Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3LUE9M)

• DOT Name: Purkinje cell protein 2 homolog (PCP2)
• Gene Name: PCP2
• Related Disease:
  Spinocerebellar ataxia type 1
  Head and neck cancer
  Head and neck carcinoma
  Neuralgia
  Pancreatic adenocarcinoma
  Autosomal dominant cerebellar ataxia type II
• UniProt ID: PCP2_HUMAN
• Pfam ID: PF02188
• Sequence:
  MMDQEEKTEEGSGPCAEAGSPDQEGFFNLLSHVQGDRMEGQRCSLQAGPGQTTKSQSDPT
  PEMDSLMDMLASTQGRRMDDQRVTVSSLPGFQPVGSKDGAQKRAGTLSPQPLLTPQDPTA
  LGFRRNSSPQPPTQAP
• Function: May function as a cell-type specific modulator for G protein-mediated cell signaling.
• Reactome Pathway: G alpha (i) signalling events (R-HSA-418594)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Spinocerebellar ataxia type 1	DISF7BO2	Definitive	Genetic Variation	[1]
Head and neck cancer	DISBPSQZ	Strong	Genetic Variation	[2]
Head and neck carcinoma	DISOU1DS	Strong	Genetic Variation	[2]
Neuralgia	DISWO58J	Strong	Genetic Variation	[2]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Biomarker	[3]
Autosomal dominant cerebellar ataxia type II	DIS0PM39	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Purkinje cell protein 2 homolog (PCP2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Purkinje cell protein 2 homolog (PCP2).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Purkinje cell protein 2 homolog (PCP2).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Purkinje cell protein 2 homolog (PCP2).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Purkinje cell protein 2 homolog (PCP2).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Purkinje cell protein 2 homolog (PCP2).	[9]

References

• [1] Reduction of protein kinase A-mediated phosphorylation of ATXN1-S776 in Purkinje cells delays onset of Ataxia in a SCA1 mouse model.Neurobiol Dis. 2018 Aug;116:93-105. doi: 10.1016/j.nbd.2018.05.002. Epub 2018 May 11.
• [2] Genome-wide association study identifies genes associated with neuropathy in patients with head and neck cancer.Sci Rep. 2018 Jun 8;8(1):8789. doi: 10.1038/s41598-018-27070-4.
• [3] Characterization of PCP-2, a novel receptor protein tyrosine phosphatase of the MAM domain family.Oncogene. 1996 Jun 20;12(12):2555-62.
• [4] Spinocerebellar ataxia type 7 cerebellar disease requires the coordinated action of mutant ataxin-7 in neurons and glia, and displays non-cell-autonomous bergmann glia degeneration.J Neurosci. 2011 Nov 9;31(45):16269-78. doi: 10.1523/JNEUROSCI.4000-11.2011.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [9] 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.
• [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.