Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM1XXYX)

DOT Name Calmodulin regulator protein PCP4 (PCP4)
Synonyms Brain-specific polypeptide PEP-19; Purkinje cell protein 4
Gene Name PCP4
Related Disease
Adenoma ( )
Adrenal gland neoplasm ( )
Alzheimer disease ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Chorioamnionitis ( )
Ciliopathy ( )
Colon cancer ( )
Colonic neoplasm ( )
Epilepsy ( )
Huntington disease ( )
Methicillin-resistant staphylococci infection ( )
Parkinson disease ( )
Pneumonia ( )
Pneumonitis ( )
Primary aldosteronism ( )
Skin and skin-structure infection ( )
Advanced cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Leiomyoma ( )
Leiomyosarcoma ( )
Status epilepticus seizure ( )
Uterine fibroids ( )
UniProt ID
PCP4_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2N77
Sequence
MSERQGAGATNGKDKTSGENDGQKKVQEEFDIDMDAPETERAAVAIQSQFRKFQKKKAGS
QS
Function
Functions as a modulator of calcium-binding by calmodulin. Thereby, regulates calmodulin activity and the different processes it controls. For instance, may play a role in neuronal differentiation through activation of calmodulin-dependent kinase signaling pathways.

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adenoma DIS78ZEV Strong Biomarker [1]
Adrenal gland neoplasm DISFK7RF Strong Altered Expression [2]
Alzheimer disease DISF8S70 Strong Biomarker [3]
Arteriosclerosis DISK5QGC Strong Biomarker [4]
Atherosclerosis DISMN9J3 Strong Biomarker [4]
Chorioamnionitis DISL1D9U Strong Altered Expression [5]
Ciliopathy DIS10G4I Strong Biomarker [6]
Colon cancer DISVC52G Strong Biomarker [7]
Colonic neoplasm DISSZ04P Strong Biomarker [7]
Epilepsy DISBB28L Strong Biomarker [8]
Huntington disease DISQPLA4 Strong Biomarker [3]
Methicillin-resistant staphylococci infection DIS6DRDZ Strong Biomarker [9]
Parkinson disease DISQVHKL Strong Altered Expression [10]
Pneumonia DIS8EF3M Strong Genetic Variation [11]
Pneumonitis DIS88E0K Strong Genetic Variation [11]
Primary aldosteronism DISOEFNH Strong Biomarker [1]
Skin and skin-structure infection DIS3F9EY Strong Biomarker [9]
Advanced cancer DISAT1Z9 moderate Biomarker [12]
Breast cancer DIS7DPX1 Limited Altered Expression [13]
Breast carcinoma DIS2UE88 Limited Altered Expression [13]
Leiomyoma DISLDDFN Limited Biomarker [14]
Leiomyosarcoma DIS6COXM Limited Altered Expression [14]
Status epilepticus seizure DISY3BIC Limited Biomarker [15]
Uterine fibroids DISBZRMJ Limited Biomarker [14]
------------------------------------------------------------------------------------
⏷ Show the Full List of 24 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Calmodulin regulator protein PCP4 (PCP4). [16]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Calmodulin regulator protein PCP4 (PCP4). [17]
Triclosan DMZUR4N Approved Triclosan increases the expression of Calmodulin regulator protein PCP4 (PCP4). [18]
Selenium DM25CGV Approved Selenium decreases the expression of Calmodulin regulator protein PCP4 (PCP4). [19]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Calmodulin regulator protein PCP4 (PCP4). [20]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Calmodulin regulator protein PCP4 (PCP4). [21]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Calmodulin regulator protein PCP4 (PCP4). [20]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Calmodulin regulator protein PCP4 (PCP4). [22]
------------------------------------------------------------------------------------
⏷ Show the Full List of 8 Drug(s)

References

1 PCP4: a regulator of aldosterone synthesis in human adrenocortical tissues.J Mol Endocrinol. 2014 Feb 24;52(2):159-67. doi: 10.1530/JME-13-0248. Print 2014 Apr.
2 Purkinje Cell Protein 4 Expression Is Associated With DNA Methylation Status in Aldosterone-Producing Adenoma.J Clin Endocrinol Metab. 2018 Mar 1;103(3):965-971. doi: 10.1210/jc.2017-01996.
3 PEP-19 immunohistochemistry defines the basal ganglia and associated structures in the adult human brain, and is dramatically reduced in Huntington's disease.Neuroscience. 1998 Oct;86(4):1055-63. doi: 10.1016/s0306-4522(98)00130-4.
4 Peptide 19 of Porphyromonas gingivalis Heat Shock Protein Is a Potent Inducer of Low-Density Lipoprotein Oxidation.J Periodontol. 2017 Feb;88(2):e58-e64. doi: 10.1902/jop.2016.160402. Epub 2016 Oct 7.
5 Expression, Regulation, and Function of the Calmodulin Accessory Protein PCP4/PEP-19 in Myometrium.Reprod Sci. 2019 Dec;26(12):1650-1660. doi: 10.1177/1933719119828072. Epub 2019 Feb 11.
6 Brain ventriculomegaly in Down syndrome mice is caused by Pcp4 dose-dependent cilia dysfunction.Hum Mol Genet. 2017 Mar 1;26(5):923-931. doi: 10.1093/hmg/ddx007.
7 Global gene expression analysis of rat colon cancers induced by a food-borne carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.Carcinogenesis. 2004 Aug;25(8):1495-505. doi: 10.1093/carcin/bgh155. Epub 2004 Apr 1.
8 Intracellular Peptides in Cell Biology and Pharmacology.Biomolecules. 2019 Apr 16;9(4):150. doi: 10.3390/biom9040150.
9 Novel antibiotics effective against gram-positive and -negative multi-resistant bacteria with limited resistance.PLoS Biol. 2019 Jul 9;17(7):e3000337. doi: 10.1371/journal.pbio.3000337. eCollection 2019 Jul.
10 Neuropeptidomics: expanding proteomics downwards.Biochem Soc Trans. 2007 Jun;35(Pt 3):588-93. doi: 10.1042/BST0350588.
11 Novel Synthetic, Host-defense Peptide Protects Against Organ Injury/Dysfunction in a Rat Model of Severe Hemorrhagic Shock.Ann Surg. 2018 Aug;268(2):348-356. doi: 10.1097/SLA.0000000000002186.
12 Anti-apoptotic effects of PCP4/PEP19 in human breast cancer cell lines: a novel oncotarget.Oncotarget. 2014 Aug 15;5(15):6076-86. doi: 10.18632/oncotarget.2161.
13 PCP4/PEP19 upregulates aromatase gene expression via CYP19A1 promoter I.1 in human breast cancer SK-BR-3 cells.Oncotarget. 2018 Jul 3;9(51):29619-29633. doi: 10.18632/oncotarget.25651. eCollection 2018 Jul 3.
14 PEP-19 overexpression in human uterine leiomyoma.Mol Hum Reprod. 2003 Nov;9(11):709-17. doi: 10.1093/molehr/gag088.
15 Transcriptome analysis of the hippocampal CA1 pyramidal cell region after kainic acid-induced status epilepticus in juvenile rats.PLoS One. 2010 May 20;5(5):e10733. doi: 10.1371/journal.pone.0010733.
16 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
17 Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
18 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
19 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
20 Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
21 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.
22 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.