Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKQCG0H)

DOT Name Galectin-4 (LGALS4)
Synonyms Gal-4; Antigen NY-CO-27; L-36 lactose-binding protein; L36LBP; Lactose-binding lectin 4
Gene Name LGALS4
Related Disease
Matthew-Wood syndrome ( )
Pancreatic cancer ( )
Type-1/2 diabetes ( )
Adenocarcinoma ( )
Adenoma ( )
Advanced cancer ( )
Al amyloidosis ( )
Alzheimer disease ( )
Astrocytoma ( )
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Burkitt lymphoma ( )
Campomelic dysplasia ( )
Carcinoma ( )
Castration-resistant prostate carcinoma ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Craniometaphyseal dysplasia, autosomal dominant ( )
Crohn disease ( )
Endometriosis ( )
Familial adenomatous polyposis ( )
Fragile X syndrome ( )
Hepatitis B virus infection ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
Herpes simplex infection ( )
Lung adenocarcinoma ( )
Neoplasm ( )
Pancreatic ductal carcinoma ( )
Parkinson disease ( )
Prostate cancer ( )
Prostate carcinoma ( )
Transitional cell carcinoma ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Urothelial carcinoma ( )
Amyotrophic lateral sclerosis ( )
Colon adenocarcinoma ( )
Colonic neoplasm ( )
Diphtheria ( )
Nervous system inflammation ( )
Neuroblastoma ( )
Pancreatic adenocarcinoma ( )
Ulcerative colitis ( )
Young-onset Parkinson disease ( )
UniProt ID
LEG4_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1X50; 4XZP; 4YLZ; 4YM0; 4YM1; 4YM2; 4YM3; 5CBL; 5DUU; 5DUV; 5DUW; 5DUX; 6WAB
Pfam ID
PF00337
Sequence
MAYVPAPGYQPTYNPTLPYYQPIPGGLNVGMSVYIQGVASEHMKRFFVNFVVGQDPGSDV
AFHFNPRFDGWDKVVFNTLQGGKWGSEERKRSMPFKKGAAFELVFIVLAEHYKVVVNGNP
FYEYGHRLPLQMVTHLQVDGDLQLQSINFIGGQPLRPQGPPMMPPYPGPGHCHQQLNSLP
TMEGPPTFNPPVPYFGRLQGGLTARRTIIIKGYVPPTGKSFAINFKVGSSGDIALHINPR
MGNGTVVRNSLLNGSWGSEEKKITHNPFGPGQFFDLSIRCGLDRFKVYANGQHLFDFAHR
LSAFQRVDTLEIQGDVTLSYVQI
Function Galectin that binds lactose and a related range of sugars. May be involved in the assembly of adherens junctions.

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Matthew-Wood syndrome DISA7HR7 Definitive Biomarker [1]
Pancreatic cancer DISJC981 Definitive Biomarker [2]
Type-1/2 diabetes DISIUHAP Definitive Genetic Variation [3]
Adenocarcinoma DIS3IHTY Strong Biomarker [4]
Adenoma DIS78ZEV Strong Altered Expression [5]
Advanced cancer DISAT1Z9 Strong Biomarker [6]
Al amyloidosis DISMHVSL Strong Altered Expression [7]
Alzheimer disease DISF8S70 Strong Altered Expression [8]
Astrocytoma DISL3V18 Strong Altered Expression [9]
Bladder cancer DISUHNM0 Strong Altered Expression [10]
Breast cancer DIS7DPX1 Strong Altered Expression [11]
Breast carcinoma DIS2UE88 Strong Altered Expression [11]
Breast neoplasm DISNGJLM Strong Altered Expression [12]
Burkitt lymphoma DIS9D5XU Strong Altered Expression [13]
Campomelic dysplasia DISVTW53 Strong Biomarker [14]
Carcinoma DISH9F1N Strong Altered Expression [15]
Castration-resistant prostate carcinoma DISVGAE6 Strong Biomarker [16]
Colon carcinoma DISJYKUO Strong Altered Expression [17]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [18]
Craniometaphyseal dysplasia, autosomal dominant DISU12OO Strong Biomarker [14]
Crohn disease DIS2C5Q8 Strong Altered Expression [19]
Endometriosis DISX1AG8 Strong Altered Expression [20]
Familial adenomatous polyposis DISW53RE Strong Altered Expression [21]
Fragile X syndrome DISE8W3A Strong Genetic Variation [22]
