Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLD0KWA)

DOT Name Leucine-rich alpha-2-glycoprotein (LRG1)
Synonyms LRG
Gene Name LRG1
Related Disease
Appendicitis ( )
Arthritis ( )
Coronary heart disease ( )
Type-1/2 diabetes ( )
Acute myelogenous leukaemia ( )
Adult glioblastoma ( )
B-cell neoplasm ( )
Breast cancer ( )
Breast carcinoma ( )
Cervical cancer ( )
Cervical carcinoma ( )
Cholangiocarcinoma ( )
Chronic kidney disease ( )
Colitis ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Crohn disease ( )
Diabetic kidney disease ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Esophageal squamous cell carcinoma ( )
Glioblastoma multiforme ( )
Glioma ( )
Hepatocellular carcinoma ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
Obesity ( )
Oral cancer ( )
Pancreatic cancer ( )
Pancreatic ductal carcinoma ( )
Retinoblastoma ( )
Stroke ( )
Systemic lupus erythematosus ( )
Thyroid gland carcinoma ( )
Triple negative breast cancer ( )
Ulcerative colitis ( )
Carcinoma ( )
Colonic neoplasm ( )
Familial adenomatous polyposis ( )
Familial adenomatous polyposis 1 ( )
Head-neck squamous cell carcinoma ( )
Osteoarthritis ( )
Adenoma ( )
Colon cancer ( )
Inflammatory bowel disease ( )
Matthew-Wood syndrome ( )
Myocardial infarction ( )
Neuroblastoma ( )
Rheumatoid arthritis ( )
UniProt ID
A2GL_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
7Q4Q; 8H24
Pfam ID
PF00560 ; PF13855
Sequence
MSSWSRQRPKSPGGIQPHVSRTLFLLLLLAASAWGVTLSPKDCQVFRSDHGSSISCQPPA
EIPGYLPADTVHLAVEFFNLTHLPANLLQGASKLQELHLSSNGLESLSPEFLRPVPQLRV
LDLTRNALTGLPPGLFQASATLDTLVLKENQLEVLEVSWLHGLKALGHLDLSGNRLRKLP
PGLLANFTLLRTLDLGENQLETLPPDLLRGPLQLERLHLEGNKLQVLGKDLLLPQPDLRY
LFLNGNKLARVAAGAFQGLRQLDMLDLSNNSLASVPEGLWASLGQPNWDMRDGFDISGNP
WICDQNLSDLYRWLQAQKDKMFSQNDTRCAGPEAVKGQTLLAVAKSQ
Tissue Specificity Plasma.
Reactome Pathway
Neutrophil degranulation (R-HSA-6798695 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Appendicitis DIS4GOLF Definitive Biomarker [1]
Arthritis DIST1YEL Definitive Biomarker [2]
Coronary heart disease DIS5OIP1 Definitive Biomarker [3]
Type-1/2 diabetes DISIUHAP Definitive Biomarker [4]
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [5]
Adult glioblastoma DISVP4LU Strong Biomarker [6]
B-cell neoplasm DISVY326 Strong Altered Expression [7]
Breast cancer DIS7DPX1 Strong Altered Expression [8]
Breast carcinoma DIS2UE88 Strong Altered Expression [8]
Cervical cancer DISFSHPF Strong Biomarker [9]
Cervical carcinoma DIST4S00 Strong Biomarker [9]
Cholangiocarcinoma DIS71F6X Strong Biomarker [10]
Chronic kidney disease DISW82R7 Strong Altered Expression [11]
Colitis DISAF7DD Strong Altered Expression [12]
Colon carcinoma DISJYKUO Strong Biomarker [13]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [14]
Crohn disease DIS2C5Q8 Strong Altered Expression [12]
Diabetic kidney disease DISJMWEY Strong Biomarker [4]
Endometrial cancer DISW0LMR Strong Altered Expression [15]
Endometrial carcinoma DISXR5CY Strong Biomarker [15]
Esophageal squamous cell carcinoma DIS5N2GV Strong Biomarker [16]
Glioblastoma multiforme DISK8246 Strong Biomarker [17]
Glioma DIS5RPEH Strong Altered Expression [18]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [19]
Non-insulin dependent diabetes DISK1O5Z Strong Biomarker [4]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [20]
Obesity DIS47Y1K Strong Biomarker [21]
Oral cancer DISLD42D Strong Biomarker [22]
Pancreatic cancer DISJC981 Strong Biomarker [23]
Pancreatic ductal carcinoma DIS26F9Q Strong Altered Expression [23]
Retinoblastoma DISVPNPB Strong Altered Expression [24]
Stroke DISX6UHX Strong Altered Expression [25]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [26]
