Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6ST2A4)

DOT Name F-box only protein 43 (FBXO43)
Synonyms Endogenous meiotic inhibitor 2
Gene Name FBXO43
Related Disease
Male infertility ( )
Oocyte maturation defect 12 ( )
Spermatogenic failure 64 ( )
UniProt ID
FBX43_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00646
Sequence
MSFKDKDERISCLEAYVTLTSKSSRFTDETEILKMSQRHSGQAGTEAGNGADSPPIVNSK
YSTFRDFCSTSSFQDSGYNELKSCSFDNIDKEYLGKKEKGPTLLYEHPETSGLGLTHPLE
SPTQKKKCILPRKEKDKTPELCETPKISGKKCLPRRRLNVSFALLKGDFESQNSSLESSI
SQVINLEKNIPSSASGFSRANNFSPLVTSTLKTEEVTSCSQKLRLNFSQQKTSTIDDSKD
DCSLFEVECISPIQGNNFKDSITHDFSDSSLCINDENACPELLGSSVSGTTCGTDEDIFV
TPISNLVANIRFNASQILSPSPEVRGSISTPEDSGFNSLSLEKSEDSLSDQEGSFQELLQ
KHKGTPKVGDTIRKTRHLGRSRRLSTLREQSSQSETEEEKQIVHPDSEKRAAAASAISEG
QLSSDESGDLTFSLKNLSKTPALQLVHELFMKSKRKRLQENSGHEFLEQGDGEKIAVLQC
ILAGLIGKKMGIEKLDILTELKYRNLKHILAMVLESLTAESLCSVWKVSRNWREIVVQDK
NANRRRKFYITQLKTDSEGAVLNVEDAATRLQLLNRSALRSVQAQARIPGSQREQGSTLS
PWGEVLTPLASSSVTHLSSKQEEYVKVAKTLFTDEALKPCPRCQSPAKYQPYKKRGLCSR
TACGFDFCVLCLCAYHGSEECSRGAAKPRNRKDALPGSAQSKRNLKRL
Function
Required to establish and maintain the arrest of oocytes at the second meiotic metaphase until fertilization. Acts by inhibiting the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase. Probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation. Plays a vital role in modulating the ubiquitilation of CCNB1 and CDK1 during gametogenesis.
Tissue Specificity Expressed in the testis.
KEGG Pathway
Oocyte meiosis (hsa04114 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Male infertility DISY3YZZ Strong Genetic Variation [1]
Oocyte maturation defect 12 DISJ6BRC Limited Unknown [2]
Spermatogenic failure 64 DISNCNAB Limited Unknown [3]
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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 increases the expression of F-box only protein 43 (FBXO43). [4]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of F-box only protein 43 (FBXO43). [5]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of F-box only protein 43 (FBXO43). [6]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of F-box only protein 43 (FBXO43). [7]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of F-box only protein 43 (FBXO43). [8]
Belinostat DM6OC53 Phase 2 Belinostat decreases the expression of F-box only protein 43 (FBXO43). [9]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of F-box only protein 43 (FBXO43). [11]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of F-box only protein 43 (FBXO43). [4]
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⏷ Show the Full List of 8 Drug(s)
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 affects the methylation of F-box only protein 43 (FBXO43). [10]
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References

1 A novel homozygous FBXO43 mutation associated with male infertility and teratozoospermia in a consanguineous Chinese family.Fertil Steril. 2019 May;111(5):909-917.e1. doi: 10.1016/j.fertnstert.2019.01.007. Epub 2019 Mar 14.
2 FBXO43 variants in patients with female infertility characterized by early embryonic arrest. Hum Reprod. 2021 Jul 19;36(8):2392-2402. doi: 10.1093/humrep/deab131.
3 The contribution of de novo coding mutations to autism spectrum disorder. Nature. 2014 Nov 13;515(7526):216-21. doi: 10.1038/nature13908. Epub 2014 Oct 29.
4 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.
5 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.
6 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.
7 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
8 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.
9 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.
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 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.