Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBX8BVZ)

DOT Name F-box and leucine-rich repeat protein 13 (FBXL13)
Synonyms Dynein regulatory complex subunit 6; F-box/LRR-repeat protein 13
Gene Name FBXL13
Related Disease
Breast carcinoma ( )
UniProt ID
FXL13_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF12937 ; PF13516
Sequence
MTPELMIKACSFYTGHLVKTHFCTWRDIARTNENVVLAEKMNRAVTCYNFRLQKSVFHHW
HSYMEDQKEKLKNILLRIQQIIYCHKLTIILTKWRNTARHKSKKKEDELILKHELQLKKW
KNRLILKRAAAEESNFPERSSSEVFLVDETLKCDISLLPERAILQIFFYLSLKDVIICGQ
VNHAWMLMTQLNSLWNAIDFSSVKNVIPDKYIVSTLQRWRLNVLRLNFRGCLLRPKTFRS
VSHCRNLQELNVSDCPTFTDESMRHISEGCPGVLCLNLSNTTITNRTMRLLPRHFHNLQN
LSLAYCRRFTDKGLQYLNLGNGCHKLIYLDLSGCTQISVQGFRYIANSCTGIMHLTINDM
PTLTDNCVKALVEKCSRITSLVFTGAPHISDCTFRALSACKLRKIRFEGNKRVTDASFKF
IDKNYPNLSHIYMADCKGITDSSLRSLSPLKQLTVLNLANCVRIGDMGLKQFLDGPASMR
IRELNLSNCVRLSDASVMKLSERCPNLNYLSLRNCEHLTAQGIGYIVNIFSLVSIDLSGT
DISNEGLNVLSRHKKLKELSVSECYRITDDGIQAFCKSSLILEHLDVSYCSQLSDMIIKA
LAIYCINLTSLSIAGCPKITDSAMEMLSAKCHYLHILDISGCVLLTDQILEDLQIGCKQL
RILKMQYCTNISKKAAQRMSSKVQQQEYNTNDPPRWFGYDREGNPVTELDNITSSKGALE
LTVKKSTYSSEDQAA
Function
Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. Specifically targets CEP192 isoform 3 for ubiquitin-mediated proteolysis and thereby acts as a regulator of microtubule nucleation activity.
Reactome Pathway
Antigen processing (R-HSA-983168 )
Neddylation (R-HSA-8951664 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast carcinoma DIS2UE88 Strong Genetic Variation [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 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 F-box and leucine-rich repeat protein 13 (FBXL13). [2]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of F-box and leucine-rich repeat protein 13 (FBXL13). [3]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of F-box and leucine-rich repeat protein 13 (FBXL13). [4]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of F-box and leucine-rich repeat protein 13 (FBXL13). [5]
Triclosan DMZUR4N Approved Triclosan decreases the expression of F-box and leucine-rich repeat protein 13 (FBXL13). [6]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of F-box and leucine-rich repeat protein 13 (FBXL13). [7]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of F-box and leucine-rich repeat protein 13 (FBXL13). [8]
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⏷ Show the Full List of 7 Drug(s)
2 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 F-box and leucine-rich repeat protein 13 (FBXL13). [9]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of F-box and leucine-rich repeat protein 13 (FBXL13). [10]
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References

1 Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
2 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.
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 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
5 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.
6 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
7 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.
8 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
9 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.
10 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.