Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9CIEO2)

• DOT Name: Endoplasmic reticulum metallopeptidase 1 (ERMP1)
• Synonyms: EC 3.4.-.-; Felix-ina
• Gene Name: ERMP1
• Related Disease:
  Endometrial cancer
  Endometrial carcinoma
  Acute myelogenous leukaemia
  Advanced cancer
• UniProt ID: ERMP1_HUMAN
• EC Number: 3.4.-.-
• Pfam ID: PF04389
• Sequence:
  MEWGSESAAVRRHRVGVERREGAAAAPPPEREARAQEPLVDGCSGGGRTRKRSPGGSGGA
  SRGAGTGLSEVRAALGLALYLIALRTLVQLSLQQLVLRGAAGHRGEFDALQARDYLEHIT
  SIGPRTTGSPENEILTVHYLLEQIKLIEVQSNSLHKISVDVQRPTGSFSIDFLGGFTSYY
  DNITNVVVKLEPRDGAQHAVLANCHFDSVANSPGASDDAVSCSVMLEVLRVLSTSSEALH
  HAVIFLFNGAEENVLQASHGFITQHPWASLIRAFINLEAAGVGGKELVFQTGPENPWLVQ
  AYVSAAKHPFASVVAQEVFQSGIIPSDTDFRIYRDFGNIPGIDLAFIENGYIYHTKYDTA
  DRILTDSIQRAGDNILAVLKHLATSDMLAAASKYRHGNMVFFDVLGLFVIAYPSRIGSII
  NYMVVMGVVLYLGKKFLQPKHKTGNYKKDFLCGLGITLISWFTSLVTVLIIAVFISLIGQ
  SLSWYNHFYVSVCLYGTATVAKIILIHTLAKRFYYMNASAQYLGEVFFDISLFVHCCFLV
  TLTYQGLCSAFISAVWVAFPLLTKLCVHKDFKQHGAQGKFIAFYLLGMFIPYLYALYLIW
  AVFEMFTPILGRSGSEIPPDVVLASILAGCTMILSSYFINFIYLAKSTKKTMLTLTLVCA
  ITFLLVCSGTFFPYSSNPANPKPKRVFLQHMTRTFHDLEGNAVKRDSGIWINGFDYTGIS
  HITPHIPEINDSIRAHCEENAPLCGFPWYLPVHFLIRKNWYLPAPEVSPRNPPHFRLISK
  EQTPWDSIKLTFEATGPSHMSFYVRAHKGSTLSQWSLGNGTPVTSKGGDYFVFYSHGLQA
  SAWQFWIEVQVSEEHPEGMVTVAIAAHYLSGEDKRSPQLDALKEKFPDWTFPSAWVCTYD
  LFVF
• Function: Within the ovary, required for the organization of somatic cells and oocytes into discrete follicular structures.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[1]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[3]

14 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 Endoplasmic reticulum metallopeptidase 1 (ERMP1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Endoplasmic reticulum metallopeptidase 1 (ERMP1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Endoplasmic reticulum metallopeptidase 1 (ERMP1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Endoplasmic reticulum metallopeptidase 1 (ERMP1).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Endoplasmic reticulum metallopeptidase 1 (ERMP1).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Endoplasmic reticulum metallopeptidase 1 (ERMP1).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Endoplasmic reticulum metallopeptidase 1 (ERMP1).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Endoplasmic reticulum metallopeptidase 1 (ERMP1).	[11]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Endoplasmic reticulum metallopeptidase 1 (ERMP1).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Endoplasmic reticulum metallopeptidase 1 (ERMP1).	[8]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid affects the expression of Endoplasmic reticulum metallopeptidase 1 (ERMP1).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Endoplasmic reticulum metallopeptidase 1 (ERMP1).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Endoplasmic reticulum metallopeptidase 1 (ERMP1).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Endoplasmic reticulum metallopeptidase 1 (ERMP1).	[16]

References

• [1] miR-148b Functions as a Tumor Suppressor by Targeting Endoplasmic Reticulum Metallo Protease 1 in Human Endometrial Cancer Cells.Oncol Res. 2018 Dec 27;27(1):81-88. doi: 10.3727/096504018X15202988139874. Epub 2018 Mar 9.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] ERMP1, a novel potential oncogene involved in UPR and oxidative stress defense, is highly expressed in human cancer.Oncotarget. 2016 Sep 27;7(39):63596-63610. doi: 10.18632/oncotarget.11550.
• [4] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [5] 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.
• [6] Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [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] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [11] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [12] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [13] Gene expression profiling of early primary biliary cirrhosis: possible insights into the mechanism of action of ursodeoxycholic acid. Liver Int. 2008 Aug;28(7):997-1010. doi: 10.1111/j.1478-3231.2008.01744.x. Epub 2008 Apr 15.
• [14] Label-free quantitative proteomic analysis identifies the oncogenic role of FOXA1 in BaP-transformed 16HBE cells. Toxicol Appl Pharmacol. 2020 Sep 15;403:115160. doi: 10.1016/j.taap.2020.115160. Epub 2020 Jul 25.
• [15] 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.
• [16] 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.