Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTED3YVO)

DOT Name Storkhead-box protein 1 (STOX1)
Synonyms Winged-helix domain-containing protein
Gene Name STOX1
Related Disease
Alzheimer disease ( )
Amyloidosis ( )
Cardiovascular disease ( )
Choriocarcinoma ( )
High blood pressure ( )
Pre-eclampsia ( )
Acute myelogenous leukaemia ( )
UniProt ID
STOX1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF10264
Sequence
MARPVQLAPGSLALVLCRLEAQKAAGAAEEPGGRAVFRAFRRANARCFWNARLARAASRL
AFQGWLRRGVLLVRAPPACLQVLRDAWRRRALRPPRGFRIRAVGDVFPVQMNPITQSQFV
PLGEVLCCAISDMNTAQIVVTQESLLERLMKHYPGIAIPSEDILYTTLGTLIKERKIYHT
GEGYFIVTPQTYFITNTTTQENKRMLPSDESRLMPASMTYLVSMESCAESAQENAAPISH
CQSCQCFRDMHTQDVQEAPVAAEVTRKSHRGLGESVSWVQNGAVSVSAEHHICESTKPLP
YTRDKEKGKKFGFSLLWRSLSRKEKPKTEHSSFSAQFPPEEWPVRDEDDLDNIPRDVEHE
IIKRINPILTVDNLIKHTVLMQKYEEQKKYNSQGTSTDMLTIGHKYPSKEGVKKRQGLSA
KPQGQGHSRRDRHKARNQGSEFQPGSIRLEKHPKLPATQPIPRIKSPNEMVGQKPLGEIT
TVLGSHLIYKKRISNPFQGLSHRGSTISKGHKIQKTSDLKPSQTGPKEKPFQKPRSLDSS
RIFDGKAKEPYAEQPNDKMEAESIYINDPTVKPINDDFRGHLFSHPQQSMLQNDGKCCPF
MESMLRYEVYGGENEVIPEVLRKSHSHFDKLGETKQTPHSLPSRGASFSDRTPSACRLVD
NTIHQFQNLGLLDYPVGVNPLRQAARQDKDSEELLRKGFVQDAETTSLENEQLSNDDQAL
YQNEVEDDDGACSSLYLEEDDISENDDLRQMLPGHSQYSFTGGSQGNHLGKQKVIERSLT
EYNSTMERVESQVLKRNECYKPTGLHATPGESQEPNLSAESCGLNSGAQFGFNYEEEPSV
AKCVQASAPADERIFDYYSARKASFEAEVIQDTIGDTGKKPASWSQSPQNQEMRKHFPQK
FQLFNTSHMPVLAQDVQYEHSHLEGTENHSMAGDSGIDSPRTQSLGSNNSVILDGLKRRQ
NFLQNVEGTKSSQPLTSNSLLPLTPVINV
Function
Involved in regulating the levels of reactive oxidative species and reactive nitrogen species and in mitochondrial homeostasis in the placenta. Required for regulation of inner ear epithelial cell proliferation via the AKT signaling pathway; [Isoform A]: Involved in cell cycle regulation by binding to the CCNB1 promoter, up-regulating its expression and promoting mitotic entry. Induces phosphorylation of MAPT/tau.
Tissue Specificity Expressed in placenta, including the invasive extravillus trophoblast cells.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alzheimer disease DISF8S70 Strong Altered Expression [1]
Amyloidosis DISHTAI2 Strong Altered Expression [2]
Cardiovascular disease DIS2IQDX Strong Genetic Variation [3]
Choriocarcinoma DISDBVNL Strong Altered Expression [4]
High blood pressure DISY2OHH Strong Biomarker [5]
Pre-eclampsia DISY7Q29 Strong SusceptibilityMutation [6]
Acute myelogenous leukaemia DISCSPTN moderate Genetic Variation [7]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 Storkhead-box protein 1 (STOX1). [8]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Storkhead-box protein 1 (STOX1). [9]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Storkhead-box protein 1 (STOX1). [10]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Storkhead-box protein 1 (STOX1). [11]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Storkhead-box protein 1 (STOX1). [12]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Storkhead-box protein 1 (STOX1). [13]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Storkhead-box protein 1 (STOX1). [15]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Storkhead-box protein 1 (STOX1). [16]
Manganese DMKT129 Investigative Manganese decreases the expression of Storkhead-box protein 1 (STOX1). [17]
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⏷ Show the Full List of 9 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Storkhead-box protein 1 (STOX1). [14]
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References

1 Targeting STOX1 in the therapy of preeclampsia.Expert Opin Ther Targets. 2016 Dec;20(12):1433-1443. doi: 10.1080/14728222.2016.1253682. Epub 2016 Nov 8.
2 The pre-eclampsia gene STOX1 controls a conserved pathway in placenta and brain upregulated in late-onset Alzheimer's disease.J Alzheimers Dis. 2010;19(2):673-9. doi: 10.3233/JAD-2010-1265.
3 Long-term cardiovascular disorders in the STOX1 mouse model of preeclampsia.Sci Rep. 2019 Aug 15;9(1):11918. doi: 10.1038/s41598-019-48427-3.
4 Re-evaluation of the role of STOX1 transcription factor in placental development and preeclampsia.J Reprod Immunol. 2009 Nov;82(2):174-81. doi: 10.1016/j.jri.2009.05.001. Epub 2009 Jul 3.
5 Alpha-1 microglobulin as a potential therapeutic candidate for treatment of hypertension and oxidative stress in the STOX1 preeclampsia mouse model.Sci Rep. 2019 Jun 12;9(1):8561. doi: 10.1038/s41598-019-44639-9.
6 STOX1: Key player in trophoblast dysfunction underlying early onset preeclampsia with growth retardation.J Pregnancy. 2011;2011:521826. doi: 10.1155/2011/521826. Epub 2010 Dec 15.
7 Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
8 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
9 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.
10 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
11 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.
12 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
13 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.
14 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.
15 Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
16 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
17 Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.