Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQQ9Q7G)

• DOT Name: Adhesion G protein-coupled receptor E1 (ADGRE1)
• Synonyms: EGF-like module receptor 1; EGF-like module-containing mucin-like hormone receptor-like 1; EMR1 hormone receptor
• Gene Name: ADGRE1
• Related Disease:
  Anemia
  Cystic fibrosis
  Hepatocellular carcinoma
  Malaria
  Polyp
  Periodontitis
  Emery-Dreifuss muscular dystrophy
• UniProt ID: AGRE1_HUMAN
• Pfam ID: PF00002 ; PF07645 ; PF01825
• Sequence:
  MRGFNLLLFWGCCVMHSWEGHIRPTRKPNTKGNNCRDSTLCPAYATCTNTVDSYYCACKQ
  GFLSSNGQNHFKDPGVRCKDIDECSQSPQPCGPNSSCKNLSGRYKCSCLDGFSSPTGNDW
  VPGKPGNFSCTDINECLTSSVCPEHSDCVNSMGSYSCSCQVGFISRNSTCEDVDECADPR
  ACPEHATCNNTVGNYSCFCNPGFESSSGHLSFQGLKASCEDIDECTEMCPINSTCTNTPG
  SYFCTCHPGFAPSNGQLNFTDQGVECRDIDECRQDPSTCGPNSICTNALGSYSCGCIAGF
  HPNPEGSQKDGNFSCQRVLFKCKEDVIPDNKQIQQCQEGTAVKPAYVSFCAQINNIFSVL
  DKVCENKTTVVSLKNTTESFVPVLKQISTWTKFTKEETSSLATVFLESVESMTLASFWKP
  SANITPAVRTEYLDIESKVINKECSEENVTLDLVAKGDKMKIGCSTIEESESTETTGVAF
  VSFVGMESVLNERFFKDHQAPLTTSEIKLKMNSRVVGGIMTGEKKDGFSDPIIYTLENIQ
  PKQKFERPICVSWSTDVKGGRWTSFGCVILEASETYTICSCNQMANLAVIMASGELTMDF
  SLYIISHVGIIISLVCLVLAIATFLLCRSIRNHNTYLHLHLCVCLLLAKTLFLAGIHKTD
  NKMGCAIIAGFLHYLFLACFFWMLVEAVILFLMVRNLKVVNYFSSRNIKMLHICAFGYGL
  PMLVVVISASVQPQGYGMHNRCWLNTETGFIWSFLGPVCTVIVINSLLLTWTLWILRQRL
  SSVNAEVSTLKDTRLLTFKAFAQLFILGCSWVLGIFQIGPVAGVMAYLFTIINSLQGAFI
  FLIHCLLNGQVREEYKRWITGKTKPSSQSQTSRILLSSMPSASKTG
• Function: Orphan receptor involved in cell adhesion and probably in cell-cell interactions specifically involving cells of the immune system. May play a role in regulatory T-cells (Treg) development.
• Tissue Specificity: Expression is restricted to eosinophils.
• Reactome Pathway: Class B/2 (Secretin family receptors) (R-HSA-373080)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anemia	DISTVL0C	Strong	Genetic Variation	[1]
Cystic fibrosis	DIS2OK1Q	Strong	Genetic Variation	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[3]
Malaria	DISQ9Y50	Strong	Biomarker	[4]
Polyp	DISRSLYF	Strong	Altered Expression	[5]
Periodontitis	DISI9JOI	moderate	Genetic Variation	[6]
Emery-Dreifuss muscular dystrophy	DISYTPR5	Limited	Altered Expression	[7]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Adhesion G protein-coupled receptor E1 (ADGRE1) decreases the response to substance of Arsenic.	[14]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Adhesion G protein-coupled receptor E1 (ADGRE1).	[8]

6 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 E1 (ADGRE1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Adhesion G protein-coupled receptor E1 (ADGRE1).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Adhesion G protein-coupled receptor E1 (ADGRE1).	[11]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Adhesion G protein-coupled receptor E1 (ADGRE1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Adhesion G protein-coupled receptor E1 (ADGRE1).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Adhesion G protein-coupled receptor E1 (ADGRE1).	[13]

References

• [1] Association of candidate gene polymorphisms and TGF-beta/IL-10 levels with malaria in three regions of Cameroon: a case-control study.Malar J. 2014 Jun 16;13:236. doi: 10.1186/1475-2875-13-236.
• [2] The genetic risk of acute seizures in African children with falciparum malaria.Epilepsia. 2013 Jun;54(6):990-1001. doi: 10.1111/epi.12173. Epub 2013 Apr 24.
• [3] Transcriptome sequencing identified hub genes for hepatocellular carcinoma by weighted-gene co-expression analysis.Oncotarget. 2016 Jun 21;7(25):38487-38499. doi: 10.18632/oncotarget.9555.
• [4] Whole-Genome Sequencing of African Dogs Provides Insights into Adaptations against Tropical Parasites.Mol Biol Evol. 2018 Feb 1;35(2):287-298. doi: 10.1093/molbev/msx258.
• [5] Macrophage depletion using clodronate liposomes decreases tumorigenesis and alters gut microbiota in the AOM/DSS mouse model of colon cancer.Am J Physiol Gastrointest Liver Physiol. 2018 Jan 1;314(1):G22-G31. doi: 10.1152/ajpgi.00229.2017. Epub 2017 Oct 12.
• [6] Exploring the genetic basis of chronic periodontitis: a genome-wide association study.Hum Mol Genet. 2013 Jun 1;22(11):2312-24. doi: 10.1093/hmg/ddt065. Epub 2013 Mar 4.
• [7] Genome-wide analysis links emerin to neuromuscular junction activity in Caenorhabditis elegans.Genome Biol. 2014 Feb 3;15(2):R21. doi: 10.1186/gb-2014-15-2-r21.
• [8] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [9] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] 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.
• [12] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [13] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [14] Gene expression levels in normal human lymphoblasts with variable sensitivities to arsenite: identification of GGT1 and NFKBIE expression levels as possible biomarkers of susceptibility. Toxicol Appl Pharmacol. 2008 Jan 15;226(2):199-205. doi: 10.1016/j.taap.2007.09.004. Epub 2007 Sep 15.