Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTODG57A)

• DOT Name: Galactoside alpha-(1,2)-fucosyltransferase 1 (FUT1)
• Synonyms: Alpha(1,2)FT 1; Blood group H alpha 2-fucosyltransferase; Fucosyltransferase 1; GDP-L-fucose:beta-D-galactoside 2-alpha-L-fucosyltransferase 1; Type 1 galactoside alpha-(1,2)-fucosyltransferase FUT1; EC 2.4.1.69; Type 2 galactoside alpha-(1,2)-fucosyltransferase FUT1; EC 2.4.1.344
• Gene Name: FUT1
• Related Disease:
  Cognitive impairment
  Myelodysplastic syndrome
  Wiskott-Aldrich syndrome
  Breast cancer
  Breast carcinoma
  Carcinoma
  Cholangiocarcinoma
  Chronic myelomonocytic leukaemia
  Colonic neoplasm
  Colorectal carcinoma
  Epithelial ovarian cancer
  Gastric cancer
  Head-neck squamous cell carcinoma
  Hematologic disease
  Hepatitis C virus infection
  Hepatocellular carcinoma
  leukaemia
  Lung cancer
  Myeloproliferative neoplasm
  Oral cancer
  Osteoarthritis
  Ovarian cancer
  Ovarian neoplasm
  Pancytopenia
  Plasma cell myeloma
  Promyelocytic leukaemia
  Prostate cancer
  Prostate carcinoma
  Squamous cell carcinoma
  Stomach cancer
  T-B+ severe combined immunodeficiency due to gamma chain deficiency
  Autoimmune disease
  Cutaneous squamous cell carcinoma
  Cystic fibrosis
  HIV infectious disease
  Leukemia
  Liver cirrhosis
  Lysosomal storage disease
  Mucopolysaccharidosis I
  Severe combined immunodeficiency
  Stroke
  Arthritis
  Colon cancer
  Colon carcinoma
  Hemoglobinopathy
  Lung adenocarcinoma
  Lung carcinoma
  Melanoma
  Sickle-cell anaemia
• UniProt ID: FUT1_HUMAN
• EC Number: 2.4.1.344; 2.4.1.69
• Pfam ID: PF01531
• Sequence:
  MWLRSHRQLCLAFLLVCVLSVIFFLHIHQDSFPHGLGLSILCPDRRLVTPPVAIFCLPGT
  AMGPNASSSCPQHPASLSGTWTVYPNGRFGNQMGQYATLLALAQLNGRRAFILPAMHAAL
  APVFRITLPVLAPEVDSRTPWRELQLHDWMSEEYADLRDPFLKLSGFPCSWTFFHHLREQ
  IRREFTLHDHLREEAQSVLGQLRLGRTGDRPRTFVGVHVRRGDYLQVMPQRWKGVVGDSA
  YLRQAMDWFRARHEAPVFVVTSNGMEWCKENIDTSQGDVTFAGDGQEATPWKDFALLTQC
  NHTIMTIGTFGFWAAYLAGGDTVYLANFTLPDSEFLKIFKPEAAFLPEWVGINADLSPLW
  TLAKP
• Function: Catalyzes the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the terminal galactose residue of glycoconjugates through an alpha(1,2) linkage leading to H antigen synthesis that is an intermediate substrate in the synthesis of ABO blood group antigens. H antigen is essential for maturation of the glomerular layer of the main olfactory bulb, in cell migration and early cell-cell contacts during tumor associated angiogenesis. Preferentially fucosylates soluble lactose and to a lesser extent fucosylates glycolipids gangliosides GA1 and GM1a.
• KEGG Pathway:
  Glycosphingolipid biosynthesis - lacto and neolacto series (hsa00601)
  Glycosphingolipid biosynthesis - globo and isoglobo series (hsa00603)
  Metabolic pathways (hsa01100)
• Reactome Pathway: ABO blood group biosynthesis (R-HSA-9033807)
• BioCyc Pathway: MetaCyc:HS10855-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cognitive impairment	DISH2ERD	Definitive	Genetic Variation	[1]
Myelodysplastic syndrome	DISYHNUI	Definitive	Altered Expression	[2]
Wiskott-Aldrich syndrome	DISATMDB	Definitive	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Carcinoma	DISH9F1N	Strong	Altered Expression	[5]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[6]
Chronic myelomonocytic leukaemia	DISDN5P7	Strong	Genetic Variation	[7]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[10]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[11]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[12]
Hematologic disease	DIS9XD9A	Strong	Biomarker	[13]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[15]
leukaemia	DISS7D1V	Strong	Biomarker	[16]
Lung cancer	DISCM4YA	Strong	Biomarker	[17]
Myeloproliferative neoplasm	DIS5KAPA	Strong	Genetic Variation	[7]
Oral cancer	DISLD42D	Strong	Biomarker	[18]
Osteoarthritis	DIS05URM	Strong	Biomarker	[19]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[5]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[5]
Pancytopenia	DISVKEHV	Strong	Biomarker	[20]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[21]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[22]
Prostate cancer	DISF190Y	Strong	Biomarker	[23]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[23]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[24]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[11]
T-B+ severe combined immunodeficiency due to gamma chain deficiency	DISDB6K2	Strong	Genetic Variation	[25]
Autoimmune disease	DISORMTM	moderate	Biomarker	[26]
Cutaneous squamous cell carcinoma	DIS3LXUG	moderate	Biomarker	[27]
Cystic fibrosis	DIS2OK1Q	moderate	Altered Expression	[28]
HIV infectious disease	DISO97HC	moderate	Biomarker	[29]
Leukemia	DISNAKFL	moderate	Biomarker	[30]
Liver cirrhosis	DIS4G1GX	moderate	Biomarker	[31]
Lysosomal storage disease	DIS6QM6U	moderate	Genetic Variation	[32]
Mucopolysaccharidosis I	DISTS29G	moderate	Biomarker	[33]
Severe combined immunodeficiency	DIS6MF4Q	moderate	Genetic Variation	[34]
Stroke	DISX6UHX	moderate	Biomarker	[35]
Arthritis	DIST1YEL	Disputed	Biomarker	[36]
Colon cancer	DISVC52G	Limited	Genetic Variation	[37]
Colon carcinoma	DISJYKUO	Limited	Genetic Variation	[37]
Hemoglobinopathy	DISCT4GX	Limited	Genetic Variation	[38]
Lung adenocarcinoma	DISD51WR	Limited	Genetic Variation	[37]
Lung carcinoma	DISTR26C	Limited	Biomarker	[17]
Melanoma	DIS1RRCY	Limited	Altered Expression	[39]
Sickle-cell anaemia	DIS5YNZB	Limited	Genetic Variation	[40]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Galactoside alpha-(1,2)-fucosyltransferase 1 (FUT1) affects the response to substance of Fluorouracil.	[55]

