Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLXM6WI)

DOT Name	Galactoside alpha-(1,2)-fucosyltransferase 2 (FUT2)
Synonyms	Alpha(1,2)FT 2; Fucosyltransferase 2; GDP-L-fucose:beta-D-galactoside 2-alpha-L-fucosyltransferase 2; SE2; Secretor blood group alpha-2-fucosyltransferase; Secretor factor; Se; Type 1 galactoside alpha-(1,2)-fucosyltransferase FUT2; EC 2.4.1.69; Type 2 galactoside alpha-(1,2)-fucosyltransferase FUT2; EC 2.4.1.344
Gene Name	FUT2
Related Disease	Non-insulin dependent diabetes ( ) Pneumonia ( ) Advanced cancer ( ) Autoimmune disease ( ) Behcet disease ( ) Breast cancer ( ) Breast carcinoma ( ) Cardiovascular disease ( ) Cholangiocarcinoma ( ) Coeliac disease ( ) Colon carcinoma ( ) Colorectal carcinoma ( ) Crohn disease ( ) Gastric cancer ( ) Graves disease ( ) Hepatocellular carcinoma ( ) HIV infectious disease ( ) Lung adenocarcinoma ( ) Lung cancer ( ) Lung carcinoma ( ) Neoplasm ( ) Oral cancer ( ) Pancreatic tumour ( ) Primary sclerosing cholangitis ( ) Psoriasis ( ) Stomach cancer ( ) Type-1 diabetes ( ) Ulcerative colitis ( ) Anemia ( ) Autoimmune disease, susceptibility to, 6 ( ) Autoimmune thyroid disease ( ) Common variable immunodeficiency ( ) Graft-versus-host disease ( ) Influenza ( ) Juvenile idiopathic arthritis ( ) Osteoarthritis ( ) STAT3-related early-onset multisystem autoimmune disease ( ) Systemic lupus erythematosus ( ) Ankylosing spondylitis ( ) Melanoma ( ) Metastatic melanoma ( ) Sclerosing cholangitis ( ) Type-1/2 diabetes ( )
UniProt ID	FUT2_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	2.4.1.344; 2.4.1.69
Pfam ID	PF01531
Sequence	MLVVQMPFSFPMAHFILFVFTVSTIFHVQQRLAKIQAMWELPVQIPVLASTSKALGPSQL RGMWTINAIGRLGNQMGEYATLYALAKMNGRPAFIPAQMHSTLAPIFRITLPVLHSATAS RIPWQNYHLNDWMEEEYRHIPGEYVRFTGYPCSWTFYHHLRQEILQEFTLHDHVREEAQK FLRGLQVNGSRPGTFVGVHVRRGDYVHVMPKVWKGVVADRRYLQQALDWFRARYSSLIFV VTSNGMAWCRENIDTSHGDVVFAGDGIEGSPAKDFALLTQCNHTIMTIGTFGIWAAYLTG GDTIYLANYTLPDSPFLKIFKPEAAFLPEWTGIAADLSPLLKH
Function	Catalyzes the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the terminal galactose on both O- and N-linked glycans chains of cell surface glycoproteins and glycolipids and the resulting epitope regulates several processes such as cell-cell interaction including host-microbe interaction, cell surface expression and cell proliferation. Preferentially fucosylates gangliosides GA1 and GM1 in the antrum, cecum and colon and in the female reproductive organs. Fucosylated host glycoproteins or glycolipids mediate interaction with intestinal microbiota influencing its composition. Creates a soluble precursor oligosaccharide FuC-alpha ((1,2)Galbeta-) called the H antigen which is an essential substrate for the final step in the soluble ABO blood group antigen synthesis pathway.
Tissue Specificity	Small intestine, colon and lung.
