Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSUEQZ1)

• DOT Name: Procollagen C-endopeptidase enhancer 2 (PCOLCE2)
• Synonyms: Procollagen COOH-terminal proteinase enhancer 2; PCPE-2; Procollagen C-proteinase enhancer 2
• Gene Name: PCOLCE2
• Related Disease:
  Non-insulin dependent diabetes
  Arteriosclerosis
  Atherosclerosis
  OPTN-related open angle glaucoma
• UniProt ID: PCOC2_HUMAN
• Pfam ID: PF00431 ; PF01759
• Sequence:
  MRGANAWAPLCLLLAAATQLSRQQSPERPVFTCGGILTGESGFIGSEGFPGVYPPNSKCT
  WKITVPEGKVVVLNFRFIDLESDNLCRYDFVDVYNGHANGQRIGRFCGTFRPGALVSSGN
  KMMVQMISDANTAGNGFMAMFSAAEPNERGDQYCGGLLDRPSGSFKTPNWPDRDYPAGVT
  CVWHIVAPKNQLIELKFEKFDVERDNYCRYDYVAVFNGGEVNDARRIGKYCGDSPPAPIV
  SERNELLIQFLSDLSLTADGFIGHYIFRPKKLPTTTEQPVTTTFPVTTGLKPTVALCQQK
  CRRTGTLEGNYCSSDFVLAGTVITTITRDGSLHATVSIINIYKEGNLAIQQAGKNMSARL
  TVVCKQCPLLRRGLNYIIMGQVGEDGRGKIMPNSFIMMFKTKNQKLLDALKNKQC
• Function: Binds to the C-terminal propeptide of types I and II procollagens and may enhance the cleavage of that propeptide by BMP1.
• Tissue Specificity: Highly expressed in the heart, trabecular meshwork, pituitary gland, bladder, mammary gland, trachea and placenta and weakly expressed in the brain. Expressed in cartilage.
• Reactome Pathway: Collagen biosynthesis and modifying enzymes (R-HSA-1650814)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[1]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[2]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[2]
OPTN-related open angle glaucoma	DISDR98A	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Procollagen C-endopeptidase enhancer 2 (PCOLCE2) affects the response to substance of Fluorouracil.	[21]
Methamphetamine	DMPM4SK	Approved	Procollagen C-endopeptidase enhancer 2 (PCOLCE2) affects the response to substance of Methamphetamine.	[22]

20 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 Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[13]
Triclosan	DMZUR4N	Approved	Triclosan affects the expression of Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[15]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[13]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[16]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[4]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[20]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Procollagen C-endopeptidase enhancer 2 (PCOLCE2).	[10]

References

• [1] Whole-genome expression analyses of type 2 diabetes in human skin reveal altered immune function and burden of infection.Oncotarget. 2017 May 23;8(21):34601-34609. doi: 10.18632/oncotarget.16118.
• [2] Procollagen C-endopeptidase Enhancer Protein 2 (PCPE2) Reduces Atherosclerosis in Mice by Enhancing Scavenger Receptor Class B1 (SR-BI)-mediated High-density Lipoprotein (HDL)-Cholesteryl Ester Uptake.J Biol Chem. 2015 Jun 19;290(25):15496-15511. doi: 10.1074/jbc.M115.646240. Epub 2015 May 6.
• [3] Identification and expression of a novel type I procollagen C-proteinase enhancer protein gene from the glaucoma candidate region on 3q21-q24.Genomics. 2000 Jun 15;66(3):264-73. doi: 10.1006/geno.2000.6229.
• [4] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [14] Primary Human Hepatocyte Spheroids as Tools to Study the Hepatotoxic Potential of Non-Pharmaceutical Chemicals. Int J Mol Sci. 2021 Oct 12;22(20):11005. doi: 10.3390/ijms222011005.
• [15] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [16] Folate deficiency in normal human fibroblasts leads to altered expression of genes primarily linked to cell signaling, the cytoskeleton and extracellular matrix. J Nutr Biochem. 2007 Aug;18(8):541-52. doi: 10.1016/j.jnutbio.2006.11.002. Epub 2007 Feb 22.
• [17] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [18] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [19] 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.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [21] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
• [22] Genome-wide association for methamphetamine dependence: convergent results from 2 samples. Arch Gen Psychiatry. 2008 Mar;65(3):345-55. doi: 10.1001/archpsyc.65.3.345.