Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6GLSUL)

DOT Name	Polymeric immunoglobulin receptor (PIGR)
Synonyms	PIgR; Poly-Ig receptor; Hepatocellular carcinoma-associated protein TB6
Gene Name	PIGR
Related Disease	B-cell neoplasm ( ) Lung carcinoma ( ) Adenocarcinoma ( ) Autosomal dominant polycystic kidney disease ( ) Bacterial infection ( ) Chronic obstructive pulmonary disease ( ) Colitis ( ) Colon cancer ( ) Colon carcinoma ( ) Colonic neoplasm ( ) Coronary atherosclerosis ( ) Cystic kidney disease ( ) Depression ( ) Hepatitis ( ) Hepatitis A virus infection ( ) Hepatitis B virus infection ( ) Hepatocellular carcinoma ( ) IgA nephropathy ( ) Insomnia ( ) Liver cirrhosis ( ) Malignant tumor of nasopharynx ( ) Metastatic malignant neoplasm ( ) Nasopharyngeal carcinoma ( ) Neoplasm ( ) Non-alcoholic fatty liver disease ( ) Pancreatic cancer ( ) Pneumococcal meningitis ( ) Polycystic kidney disease ( ) Small-cell lung cancer ( ) Bone osteosarcoma ( ) Non-small-cell lung cancer ( ) Osteosarcoma ( ) Asthma ( ) Crohn disease ( ) Advanced cancer ( ) Carcinoma ( ) Lung cancer ( ) Matthew-Wood syndrome ( ) Pancreatic ductal carcinoma ( ) Rheumatoid arthritis ( ) Small lymphocytic lymphoma ( ) Squamous cell carcinoma ( )
UniProt ID	PIGR_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1XED; 2OCW; 3CHN; 3CM9; 5D4K; 6KXS; 6LX3; 6LXW; 6UE7; 6UE8; 6UE9; 6UEA; 7K0C; 7YSG; 8SKU; 8SKV
Pfam ID	PF07686
Sequence	MLLFVLTCLLAVFPAISTKSPIFGPEEVNSVEGNSVSITCYYPPTSVNRHTRKYWCRQGA RGGCITLISSEGYVSSKYAGRANLTNFPENGTFVVNIAQLSQDDSGRYKCGLGINSRGLS FDVSLEVSQGPGLLNDTKVYTVDLGRTVTINCPFKTENAQKRKSLYKQIGLYPVLVIDSS GYVNPNYTGRIRLDIQGTGQLLFSVVINQLRLSDAGQYLCQAGDDSNSNKKNADLQVLKP EPELVYEDLRGSVTFHCALGPEVANVAKFLCRQSSGENCDVVVNTLGKRAPAFEGRILLN PQDKDGSFSVVITGLRKEDAGRYLCGAHSDGQLQEGSPIQAWQLFVNEESTIPRSPTVVK GVAGGSVAVLCPYNRKESKSIKYWCLWEGAQNGRCPLLVDSEGWVKAQYEGRLSLLEEPG NGTFTVILNQLTSRDAGFYWCLTNGDTLWRTTVEIKIIEGEPNLKVPGNVTAVLGETLKV PCHFPCKFSSYEKYWCKWNNTGCQALPSQDEGPSKAFVNCDENSRLVSLTLNLVTRADEG WYWCGVKQGHFYGETAAVYVAVEERKAAGSRDVSLAKADAAPDEKVLDSGFREIENKAIQ DPRLFAEEKAVADTRDQADGSRASVDSGSSEEQGGSSRALVSTLVPLGLVLAVGAVAVGV ARARHRKNVDRVSIRSYRTDISMSDFENSREFGANDNMGASSITQETSLGGKEEFVATTE STTETKEPKKAKRSSKEEAEMAYKDFLLQSSTVAAEAQDGPQEA
Function	[Polymeric immunoglobulin receptor]: Mediates selective transcytosis of polymeric IgA and IgM across mucosal epithelial cells. Binds polymeric IgA and IgM at the basolateral surface of epithelial cells. The complex is then transported across the cell to be secreted at the apical surface. During this process, a cleavage occurs that separates the extracellular (known as the secretory component) from the transmembrane segment; [Secretory component]: Through its N-linked glycans ensures anchoring of secretory IgA (sIgA) molecules to mucus lining the epithelial surface to neutralize extracellular pathogens. On its own (free form) may act as a non-specific microbial scavenger to prevent pathogen interaction with epithelial cells.
KEGG Pathway	Intesti.l immune network for IgA production (hsa04672 )
Reactome Pathway	Neutrophil degranulation (R-HSA-6798695 )

