Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUIBJD0)

• DOT Name: UL16-binding protein 1
• Synonyms: ALCAN-beta; NKG2D ligand 1; N2DL-1; NKG2DL1; Retinoic acid early transcript 1I
• Gene Name: ULBP1
• UniProt ID: ULBP1_HUMAN
• Pfam ID: PF00129
• Sequence:
  MAAAASPAFLLCLPLLHLLSGWSRAGWVDTHCLCYDFIITPKSRPEPQWCEVQGLVDERP
  FLHYDCVNHKAKAFASLGKKVNVTKTWEEQTETLRDVVDFLKGQLLDIQVENLIPIEPLT
  LQARMSCEHEAHGHGRGSWQFLFNGQKFLLFDSNNRKWTALHPGAKKMTEKWEKNRDVTM
  FFQKISLGDCKMWLEEFLMYWEQMLDPTKPPSLAPGTTQPKAMATTLSPWSLLIIFLCFI
  LAGR
• Function: Binds and activates the KLRK1/NKG2D receptor, mediating natural killer cell cytotoxicity.
• Tissue Specificity: Expressed in T-cells, B-cells, erythroleukemia cell lines and in a wide range of tissues including heart, brain, lung, liver, testis, lymph node, thymus, tonsil and bone marrow. Also found in fetal heart, brain, lung and liver.
• KEGG Pathway: .tural killer cell mediated cytotoxicity (hsa04650)
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

19 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 UL16-binding protein 1.	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of UL16-binding protein 1.	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of UL16-binding protein 1.	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of UL16-binding protein 1.	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of UL16-binding protein 1.	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of UL16-binding protein 1.	[6]
Gefitinib	DM15F0X	Approved	Gefitinib increases the expression of UL16-binding protein 1.	[7]
Plicamycin	DM7C8YV	Approved	Plicamycin increases the expression of UL16-binding protein 1.	[8]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of UL16-binding protein 1.	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of UL16-binding protein 1.	[10]
PMID26560530-Compound-35	DMO36RL	Patented	PMID26560530-Compound-35 increases the expression of UL16-binding protein 1.	[11]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of UL16-binding protein 1.	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of UL16-binding protein 1.	[13]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of UL16-binding protein 1.	[14]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of UL16-binding protein 1.	[15]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of UL16-binding protein 1.	[16]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of UL16-binding protein 1.	[17]
G6976	DMEZO4M	Investigative	G6976 increases the expression of UL16-binding protein 1.	[11]
RO-316233	DMAGLPW	Investigative	RO-316233 increases the expression of UL16-binding protein 1.	[11]

References

• [1] 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.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] 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.
• [4] Quercetin enhances susceptibility to NK cell-mediated lysis of tumor cells through induction of NKG2D ligands and suppression of HSP70. J Immunother. 2010 May;33(4):391-401. doi: 10.1097/CJI.0b013e3181d32f22.
• [5] 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.
• [6] Induction of NKG2D ligands and subsequent enhancement of NK cell-mediated lysis of cancer cells by arsenic trioxide. J Immunother. 2008 Jun;31(5):475-86. doi: 10.1097/CJI.0b013e3181755deb.
• [7] EGFR inhibitors enhanced the susceptibility to NK cell-mediated lysis of lung cancer cells. J Immunother. 2011 May;34(4):372-81. doi: 10.1097/CJI.0b013e31821b724a.
• [8] The activity of a novel mithramycin analog is related to its binding to DNA, cellular accumulation, and inhibition of Sp1-driven gene transcription. Chem Biol Interact. 2014 Aug 5;219:123-32. doi: 10.1016/j.cbi.2014.05.019. Epub 2014 Jun 4.
• [9] Resveratrol sensitized leukemia stem cell-like KG-1a cells to cytokine-induced killer cells-mediated cytolysis through NKG2D ligands and TRAIL receptors. Cancer Biol Ther. 2012 May;13(7):516-26. doi: 10.4161/cbt.19601. Epub 2012 May 1.
• [10] 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.
• [11] Susceptibility to natural killer cell-mediated lysis of colon cancer cells is enhanced by treatment with epidermal growth factor receptor inhibitors through UL16-binding protein-1 induction. Cancer Sci. 2012 Jan;103(1):7-16. doi: 10.1111/j.1349-7006.2011.02109.x. Epub 2011 Nov 15.
• [12] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [13] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [16] 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.
• [17] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.