Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB6TMGY)

• DOT Name: Pancreatic secretory granule membrane major glycoprotein GP2 (GP2)
• Synonyms: Pancreatic zymogen granule membrane protein GP-2; ZAP75
• Gene Name: GP2
• Related Disease:
  Chronic pancreatitis
  Behcet disease
  Classic galactosemia
  Colorectal carcinoma
  Crohn disease
  Cystic fibrosis
  Gallbladder disease
  Hepatitis C virus infection
  Herpes zoster
  Matthew-Wood syndrome
  Pancreas disorder
  Pancreatic cancer
  Pancreatic tumour
  Acute myelogenous leukaemia
  Hepatocellular carcinoma
  Ulcerative colitis
  Congenital contractural arachnodactyly
  Ebola virus infection
  Non-insulin dependent diabetes
• UniProt ID: GP2_HUMAN
• PDB ID: 7P6R; 7P6S; 7P6T
• Pfam ID: PF00100
• Sequence:
  MPHLMERMVGSGLLWLALVSCILTQASAVQRGYGNPIEASSYGLDLDCGAPGTPEAHVCF
  DPCQNYTLLDEPFRSTENSAGSQGCDKNMSGWYRFVGEGGVRMSETCVQVHRCQTDAPMW
  LNGTHPALGDGITNHTACAHWSGNCCFWKTEVLVKACPGGYHVYRLEGTPWCNLRYCTVP
  RDPSTVEDKCEKACRPEEECLALNSTWGCFCRQDLNSSDVHSLQPQLDCGPREIKVKVDK
  CLLGGLGLGEEVIAYLRDPNCSSILQTEERNWVSVTSPVQASACRNILERNQTHAIYKNT
  LSLVNDFIIRDTILNINFQCAYPLDMKVSLQAALQPIVSSLNVSVDGNGEFIVRMALFQD
  QNYTNPYEGDAVELSVESVLYVGAILEQGDTSRFNLVLRNCYATPTEDKADLVKYFIIRN
  SCSNQRDSTIHVEENGQSSESRFSVQMFMFAGHYDLVFLHCEIHLCDSLNEQCQPSCSRS
  QVRSEVPAIDLARVLDLGPITRRGAQSPGVMNGTPSTAGFLVAWPMVLLTVLLAWLF
• Function: Functions as an intestinal M-cell transcytotic receptor specific for type-I-piliated bacteria that participates in the mucosal immune response toward these bacteria. At the apical membrane of M-cells it binds fimH, a protein of the bacteria type I pilus tip. Internalizes bound bacteria, like E.coli and S.typhimurium, from the lumen of the intestine and delivers them, through M-cells, to the underlying organized lymphoid follicles where they are captured by antigen-presenting dendritic cells to elicit a mucosal immune response.
• Tissue Specificity: Expressed in pancreas (at protein level) . Specifically expressed by M (microfold) cells which are atypical epithelial cells of the intestine (at protein level) .
• Reactome Pathway: Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic pancreatitis	DISBUOMJ	Definitive	Biomarker	[1]
Behcet disease	DISSYMBS	Strong	Biomarker	[2]
Classic galactosemia	DISX7P8M	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[5]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[6]
Gallbladder disease	DISA6W3T	Strong	Biomarker	[1]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[7]
Herpes zoster	DISNSMNY	Strong	Biomarker	[8]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[9]
Pancreas disorder	DISDH7NI	Strong	Biomarker	[9]
Pancreatic cancer	DISJC981	Strong	Biomarker	[9]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[10]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[11]
Ulcerative colitis	DIS8K27O	moderate	Altered Expression	[5]
Congenital contractural arachnodactyly	DISOM1K7	Limited	Biomarker	[12]
Ebola virus infection	DISJAVM1	Limited	Biomarker	[13]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Pancreatic secretory granule membrane major glycoprotein GP2 (GP2).	[15]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Pancreatic secretory granule membrane major glycoprotein GP2 (GP2).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Pancreatic secretory granule membrane major glycoprotein GP2 (GP2).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Pancreatic secretory granule membrane major glycoprotein GP2 (GP2).	[18]

References

• [1] Serological diagnosis and prognosis of severe acute pancreatitis by analysis of serum glycoprotein 2.Clin Chem Lab Med. 2017 May 1;55(6):854-864. doi: 10.1515/cclm-2016-0797.
• [2] Antibodies against glycoprotein 2 display diagnostic advantages over ASCA in distinguishing CD from intestinal tuberculosis and intestinal Behet's disease.Clin Transl Gastroenterol. 2018 Feb 15;9(2):e133. doi: 10.1038/ctg.2018.1.
• [3] GALT carcinoma: three case reports with glycoprotein 2 immunohistochemistry and electron microscopic observations.Histopathology. 2018 Sep;73(3):521-528. doi: 10.1111/his.13639. Epub 2018 Jun 6.
• [4] MAGP2, a Component of Extracellular Matrix, Is Upregulated in Colorectal Cancer and Negatively Modulated by miR-200b-3p.Technol Cancer Res Treat. 2019 Jan 1;18:1533033819870777. doi: 10.1177/1533033819870777.
• [5] Differential diagnosis of Crohn's disease using antibodies to glycoprotein 2 and Saccharomyces cerevisiae.Turk J Gastroenterol. 2019 Jan;30(1):21-27. doi: 10.5152/tjg.2018.18135.
• [6] Mucosal Autoimmunity to Cell-Bound GP2 Isoforms Is a Sensitive Marker in PSC and Associated With the Clinical Phenotype.Front Immunol. 2018 Aug 28;9:1959. doi: 10.3389/fimmu.2018.01959. eCollection 2018.
• [7] Tree shrew, a potential animal model for hepatitis C, supports the infection and replication of HCV in vitro and in vivo.J Gen Virol. 2017 Aug;98(8):2069-2078. doi: 10.1099/jgv.0.000869. Epub 2017 Jul 31.
• [8] B-cell epitopes of varicella-zoster virus glycoprotein II.Arch Virol. 1996;141(12):2465-9. doi: 10.1007/BF01718644.
• [9] Glypican-1 and glycoprotein 2 bearing extracellular vesicles do not discern pancreatic cancer from benign pancreatic diseases.Oncotarget. 2019 Feb 1;10(10):1045-1055. doi: 10.18632/oncotarget.26620. eCollection 2019 Feb 1.
• [10] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [11] Methylation analysis of p16, SLIT2, SCARA5, and Runx3 genes in hepatocellular carcinoma.Medicine (Baltimore). 2017 Oct;96(41):e8279. doi: 10.1097/MD.0000000000008279.
• [12] Cholangiocarcinoma in Patients with Primary Sclerosing Cholangitis (PSC): a Comprehensive Review.Clin Rev Allergy Immunol. 2020 Feb;58(1):134-149. doi: 10.1007/s12016-019-08764-7.
• [13] Identification of Ebola Virus Inhibitors Targeting GP2 Using Principles of Molecular Mimicry.J Virol. 2019 Jul 17;93(15):e00676-19. doi: 10.1128/JVI.00676-19. Print 2019 Aug 1.
• [14] Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population.Nat Genet. 2019 Mar;51(3):379-386. doi: 10.1038/s41588-018-0332-4. Epub 2019 Feb 4.
• [15] 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.
• [16] 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.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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.