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
B-cell neoplasm	DISVY326	Definitive	Biomarker	[1]
Lung carcinoma	DISTR26C	Definitive	Altered Expression	[2]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[2]
Autosomal dominant polycystic kidney disease	DISBHWUI	Strong	Biomarker	[3]
Bacterial infection	DIS5QJ9S	Strong	Genetic Variation	[4]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Altered Expression	[5]
Colitis	DISAF7DD	Strong	Biomarker	[6]
Colon cancer	DISVC52G	Strong	Altered Expression	[7]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[7]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[7]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[8]
Cystic kidney disease	DISRT1LM	Strong	Biomarker	[3]
Depression	DIS3XJ69	Strong	Altered Expression	[9]
Hepatitis	DISXXX35	Strong	Biomarker	[4]
Hepatitis A virus infection	DISUMFQV	Strong	Biomarker	[4]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[10]
IgA nephropathy	DISZ8MTK	Strong	Genetic Variation	[11]
Insomnia	DIS0AFR7	Strong	Altered Expression	[12]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[13]
Malignant tumor of nasopharynx	DISTGIGF	Strong	Genetic Variation	[14]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[4]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Altered Expression	[15]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[13]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[16]
Pneumococcal meningitis	DISM5U0L	Strong	Biomarker	[17]
Polycystic kidney disease	DISWS3UY	Strong	Biomarker	[3]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[18]
Bone osteosarcoma	DIST1004	moderate	Altered Expression	[19]
Non-small-cell lung cancer	DIS5Y6R9	moderate	Altered Expression	[20]
Osteosarcoma	DISLQ7E2	moderate	Altered Expression	[19]
Asthma	DISW9QNS	Disputed	Altered Expression	[21]
Crohn disease	DIS2C5Q8	Disputed	Altered Expression	[22]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[23]
Carcinoma	DISH9F1N	Limited	Altered Expression	[20]
Lung cancer	DISCM4YA	Limited	Altered Expression	[2]
Matthew-Wood syndrome	DISA7HR7	Limited	Altered Expression	[23]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Altered Expression	[23]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[24]
Small lymphocytic lymphoma	DIS30POX	Limited	Biomarker	[25]
Squamous cell carcinoma	DISQVIFL	Limited	Altered Expression	[20]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

1 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 Polymeric immunoglobulin receptor (PIGR).	[26]
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7 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 Polymeric immunoglobulin receptor (PIGR).	[27]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Polymeric immunoglobulin receptor (PIGR).	[28]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Polymeric immunoglobulin receptor (PIGR).	[29]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Polymeric immunoglobulin receptor (PIGR).	[30]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Polymeric immunoglobulin receptor (PIGR).	[31]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline increases the expression of Polymeric immunoglobulin receptor (PIGR).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Polymeric immunoglobulin receptor (PIGR).	[33]
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⏷ Show the Full List of 7 Drug(s)

