Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN0EL6L)

• DOT Name: snRNA-activating protein complex subunit 2 (SNAPC2)
• Synonyms: SNAPc subunit 2; Proximal sequence element-binding transcription factor subunit delta; PSE-binding factor subunit delta; PTF subunit delta; Small nuclear RNA-activating complex polypeptide 2; snRNA-activating protein complex 45 kDa subunit; SNAPc 45 kDa subunit
• Gene Name: SNAPC2
• Related Disease:
  Mental disorder
  Panic disorder
  Adult glioblastoma
  Glioblastoma multiforme
• UniProt ID: SNPC2_HUMAN
• Pfam ID: PF11035
• Sequence:
  MKPPPRRRAAPARYLGEVTGPATWSAREKRQLVRLLQARQGQPEPDATELARELRGRSEA
  EIRVFLQQLKGRVAREAIQKVHPGGLQGPRRREAQPPAPIEVWTDLAEKITGPLEEALAV
  AFSQVLTIAATEPVTLLHSKPPKPTQARGKPLLLSAPGGQEDPAPEIPSSAPAAPSSAPR
  TPDPAPEKPSESSAGPSTEEDFAVDFEKIYKYLSSVSRSGRSPELSAAESAVVLDLLMSL
  PEELPLLPCTALVEHMTETYLRLTAPQPIPAGGSLGPAAEGDGAGSKAPEETPPATEKAE
  HSELKSPWQAAGICPLNPFLVPLELLGRAATPAR
• 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

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mental disorder	DIS3J5R8	Strong	Biomarker	[1]
Panic disorder	DISD3VNY	Strong	Genetic Variation	[1]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[2]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[2]

3 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 snRNA-activating protein complex subunit 2 (SNAPC2).	[3]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of snRNA-activating protein complex subunit 2 (SNAPC2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of snRNA-activating protein complex subunit 2 (SNAPC2).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of snRNA-activating protein complex subunit 2 (SNAPC2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of snRNA-activating protein complex subunit 2 (SNAPC2).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of snRNA-activating protein complex subunit 2 (SNAPC2).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of snRNA-activating protein complex subunit 2 (SNAPC2).	[8]

References

• [1] Association between genes on chromosome 19p13.2 and panic disorder.Psychiatr Genet. 2016 Dec;26(6):287-292. doi: 10.1097/YPG.0000000000000147.
• [2] Genome-wide methylation profiling reveals new biomarkers for prognosis prediction of glioblastoma.J Cancer Res Ther. 2015 Oct;11 Suppl 2:C212-5. doi: 10.4103/0973-1482.168188.
• [3] 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.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 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.
• [6] 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.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.