Thyroid gland carcinoma DISMNGZ0 Strong Biomarker [27]
Triple negative breast cancer DISAMG6N Strong Biomarker [28]
Ulcerative colitis DIS8K27O Strong Altered Expression [29]
Carcinoma DISH9F1N moderate Biomarker [30]
Colonic neoplasm DISSZ04P moderate Biomarker [31]
Familial adenomatous polyposis DISW53RE moderate Biomarker [31]
Familial adenomatous polyposis 1 DISM44VR moderate Biomarker [31]
Head-neck squamous cell carcinoma DISF7P24 moderate Altered Expression [32]
Osteoarthritis DIS05URM moderate Biomarker [33]
Adenoma DIS78ZEV Limited Biomarker [14]
Colon cancer DISVC52G Limited Biomarker [13]
Inflammatory bowel disease DISGN23E Limited Biomarker [34]
Matthew-Wood syndrome DISA7HR7 Limited Altered Expression [23]
Myocardial infarction DIS655KI Limited Genetic Variation [35]
Neuroblastoma DISVZBI4 Limited Posttranslational Modification [36]
Rheumatoid arthritis DISTSB4J Limited Biomarker [34]
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⏷ Show the Full List of 49 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Leucine-rich alpha-2-glycoprotein (LRG1). [37]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Leucine-rich alpha-2-glycoprotein (LRG1). [38]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Leucine-rich alpha-2-glycoprotein (LRG1). [39]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Leucine-rich alpha-2-glycoprotein (LRG1). [40]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Leucine-rich alpha-2-glycoprotein (LRG1). [41]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Leucine-rich alpha-2-glycoprotein (LRG1). [42]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Leucine-rich alpha-2-glycoprotein (LRG1). [43]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Leucine-rich alpha-2-glycoprotein (LRG1). [44]
Triclosan DMZUR4N Approved Triclosan increases the expression of Leucine-rich alpha-2-glycoprotein (LRG1). [45]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Leucine-rich alpha-2-glycoprotein (LRG1). [46]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Leucine-rich alpha-2-glycoprotein (LRG1). [47]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of Leucine-rich alpha-2-glycoprotein (LRG1). [50]
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⏷ Show the Full List of 12 Drug(s)
2 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 decreases the methylation of Leucine-rich alpha-2-glycoprotein (LRG1). [48]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Leucine-rich alpha-2-glycoprotein (LRG1). [49]
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References

1 A novel noninvasive appendicitis score with a urine biomarker.J Pediatr Surg. 2019 Jan;54(1):91-96. doi: 10.1016/j.jpedsurg.2018.10.025. Epub 2018 Oct 5.
2 Leucine-rich alpha 2 glycoprotein promotes Th17 differentiation and collagen-induced arthritis in mice through enhancement of TGF--Smad2 signaling in nave helper T cells.Arthritis Res Ther. 2017 Jun 14;19(1):137. doi: 10.1186/s13075-017-1349-2.
3 Novel protein biomarkers associated with coronary artery disease in statin-treated patients with familial hypercholesterolemia.J Clin Lipidol. 2017 May-Jun;11(3):682-693. doi: 10.1016/j.jacl.2017.03.014. Epub 2017 Apr 4.
4 LRG1 Promotes Diabetic Kidney Disease Progression by Enhancing TGF--Induced Angiogenesis.J Am Soc Nephrol. 2019 Apr;30(4):546-562. doi: 10.1681/ASN.2018060599. Epub 2019 Mar 11.
5 Leucine-Rich Alpha-2-Glycoprotein1 Gene Interferes with Regulation of Apoptosis in Leukemia KASUMI-1 Cells.Med Sci Monit. 2018 Nov 20;24:8348-8356. doi: 10.12659/MSM.911249.
