Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAV5SE7)

• DOT Name: ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 (BST1)
• Synonyms: EC 3.2.2.6; ADP-ribosyl cyclase 2; Bone marrow stromal cell antigen 1; BST-1; Cyclic ADP-ribose hydrolase 2; cADPR hydrolase 2; CD antigen CD157
• Gene Name: BST1
• Related Disease:
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Asthma
  Autism
  Depression
  Epithelial ovarian cancer
  High blood pressure
  Lung cancer
  Lung carcinoma
  Malignant pleural mesothelioma
  Pervasive developmental disorder
  Pleural mesothelioma
  Pleural tuberculosis
  Pneumonia
  Prion disease
  Prostate cancer
  Prostate carcinoma
  Tuberculosis
  Small lymphocytic lymphoma
  Autism spectrum disorder
  Malignant mesothelioma
  Mesothelioma
  Neoplasm
  Paroxysmal nocturnal haemoglobinuria
  Pulmonary disease
• UniProt ID: BST1_HUMAN
• PDB ID: 1ISF; 1ISG; 1ISH; 1ISI; 1ISJ; 1ISM
• EC Number: 3.2.2.6
• Pfam ID: PF02267
• Sequence:
  MAAQGCAASRLLQLLLQLLLLLLLLAAGGARARWRGEGTSAHLRDIFLGRCAEYRALLSP
  EQRNKNCTAIWEAFKVALDKDPCSVLPSDYDLFINLSRHSIPRDKSLFWENSHLLVNSFA
  DNTRRFMPLSDVLYGRVADFLSWCRQKNDSGLDYQSCPTSEDCENNPVDSFWKRASIQYS
  KDSSGVIHVMLNGSEPTGAYPIKGFFADYEIPNLQKEKITRIEIWVMHEIGGPNVESCGE
  GSMKVLEKRLKDMGFQYSCINDYRPVKLLQCVDHSTHPDCALKSAAAATQRKAPSLYTEQ
  RAGLIIPLFLVLASRTQL
• Function: Catalyzes both the synthesis of cyclic ADP-beta-D-ribose (cADPR) from NAD(+), and its hydrolysis to ADP-D-ribose (ADPR). Cyclic ADPR is known to serve as an endogenous second messenger that elicits calcium release from intracellular stores, and thus regulates the mobilization of intracellular calcium (Probable). May be involved in pre-B-cell growth (Probable).
• Tissue Specificity: Expressed in various tissues including placenta, lung, liver and kidney.
• KEGG Pathway:
  Nicoti.te and nicoti.mide metabolism (hsa00760)
  Metabolic pathways (hsa01100)
  Salivary secretion (hsa04970)
  Pancreatic secretion (hsa04972)
• Reactome Pathway:
  Nicotinate metabolism (R-HSA-196807)
  Neutrophil degranulation (R-HSA-6798695)
  Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Asthma	DISW9QNS	Strong	Genetic Variation	[3]
Autism	DISV4V1Z	Strong	Genetic Variation	[3]
Depression	DIS3XJ69	Strong	Biomarker	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[5]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[6]
Lung cancer	DISCM4YA	Strong	Biomarker	[7]
Lung carcinoma	DISTR26C	Strong	Biomarker	[7]
Malignant pleural mesothelioma	DIST2R60	Strong	Biomarker	[5]
Pervasive developmental disorder	DIS51975	Strong	Genetic Variation	[8]
Pleural mesothelioma	DISTTZOD	Strong	Biomarker	[5]
Pleural tuberculosis	DISD09EG	Strong	Biomarker	[7]
Pneumonia	DIS8EF3M	Strong	Biomarker	[7]
Prion disease	DISOUMB0	Strong	Genetic Variation	[9]
Prostate cancer	DISF190Y	Strong	Altered Expression	[10]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[10]
Tuberculosis	DIS2YIMD	Strong	Altered Expression	[7]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[11]
Autism spectrum disorder	DISXK8NV	Limited	Genetic Variation	[8]
Malignant mesothelioma	DISTHJGH	Limited	Biomarker	[12]
Mesothelioma	DISKWK9M	Limited	Altered Expression	[12]
Neoplasm	DISZKGEW	Limited	Altered Expression	[12]
Paroxysmal nocturnal haemoglobinuria	DISBHMYH	Limited	Posttranslational Modification	[13]
Pulmonary disease	DIS6060I	Limited	Biomarker	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Artesunate	DMR27C8	Approved	ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 (BST1) increases the response to substance of Artesunate.	[20]

