Details of Drug Off-Target (DOT)

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

• DOT Name: Adhesion G protein-coupled receptor B1 (ADGRB1)
• Synonyms: Brain-specific angiogenesis inhibitor 1
• Gene Name: ADGRB1
• Related Disease:
  Bladder transitional cell carcinoma
  Neuroblastoma
  Parkinson disease
  Advanced cancer
  Colitis
  Colorectal carcinoma
  Gastric cancer
  Herpes simplex infection
  Immunodeficiency
  Malignant glioma
  Medulloblastoma
  Neoplasm
  Stomach cancer
  Vascular disease
  Adult glioblastoma
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Brain neoplasm
  Glioma
• UniProt ID: AGRB1_HUMAN
• Pfam ID: PF00002 ; PF19188 ; PF16489 ; PF01825 ; PF02793 ; PF00090
• Sequence:
  MRGQAAAPGPVWILAPLLLLLLLLGRRARAAAGADAGPGPEPCATLVQGKFFGYFSAAAV
  FPANASRCSWTLRNPDPRRYTLYMKVAKAPVPCSGPGRVRTYQFDSFLESTRTYLGVESF
  DEVLRLCDPSAPLAFLQASKQFLQMRRQQPPQHDGLRPRAGPPGPTDDFSVEYLVVGNRN
  PSRAACQMLCRWLDACLAGSRSSHPCGIMQTPCACLGGEAGGPAAGPLAPRGDVCLRDAV
  AGGPENCLTSLTQDRGGHGATGGWKLWSLWGECTRDCGGGLQTRTRTCLPAPGVEGGGCE
  GVLEEGRQCNREACGPAGRTSSRSQSLRSTDARRREELGDELQQFGFPAPQTGDPAAEEW
  SPWSVCSSTCGEGWQTRTRFCVSSSYSTQCSGPLREQRLCNNSAVCPVHGAWDEWSPWSL
  CSSTCGRGFRDRTRTCRPPQFGGNPCEGPEKQTKFCNIALCPGRAVDGNWNEWSSWSACS
  ASCSQGRQQRTRECNGPSYGGAECQGHWVETRDCFLQQCPVDGKWQAWASWGSCSVTCGA
  GSQRRERVCSGPFFGGAACQGPQDEYRQCGTQRCPEPHEICDEDNFGAVIWKETPAGEVA
  AVRCPRNATGLILRRCELDEEGIAYWEPPTYIRCVSIDYRNIQMMTREHLAKAQRGLPGE
  GVSEVIQTLVEISQDGTSYSGDLLSTIDVLRNMTEIFRRAYYSPTPGDVQNFVQILSNLL
  AEENRDKWEEAQLAGPNAKELFRLVEDFVDVIGFRMKDLRDAYQVTDNLVLSIHKLPASG
  ATDISFPMKGWRATGDWAKVPEDRVTVSKSVFSTGLTEADEASVFVVGTVLYRNLGSFLA
  LQRNTTVLNSKVISVTVKPPPRSLRTPLEIEFAHMYNGTTNQTCILWDETDVPSSSAPPQ
  LGPWSWRGCRTVPLDALRTRCLCDRLSTFAILAQLSADANMEKATLPSVTLIVGCGVSSL
  TLLMLVIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHF
  FFLSSFCWVLTEAWQSYMAVTGHLRNRLIRKRFLCLGWGLPALVVAISVGFTKAKGYSTM
  NYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSKDGITDKKLKERAGASLWSSC
  VVLPLLALTWMSAVLAVTDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQDAVKCRVV
  DRQEEGNGDSGGSFQNGHAQLMTDFEKDVDLACRSVLNKDIAACRTATITGTLKRPSLPE
  EEKLKLAHAKGPPTNFNSLPANVSKLHLHGSPRYPGGPLPDFPNHSLTLKRDKAPKSSFV
  GDGDIFKKLDSELSRAQEKALDTSYVILPTATATLRPKPKEEPKYSIHIDQMPQTRLIHL
  STAPEASLPARSPPSRQPPSGGPPEAPPAQPPPPPPPPPPPPQQPLPPPPNLEPAPPSLG
  DPGEPAAHPGPSTGPSTKNENVATLSVSSLERRKSRYAELDFEKIMHTRKRHQDMFQDLN
  RKLQHAAEKDKEVLGPDSKPEKQQTPNKRPWESLRKAHGTPTWVKKELEPLQPSPLELRS
  VEWERSGATIPLVGQDIIDLQTEV
• Function: Phosphatidylserine receptor which enhances the engulfment of apoptotic cells. Also mediates the binding and engulfment of Gram-negative bacteria. Stimulates production of reactive oxygen species by macrophages in response to Gram-negative bacteria, resulting in enhanced microbicidal macrophage activity. In the gastric mucosa, required for recognition and engulfment of apoptotic gastric epithelial cells. Promotes myoblast fusion. Activates the Rho pathway in a G-protein-dependent manner. Inhibits MDM2-mediated ubiquitination and degradation of DLG4/PSD95, promoting DLG4 stability and regulating synaptic plasticity. Required for the formation of dendritic spines by ensuring the correct localization of PARD3 and TIAM1. Potent inhibitor of angiogenesis in brain and may play a significant role as a mediator of the p53/TP53 signal in suppression of glioblastoma ; [Vasculostatin-120]: Inhibits angiogenesis in a CD36-dependent manner; [Vasculostatin-40]: Inhibits angiogenesis.
• Tissue Specificity: Expressed in brain (at protein level) . Expressed on mononuclear phagocytes and monocyte-derived macrophages in the gastric mucosa (at protein level) . Expressed in normal pancreatic tissue but not in pancreatic tumor tissue . Reduced or no expression is observed in some glioblastomas .
• KEGG Pathway:
  p53 sig.ling pathway (hsa04115)
  Efferocytosis (hsa04148)