KEGG Pathway	Glycosphingolipid biosynthesis - lacto and neolacto series (hsa00601 ) Glycosphingolipid biosynthesis - globo and isoglobo series (hsa00603 ) Metabolic pathways (hsa01100 )
Reactome Pathway	Lewis blood group biosynthesis (R-HSA-9037629 ) ABO blood group biosynthesis (R-HSA-9033807 )
BioCyc Pathway	MetaCyc:HS11104-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[1]
Pneumonia	DIS8EF3M	Definitive	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[4]
Behcet disease	DISSYMBS	Strong	Genetic Variation	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[7]
Cholangiocarcinoma	DIS71F6X	Strong	Genetic Variation	[8]
Coeliac disease	DISIY60C	Strong	Genetic Variation	[9]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[11]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[12]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[13]
Graves disease	DISU4KOQ	Strong	Genetic Variation	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[15]
HIV infectious disease	DISO97HC	Strong	Genetic Variation	[16]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[3]
Lung cancer	DISCM4YA	Strong	Biomarker	[17]
Lung carcinoma	DISTR26C	Strong	Biomarker	[17]
Neoplasm	DISZKGEW	Strong	Altered Expression	[18]
Oral cancer	DISLD42D	Strong	Genetic Variation	[19]
Pancreatic tumour	DIS3U0LK	Strong	Altered Expression	[20]
Primary sclerosing cholangitis	DISTH5WJ	Strong	Genetic Variation	[21]
Psoriasis	DIS59VMN	Strong	Biomarker	[22]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[13]
Type-1 diabetes	DIS7HLUB	Strong	Biomarker	[23]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[24]
Anemia	DISTVL0C	moderate	Genetic Variation	[25]
Autoimmune disease, susceptibility to, 6	DISHNUXI	moderate	Genetic Variation	[9]
Autoimmune thyroid disease	DISIHC6A	moderate	Genetic Variation	[9]
Common variable immunodeficiency	DISHE7JQ	moderate	Genetic Variation	[9]
Graft-versus-host disease	DIS0QADF	moderate	Genetic Variation	[26]
Influenza	DIS3PNU3	moderate	Altered Expression	[4]
Juvenile idiopathic arthritis	DISQZGBV	moderate	Genetic Variation	[9]
Osteoarthritis	DIS05URM	moderate	Biomarker	[27]
STAT3-related early-onset multisystem autoimmune disease	DISAXTN7	moderate	Genetic Variation	[9]
Systemic lupus erythematosus	DISI1SZ7	moderate	Genetic Variation	[9]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[28]
Melanoma	DIS1RRCY	Limited	Altered Expression	[29]
Metastatic melanoma	DISSL43L	Limited	Biomarker	[30]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[28]
Type-1/2 diabetes	DISIUHAP	Limited	Genetic Variation	[23]
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⏷ Show the Full List of 43 Disease(s)

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
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Galactoside alpha-(1,2)-fucosyltransferase 2 (FUT2).	[31]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Galactoside alpha-(1,2)-fucosyltransferase 2 (FUT2).	[32]
Ganoderic acid A	DM42EVG	Investigative	Ganoderic acid A decreases the expression of Galactoside alpha-(1,2)-fucosyltransferase 2 (FUT2).	[33]
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References

1	Are serum concentrations of vitamin B-12 causally related to cardiometabolic risk factors and disease? A Mendelian randomization study.Am J Clin Nutr. 2018 Aug 1;108(2):398-404. doi: 10.1093/ajcn/nqy101.
2	FUT2 Genetic Variants and Reported Respiratory and Gastrointestinal Illnesses During Infancy.J Infect Dis. 2019 Feb 15;219(5):836-843. doi: 10.1093/infdis/jiy582.
3	Fucosyltransferase 2 induced epithelial-mesenchymal transition via TGF-/Smad signaling pathway in lung adenocarcinaoma.Exp Cell Res. 2018 Sep 15;370(2):613-622. doi: 10.1016/j.yexcr.2018.07.026. Epub 2018 Jul 18.
4	FUT2 Variants Confer Susceptibility to Familial Otitis Media.Am J Hum Genet. 2018 Nov 1;103(5):679-690. doi: 10.1016/j.ajhg.2018.09.010. Epub 2018 Oct 25.
5	FUT2: filling the gap between genes and environment in Behet's disease?.Ann Rheum Dis. 2015 Mar;74(3):618-24. doi: 10.1136/annrheumdis-2013-204475. Epub 2013 Dec 10.
6	Expression of Globo H and SSEA3 in breast cancer stem cells and the involvement of fucosyl transferases 1 and 2 in Globo H synthesis.Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11667-72. doi: 10.1073/pnas.0804979105. Epub 2008 Aug 6.
7	Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
8	FUT2 and FUT3 genotype determines CA19-9 cut-off values for detection of cholangiocarcinoma in patients with primary sclerosing cholangitis.J Hepatol. 2013 Dec;59(6):1278-84. doi: 10.1016/j.jhep.2013.08.005. Epub 2013 Aug 16.
9	Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.Nat Med. 2015 Sep;21(9):1018-27. doi: 10.1038/nm.3933. Epub 2015 Aug 24.
10	Increase of rat colon carcinoma cells tumorigenicity by alpha(1-2) fucosyltransferase gene transfection.Glycobiology. 1997 Mar;7(2):221-9. doi: 10.1093/glycob/7.2.221.
11	Genetic variations affecting serum carcinoembryonic antigen levels and status of regional lymph nodes in patients with sporadic colorectal cancer from Southern China.PLoS One. 2014 Jun 18;9(6):e97923. doi: 10.1371/journal.pone.0097923. eCollection 2014.
