Details of Drug Off-Target (DOT)

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

• DOT Name: Peptidyl-prolyl cis-trans isomerase FKBP9 (FKBP9)
• Synonyms: PPIase FKBP9; EC 5.2.1.8; 63 kDa FK506-binding protein; 63 kDa FKBP; FKBP-63; FK506-binding protein 9; FKBP-9; Rotamase
• Gene Name: FKBP9
• Related Disease:
  Abscess
  Advanced cancer
  Amyotrophic lateral sclerosis type 1
  Gastric disease
  Parkinson disease
  Prostate cancer
  Prostate carcinoma
• UniProt ID: FKBP9_HUMAN
• EC Number: 5.2.1.8
• Pfam ID: PF00254
• Sequence:
  MAFRGWRPPPPPLLLLLLWVTGQAAPVAGLGSDAELQIERRFVPDECPRTVRSGDFVRYH
  YVGTFPDGQKFDSSYDRDSTFNVFVGKGQLITGMDQALVGMCVNERRFVKIPPKLAYGNE
  GVSGVIPPNSVLHFDVLLMDIWNSEDQVQIHTYFKPPSCPRTIQVSDFVRYHYNGTFLDG
  TLFDSSHNRMKTYDTYVGIGWLIPGMDKGLLGMCVGEKRIITIPPFLAYGEDGDGKDIPG
  QASLVFDVALLDLHNPKDSISIENKVVPENCERISQSGDFLRYHYNGTLLDGTLFDSSYS
  RNRTFDTYIGQGYVIPGMDEGLLGVCIGEKRRIVVPPHLGYGEEGRGNIPGSAVLVFDIH
  VIDFHNPSDSISITSHYKPPDCSVLSKKGDYLKYHYNASLLDGTLLDSTWNLGKTYNIVL
  GSGQVVLGMDMGLREMCVGEKRTVIIPPHLGYGEAGVDGEVPGSAVLVFDIELLELVAGL
  PEGYMFIWNGEVSPNLFEEIDKDGNGEVLLEEFSEYIHAQVASGKGKLAPGFDAELIVKN
  MFTNQDRNGDGKVTAEEFKLKDQEAKHDEL
• Function: PPIases accelerate the folding of proteins during protein synthesis.
• Reactome Pathway: Association of TriC/CCT with target proteins during biosynthesis (R-HSA-390471)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Abscess	DISAP982	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Amyotrophic lateral sclerosis type 1	DIS5A2M0	Strong	Biomarker	[3]
Gastric disease	DISNZNTG	Strong	Biomarker	[4]
Parkinson disease	DISQVHKL	Strong	Biomarker	[5]
Prostate cancer	DISF190Y	Strong	Altered Expression	[2]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[2]

9 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 Peptidyl-prolyl cis-trans isomerase FKBP9 (FKBP9).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Peptidyl-prolyl cis-trans isomerase FKBP9 (FKBP9).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Peptidyl-prolyl cis-trans isomerase FKBP9 (FKBP9).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Peptidyl-prolyl cis-trans isomerase FKBP9 (FKBP9).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Peptidyl-prolyl cis-trans isomerase FKBP9 (FKBP9).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Peptidyl-prolyl cis-trans isomerase FKBP9 (FKBP9).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP9 (FKBP9).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Peptidyl-prolyl cis-trans isomerase FKBP9 (FKBP9).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Peptidyl-prolyl cis-trans isomerase FKBP9 (FKBP9).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Peptidyl-prolyl cis-trans isomerase FKBP9 (FKBP9).	[10]

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] Increasing of FKBP9 can predict poor prognosis in patients with prostate cancer.Pathol Res Pract. 2020 Jan;216(1):152732. doi: 10.1016/j.prp.2019.152732. Epub 2019 Nov 11.
• [3] 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.
• [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] 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.
• [6] 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.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [11] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [12] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [13] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [14] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [15] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.