6 Stable knockdown of LRG1 by RNA interference inhibits growth and promotes apoptosis of glioblastoma cells in vitro and in vivo.Tumour Biol. 2015 Jun;36(6):4271-8. doi: 10.1007/s13277-015-3065-3. Epub 2015 Jan 15.
7 LRG1 promotes proliferation and inhibits apoptosis in colorectal cancer cells via RUNX1 activation.PLoS One. 2017 Apr 4;12(4):e0175122. doi: 10.1371/journal.pone.0175122. eCollection 2017.
8 LRG1 mRNA expression in breast cancer associates with PIK3CA genotype and with aromatase inhibitor therapy outcome.Mol Oncol. 2016 Oct;10(8):1363-73. doi: 10.1016/j.molonc.2016.07.004. Epub 2016 Jul 25.
9 Urinary biomarkers for the diagnosis of cervical cancer by quantitative label-free mass spectrometry analysis.Oncol Lett. 2019 Jun;17(6):5453-5468. doi: 10.3892/ol.2019.10227. Epub 2019 Apr 8.
10 Identification of a serum biomarker panel for the differential diagnosis of cholangiocarcinoma and primary sclerosing cholangitis.Oncotarget. 2018 Apr 3;9(25):17430-17442. doi: 10.18632/oncotarget.24732. eCollection 2018 Apr 3.
11 Plasma Leucine-Rich -2-Glycoprotein 1 Predicts Rapid eGFR Decline and Albuminuria Progression in Type 2 Diabetes Mellitus.J Clin Endocrinol Metab. 2017 Oct 1;102(10):3683-3691. doi: 10.1210/jc.2017-00930.
12 Serum leucine-rich alpha-2 glycoprotein is a disease activity biomarker in ulcerative colitis.Inflamm Bowel Dis. 2012 Nov;18(11):2169-79. doi: 10.1002/ibd.22936. Epub 2012 Feb 28.
13 Serum extracellular vesicles contain SPARC and LRG1 as biomarkers of colon cancer and differ by tumour primary location.EBioMedicine. 2019 Dec;50:211-223. doi: 10.1016/j.ebiom.2019.11.003. Epub 2019 Nov 18.
14 Proteins in stool as biomarkers for non-invasive detection of colorectal adenomas with high risk of progression.J Pathol. 2020 Mar;250(3):288-298. doi: 10.1002/path.5369. Epub 2020 Jan 13.
15 LRG1 is an independent prognostic factor for endometrial carcinoma.Tumour Biol. 2014 Jul;35(7):7125-33. doi: 10.1007/s13277-014-1953-6. Epub 2014 Apr 24.
16 The Clinical Prognostic Value of LRG1 in Esophageal Squamous Cell Carcinoma.Curr Cancer Drug Targets. 2019;19(9):756-763. doi: 10.2174/1568009619666190204095942.
17 Identification of blood biomarkers in glioblastoma by SWATH mass spectrometry and quantitative targeted absolute proteomics.PLoS One. 2018 Mar 7;13(3):e0193799. doi: 10.1371/journal.pone.0193799. eCollection 2018.
18 LRG1 modulates invasion and migration of glioma cell lines through TGF- signaling pathway.Acta Histochem. 2015 Jul;117(6):551-8. doi: 10.1016/j.acthis.2015.05.001. Epub 2015 Jun 3.
19 LRG1 suppresses the migration and invasion of hepatocellular carcinoma cells.Med Oncol. 2015 May;32(5):146. doi: 10.1007/s12032-015-0598-7. Epub 2015 Mar 27.
20 Exosomal Leucine-Rich-Alpha2-Glycoprotein 1 Derived from Non-Small-Cell Lung Cancer Cells Promotes Angiogenesis via TGF- Signal Pathway.Mol Ther Oncolytics. 2019 Aug 7;14:313-322. doi: 10.1016/j.omto.2019.08.001. eCollection 2019 Sep 27.
21 Association of circulating proinflammatory marker, leucine-rich-2-glycoprotein (LRG1), following metabolic/bariatric surgery.Diabetes Metab Res Rev. 2018 Oct;34(7):e3029. doi: 10.1002/dmrr.3029. Epub 2018 Jul 23.
