Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW39W2I)

DOT Name Zinc finger protein 143
Synonyms SPH-binding factor; Selenocysteine tRNA gene transcription-activating factor; hStaf
Gene Name ZNF143
Related Disease
Methylmalonic aciduria and homocystinuria ( )
UniProt ID
ZN143_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00096
Sequence
MLLAQINRDSQGMTEFPGGGMEAQHVTLCLTEAVTVADGDNLENMEGVSLQAVTLADGST
AYIQHNSKDAKLIDGQVIQLEDGSAAYVQHVPIPKSTGDSLRLEDGQAVQLEDGTTAFIH
HTSKDSYDQSALQAVQLEDGTTAYIHHAVQVPQSDTILAIQADGTVAGLHTGDATIDPDT
ISALEQYAAKVSIDGSESVAGTGMIGENEQEKKMQIVLQGHATRVTAKSQQSGEKAFRCE
YDGCGKLYTTAHHLKVHERSHTGDRPYQCEHAGCGKAFATGYGLKSHVRTHTGEKPYRCS
EDNCTKSFKTSGDLQKHIRTHTGERPFKCPFEGCGRSFTTSNIRKVHVRTHTGERPYYCT
EPGCGRAFASATNYKNHVRIHTGEKPYVCTVPGCDKRFTEYSSLYKHHVVHTHSKPYNCN
HCGKTYKQISTLAMHKRTAHNDTEPIEEEQEAFFEPPPGQGEDVLKGSQITYVTGVEGDD
VVSTQVATVTQSGLSQQVTLISQDGTQHVNISQADMQAIGNTITMVTQDGTPITVPAHDA
VISSAGTHSVAMVTAEGTEGEQVAIVAQDLAAFHTASSEMGHQQHSHHLVTTETRPLTLV
ATSNGTQIAVQLGEQPSLEEAIRIASRIQQGETPGLDD
Function
Transcriptional activator. Activates the gene for selenocysteine tRNA (tRNAsec). Binds to the SPH motif of small nuclear RNA (snRNA) gene promoters. Participates in efficient U6 RNA polymerase III transcription via its interaction with CHD8.
Tissue Specificity Expressed in all tissues tested, with the strongest expression in ovary.
KEGG Pathway
Cobalamin transport and metabolism (hsa04980 )
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
Methylmalonic aciduria and homocystinuria DIS5921T Moderate Autosomal recessive [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 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 Zinc finger protein 143. [2]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Zinc finger protein 143. [3]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Zinc finger protein 143. [4]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Zinc finger protein 143. [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Zinc finger protein 143. [6]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Zinc finger protein 143. [7]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Zinc finger protein 143. [9]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Zinc finger protein 143. [11]
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⏷ Show the Full List of 8 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Zinc finger protein 143. [8]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Zinc finger protein 143. [10]
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References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
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 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
6 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.
7 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
8 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
9 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
10 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.
11 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.