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder transitional cell carcinoma	DISNL46A	Definitive	Biomarker	[1]
Neuroblastoma	DISVZBI4	Definitive	Altered Expression	[2]
Parkinson disease	DISQVHKL	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Colitis	DISAF7DD	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Gastric cancer	DISXGOUK	Strong	Biomarker	[6]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[7]
Immunodeficiency	DIS093I0	Strong	Altered Expression	[8]
Malignant glioma	DISFXKOV	Strong	Altered Expression	[9]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Stomach cancer	DISKIJSX	Strong	Biomarker	[6]
Vascular disease	DISVS67S	Strong	Biomarker	[12]
Adult glioblastoma	DISVP4LU	moderate	Altered Expression	[13]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	moderate	Genetic Variation	[14]
Brain neoplasm	DISY3EKS	Limited	Biomarker	[13]
Glioma	DIS5RPEH	Limited	Altered Expression	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Adhesion G protein-coupled receptor B1 (ADGRB1).	[16]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Adhesion G protein-coupled receptor B1 (ADGRB1).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Adhesion G protein-coupled receptor B1 (ADGRB1).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Adhesion G protein-coupled receptor B1 (ADGRB1).	[18]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Adhesion G protein-coupled receptor B1 (ADGRB1).	[19]
Selenium	DM25CGV	Approved	Selenium increases the expression of Adhesion G protein-coupled receptor B1 (ADGRB1).	[20]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Adhesion G protein-coupled receptor B1 (ADGRB1).	[20]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Adhesion G protein-coupled receptor B1 (ADGRB1).	[22]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Adhesion G protein-coupled receptor B1 (ADGRB1).	[23]

