Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1VEFSL)

DOT Name Centrosomal protein of 89 kDa (CEP89)
Synonyms Cep89; Centrosomal protein 123; Cep123; Coiled-coil domain-containing protein 123
Gene Name CEP89
Related Disease
Cytochrome-c oxidase deficiency disease ( )
Rheumatoid arthritis ( )
Intellectual disability ( )
UniProt ID
CEP89_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MLLGFRRGRRSHFKHIIHGLLPAASVAPKAAVPRTPPPRSPNPSPERPRSALAAAILATT
LTGRTVAIPQPRQRSRSESDVSSVEQDSFIEPYATTSQLRPRPNWQSEMGRRSSLPSFET
LDYGDEEDIETQLSSSGKELGDVSAREDRGGHSDDLYAVPHRNQVPLLHEVNSEDDENIS
HQDGFPGSPPAPQRTQQKDGKHPVLNLKDEKPPLCEKPPPSPDITGRARQRYTEITREKF
EALKEENMDLNNMNQSLTLELNTMKQAMKELQLKLKGMEKEKRKLKEAEKASSQEVAAPE
LLYLRKQAQELVDENDGLKMTVHRLNVELSRYQTKFRHLSKEESLNIEGLPSKGPIPPWL
LDIKYLSPLLLAYEDMMKEKDELNATLKEEMRMFRMRVQEVVKENEELHQELNKSSAVTS
EEWRQLQTQAKLVLEENKLLLEQLEIQQRKAKDSHQERLQEVSKLTKQLMLLEAKTHGQE
KELAENREQLEILRAKCQELKTHSDGKIAVEVHKSIVNELKSQLQKEEEKERAEMEELME
KLTVLQAQKKSLLLEKNSLTEQNKALEAELERAQKINRKSQKKIEVLKKQVEKAMGNEMS
AHQYLANLVGLAENITQERDSLMCLAKCLESEKDGVLNKVIKSNIRLGKLEEKVKGYKKQ
AALKLGDISHRLLEQQEDFAGKTAQYRQEMRHLHQVLKDKQEVLDQALQQNREMEGELEV
IWESTFRENRRIRELLQDTLTRTGVQDNPRALVAPSLNGVSQADLLDGCDVCSYDLKSHA
PTC
Function Required for ciliogenesis. Also plays a role in mitochondrial metabolism where it may modulate complex IV activity.
Reactome Pathway
Anchoring of the basal body to the plasma membrane (R-HSA-5620912 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cytochrome-c oxidase deficiency disease DISK7N3G Strong Genetic Variation [1]
Rheumatoid arthritis DISTSB4J Strong Genetic Variation [2]
Intellectual disability DISMBNXP Limited Autosomal dominant [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
14 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 Centrosomal protein of 89 kDa (CEP89). [4]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Centrosomal protein of 89 kDa (CEP89). [5]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Centrosomal protein of 89 kDa (CEP89). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Centrosomal protein of 89 kDa (CEP89). [7]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Centrosomal protein of 89 kDa (CEP89). [8]
Quercetin DM3NC4M Approved Quercetin increases the expression of Centrosomal protein of 89 kDa (CEP89). [9]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Centrosomal protein of 89 kDa (CEP89). [10]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Centrosomal protein of 89 kDa (CEP89). [11]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Centrosomal protein of 89 kDa (CEP89). [12]
Geldanamycin DMS7TC5 Discontinued in Phase 2 Geldanamycin increases the expression of Centrosomal protein of 89 kDa (CEP89). [14]
Torcetrapib DMDHYM7 Discontinued in Phase 2 Torcetrapib increases the expression of Centrosomal protein of 89 kDa (CEP89). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Centrosomal protein of 89 kDa (CEP89). [16]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Centrosomal protein of 89 kDa (CEP89). [17]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Centrosomal protein of 89 kDa (CEP89). [18]
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⏷ Show the Full List of 14 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 Centrosomal protein of 89 kDa (CEP89). [13]
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References

1 CEP89 is required for mitochondrial metabolism and neuronal function in man and fly.Hum Mol Genet. 2013 Aug 1;22(15):3138-51. doi: 10.1093/hmg/ddt170. Epub 2013 Apr 10.
2 Genome-wide association study of rheumatoid arthritis in Koreans: population-specific loci as well as overlap with European susceptibility loci.Arthritis Rheum. 2011 Apr;63(4):884-93. doi: 10.1002/art.30235.
3 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
4 Antiepileptic drugs are endocrine disruptors for the human fetal testis ex vivo. Toxicol Sci. 2023 Sep 28;195(2):169-183. doi: 10.1093/toxsci/kfad076.
5 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
6 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.
7 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.
8 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
9 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.
10 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.
11 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.
12 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
13 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.
14 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
15 Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
16 Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
17 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.
18 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.