References

1	The IgA/IgM receptor expressed on a murine B cell lymphoma is poly-Ig receptor.J Immunol. 2000 Sep 1;165(5):2544-55. doi: 10.4049/jimmunol.165.5.2544.
2	Loss of polymeric immunoglobulin receptor expression is associated with lung tumourigenesis.Eur Respir J. 2012 May;39(5):1171-80. doi: 10.1183/09031936.00184410. Epub 2011 Sep 29.
3	Exploitation of the Polymeric Immunoglobulin Receptor for Antibody Targeting to Renal Cyst Lumens in Polycystic Kidney Disease.J Biol Chem. 2015 Jun 19;290(25):15679-15686. doi: 10.1074/jbc.M114.607929. Epub 2015 Apr 28.
4	The role of polymeric immunoglobulin receptor in inflammation-induced tumor metastasis of human hepatocellular carcinoma.J Natl Cancer Inst. 2011 Nov 16;103(22):1696-712. doi: 10.1093/jnci/djr360. Epub 2011 Oct 24.
5	TGF-1 Impairs Vitamin D-Induced and Constitutive Airway Epithelial Host Defense Mechanisms.J Innate Immun. 2020;12(1):74-89. doi: 10.1159/000497415. Epub 2019 Apr 10.
6	Contribution of polymeric immunoglobulin receptor to regulation of intestinal inflammation in dextran sulfate sodium-induced colitis.J Gastroenterol Hepatol. 2006 Sep;21(9):1372-80. doi: 10.1111/j.1440-1746.2006.04312.x.
7	Characterization of the human polymeric immunoglobulin receptor (PIGR) 3'UTR and differential expression of PIGR mRNA during colon tumorigenesis.J Biomed Sci. 2003 Nov-Dec;10(6 Pt 2):792-804. doi: 10.1159/000073967.
8	A genome-wide trans-ethnic interaction study links the PIGR-FCAMR locus to coronary atherosclerosis via interactions between genetic variants and residential exposure to traffic.PLoS One. 2017 Mar 29;12(3):e0173880. doi: 10.1371/journal.pone.0173880. eCollection 2017.
9	Depression in the quantity of intestinal secretory IgA and in the expression of the polymeric immunoglobulin receptor in caloric deficiency of the weanling mouse.Lab Invest. 1998 Oct;78(10):1255-66.
10	Polymeric immunoglobulin receptor promotes tumor growth in hepatocellular carcinoma.Hepatology. 2017 Jun;65(6):1948-1962. doi: 10.1002/hep.29036. Epub 2017 Apr 28.
11	Association of single-nucleotide polymorphisms in the polymeric immunoglobulin receptor gene with immunoglobulin A nephropathy (IgAN) in Japanese patients.J Hum Genet. 2003;48(6):293-299. doi: 10.1007/s10038-003-0027-1. Epub 2003 May 10.
12	Personalized goal for insomnia and clinical response in advanced cancer patients.Support Care Cancer. 2020 Mar;28(3):1089-1096. doi: 10.1007/s00520-019-04912-z. Epub 2019 Jun 12.
13	Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease.Mol Syst Biol. 2019 Mar 1;15(3):e8793. doi: 10.15252/msb.20188793.
14	Polymeric immunoglobulin receptor polymorphisms and risk of nasopharyngeal cancer.BMC Genet. 2003 Jan 21;4:3. doi: 10.1186/1471-2156-4-3. Epub 2003 Jan 21.
15	Differential expression of osteoblast-specific factor 2 and polymeric immunoglobulin receptor genes in nasopharyngeal carcinoma.Head Neck. 2005 Oct;27(10):873-82. doi: 10.1002/hed.20253.
16	Imbalance of desmoplastic stromal cell numbers drives aggressive cancer processes.J Pathol. 2013 May;230(1):107-17. doi: 10.1002/path.4172. Epub 2013 Mar 21.
17	pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion.J Exp Med. 2017 Jun 5;214(6):1619-1630. doi: 10.1084/jem.20161668. Epub 2017 May 17.
18	Nonspecific increased serum levels of secretory component in lung tumors: relationship to the gene expression of the transmembrane receptor form.Am J Respir Cell Mol Biol. 1993 Sep;9(3):341-6. doi: 10.1165/ajrcmb/9.3.341.
19	Polymeric immunoglobulin receptor expression is correlated with poor prognosis in patients with osteosarcoma.Mol Med Rep. 2014 Jun;9(6):2105-10. doi: 10.3892/mmr.2014.2110. Epub 2014 Apr 2.
20	Down-regulation of the polymeric immunoglobulin receptor in non-small cell lung carcinoma: correlation with dysregulated expression of the transcription factors USF and AP2.J Biomed Sci. 2005;12(1):65-77. doi: 10.1007/s11373-004-8185-5.
21	Bronchial Epithelial IgA Secretion Is Impaired in Asthma. Role of IL-4/IL-13.Am J Respir Crit Care Med. 2018 Jun 1;197(11):1396-1409. doi: 10.1164/rccm.201703-0561OC.
22	Signature biomarkers in Crohn's disease: toward a molecular classification.Mucosal Immunol. 2008 Sep;1(5):399-411. doi: 10.1038/mi.2008.32. Epub 2008 Jul 2.
23	Expression of polymeric immunoglobulin receptor and stromal activity in pancreatic ductal adenocarcinoma.Pancreatology. 2017 Mar-Apr;17(2):295-302. doi: 10.1016/j.pan.2017.01.013. Epub 2017 Feb 1.
24	Vitamin A is required for regulation of polymeric immunoglobulin receptor (pIgR) expression by interleukin-4 and interferon-gamma in a human intestinal epithelial cell line.J Nutr. 1998 Jul;128(7):1063-9. doi: 10.1093/jn/128.7.1063.
25	Proteomics Profiling of CLL Versus Healthy B-cells Identifies Putative Therapeutic Targets and a Subtype-independent Signature of Spliceosome Dysregulation.Mol Cell Proteomics. 2018 Apr;17(4):776-791. doi: 10.1074/mcp.RA117.000539. Epub 2018 Jan 24.
26	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.
27	Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
28	Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
29	Fetal-sex dependent genomic responses in the circulating lymphocytes of arsenic-exposed pregnant women in New Hampshire. Reprod Toxicol. 2017 Oct;73:184-195. doi: 10.1016/j.reprotox.2017.07.023. Epub 2017 Aug 6.
30	Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
31	Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
32	Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers. J Allergy Clin Immunol. 2016 Dec;138(6):1690-1700. doi: 10.1016/j.jaci.2016.02.038. Epub 2016 Apr 24.
33	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.