22 Glycoproteomic identification of novel plasma biomarkers for oral cancer.J Food Drug Anal. 2019 Apr;27(2):483-493. doi: 10.1016/j.jfda.2018.12.008. Epub 2019 Jan 8.
23 LRG-1 promotes pancreatic cancer growth and metastasis via modulation of the EGFR/p38 signaling.J Exp Clin Cancer Res. 2019 Feb 13;38(1):75. doi: 10.1186/s13046-019-1088-0.
24 Leucine-Rich -2-Glycoprotein-1 (LRG-1) Expression in Retinoblastoma.Invest Ophthalmol Vis Sci. 2018 Feb 1;59(2):685-692. doi: 10.1167/iovs.17-22785.
25 LRG1 Promotes Apoptosis and Autophagy through the TGF-smad1/5 Signaling Pathway to Exacerbate Ischemia/Reperfusion Injury.Neuroscience. 2019 Aug 10;413:123-134. doi: 10.1016/j.neuroscience.2019.06.008. Epub 2019 Jun 18.
26 Serum leucine-rich 2-glycoprotein is elevated in patients with systemic lupus erythematosus and correlates with disease activity.Clin Chim Acta. 2018 Nov;486:253-258. doi: 10.1016/j.cca.2018.08.020. Epub 2018 Aug 14.
27 LRG? enhances the migration of thyroid carcinoma cells through promotion of the epithelialmesenchymal transition by activating MAPK/p38 signaling.Oncol Rep. 2019 Jun;41(6):3270-3280. doi: 10.3892/or.2019.7123. Epub 2019 Apr 17.
28 Dysregulation of non-histone molecule miR205 and LRG1 post-transcriptional de-regulation by SETD1A in triple negative breast cancer.Mol Biol Rep. 2019 Dec;46(6):6617-6624. doi: 10.1007/s11033-019-05079-w. Epub 2019 Sep 24.
29 Leucine-rich Alpha-2 Glycoprotein is a Serum Biomarker of Mucosal Healing in Ulcerative Colitis.J Crohns Colitis. 2017 Jan;11(1):84-91. doi: 10.1093/ecco-jcc/jjw132. Epub 2016 Jul 27.
30 Electrochemical peptide sensor for diagnosing adenoma-carcinoma transition in colon cancer.Biosens Bioelectron. 2017 Dec 15;98:330-337. doi: 10.1016/j.bios.2017.07.013. Epub 2017 Jul 6.
31 The concentrations of EGFR, LRG1, ITIH4, and F5 in serum correlate with the number of colonic adenomas in ApcPirc/+ rats.Cancer Prev Res (Phila). 2014 Nov;7(11):1160-9. doi: 10.1158/1940-6207.CAPR-14-0056. Epub 2014 Sep 8.
32 Downregulation of leucinerich?glycoprotein1 expression is associated with the tumorigenesis of head and neck squamous cell carcinoma.Oncol Rep. 2017 Mar;37(3):1503-1510. doi: 10.3892/or.2017.5377. Epub 2017 Jan 17.
33 TNF--induced LRG1 promotes angiogenesis and mesenchymal stem cell migration in the subchondral bone during osteoarthritis.Cell Death Dis. 2017 Mar 30;8(3):e2715. doi: 10.1038/cddis.2017.129.
34 Leucine rich -2 glycoprotein is a potential urinary biomarker for renal tubular injury.Biochem Biophys Res Commun. 2018 Apr 15;498(4):1045-1051. doi: 10.1016/j.bbrc.2018.03.111. Epub 2018 Mar 17.
35 Screening and Identification of Pregnancy Zone Protein and Leucine-Rich Alpha-2-Glycoprotein as Potential Serum Biomarkers for Early-Onset Myocardial Infarction using Protein Profile Analysis.Proteomics Clin Appl. 2019 May;13(3):e1800079. doi: 10.1002/prca.201800079. Epub 2018 Nov 28.
36 MiRNA-335 suppresses neuroblastoma cell invasiveness by direct targeting of multiple genes from the non-canonical TGF- signalling pathway.Carcinogenesis. 2012 May;33(5):976-85. doi: 10.1093/carcin/bgs114. Epub 2012 Mar 1.
37 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.
38 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
39 Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
40 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
41 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
42 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
43 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
44 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
45 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
46 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
47 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
48 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.
49 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
50 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.