Details of Drug Off-Target (DOT)

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

DOT Name Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2)
Synonyms EC 1.14.11.4; Lysyl hydroxylase 2; LH2
Gene Name PLOD2
Related Disease
Bruck syndrome 2 ( )
Bruck syndrome ( )
UniProt ID
PLOD2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
1.14.11.4
Pfam ID
PF03171
Sequence
MGGCTVKPQLLLLALVLHPWNPCLGADSEKPSSIPTDKLLVITVATKESDGFHRFMQSAK
YFNYTVKVLGQGEEWRGGDGINSIGGGQKVRLMKEVMEHYADQDDLVVMFTECFDVIFAG
GPEEVLKKFQKANHKVVFAADGILWPDKRLADKYPVVHIGKRYLNSGGFIGYAPYVNRIV
QQWNLQDNDDDQLFYTKVYIDPLKREAINITLDHKCKIFQTLNGAVDEVVLKFENGKARA
KNTFYETLPVAINGNGPTKILLNYFGNYVPNSWTQDNGCTLCEFDTVDLSAVDVHPNVSI
GVFIEQPTPFLPRFLDILLTLDYPKEALKLFIHNKEVYHEKDIKVFFDKAKHEIKTIKIV
GPEENLSQAEARNMGMDFCRQDEKCDYYFSVDADVVLTNPRTLKILIEQNRKIIAPLVTR
HGKLWSNFWGALSPDGYYARSEDYVDIVQGNRVGVWNVPYMANVYLIKGKTLRSEMNERN
YFVRDKLDPDMALCRNAREMGVFMYISNRHEFGRLLSTANYNTSHYNNDLWQIFENPVDW
KEKYINRDYSKIFTENIVEQPCPDVFWFPIFSEKACDELVEEMEHYGKWSGGKHHDSRIS
GGYENVPTDDIHMKQVDLENVWLHFIREFIAPVTLKVFAGYYTKGFALLNFVVKYSPERQ
RSLRPHHDASTFTINIALNNVGEDFQGGGCKFLRYNCSIESPRKGWSFMHPGRLTHLHEG
LPVKNGTRYIAVSFIDP
Function
Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens. These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen cross-links.
Tissue Specificity Highly expressed in pancreas and muscle. Isoform 1 and isoform 2 are expressed in the majority of the examined cell types. Isoform 2 is specifically expressed in skin, lung, dura and aorta.
KEGG Pathway
Lysine degradation (hsa00310 )
Metabolic pathways (hsa01100 )
Reactome Pathway
Collagen biosynthesis and modifying enzymes (R-HSA-1650814 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Bruck syndrome 2 DISOATHK Definitive Autosomal recessive [1]
Bruck syndrome DIS9PCZ6 Supportive Autosomal recessive [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Topotecan DMP6G8T Approved Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) affects the response to substance of Topotecan. [31]
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33 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-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [3]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [4]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [5]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [8]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [9]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [10]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [11]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [4]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [12]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [13]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [14]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [15]
Selenium DM25CGV Approved Selenium decreases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [16]
Fluorouracil DMUM7HZ Approved Fluorouracil decreases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [17]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [13]
Dexamethasone DMMWZET Approved Dexamethasone decreases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [18]
Ethanol DMDRQZU Approved Ethanol increases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [6]
Testosterone enanthate DMB6871 Approved Testosterone enanthate affects the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [19]
Mifepristone DMGZQEF Approved Mifepristone increases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [20]
Enzalutamide DMGL19D Approved Enzalutamide decreases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [21]
Bexarotene DMOBIKY Approved Bexarotene increases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [22]
Isoniazid DM5JVS3 Approved Isoniazid increases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [6]
Vandetanib DMRICNP Approved Vandetanib increases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [23]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [21]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [13]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [16]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [25]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [27]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [28]
chloropicrin DMSGBQA Investigative chloropicrin decreases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [29]
PP-242 DM2348V Investigative PP-242 decreases the expression of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [30]
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⏷ Show the Full List of 33 Drug(s)
2 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 decreases the methylation of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [24]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). [26]
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References

1 Bruck syndrome in 13 new patients: Identification of five novel FKBP10 and PLOD2 variants and further expansion of the phenotypic spectrum. Am J Med Genet A. 2022 Jun;188(6):1815-1825. doi: 10.1002/ajmg.a.62718. Epub 2022 Mar 12.
2 Phenotypic and molecular characterization of Bruck syndrome (osteogenesis imperfecta with contractures of the large joints) caused by a recessive mutation in PLOD2. Am J Med Genet A. 2004 Dec 1;131(2):115-20. doi: 10.1002/ajmg.a.30231.
3 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
4 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.
5 Constitutive gene expression predisposes morphogen-mediated cell fate responses of NT2/D1 and 27X-1 human embryonal carcinoma cells. Stem Cells. 2007 Mar;25(3):771-8. doi: 10.1634/stemcells.2006-0271. Epub 2006 Nov 30.
6 Identification of differentially expressed genes in hepatic HepG2 cells treated with acetaminophen using suppression subtractive hybridization. Biol Pharm Bull. 2005 Jul;28(7):1148-53. doi: 10.1248/bpb.28.1148.
7 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
8 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
10 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.
11 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
12 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.
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 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
15 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
16 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.
17 Transcriptional profiling of MCF7 breast cancer cells in response to 5-Fluorouracil: relationship with cell cycle changes and apoptosis, and identification of novel targets of p53. Int J Cancer. 2006 Sep 1;119(5):1164-75.
18 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
19 Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
20 Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
21 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
22 Identification of biomarkers modulated by the rexinoid LGD1069 (bexarotene) in human breast cells using oligonucleotide arrays. Cancer Res. 2006 Dec 15;66(24):12009-18.
23 ZD6474 inhibits tumor growth and intraperitoneal dissemination in a highly metastatic orthotopic gastric cancer model. Int J Cancer. 2006 Jan 15;118(2):483-9. doi: 10.1002/ijc.21340.
24 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.
25 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.
26 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
27 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.
28 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
29 Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.
30 Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.
31 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.