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 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 (BST1).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 (BST1).	[16]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 (BST1).	[17]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 (BST1).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 (BST1).	[18]

References

• [1] Targeting CD157 in AML using a novel, Fc-engineered antibody construct.Oncotarget. 2017 May 30;8(22):35707-35717. doi: 10.18632/oncotarget.16060.
• [2] CD157: From Myeloid Cell Differentiation Marker to Therapeutic Target in Acute Myeloid Leukemia.Cells. 2019 Dec 5;8(12):1580. doi: 10.3390/cells8121580.
• [3] A deletion involving CD38 and BST1 results in a fusion transcript in a patient with autism and asthma.Autism Res. 2014 Apr;7(2):254-63. doi: 10.1002/aur.1365. Epub 2014 Mar 13.
• [4] Selegiline Ameliorates Depression-Like Behavior in Mice Lacking the CD157/BST1 Gene, a Risk Factor for Parkinson's Disease.Front Behav Neurosci. 2017 May 3;11:75. doi: 10.3389/fnbeh.2017.00075. eCollection 2017.
• [5] CD157: From immunoregulatory protein to potential therapeutic target.Immunol Lett. 2019 Jan;205:59-64. doi: 10.1016/j.imlet.2018.06.007. Epub 2018 Jun 21.
• [6] Genome-Wide Meta-Analysis of Blood Pressure Response to (1)-Blockers: Results From ICAPS (International Consortium of Antihypertensive Pharmacogenomics Studies).J Am Heart Assoc. 2019 Aug 20;8(16):e013115. doi: 10.1161/JAHA.119.013115. Epub 2019 Aug 19.
• [7] CD157 Confers Host Resistance to Mycobacterium tuberculosis via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production.mBio. 2019 Aug 27;10(4):e01949-19. doi: 10.1128/mBio.01949-19.
• [8] An immunohistochemical, enzymatic, and behavioral study of CD157/BST-1 as a neuroregulator.BMC Neurosci. 2017 Mar 24;18(1):35. doi: 10.1186/s12868-017-0350-7.
• [9] Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP.Hum Mol Genet. 2012 Apr 15;21(8):1897-906. doi: 10.1093/hmg/ddr607. Epub 2011 Dec 30.
• [10] Multi-lectin Affinity Chromatography and Quantitative Proteomic Analysis Reveal Differential Glycoform Levels between Prostate Cancer and Benign Prostatic Hyperplasia Sera.Sci Rep. 2018 Apr 25;8(1):6509. doi: 10.1038/s41598-018-24270-w.
• [11] CD38 and CD157: a long journey from activation markers to multifunctional molecules.Cytometry B Clin Cytom. 2013 Jul-Aug;84(4):207-17. doi: 10.1002/cyto.b.21092. Epub 2013 Apr 10.
• [12] Soluble CD157 in pleural effusions: a complementary tool for the diagnosis of malignant mesothelioma.Oncotarget. 2018 Apr 27;9(32):22785-22801. doi: 10.18632/oncotarget.25237. eCollection 2018 Apr 27.
• [13] Diagnosis of paroxysmal nocturnal hemoglobinuria with flowcytometry panels including CD157: Data from the real world.Cytometry B Clin Cytom. 2020 Mar;98(2):193-202. doi: 10.1002/cyto.b.21847. Epub 2019 Sep 30.
• [14] Blood gene expression profiling detects silica exposure and toxicity.Toxicol Sci. 2011 Aug;122(2):253-64. doi: 10.1093/toxsci/kfr125. Epub 2011 May 19.
• [15] 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.
• [16] 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.
• [17] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [18] 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.
• [19] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
• [20] Factors determining sensitivity or resistance of tumor cell lines towards artesunate. Chem Biol Interact. 2010 Apr 15;185(1):42-52.