Sep;21(3):499-507.
• [2] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [3] 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.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] Proteomic analysis of antiproliferative effects by treatment of 5-fluorouracil in cervical cancer cells. DNA Cell Biol. 2004 Nov;23(11):769-76.
• [12] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [13] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [14] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [15] 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.
• [16] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [17] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [18] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [20] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.
• [21] 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.
• [22] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.