References

• [1] Expression of brainspecific angiogenesis inhibitor? and association with p53, microvessel density and vascular endothelial growth factor in the tissue of human bladder transitional cell carcinoma.Mol Med Rep. 2015 Sep;12(3):4522-4529. doi: 10.3892/mmr.2015.3984. Epub 2015 Jun 23.
• [2] New Targets for Parkinson's Disease: Adhesion G Protein-Coupled Receptor B1 is Downregulated by AMP-Activated Protein Kinase Activation.OMICS. 2018 Jul;22(7):493-501. doi: 10.1089/omi.2018.0047.
• [3] Regulatory roles of brain-specific angiogenesis inhibitor 1(BAI1) protein in inflammation, tumorigenesis and phagocytosis: A brief review.Crit Rev Oncol Hematol. 2017 Mar;111:81-86. doi: 10.1016/j.critrevonc.2017.01.006. Epub 2017 Jan 16.
• [4] Boosting Apoptotic Cell Clearance by Colonic Epithelial Cells Attenuates Inflammation In Vivo.Immunity. 2016 Apr 19;44(4):807-20. doi: 10.1016/j.immuni.2016.02.005. Epub 2016 Mar 29.
• [5] Expression of angiostatic factors in colorectal cancer.Int J Oncol. 1999 Dec;15(6):1221-5. doi: 10.3892/ijo.15.6.1221.
• [6] Augmentation of antitumor effects of p53 gene therapy by combination with HDAC inhibitor.Cancer Biol Ther. 2005 Apr;4(4):421-8. doi: 10.4161/cbt.4.4.1620. Epub 2005 Apr 21.
• [7] BAI1 Orchestrates Macrophage Inflammatory Response to HSV Infection-Implications for Oncolytic Viral Therapy.Clin Cancer Res. 2017 Apr 1;23(7):1809-1819. doi: 10.1158/1078-0432.CCR-16-1818. Epub 2016 Nov 9.
• [8] Overexpression of the p53-inducible brain-specific angiogenesis inhibitor 1 suppresses efficiently tumour angiogenesis.Br J Cancer. 2002 Feb 1;86(3):490-6. doi: 10.1038/sj.bjc.6600067.
• [9] The integrin inhibitor cilengitide enhances the anti-glioma efficacy of vasculostatin-expressing oncolytic virus.Cancer Gene Ther. 2013 Aug;20(8):437-44. doi: 10.1038/cgt.2013.38. Epub 2013 Jul 5.
• [10] EZH2 targeting reduces medulloblastoma growth through epigenetic reactivation of the BAI1/p53 tumor suppressor pathway.Oncogene. 2020 Jan;39(5):1041-1048. doi: 10.1038/s41388-019-1036-7. Epub 2019 Oct 3.
• [11] BAI1 Suppresses Medulloblastoma Formation by Protecting p53 from Mdm2-Mediated Degradation.Cancer Cell. 2018 Jun 11;33(6):1004-1016.e5. doi: 10.1016/j.ccell.2018.05.006.
• [12] A proprotein convertase/MMP-14 proteolytic cascade releases a novel 40kDa vasculostatin from tumor suppressor BAI1.Oncogene. 2012 Dec 13;31(50):5144-52. doi: 10.1038/onc.2012.1. Epub 2012 Feb 13.
• [13] Antiangiogenic activity of BAI1 in vivo: implications for gene therapy of human glioblastomas.Cancer Gene Ther. 2006 Apr;13(4):385-92. doi: 10.1038/sj.cgt.7700898.
• [14] Genetic Features of Aflatoxin-Associated Hepatocellular Carcinoma.Gastroenterology. 2017 Jul;153(1):249-262.e2. doi: 10.1053/j.gastro.2017.03.024. Epub 2017 Mar 29.
• [15] Brain angiogenesis inhibitor 1 is differentially expressed in normal brain and glioblastoma independently of p53 expression.Am J Pathol. 2003 Jan;162(1):19-27. doi: 10.1016/S0002-9440(10)63794-7.
• [16] 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.
• [17] 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.
• [18] Quercetin and Its Fermented Extract as a Potential Inhibitor of Bisphenol A-Exposed HT-29 Colon Cancer Cells' Viability. Int J Mol Sci. 2023 Mar 15;24(6):5604. doi: 10.3390/ijms24065604.
• [19] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [20] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [21] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [22] 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.
• [23] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.