Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB3HCLB)

• DOT Name: Peptidyl-prolyl cis-trans isomerase H (PPIH)
• Synonyms: PPIase H; EC 5.2.1.8; Rotamase H; Small nuclear ribonucleoprotein particle-specific cyclophilin H; CypH; U-snRNP-associated cyclophilin SnuCyp-20; USA-CYP
• Gene Name: PPIH
• Related Disease:
  Cardiovascular disease
  Retinitis pigmentosa
• UniProt ID: PPIH_HUMAN
• PDB ID: 1MZW; 1QOI; 5O9Z; 6AHD
• EC Number: 5.2.1.8
• Pfam ID: PF00160
• Sequence:
  MAVANSSPVNPVVFFDVSIGGQEVGRMKIELFADVVPKTAENFRQFCTGEFRKDGVPIGY
  KGSTFHRVIKDFMIQGGDFVNGDGTGVASIYRGPFADENFKLRHSAPGLLSMANSGPSTN
  GCQFFITCSKCDWLDGKHVVFGKIIDGLLVMRKIENVPTGPNNKPKLPVVISQCGEM
• Function: PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding. Participates in pre-mRNA splicing. May play a role in the assembly of the U4/U5/U6 tri-snRNP complex, one of the building blocks of the spliceosome. May act as a chaperone.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway:
  SARS-CoV-1 activates/modulates innate immune responses (R-HSA-9692916)
  mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[1]
Retinitis pigmentosa	DISCGPY8	Limited	Genetic Variation	[2]

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 H (PPIH).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Peptidyl-prolyl cis-trans isomerase H (PPIH).	[12]

13 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 H (PPIH).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Peptidyl-prolyl cis-trans isomerase H (PPIH).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Peptidyl-prolyl cis-trans isomerase H (PPIH).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Peptidyl-prolyl cis-trans isomerase H (PPIH).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Peptidyl-prolyl cis-trans isomerase H (PPIH).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Peptidyl-prolyl cis-trans isomerase H (PPIH).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Peptidyl-prolyl cis-trans isomerase H (PPIH).	[9]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Peptidyl-prolyl cis-trans isomerase H (PPIH).	[10]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Peptidyl-prolyl cis-trans isomerase H (PPIH).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Peptidyl-prolyl cis-trans isomerase H (PPIH).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Peptidyl-prolyl cis-trans isomerase H (PPIH).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Peptidyl-prolyl cis-trans isomerase H (PPIH).	[15]
PP-242	DM2348V	Investigative	PP-242 increases the expression of Peptidyl-prolyl cis-trans isomerase H (PPIH).	[16]

References

• [1] Detrimental Effects of Testosterone Addition to Estrogen Therapy Involve Cytochrome P-450-Induced 20-HETE Synthesis in Aorta of Ovariectomized Spontaneously Hypertensive Rat (SHR), a Model of Postmenopausal Hypertension.Front Physiol. 2018 May 8;9:490. doi: 10.3389/fphys.2018.00490. eCollection 2018.
• [2] PRPF4 is a novel therapeutic target for the treatment of breast cancer by influencing growth, migration, invasion, and apoptosis of breast cancer cells via p38 MAPK signaling pathway.Mol Cell Probes. 2019 Oct;47:101440. doi: 10.1016/j.mcp.2019.101440. Epub 2019 Aug 22.
• [3] 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.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] 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.
• [6] 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.
• [7] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [10] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [11] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [12] 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.
• [13] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [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] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [16] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.