Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7ZLJVV)

DOT Name	Intelectin-1 (ITLN1)
Synonyms	ITLN-1; Endothelial lectin HL-1; Galactofuranose-binding lectin; Intestinal lactoferrin receptor; Omentin
Gene Name	ITLN1
Related Disease	Primary biliary cholangitis ( ) Atopic dermatitis ( ) Barrett esophagus ( ) Carcinoma ( ) Crohn disease ( ) Gastric cancer ( ) Inflammatory bowel disease ( ) Mesothelioma ( ) Multiple sclerosis ( ) Nasal polyp ( ) Non-insulin dependent diabetes ( ) Obesity ( ) Polycystic ovarian syndrome ( ) Postmenopausal osteoporosis ( ) Pouchitis ( ) Psoriasis ( ) Stomach cancer ( ) Advanced cancer ( ) Colorectal carcinoma ( ) Adenocarcinoma ( ) Asthma ( ) Bacterial infection ( ) Coronary atherosclerosis ( ) Coronary heart disease ( ) Epithelioid mesothelioma ( ) Myocardial ischemia ( ) Neoplasm ( ) Neuroblastoma ( ) Streptococcal pneumonia ( ) Type-1/2 diabetes ( )
UniProt ID	ITLN1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	4WMQ; 4WMY; 6USC
Sequence	MNQLSFLLFLIATTRGWSTDEANTYFKEWTCSSSPSLPRSCKEIKDECPSAFDGLYFLRT ENGVIYQTFCDMTSGGGGWTLVASVHENDMRGKCTVGDRWSSQQGSKAVYPEGDGNWANY NTFGSAEAATSDDYKNPGYYDIQAKDLGIWHVPNKSPMQHWRNSSLLRYRTDTGFLQTLG HNLFGIYQKYPVKYGEGKCWTDNGPVIPVVYDFGDAQKTASYYSPYGQREFTAGFVQFRV FNNERAANALCAGMRVTGCNTEHHCIGGGGYFPEASPQQCGDFSGFDWSGYGTHVGYSSS REITEAAVLLFYR
Function	Lectin that specifically recognizes microbial carbohydrate chains in a calcium-dependent manner. Binds to microbial glycans that contain a terminal acyclic 1,2-diol moiety, including beta-linked D-galactofuranose (beta-Galf), D-phosphoglycerol-modified glycans, D-glycero-D-talo-oct-2-ulosonic acid (KO) and 3-deoxy-D-manno-oct-2-ulosonic acid (KDO). Binds to glycans from Gram-positive and Gram-negative bacteria, including K.pneumoniae, S.pneumoniae, Y.pestis, P.mirabilis and P.vulgaris. Does not bind human glycans. Probably plays a role in the defense system against microorganisms (Probable). May function as adipokine that has no effect on basal glucose uptake but enhances insulin-stimulated glucose uptake in adipocytes. Increases AKT phosphorylation in the absence and presence of insulin. May interact with lactoferrin/LTF and increase its uptake, and may thereby play a role in iron absorption.
Tissue Specificity	Highly expressed in omental adipose tissue where it is found in stromal vascular cells but not in fat cells but is barely detectable in subcutaneous adipose tissue (at protein level) . Highly expressed in the small intestine. Also found in the heart, testis, colon, salivary gland, skeletal muscle, pancreas and thyroid and, to a lesser degree, in the uterus, spleen, prostate, lymph node and thymus.
Reactome Pathway	Antimicrobial peptides (R-HSA-6803157 )

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Primary biliary cholangitis	DIS43E0O	Definitive	Biomarker	[1]
Atopic dermatitis	DISTCP41	Strong	Altered Expression	[2]
Barrett esophagus	DIS416Y7	Strong	Biomarker	[3]
Carcinoma	DISH9F1N	Strong	Altered Expression	[4]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[5]
Gastric cancer	DISXGOUK	Strong	Biomarker	[6]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[7]
Mesothelioma	DISKWK9M	Strong	Biomarker	[8]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[9]
Nasal polyp	DISLP3XE	Strong	Altered Expression	[10]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[11]
Obesity	DIS47Y1K	Strong	Genetic Variation	[12]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Altered Expression	[13]
Postmenopausal osteoporosis	DISS0RQZ	Strong	Genetic Variation	[14]
Pouchitis	DISE28DD	Strong	Genetic Variation	[15]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[16]
Stomach cancer	DISKIJSX	Strong	Biomarker	[6]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[17]
Colorectal carcinoma	DIS5PYL0	moderate	Genetic Variation	[18]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[8]
Asthma	DISW9QNS	Limited	Biomarker	[19]
Bacterial infection	DIS5QJ9S	Limited	Biomarker	[20]
Coronary atherosclerosis	DISKNDYU	Limited	Altered Expression	[21]
Coronary heart disease	DIS5OIP1	Limited	Altered Expression	[21]
Epithelioid mesothelioma	DIS17SNY	Limited	Biomarker	[8]
Myocardial ischemia	DISFTVXF	Limited	Altered Expression	[21]
Neoplasm	DISZKGEW	Limited	Altered Expression	[8]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[22]
Streptococcal pneumonia	DIS2EKMJ	Limited	Biomarker	[23]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[21]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

4 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 Intelectin-1 (ITLN1).	[24]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Intelectin-1 (ITLN1).	[25]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Intelectin-1 (ITLN1).	[11]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline increases the expression of Intelectin-1 (ITLN1).	[27]
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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 affects the methylation of Intelectin-1 (ITLN1).	[28]
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References

