Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHBZHX0)

• DOT Name: Peptidyl-prolyl cis-trans isomerase FKBP2 (FKBP2)
• Synonyms: PPIase FKBP2; EC 5.2.1.8; 13 kDa FK506-binding protein; 13 kDa FKBP; FKBP-13; FK506-binding protein 2; FKBP-2; Immunophilin FKBP13; Rotamase
• Gene Name: FKBP2
• Related Disease:
  Abscess
  Amyotrophic lateral sclerosis type 1
  Gastric cancer
  Gastric disease
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Multiple endocrine neoplasia type 1
  Parkinson disease
  Advanced cancer
• UniProt ID: FKBP2_HUMAN
• PDB ID: 2PBC; 4NNR
• EC Number: 5.2.1.8
• Pfam ID: PF00254
• Sequence:
  MRLSWFRVLTVLSICLSAVATATGAEGKRKLQIGVKKRVDHCPIKSRKGDVLHMHYTGKL
  EDGTEFDSSLPQNQPFVFSLGTGQVIKGWDQGLLGMCEGEKRKLVIPSELGYGERGAPPK
  IPGGATLVFEVELLKIERRTEL
• Function: PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.
• Tissue Specificity: T-cells and thymus.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Abscess	DISAP982	Strong	Biomarker	[1]
Amyotrophic lateral sclerosis type 1	DIS5A2M0	Strong	Biomarker	[2]
Gastric cancer	DISXGOUK	Strong	Biomarker	[3]
Gastric disease	DISNZNTG	Strong	Biomarker	[4]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[3]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[3]
Multiple endocrine neoplasia type 1	DIS0RJRK	Strong	Biomarker	[5]
Parkinson disease	DISQVHKL	Strong	Biomarker	[6]
Advanced cancer	DISAT1Z9	Limited	Posttranslational Modification	[7]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Peptidyl-prolyl cis-trans isomerase FKBP2 (FKBP2) affects the response to substance of Cisplatin.	[18]

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 Peptidyl-prolyl cis-trans isomerase FKBP2 (FKBP2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Peptidyl-prolyl cis-trans isomerase FKBP2 (FKBP2).	[13]

8 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 Peptidyl-prolyl cis-trans isomerase FKBP2 (FKBP2).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP2 (FKBP2).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Peptidyl-prolyl cis-trans isomerase FKBP2 (FKBP2).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP2 (FKBP2).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP2 (FKBP2).	[14]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP2 (FKBP2).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Peptidyl-prolyl cis-trans isomerase FKBP2 (FKBP2).	[16]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP2 (FKBP2).	[17]

References

• [1] Novel Regulation of Alpha-Toxin and the Phenol-Soluble Modulins by Peptidyl-Prolyl cis/trans Isomerase Enzymes in Staphylococcus aureus.Toxins (Basel). 2019 Jun 16;11(6):343. doi: 10.3390/toxins11060343.
• [2] The role of immunophilins in mutant superoxide dismutase-1linked familial amyotrophic lateral sclerosis.Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3251-6. doi: 10.1073/pnas.96.6.3251.
• [3] A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients.PLoS One. 2011 Feb 18;6(2):e16694. doi: 10.1371/journal.pone.0016694.
• [4] Differential Proteomic Analysis Reveals Protein Networks and Pathways that May Contribute to Helicobacter pylori FKBP-Type PPIase-Associated Gastric Diseases.Proteomics Clin Appl. 2018 May;12(3):e1700127. doi: 10.1002/prca.201700127. Epub 2017 Dec 5.
• [5] Exclusion of the 13-kDa rapamycin binding protein gene (FKBP2) as a candidate gene for multiple endocrine neoplasia type 1.Hum Genet. 1995 Apr;95(4):455-8. doi: 10.1007/BF00208976.
• [6] The Molecular Basis of the Interaction of CyclophilinA with -Synuclein.Angew Chem Int Ed Engl. 2020 Mar 27;59(14):5643-5646. doi: 10.1002/anie.201914878. Epub 2020 Jan 29.
• [7] Pin1 inhibition potently suppresses gastric cancer growth and blocks PI3K/AKT and Wnt/-catenin oncogenic pathways.Mol Carcinog. 2019 Aug;58(8):1450-1464. doi: 10.1002/mc.23027. Epub 2019 Apr 26.
• [8] 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.
• [9] 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.
• [10] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [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] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [13] 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.
• [14] 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.
• [15] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [16] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [17] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.
• [18] 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.