Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKXNR5B)

• DOT Name: Cytosolic endo-beta-N-acetylglucosaminidase (ENGASE)
• Synonyms: ENGase; EC 3.2.1.96
• Gene Name: ENGASE
• Related Disease:
  Breast cancer
  Breast carcinoma
  Congenital disorder of deglycosylation
  Rheumatoid arthritis
• UniProt ID: ENASE_HUMAN
• EC Number: 3.2.1.96
• Pfam ID: PF03644
• Sequence:
  MEAAAVTVTRSATRRRRRQLQGLAAPEAGTQEEQEDQEPRPRRRRPGRSIKDEEEETVFR
  EVVSFSPDPLPVRYYDKDTTKPISFYLSSLEELLAWKPRLEDGFNVALEPLACRQPPLSS
  QRPRTLLCHDMMGGYLDDRFIQGSVVQTPYAFYHWQCIDVFVYFSHHTVTIPPVGWTNTA
  HRHGVCVLGTFITEWNEGGRLCEAFLAGDERSYQAVADRLVQITQFFRFDGWLINIENSL
  SLAAVGNMPPFLRYLTTQLHRQVPGGLVLWYDSVVQSGQLKWQDELNQHNRVFFDSCDGF
  FTNYNWREEHLERMLGQAGERRADVYVGVDVFARGNVVGGRFDTDKSLELIRKHGFSVAL
  FAPGWVYECLEKKDFFQNQDKFWGRLERYLPTHSICSLPFVTSFCLGMGARRVCYGQEEA
  VGPWYHLSAQEIQPLFGEHRLGGDGRGWVRTHCCLEDAWHGGSSLLVRGVIPPEVGNVAV
  RLFSLQAPVPPKIYLSMVYKLEGPTDVTVALELTTGDAGSCHIGGISVLNAETSSRHSLR
  PLRVPPTKLARWVGRCGRQLSGGWVQHCYEVSLRGCLLLDLLVCFSRPPGSREEESFTCR
  LGEIQVVDAASLLAPLPQVQAVTISHIRWQPSASEREGPPALLQLSCTLHWSFLLSQVRC
  FRIHCWGGMSDDSPGRELPRPEMPMFLGLAFATQYRIVDLLVEAAGPGQDRRMEFLVEPV
  PKEGFRVPQAEWGRAVLLYSAPA
• Function: Endoglycosidase that releases N-glycans from glycoproteins by cleaving the beta-1,4-glycosidic bond in the N,N'-diacetylchitobiose core. Involved in the processing of free oligosaccharides in the cytosol.
• Tissue Specificity: Widely expressed. Expressed at higher level in thymus and spleen.
• KEGG Pathway: Other glycan degradation (hsa00511)
• Reactome Pathway: N-glycan trimming in the ER and Calnexin/Calreticulin cycle (R-HSA-532668)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Congenital disorder of deglycosylation	DISF7BSZ	moderate	Biomarker	[3]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[4]

2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cytosolic endo-beta-N-acetylglucosaminidase (ENGASE).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cytosolic endo-beta-N-acetylglucosaminidase (ENGASE).	[7]

3 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 Cytosolic endo-beta-N-acetylglucosaminidase (ENGASE).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cytosolic endo-beta-N-acetylglucosaminidase (ENGASE).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cytosolic endo-beta-N-acetylglucosaminidase (ENGASE).	[9]

References

• [1] Increased secretion, altered processing, and glycosylation of pro-cathepsin D in human mammary cancer cells.Cancer Res. 1989 Jul 15;49(14):3904-9.
• [2] Phosphorylation, glycosylation, and proteolytic activity of the 52-kD estrogen-induced protein secreted by MCF7 cells.J Cell Biol. 1987 Feb;104(2):253-62. doi: 10.1083/jcb.104.2.253.
• [3] Lethality of mice bearing a knockout of the Ngly1-gene is partially rescued by the additional deletion of the Engase gene.PLoS Genet. 2017 Apr 20;13(4):e1006696. doi: 10.1371/journal.pgen.1006696. eCollection 2017 Apr.
• [4] Synovial fluid exoglycosidases are predictors of rheumatoid arthritis and are effective in cartilage glycosaminoglycan depletion.Arthritis Rheum. 2003 Aug;48(8):2163-72. doi: 10.1002/art.11093.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [8] 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.
• [9] 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.