1	Role of lactoferrin and its receptors on biliary epithelium.Biometals. 2018 Jun;31(3):369-379. doi: 10.1007/s10534-018-0094-6. Epub 2018 Mar 17.
2	Intelectin contributes to allergen-induced IL-25, IL-33, and TSLP expression and type 2 response in asthma and atopic dermatitis.Mucosal Immunol. 2017 Nov;10(6):1491-1503. doi: 10.1038/mi.2017.10. Epub 2017 Feb 22.
3	Single cell RNA-seq reveals profound transcriptional similarity between Barrett's oesophagus and oesophageal submucosal glands.Nat Commun. 2018 Oct 15;9(1):4261. doi: 10.1038/s41467-018-06796-9.
4	Aberrant expression of intelectin-1 in gastric cancer: its relationship with clinicopathological features and prognosis.J Cancer Res Clin Oncol. 2012 Jan;138(1):163-72. doi: 10.1007/s00432-011-1088-8. Epub 2011 Nov 15.
5	Phenotype-genotype profiles in Crohn's disease predicted by genetic markers in autophagy-related genes (GOIA study II).Inflamm Bowel Dis. 2013 Feb;19(2):230-9. doi: 10.1002/ibd.23007.
6	Intelectin 1 suppresses tumor progression and is associated with improved survival in gastric cancer.Oncotarget. 2015 Jun 30;6(18):16168-82. doi: 10.18632/oncotarget.3753.
7	Quantitative Proteomic Analysis Reveals the Deregulation of Nicotinamide Adenine Dinucleotide Metabolism and CD38 in Inflammatory Bowel Disease.Biomed Res Int. 2019 Apr 23;2019:3950628. doi: 10.1155/2019/3950628. eCollection 2019.
8	Identification of DAB2 and Intelectin-1 as Novel Positive Immunohistochemical Markers of Epithelioid Mesothelioma by Transcriptome Microarray Analysis for Its Differentiation From Pulmonary Adenocarcinoma.Am J Surg Pathol. 2017 Aug;41(8):1045-1052. doi: 10.1097/PAS.0000000000000852.
9	Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci.Ann Neurol. 2011 Dec;70(6):897-912. doi: 10.1002/ana.22609.
10	Increased expression of intelectin-1 in nasal polyps.Am J Rhinol Allergy. 2012 Jul-Aug;26(4):274-7. doi: 10.2500/ajra.2012.26.3771.
11	Cardioprotective properties of omentin-1 in type 2 diabetes: evidence from clinical and in vitro studies. PLoS One. 2013;8(3):e59697. doi: 10.1371/journal.pone.0059697. Epub 2013 Mar 29.
12	The association of Val109Asp polymorphic marker of intelectin 1 gene with abdominal obesity in Kyrgyz population.BMC Endocr Disord. 2018 Feb 27;18(1):15. doi: 10.1186/s12902-018-0242-6.
13	Omentin-1, a novel adipokine, is decreased in overweight insulin-resistant women with polycystic ovary syndrome: ex vivo and in vivo regulation of omentin-1 by insulin and glucose.Diabetes. 2008 Apr;57(4):801-8. doi: 10.2337/db07-0990. Epub 2008 Jan 3.
14	Omentin Polymorphism and its Relations to Bone Mineral Density in Women.Arch Med Res. 2015 Apr;46(3):173-80. doi: 10.1016/j.arcmed.2015.03.012. Epub 2015 May 14.
15	A Polymorphism in Interleukin-1 Gene Is Associated with the Development of Pouchitis in Japanese Patients with Ulcerative Colitis.Digestion. 2021;102(3):489-498. doi: 10.1159/000503283. Epub 2019 Oct 31.
16	Omentin serum levels and omentin gene Val109Asp polymorphism in patients with psoriasis.Int J Dermatol. 2014 May;53(5):601-5. doi: 10.1111/ijd.12306. Epub 2013 Dec 10.
17	Activating transcription factor 3 promotes colon cancer metastasis.Tumour Biol. 2014 Aug;35(8):8329-34. doi: 10.1007/s13277-014-2044-4. Epub 2014 May 24.
18	Associations between single-nucleotide polymorphisms and inflammatory bowel disease-associated colorectal cancers in inflammatory bowel disease patients: a meta-analysis.Clin Transl Oncol. 2017 Aug;19(8):1018-1027. doi: 10.1007/s12094-017-1634-1. Epub 2017 Feb 27.
19	Expression of intelectin-1 in bronchial epithelial cells of asthma is correlated with T-helper 2 (Type-2) related parameters and its function.Allergy Asthma Clin Immunol. 2017 Aug 1;13:35. doi: 10.1186/s13223-017-0207-8. eCollection 2017.
20	ITLN in diploid hybrid fish (Carassius auratus cuvieri Carassius auratus red var ? is involved in host defense against bacterial infection.Dev Comp Immunol. 2020 Feb;103:103520. doi: 10.1016/j.dci.2019.103520. Epub 2019 Oct 15.
21	Joint analysis of left ventricular expression and circulating plasma levels of Omentin after myocardial ischemia.Cardiovasc Diabetol. 2017 Jul 7;16(1):87. doi: 10.1186/s12933-017-0567-x.
22	Intelectin 1 suppresses the growth, invasion and metastasis of neuroblastoma cells through up-regulation of N-myc downstream regulated gene 2.Mol Cancer. 2015 Feb 21;14:47. doi: 10.1186/s12943-015-0320-6.
23	ASC and NLRP3 maintain innate immune homeostasis in the airway through an inflammasome-independent mechanism.Mucosal Immunol. 2019 Sep;12(5):1092-1103. doi: 10.1038/s41385-019-0181-1. Epub 2019 Jul 5.
24	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.
25	Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
26	Cardioprotective properties of omentin-1 in type 2 diabetes: evidence from clinical and in vitro studies. PLoS One. 2013;8(3):e59697. doi: 10.1371/journal.pone.0059697. Epub 2013 Mar 29.
27	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.
28	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.