Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZLD83K)

• DOT Name: Centrosomal protein of 44 kDa (CEP44)
• Synonyms: Cep44; HBV PreS1-transactivated protein 3; PS1TP3
• Gene Name: CEP44
• UniProt ID: CEP44_HUMAN
• PDB ID: 7PT5
• Pfam ID: PF15007
• Sequence:
  MATGDLKRSLRNLEQVLRLLNYPEEVDCVGLIKGDPAASLPIISYSFTSYSPYVTELIME
  SNVELIAKNDLRFIDAVYKLLRDQFNYKPILTKKQFIQCGFAEWKIQIVCDILNCVMKKH
  KELSSLQKIPSQQRKKISSGKSEPPLGNEKISAEAVGVDISGRFMTSGKKKAVVIRHLYN
  EDNVDISEDTLSPITDVNEAVDVSDLNATEIKMPEVKVPEIKAEQQDVNVNPEITALQTM
  LAECQENLKKLTSIEKRLDCLEQKMKGKVMVDENTWTNLLSRVTLLETEMLLSKKNDEFI
  EFNEVSEDYASCSDMDLLNPHRKSEVERPASIPLSSGYSTASSDSTPRASTVNYCGLNEI
  SEETTIQKMERMKKMFEETAELLKCPNHYL
• Function: Centriole-enriched microtubule-binding protein involved in centriole biogenesis. In collaboration with CEP295 and POC1B, is required for the centriole-to-centrosome conversion by ensuring the formation of bona fide centriole wall. Functions as a linker component that maintains centrosome cohesion. Associates with CROCC and regulates its stability and localization to the centrosome.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Centrosomal protein of 44 kDa (CEP44) increases the Hepatotoxicity ADR of Acetaminophen.	[12]
NAPQI	DM8F5LR	Investigative	Centrosomal protein of 44 kDa (CEP44) affects the response to substance of NAPQI.	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Centrosomal protein of 44 kDa (CEP44).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Centrosomal protein of 44 kDa (CEP44).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Centrosomal protein of 44 kDa (CEP44).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Centrosomal protein of 44 kDa (CEP44).	[4]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Centrosomal protein of 44 kDa (CEP44).	[5]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Centrosomal protein of 44 kDa (CEP44).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Centrosomal protein of 44 kDa (CEP44).	[7]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Centrosomal protein of 44 kDa (CEP44).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Centrosomal protein of 44 kDa (CEP44).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Centrosomal protein of 44 kDa (CEP44).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Centrosomal protein of 44 kDa (CEP44).	[11]

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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] 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.
• [4] 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.
• [5] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [6] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [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] 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.
• [11] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [12] Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 2011 Mar;120(1):33-41. doi: 10.1093/toxsci/kfq375. Epub 2010 Dec 22.