Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYNAQ75)

• DOT Name: Adhesion G protein-coupled receptor E3 (ADGRE3)
• Synonyms: EGF-like module receptor 3; EGF-like module-containing mucin-like hormone receptor-like 3
• Gene Name: ADGRE3
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Glioma
• UniProt ID: AGRE3_HUMAN
• Pfam ID: PF00002 ; PF07645 ; PF16489 ; PF01825
• Sequence:
  MQGPLLLPGLCFLLSLFGAVTQKTKTSCAKCPPNASCVNNTHCTCNHGYTSGSGQKLFTF
  PLETCNDINECTPPYSVYCGFNAVCYNVEGSFYCQCVPGYRLHSGNEQFSNSNENTCQDT
  TSSKTTEGRKELQKIVDKFESLLTNQTLWRTEGRQEISSTATTILRDVESKVLETALKDP
  EQKVLKIQNDSVAIETQAITDNCSEERKTFNLNVQMNSMDIRCSDIIQGDTQGPSAIAFI
  SYSSLGNIINATFFEEMDKKDQVYLNSQVVSAAIGPKRNVSLSKSVTLTFQHVKMTPSTK
  KVFCVYWKSTGQGSQWSRDGCFLIHVNKSHTMCNCSHLSSFAVLMALTSQEEDPVLTVIT
  YVGLSVSLLCLLLAALTFLLCKAIRNTSTSLHLQLSLCLFLAHLLFLVGIDRTEPKVLCS
  IIAGALHYLYLAAFTWMLLEGVHLFLTARNLTVVNYSSINRLMKWIMFPVGYGVPAVTVA
  ISAASWPHLYGTADRCWLHLDQGFMWSFLGPVCAIFSANLVLFILVFWILKRKLSSLNSE
  VSTIQNTRMLAFKATAQLFILGCTWCLGLLQVGPAAQVMAYLFTIINSLQGFFIFLVYCL
  LSQQVQKQYQKWFREIVKSKSESETYTLSSKMGPDSKPSEGDVFPGQVKRKY
• Function: Orphan receptor that may play a role myeloid-myeloid interactions during immune and inflammatory responses. A ligand for the soluble form of this receptor is present at the surface of monocytes-derived macrophages and activated neutrophils.
• Tissue Specificity: Displays a predominantly leukocyte-restricted expression, with highest levels in neutrophils, monocytes and macrophages.
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Class B/2 (Secretin family receptors) (R-HSA-373080)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Glioma	DIS5RPEH	Definitive	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Adhesion G protein-coupled receptor E3 (ADGRE3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Adhesion G protein-coupled receptor E3 (ADGRE3).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Adhesion G protein-coupled receptor E3 (ADGRE3).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Adhesion G protein-coupled receptor E3 (ADGRE3).	[5]

References

• [1] EMR-3: a potential mediator of invasive phenotypic variation in glioblastoma and novel therapeutic target.Neuroreport. 2010 Nov 17;21(16):1018-22. doi: 10.1097/WNR.0b013e32833f19f2.
• [2] 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.
• [3] 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.
• [4] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [5] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.