Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHD4FIH)

• DOT Name: Centrosomal protein POC5 (POC5)
• Synonyms: Protein of centriole 5; hPOC5
• Gene Name: POC5
• Related Disease:
  Androgen insensitivity syndrome
  Glomerulonephritis
  Inherited retinal dystrophy
  Non-insulin dependent diabetes
  Obesity
  Retinitis pigmentosa
• UniProt ID: POC5_HUMAN
• Sequence:
  MSSDEEKYSLPVVQNDSSRGSSVSSNLQEEYEELLHYAIVTPNIEPCASQSSHPKGELVP
  DVRISTIHDILHSQGNNSEVRETAIEVGKGCDFHISSHSKTDESSPVLSPRKPSHPVMDF
  FSSHLLADSSSPATNSSHTDAHEILVSDFLVSDENLQKMENVLDLWSSGLKTNIISELSK
  WRLNFIDWHRMEMRKEKEKHAAHLKQLCNQINELKELQKTFEISIGRKDEVISSLSHAIG
  KQKEKIELMRTFFHWRIGHVRARQDVYEGKLADQYYQRTLLKKVWKVWRSVVQKQWKDVV
  ERACQARAEEVCIQISNDYEAKVAMLSGALENAKAEIQRMQHEKEHFEDSMKKAFMRGVC
  ALNLEAMTIFQNRNDAGIDSTNNKKEEYGPGVQGKEHSAHLDPSAPPMPLPVTSPLLPSP
  PAAVGGASATAVPSAASMTSTRAASASSVHVPVSALGAGSAATAASEEMYVPRVVTSAQQ
  KAGRTITARITGRCDFASKNRISSSLAIMGVSPPMSSVVVEKHHPVTVQTIPQATAAKYP
  RTIHPESSTSASRSLGTRSAHTQSLTSVHSIKVVD
• Function: Essential for the assembly of the distal half of centrioles, required for centriole elongation.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Androgen insensitivity syndrome	DISUZBBO	Strong	Genetic Variation	[1]
Glomerulonephritis	DISPZIQ3	Strong	Genetic Variation	[2]
Inherited retinal dystrophy	DISGGL77	Strong	Genetic Variation	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[3]
Obesity	DIS47Y1K	Strong	Genetic Variation	[4]
Retinitis pigmentosa	DISCGPY8	Limited	Autosomal recessive	[2]

2 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 POC5 (POC5).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Centrosomal protein POC5 (POC5).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Centrosomal protein POC5 (POC5).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Centrosomal protein POC5 (POC5).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Centrosomal protein POC5 (POC5).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Centrosomal protein POC5 (POC5).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Centrosomal protein POC5 (POC5).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Centrosomal protein POC5 (POC5).	[11]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Centrosomal protein POC5 (POC5).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Centrosomal protein POC5 (POC5).	[13]

References

• [1] Adolescent idiopathic scoliosis associated POC5 mutation impairs cell cycle, cilia length and centrosome protein interactions.PLoS One. 2019 Mar 7;14(3):e0213269. doi: 10.1371/journal.pone.0213269. eCollection 2019.
• [2] Whole-exome sequencing reveals POC5 as a novel gene associated with autosomal recessive retinitis pigmentosa. Hum Mol Genet. 2018 Feb 15;27(4):614-624. doi: 10.1093/hmg/ddx428.
• [3] Genetic polymorphisms associated with pediatric-onset type 2 diabetes: A family-based transmission disequilibrium test and case-control study.Pediatr Diabetes. 2019 May;20(3):239-245. doi: 10.1111/pedi.12818. Epub 2019 Feb 6.
• [4] Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.Nat Genet. 2013 May;45(5):501-12. doi: 10.1038/ng.2606. Epub 2013 Apr 7.
• [5] 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.
• [6] 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.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [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] 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.
• [12] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [13] 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.