Hepatitis B virus infection DISLQ2XY Strong Altered Expression [23]
Hepatitis C virus infection DISQ0M8R Strong Genetic Variation [24]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [23]
Herpes simplex infection DISL1SAV Strong Biomarker [25]
Lung adenocarcinoma DISD51WR Strong Altered Expression [26]
Neoplasm DISZKGEW Strong Biomarker [6]
Pancreatic ductal carcinoma DIS26F9Q Strong Altered Expression [27]
Parkinson disease DISQVHKL Strong Biomarker [28]
Prostate cancer DISF190Y Strong Biomarker [16]
Prostate carcinoma DISMJPLE Strong Biomarker [16]
Transitional cell carcinoma DISWVVDR Strong Biomarker [29]
Urinary bladder cancer DISDV4T7 Strong Altered Expression [10]
Urinary bladder neoplasm DIS7HACE Strong Altered Expression [10]
Urothelial carcinoma DISRTNTN Strong Biomarker [29]
Amyotrophic lateral sclerosis DISF7HVM Limited Genetic Variation [30]
Colon adenocarcinoma DISDRE0J Limited Biomarker [31]
Colonic neoplasm DISSZ04P Limited Altered Expression [32]
Diphtheria DISZWM55 Limited Genetic Variation [33]
Nervous system inflammation DISB3X5A Limited Biomarker [34]
Neuroblastoma DISVZBI4 Limited Biomarker [35]
Pancreatic adenocarcinoma DISKHX7S Limited Genetic Variation [18]
Ulcerative colitis DIS8K27O Limited Altered Expression [36]
Young-onset Parkinson disease DIS05LFS Limited Biomarker [37]
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⏷ Show the Full List of 47 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Paclitaxel DMLB81S Approved Galectin-4 (LGALS4) decreases the response to substance of Paclitaxel. [45]
Capecitabine DMTS85L Approved Galectin-4 (LGALS4) increases the response to substance of Capecitabine. [45]
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6 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 Galectin-4 (LGALS4). [38]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Galectin-4 (LGALS4). [39]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Galectin-4 (LGALS4). [40]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Galectin-4 (LGALS4). [41]
Amphotericin B DMTAJQE Approved Amphotericin B increases the expression of Galectin-4 (LGALS4). [43]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Galectin-4 (LGALS4). [44]
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⏷ Show the Full List of 6 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Fulvestrant DM0YZC6 Approved Fulvestrant increases the methylation of Galectin-4 (LGALS4). [42]
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References

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2 Galectin 4 is a biomarker for early recurrence and death after surgical resection for pancreatic ductal adenocarcinoma.Scand J Gastroenterol. 2019 Jan;54(1):95-100. doi: 10.1080/00365521.2018.1561937. Epub 2019 Jan 20.
3 Using a Targeted Proteomics Chip to Explore Pathophysiological Pathways for Incident Diabetes- The Malm Preventive Project.Sci Rep. 2019 Jan 22;9(1):272. doi: 10.1038/s41598-018-36512-y.
4 Strategies and limitations associated with in vitro characterization of vitamin D receptor activators.Biochem Pharmacol. 2018 Sep;155:547-561. doi: 10.1016/j.bcp.2018.07.015. Epub 2018 Jul 18.
5 Abrogation of galectin-4 expression promotes tumorigenesis in colorectal cancer.Cell Oncol (Dordr). 2013 Apr;36(2):169-78. doi: 10.1007/s13402-013-0124-x. Epub 2013 Feb 2.