12	Association of FUT2 and ABO with Crohn's disease in Koreans.J Gastroenterol Hepatol. 2020 Jan;35(1):104-109. doi: 10.1111/jgh.14766. Epub 2019 Aug 7.
13	Variation at ABO histo-blood group and FUT loci and diffuse and intestinal gastric cancer risk in a European population.Int J Cancer. 2015 Feb 15;136(4):880-93. doi: 10.1002/ijc.29034. Epub 2014 Jul 1.
14	Evidence for a new Graves disease susceptibility locus at chromosome 18q21.Am J Hum Genet. 2000 May;66(5):1710-4. doi: 10.1086/302908. Epub 2000 Apr 3.
15	Downregulation of microRNA-15b by hepatitis B virus X enhances hepatocellular carcinoma proliferation via fucosyltransferase 2-induced Globo H expression.Int J Cancer. 2014 Apr 1;134(7):1638-47. doi: 10.1002/ijc.28501. Epub 2013 Oct 15.
16	Secretor polymorphism and human immunodeficiency virus infection in Senegalese women.J Infect Dis. 2000 Feb;181(2):737-9. doi: 10.1086/315234.
17	Clinical significance and biological function of fucosyltransferase 2 in lung adenocarcinoma.Oncotarget. 2017 Oct 19;8(57):97246-97259. doi: 10.18632/oncotarget.21896. eCollection 2017 Nov 14.
18	Effects of ABO and FUT2 genetic transcription absence on ABH histo-blood group antigen expression in lung cancer patients.Asian Pac J Cancer Prev. 2011;12(12):3201-6.
19	Combinations of FUT2 gene polymorphisms and environmental factors are associated with oral cancer risk.Tumour Biol. 2016 May;37(5):6647-52. doi: 10.1007/s13277-015-4367-1. Epub 2015 Dec 8.
20	Hypoxia inducible factor 1 down regulates cell surface expression of 1,2-fucosylated glycans in human pancreatic adenocarcinoma cells.FEBS Lett. 2015 Aug 19;589(18):2359-66. doi: 10.1016/j.febslet.2015.07.035. Epub 2015 Jul 29.
21	Knockout of the primary sclerosing cholangitis-risk gene Fut2 causes liver disease in mice.Hepatology. 2017 Aug;66(2):542-554. doi: 10.1002/hep.29029. Epub 2017 Jun 19.
22	Genotypic variability-based genome-wide association study identifies non-additive loci HLA-C and IL12B for psoriasis.J Hum Genet. 2018 Mar;63(3):289-296. doi: 10.1038/s10038-017-0350-6. Epub 2017 Dec 19.
23	FUT2 non-secretor status is associated with Type 1 diabetes susceptibility in Japanese children.Diabet Med. 2017 Apr;34(4):586-589. doi: 10.1111/dme.13288. Epub 2016 Dec 15.
24	Association of Fucosyltransferase 2 Gene Variant with Inflammatory Bowel Diseases: A Meta-Analysis.Med Sci Monit. 2019 Jan 7;25:184-192. doi: 10.12659/MSM.911857.
25	Gastric intrinsic factor deficiency with combined GIF heterozygous mutations and FUT2 secretor variant.Biochimie. 2013 May;95(5):995-1001. doi: 10.1016/j.biochi.2013.01.022. Epub 2013 Feb 8.
26	A Genetic Modifier of the Gut Microbiome Influences the Risk of Graft-versus-Host Disease and Bacteremia After Hematopoietic Stem Cell Transplantation.Biol Blood Marrow Transplant. 2016 Mar;22(3):418-22. doi: 10.1016/j.bbmt.2015.11.017. Epub 2015 Nov 28.
27	Long non-coding RNA HOTAIR promotes osteoarthritis progression via miR-17-5p/FUT2/-catenin axis.Cell Death Dis. 2018 Jun 15;9(7):711. doi: 10.1038/s41419-018-0746-z.
28	Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.Nat Genet. 2016 May;48(5):510-8. doi: 10.1038/ng.3528. Epub 2016 Mar 14.
29	The fucose salvage pathway inhibits invadopodia formation and extracellular matrix degradation in melanoma cells.PLoS One. 2018 Jun 20;13(6):e0199128. doi: 10.1371/journal.pone.0199128. eCollection 2018.
30	A Systems Biology Approach Identifies FUT8 as a Driver of Melanoma Metastasis.Cancer Cell. 2017 Jun 12;31(6):804-819.e7. doi: 10.1016/j.ccell.2017.05.007.
31	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.
32	CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
33	Ganoderic Acid A improves high fat diet-induced obesity, lipid accumulation and insulin sensitivity through regulating SREBP pathway. Chem Biol Interact. 2018 Jun 25;290:77-87.