Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRHBVM5)

• DOT Name: 5'-nucleotidase domain-containing protein 3 (NT5DC3)
• Synonyms: EC 3.1.3.-; GRP94-neighboring nucleotidase
• Gene Name: NT5DC3
• Related Disease:
  Pancreatic cancer
  Pancreatic tumour
  Acute myelogenous leukaemia
  Adult lymphoma
  Lymphoma
  Pediatric lymphoma
• UniProt ID: NT5D3_HUMAN
• EC Number: 3.1.3.-
• Pfam ID: PF05761
• Sequence:
  MTMAAAAVVARGAGARAATAAALRGGCGTAARGRPCAGPARPLCTAPGTAPDMKRYLWER
  YREAKRSTEELVPSIMSNLLNPDAIFSNNEMSLSDIEIYGFDYDYTLVFYSKHLHTLIFN
  AARDLLINEHRYPAEIRKYEYDPNFAIRGLHYDVQRAVLMKIDAFHYIQLGTVYRGLSVV
  PDEEVIEMYEGSHVPLEQMSDFYGKSSHGNTMKQFMDIFSLPEMTLLSCVNEYFLKNNID
  YEPVHLYKDVKDSIRDVHIKGIMYRAIEADIEKYICYAEQTRAVLAKLADHGKKMFLITN
  SPSSFVDKGMSYIVGKDWRDLFDVVIVQAEKPNFFNDKRRPFRKMNEKGVLLWDKIHKLQ
  KGQIYKQGNLYEFLKLTGWRGSRVLYFGDHIYSDLADLTLKHGWRTGAIIPELRSELKIM
  NTEQYIQTMTWLQTLTGLLEQMQVHRDAESQLVLQEWKKERKEMREMTKSFFNAQFGSLF
  RTDQNPTYFLRRLSRFADIYMASLSCLLNYDVSHTFYPRRTPLQHELPAWSERPPTFGTP
  LLQEAQAK
• Tissue Specificity: Expressed in brain, placenta, skeletal muscle, pancreas, testis, uterus, and small intestine. Reduced expression in pancreatic cancer cells.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pancreatic cancer	DISJC981	Strong	Biomarker	[1]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Disputed	Altered Expression	[2]
Adult lymphoma	DISK8IZR	Disputed	Genetic Variation	[2]
Lymphoma	DISN6V4S	Disputed	Genetic Variation	[2]
Pediatric lymphoma	DIS51BK2	Disputed	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of 5'-nucleotidase domain-containing protein 3 (NT5DC3).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 5'-nucleotidase domain-containing protein 3 (NT5DC3).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of 5'-nucleotidase domain-containing protein 3 (NT5DC3).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of 5'-nucleotidase domain-containing protein 3 (NT5DC3).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of 5'-nucleotidase domain-containing protein 3 (NT5DC3).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of 5'-nucleotidase domain-containing protein 3 (NT5DC3).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of 5'-nucleotidase domain-containing protein 3 (NT5DC3).	[10]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of 5'-nucleotidase domain-containing protein 3 (NT5DC3).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of 5'-nucleotidase domain-containing protein 3 (NT5DC3).	[12]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of 5'-nucleotidase domain-containing protein 3 (NT5DC3).	[13]

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 5'-nucleotidase domain-containing protein 3 (NT5DC3).	[7]

References

• [1] TU12B1-TY, a novel gene in the region at 12q22-q23.1 frequently deleted in pancreatic cancer, shows reduced expression in pancreatic cancer cells.Oncol Rep. 2004 Dec;12(6):1263-8.
• [2] The common viral insertion site Evi12 is located in the 5'-noncoding region of Gnn, a novel gene with enhanced expression in two subclasses of human acute myeloid leukemia.J Virol. 2005 May;79(9):5249-58. doi: 10.1128/JVI.79.9.5249-5258.2005.
• [3] 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.
• [4] 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.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] 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.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] 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.
• [10] 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.
• [11] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [12] 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.
• [13] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.