6 Detection of malignancy-associated phosphoproteome changes in human colorectal cancer induced by cell surface binding of growth-inhibitory galectin-4.IUBMB Life. 2019 Mar;71(3):364-375. doi: 10.1002/iub.1987. Epub 2018 Dec 14.
7 Zebrafish model of amyloid light chain cardiotoxicity: regeneration versus degeneration.Am J Physiol Heart Circ Physiol. 2019 May 1;316(5):H1158-H1166. doi: 10.1152/ajpheart.00788.2018. Epub 2019 Mar 15.
8 Targeted Downregulation of kdm4a Ameliorates Tau-engendered Defects in Drosophila melanogaster.J Korean Med Sci. 2019 Aug 26;34(33):e225. doi: 10.3346/jkms.2019.34.e225.
9 The IE2 regulatory protein of human cytomegalovirus induces expression of the human transforming growth factor beta1 gene through an Egr-1 binding site.J Virol. 1996 Oct;70(10):7062-70. doi: 10.1128/JVI.70.10.7062-7070.1996.
10 An enhanced hTERT promoter-driven CRISPR/Cas9 system selectively inhibits the progression of bladder cancer cells.Mol Biosyst. 2017 Aug 22;13(9):1713-1721. doi: 10.1039/c7mb00354d.
11 Bisected, complex N-glycans and galectins in mouse mammary tumor progression and human breast cancer.Glycobiology. 2013 Dec;23(12):1477-90. doi: 10.1093/glycob/cwt075. Epub 2013 Sep 13.
12 The FEL (AF-4) protein donates transcriptional activation sequences to Hrx-Fel fusion proteins in leukemias containing T(4;11)(Q21;Q23) chromosomal translocations.Leuk Res. 1997 Oct;21(10):911-7. doi: 10.1016/s0145-2126(97)00012-x.
13 Ongoing mutations in the N-terminal domain of c-Myc affect transactivation in Burkitt's lymphoma cell lines.Oncogene. 1994 Mar;9(3):759-63.
14 Protein biomarkers and coronary microvascular dilatation assessed by rubidium-82 PET in women with angina pectoris and no obstructive coronary artery disease.Atherosclerosis. 2018 Aug;275:319-327. doi: 10.1016/j.atherosclerosis.2018.06.864. Epub 2018 Jun 19.
15 Galectin-4 functions as a tumor suppressor of human colorectal cancer.Int J Cancer. 2011 Aug 15;129(4):799-809. doi: 10.1002/ijc.25750. Epub 2010 Dec 9.
16 O-Glycosylation-mediated signaling circuit drives metastatic castration-resistant prostate cancer.FASEB J. 2018 Jun 15:fj201800687. doi: 10.1096/fj.201800687. Online ahead of print.
17 Cloning and expression of the mRNA of human galectin-4, an S-type lectin down-regulated in colorectal cancer.Eur J Biochem. 1997 Aug 15;248(1):225-30. doi: 10.1111/j.1432-1033.1997.00225.x.
18 Promoter hypermethylation of LGALS4 correlates with poor prognosis in patients with urothelial carcinoma.Oncotarget. 2017 Apr 4;8(14):23787-23802. doi: 10.18632/oncotarget.15865.
19 Galectin-4 interacts with the drug transporter human concentrative nucleoside transporter 3 to regulate its function.FASEB J. 2016 Feb;30(2):544-54. doi: 10.1096/fj.15-272773. Epub 2015 Oct 19.
20 Nuclear peroxisome proliferator-activated receptors alpha and gamma have opposing effects on monocyte chemotaxis in endometriosis.J Clin Endocrinol Metab. 2001 Jul;86(7):3108-14. doi: 10.1210/jcem.86.7.7615.
21 A mammalian two-hybrid system for adenomatous polyposis coli-mutated colon cancer therapeutics.Cancer Res. 2001 Feb 1;61(3):854-8.
