Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKB9WL6)

DOT Name snRNA-activating protein complex subunit 4 (SNAPC4)
Synonyms
SNAPc subunit 4; Proximal sequence element-binding transcription factor subunit alpha; PSE-binding factor subunit alpha; PTF subunit alpha; snRNA-activating protein complex 190 kDa subunit; SNAPc 190 kDa subunit
Gene Name SNAPC4
Related Disease
Ankylosing spondylitis ( )
UniProt ID
SNPC4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7XUR; 7ZWC; 7ZWD; 7ZX7; 7ZX8; 7ZXE; 8ITY; 8IUE; 8IUH
Pfam ID
PF13921
Sequence
MDVDAEREKITQEIKELERILDPGSSGSHVEISESSLESDSEADSLPSEDLDPADPPISE
EERWGEASNDEDDPKDKTLPEDPETCLQLNMVYQEVIQEKLAEANLLLAQNREQQEELMR
DLAGSKGTKVKDGKSLPPSTYMGHFMKPYFKDKVTGVGPPANEDTREKAAQGIKAFEELL
VTKWKNWEKALLRKSVVSDRLQRLLQPKLLKLEYLHQKQSKVSSELERQALEKQGREAEK
EIQDINQLPEEALLGNRLDSHDWEKISNINFEGSRSAEEIRKFWQNSEHPSINKQEWSRE
EEERLQAIAAAHGHLEWQKIAEELGTSRSAFQCLQKFQQHNKALKRKEWTEEEDRMLTQL
VQEMRVGSHIPYRRIVYYMEGRDSMQLIYRWTKSLDPGLKKGYWAPEEDAKLLQAVAKYG
EQDWFKIREEVPGRSDAQCRDRYLRRLHFSLKKGRWNLKEEEQLIELIEKYGVGHWAKIA
SELPHRSGSQCLSKWKIMMGKKQGLRRRRRRARHSVRWSSTSSSGSSSGSSGGSSSSSSS
SSEEDEPEQAQAGEGDRALLSPQYMVPDMDLWVPARQSTSQPWRGGAGAWLGGPAASLSP
PKGSSASQGGSKEASTTAAAPGEETSPVQVPARAHGPVPRSAQASHSADTRPAGAEKQAL
EGGRRLLTVPVETVLRVLRANTAARSCTQKEQLRQPPLPTSSPGVSSGDSVARSHVQWLR
HRATQSGQRRWRHALHRRLLNRRLLLAVTPWVGDVVVPCTQASQRPAVVQTQADGLREQL
QQARLASTPVFTLFTQLFHIDTAGCLEVVRERKALPPRLPQAGARDPPVHLLQASSSAQS
TPGHLFPNVPAQEASKSASHKGSRRLASSRVERTLPQASLLASTGPRPKPKTVSELLQEK
RLQEARAREATRGPVVLPSQLLVSSSVILQPPLPHTPHGRPAPGPTVLNVPLSGPGAPAA
AKPGTSGSWQEAGTSAKDKRLSTMQALPLAPVFSEAEGTAPAASQAPALGPGQISVSCPE
SGLGQSQAPAASRKQGLPEAPPFLPAAPSPTPLPVQPLSLTHIGGPHVATSVPLPVTWVL
TAQGLLPVPVPAVVSLPRPAGTPGPAGLLATLLPPLTETRAAQGPRAPALSSSWQPPANM
NREPEPSCRTDTPAPPTHALSQSPAEADGSVAFVPGEAQVAREIPEPRTSSHADPPEAEP
PWSGRLPAFGGVIPATEPRGTPGSPSGTQEPRGPLGLEKLPLRQPGPEKGALDLEKPPLP
QPGPEKGALDLGLLSQEGEAATQQWLGGQRGVRVPLLGSRLPYQPPALCSLRALSGLLLH
KKALEHKATSLVVGGEAERPAGALQASLGLVRGQLQDNPAYLLLRARFLAAFTLPALLAT
LAPQGVRTTLSVPSRVGSESEDEDLLSELELADRDGQPGCTTATCPIQGAPDSGKCSASS
CLDTSNDPDDLDVLRTRHARHTRKRRRLV
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
Ankylosing spondylitis DISRC6IR Strong Genetic Variation [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 4 (SNAPC4). [2]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of snRNA-activating protein complex subunit 4 (SNAPC4). [10]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of snRNA-activating protein complex subunit 4 (SNAPC4). [10]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of snRNA-activating protein complex subunit 4 (SNAPC4). [3]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of snRNA-activating protein complex subunit 4 (SNAPC4). [4]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of snRNA-activating protein complex subunit 4 (SNAPC4). [5]
Estradiol DMUNTE3 Approved Estradiol increases the expression of snRNA-activating protein complex subunit 4 (SNAPC4). [6]
Quercetin DM3NC4M Approved Quercetin increases the expression of snRNA-activating protein complex subunit 4 (SNAPC4). [7]
Temozolomide DMKECZD Approved Temozolomide increases the expression of snRNA-activating protein complex subunit 4 (SNAPC4). [8]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of snRNA-activating protein complex subunit 4 (SNAPC4). [9]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of snRNA-activating protein complex subunit 4 (SNAPC4). [11]
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⏷ Show the Full List of 8 Drug(s)

References

1 Determination of IL1 R2, ANTXR2, CARD9, and SNAPC4 single nucleotide polymorphisms in Iranian patients with ankylosing spondylitis.Rheumatol Int. 2016 Mar;36(3):429-35. doi: 10.1007/s00296-015-3391-1. Epub 2015 Nov 21.
2 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.
3 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
4 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.
5 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
6 Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
7 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
8 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.
9 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
10 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
11 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.