Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYSE1ZB)

• DOT Name: Prickle planar cell polarity protein 3 (PRICKLE3)
• Synonyms: LIM domain only protein 6; LMO-6; Prickle-like protein 3; Pk3; Triple LIM domain protein 6
• Gene Name: PRICKLE3
• UniProt ID: PRIC3_HUMAN
• Pfam ID: PF00412 ; PF06297
• Sequence:
  MFARGSRRRRSGRAPPEAEDPDRGQPCNSCREQCPGFLLHGWRKICQHCKCPREEHAVHA
  VPVDLERIMCRLISDFQRHSISDDDSGCASEEYAWVPPGLKPEQVYQFFSCLPEDKVPYV
  NSPGEKYRIKQLLHQLPPHDSEAQYCTALEEEEKKELRAFSQQRKRENLGRGIVRIFPVT
  ITGAICEECGKQIGGGDIAVFASRAGLGACWHPQCFVCTTCQELLVDLIYFYHVGKVYCG
  RHHAECLRPRCQACDEIIFSPECTEAEGRHWHMDHFCCFECEASLGGQRYVMRQSRPHCC
  ACYEARHAEYCDGCGEHIGLDQGQMAYEGQHWHASDRCFCCSRCGRALLGRPFLPRRGLI
  FCSRACSLGSEPTAPGPSRRSWSAGPVTAPLAASTASFSAVKGASETTTKGTSTELAPAT
  GPEEPSRFLRGAPHRHSMPELGLRSVPEPPPESPGQPNLRPDDSAFGRQSTPRVSFRDPL
  VSEGGPRRTLSAPPAQRRRPRSPPPRAPSRRRHHHHNHHHHHNRHPSRRRHYQCDAGSGS
  DSESCSSSPSSSSSESSEDDGFFLGERIPLPPHLCRPMPAQDTAMETFNSPSLSLPRDSR
  AGMPRQARDKNCIVA
• Function: Involved in the planar cell polarity (PCP) pathway that is essential for the polarization of epithelial cells during morphogenetic processes, including gastrulation and neurulation. PCP is maintained by two molecular modules, the global and the core modules, PRICKLE3 being part of the core module. Distinct complexes of the core module segregate to opposite sides of the cell, where they interact with the opposite complex in the neighboring cell at or near the adherents junctions. Involved in the organization of the basal body. Involved in cilia growth and positioning. Required for proper assembly, stability, and function of mitochondrial membrane ATP synthase (mitochondrial complex V).
• Tissue Specificity: Widely expressed.
• KEGG Pathway: Wnt sig.ling pathway (hsa04310)

Molecular Interaction Atlas (MIA) of This DOT

2 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 Prickle planar cell polarity protein 3 (PRICKLE3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Prickle planar cell polarity protein 3 (PRICKLE3).	[5]

5 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 Prickle planar cell polarity protein 3 (PRICKLE3).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Prickle planar cell polarity protein 3 (PRICKLE3).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Prickle planar cell polarity protein 3 (PRICKLE3).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Prickle planar cell polarity protein 3 (PRICKLE3).	[6]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Prickle planar cell polarity protein 3 (PRICKLE3).	[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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [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] 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.
• [7] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.