22 Application of Drosophila Model Toward Understanding the Molecular Basis of Fragile X Syndrome.Methods Mol Biol. 2019;1942:141-153. doi: 10.1007/978-1-4939-9080-1_12.
23 Galectin-4 serves as a prognostic biomarker for the early recurrence / metastasis of hepatocellular carcinoma.Cancer Sci. 2014 Nov;105(11):1510-7. doi: 10.1111/cas.12536. Epub 2014 Oct 27.
24 Hepatitis C virus nonstructural region 5A protein is a potent transcriptional activator.J Virol. 1997 Nov;71(11):8856-9. doi: 10.1128/JVI.71.11.8856-8859.1997.
25 Development of a Reporter System Monitoring Regulated Intramembrane Proteolysis of the Transmembrane bZIP Transcription Factor ATF6.Mol Cells. 2019 Nov 30;42(11):783-793. doi: 10.14348/molcells.2019.0104.
26 Inverse correlation between galectin-4 and TTF-1 in lung adenocarcinoma.Virchows Arch. 2017 Sep;471(3):375-382. doi: 10.1007/s00428-017-2202-3. Epub 2017 Jul 19.
27 Profiling of different pancreatic cancer cells used as models for metastatic behaviour shows large variation in their N-glycosylation.Sci Rep. 2017 Nov 30;7(1):16623. doi: 10.1038/s41598-017-16811-6.
28 Modeling Parkinson's disease in adult Drosophila.J Neurosci Methods. 2019 Jan 1;311:89-94. doi: 10.1016/j.jneumeth.2018.10.018. Epub 2018 Oct 15.
29 LGALS4 as a Prognostic Factor in Urothelial Carcinoma of Bladder Affects Cell Functions.Technol Cancer Res Treat. 2019 Jan 1;18:1533033819876601. doi: 10.1177/1533033819876601.
30 Expression of human FUS protein in Drosophila leads to progressive neurodegeneration.Protein Cell. 2011 Jun;2(6):477-86. doi: 10.1007/s13238-011-1065-7. Epub 2011 Jul 12.
31 Strikingly different localization of galectin-3 and galectin-4 in human colon adenocarcinoma T84 cells. Galectin-4 is localized at sites of cell adhesion.J Biol Chem. 1997 May 30;272(22):14294-303. doi: 10.1074/jbc.272.22.14294.
32 Integrative genomic approaches to dissect clinically-significant relationships between the VDR cistrome and gene expression in primary colon cancer.J Steroid Biochem Mol Biol. 2017 Oct;173:130-138. doi: 10.1016/j.jsbmb.2016.12.013. Epub 2016 Dec 24.
33 A multi-domain protein system based on the HC fragment of tetanus toxin for targeting DNA to neuronal cells.J Drug Target. 2003 Jul;11(6):333-43. doi: 10.1080/1061186310001634667.
34 Galectin-4, a Negative Regulator of Oligodendrocyte Differentiation, Is Persistently Present in Axons and Microglia/Macrophages in Multiple Sclerosis Lesions.J Neuropathol Exp Neurol. 2018 Nov 1;77(11):1024-1038. doi: 10.1093/jnen/nly081.
35 Novel Notch signaling inhibitor NSI? suppresses nuclear translocation of the Notch intracellular domain.Int J Mol Med. 2019 Oct;44(4):1574-1584. doi: 10.3892/ijmm.2019.4280. Epub 2019 Jul 19.
36 Immunohistochemical Studies on Galectin Expression in Colectomised Patients with Ulcerative Colitis. Biomed Res Int. 2016;2016:5989128.
37 Overexpression of Buffy enhances the loss of parkin and suppresses the loss of Pink1 phenotypes in Drosophila.Genome. 2017 Mar;60(3):241-247. doi: 10.1139/gen-2016-0165. Epub 2016 Dec 22.
38 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.
39 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.
40 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
41 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.
42 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.
43 Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
44 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.
45 Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.