Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9EPHV3)

• DOT Name: NKG2-E type II integral membrane protein (KLRC3)
• Synonyms: NK cell receptor E; NKG2-E-activating NK receptor
• Gene Name: KLRC3
• Related Disease:
  Endometrial cancer
  Endometrial carcinoma
  Adult glioblastoma
  Glioblastoma multiforme
  Sickle-cell anaemia
  Type-1 diabetes
• UniProt ID: NKG2E_HUMAN
• Pfam ID: PF00059
• Sequence:
  MSKQRGTFSEVSLAQDPKWQQRKPKGNKSSISGTEQEIFQVELNLQNASLNHQGIDKIYD
  CQGLLPPPEKLTAEVLGIICIVLMATVLKTIVLIPFLEQNNSSPNARTQKARHCGHCPEE
  WITYSNSCYYIGKERRTWEESLQACASKNSSSLLCIDNEEEMKFLASILPSSWIGVFRNS
  SHHPWVTINGLAFKHEIKDSDHAERNCAMLHVRGLISDQCGSSRIIRRGFIMLTRLVLNS
• Function: Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells.
• Tissue Specificity: Natural killer cells.
• KEGG Pathway:
  Antigen processing and presentation (hsa04612)
  .tural killer cell mediated cytotoxicity (hsa04650)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Endometrial cancer	DISW0LMR	Strong	Biomarker	[1]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[2]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[2]
Sickle-cell anaemia	DIS5YNZB	Limited	Genetic Variation	[3]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of NKG2-E type II integral membrane protein (KLRC3).	[5]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of NKG2-E type II integral membrane protein (KLRC3).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of NKG2-E type II integral membrane protein (KLRC3).	[7]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of NKG2-E type II integral membrane protein (KLRC3).	[8]

References

• [1] Adenylosuccinate lyase enhances aggressiveness of endometrial cancer by increasing killer cell lectin-like receptor C3 expression by fumarate.Lab Invest. 2018 Apr;98(4):449-461. doi: 10.1038/s41374-017-0017-0. Epub 2018 Feb 21.
• [2] KLRC3, a Natural Killer receptor gene, is a key factor involved in glioblastoma tumourigenesis and aggressiveness.J Cell Mol Med. 2017 Feb;21(2):244-253. doi: 10.1111/jcmm.12960. Epub 2016 Sep 19.
• [3] Whole-exome sequencing of sickle cell disease patients with hyperhemolysis syndrome suggests a role for rare variation in disease predisposition.Transfusion. 2018 Mar;58(3):726-735. doi: 10.1111/trf.14431. Epub 2017 Dec 6.
• [4] Low gene expression levels of activating receptors of natural killer cells (NKG2E and CD94) in patients with fulminant type 1 diabetes.Immunol Lett. 2013 Nov-Dec;156(1-2):149-55. doi: 10.1016/j.imlet.2013.10.004. Epub 2013 Oct 25.
• [5] Multiple transcription factor elements collaborate with estrogen receptor alpha to activate an inducible estrogen response element in the NKG2E gene. Endocrinology. 2007 Jul;148(7):3449-58. doi: 10.1210/en.2006-1632. Epub 2007 Mar 29.
• [6] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [7] 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.
• [8] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.