Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAJE9AN)

• DOT Name: Centrosomal protein of 85 kDa (CEP85)
• Synonyms: Cep85; Coiled-coil domain-containing protein 21
• Gene Name: CEP85
• UniProt ID: CEP85_HUMAN
• PDB ID: 5OI7; 5OID
• Sequence:
  MAMQEKYPTEGISHVTSPSSDVIQKGSSLGTEWQTPVISEPFRSRFSRCSSVADSGDTAI
  GTSCSDIAEDFCSSSGSPPFQPIKSHVTIPTAHVMPSTLGTSPAKPNSTPVGPSSSKLPL
  SGLAESVGMTRNGDLGAMKHSPGLSRDLMYFSGATGENGIEQSWFPAVGHERQEEARKFD
  IPSMESTLNQSAMMETLYSDPHHRVRFHNPRTSTSKELYRVLPEAKKAPGSGAVFERNGP
  HSNSSGVLPLGLQPAPGLSKPLPSQVWQPSPDTWHPREQSCELSTCRQQLELIRLQMEQM
  QLQNGAICHHPAAFGPSLPILEPAQWISILNSNEHLLKEKELLIDKQRKHISQLEQKVRE
  SELQVHSALLGRPAPFGDVCLLRLQELQRENTFLRAQFAQKTEALSREKIDLEKKLSASE
  VEVQLIRESLKVALQKHSEEVKKQEERVKGRDKHINNLKKKCQKESEQNREKQQRIETLE
  RYLADLPTLEDHQKQSQQLKDSELKSTELQEKVTELESLLEETQAICREKEIQLESLRQR
  EAEFSSAGHSLQDKQSVEETSGEGPEVEMESWQKRYDSLQKIVEKQQQKMDQLRSQVQSL
  EQEVAQEEGTSQALREEAQRRDSALQQLRTAVKELSVQNQDLIEKNLTLQEHLRQAQPGS
  PPSPDTAQLALELHQELASCLQDLQAVCSIVTQRAQGHDPNLSLLLGIHSAQHPETQLDL
  QKPDVIKRKLEEVQQLRRDIEDLRTTMSDRYAQDMGENCVTQ
• Function: Acts as a regulator of centriole duplication through a direct interaction with STIL, a key factor involved in the early steps of centriole formation. The CEP85-STIL protein complex acts as a modulator of PLK4-driven cytoskeletal rearrangements and directional cell motility. Acts as a negative regulator of NEK2 to maintain the centrosome integrity in interphase. Suppresses centrosome disjunction by inhibiting NEK2 kinase activity.

Molecular Interaction Atlas (MIA) of This DOT

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Centrosomal protein of 85 kDa (CEP85).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Centrosomal protein of 85 kDa (CEP85).	[5]
Octanal	DMTN0OK	Investigative	Octanal increases the methylation of Centrosomal protein of 85 kDa (CEP85).	[8]

5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Centrosomal protein of 85 kDa (CEP85).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Centrosomal protein of 85 kDa (CEP85).	[3]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Centrosomal protein of 85 kDa (CEP85).	[4]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Centrosomal protein of 85 kDa (CEP85).	[6]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Centrosomal protein of 85 kDa (CEP85).	[7]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] 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.
• [3] 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.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] 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.
• [6] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [7] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [8] DNA Methylome Analysis of Saturated Aliphatic Aldehydes in Pulmonary Toxicity. Sci Rep. 2018 Jul 12;8(1):10497. doi: 10.1038/s41598-018-28813-z.