14 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Galactoside alpha-(1,2)-fucosyltransferase 1 (FUT1).	[41]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Galactoside alpha-(1,2)-fucosyltransferase 1 (FUT1).	[42]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Galactoside alpha-(1,2)-fucosyltransferase 1 (FUT1).	[43]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Galactoside alpha-(1,2)-fucosyltransferase 1 (FUT1).	[44]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Galactoside alpha-(1,2)-fucosyltransferase 1 (FUT1).	[45]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Galactoside alpha-(1,2)-fucosyltransferase 1 (FUT1).	[46]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Galactoside alpha-(1,2)-fucosyltransferase 1 (FUT1).	[45]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Galactoside alpha-(1,2)-fucosyltransferase 1 (FUT1).	[47]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Galactoside alpha-(1,2)-fucosyltransferase 1 (FUT1).	[48]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate decreases the expression of Galactoside alpha-(1,2)-fucosyltransferase 1 (FUT1).	[49]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Galactoside alpha-(1,2)-fucosyltransferase 1 (FUT1).	[50]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Galactoside alpha-(1,2)-fucosyltransferase 1 (FUT1).	[52]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Galactoside alpha-(1,2)-fucosyltransferase 1 (FUT1).	[53]
(E)-4-(3,5-dimethoxystyryl)phenol	DMYXI2V	Investigative	(E)-4-(3,5-dimethoxystyryl)phenol increases the expression of Galactoside alpha-(1,2)-fucosyltransferase 1 (FUT1).	[54]

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 1 (FUT1).	[51]

References

• [1] From the psychosis prodrome to the first-episode of psychosis: No evidence of a cognitive decline.J Psychiatr Res. 2018 Jan;96:231-238. doi: 10.1016/j.jpsychires.2017.10.014. Epub 2017 Oct 19.
• [2] High expression of PIM2 induces HSC proliferation in myelodysplastic syndromes via the IDH1/HIF1- signaling pathway.Oncol Lett. 2019 Jun;17(6):5395-5402. doi: 10.3892/ol.2019.10256. Epub 2019 Apr 16.
• [3] Outcomes following gene therapy in patients with severe Wiskott-Aldrich syndrome.JAMA. 2015 Apr 21;313(15):1550-63. doi: 10.1001/jama.2015.3253.
• [4] 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.
• [5] c-Fos mediates 1, 2-fucosyltransferase 1 and Lewisy expression in response to TGF-1 in ovarian cancer.Oncol Rep. 2017 Dec;38(6):3355-3366. doi: 10.3892/or.2017.6052. Epub 2017 Oct 23.
• [6] Terminal fucose mediates progression of human cholangiocarcinoma through EGF/EGFR activation and the Akt/Erk signaling pathway.Sci Rep. 2019 Nov 21;9(1):17266. doi: 10.1038/s41598-019-53601-8.
• [7] Yolk sac erythromyeloid progenitors expressing gain of function PTPN11 have functional features of JMML but are not sufficient to cause disease in mice.Dev Dyn. 2017 Dec;246(12):1001-1014. doi: 10.1002/dvdy.24598. Epub 2017 Oct 23.
• [8] Changes in the invasive and metastatic capacities of HT-29/M3 cells induced by the expression of fucosyltransferase 1.Cancer Sci. 2007 Jul;98(7):1000-5. doi: 10.1111/j.1349-7006.2007.00484.x. Epub 2007 Apr 23.
• [9] POFUT1 as a Promising Novel Biomarker of Colorectal Cancer.Cancers (Basel). 2018 Oct 30;10(11):411. doi: 10.3390/cancers10110411.
• [10] Alpha1,2-fucosyl transferase gene, the key enzyme of Lewis y synthesis, promotes Taxol resistance of ovarian carcinoma through apoptosis-related proteins.Neoplasma. 2018;65(4):515-522. doi: 10.4149/neo_2018_170823N552.
• [11] 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.
• [12] CDK2 knockdown enhances head and neck cancer cell radiosensitivity.Int J Radiat Biol. 2013 Jul;89(7):523-31. doi: 10.3109/09553002.2013.782108. Epub 2013 Apr 16.
• [13] Promises and Challenges in Hematopoietic Stem Cell Gene Therapy.Hum Gene Ther. 2017 Oct;28(10):782-799. doi: 10.1089/hum.2017.141.
• [14] HIV and HCV Co-Culture Promotes Profibrogenic Gene Expression through an Epimorphin-Mediated ERK Signaling Pathway in Hepatic Stellate Cells.PLoS One. 2016 Jun 30;11(6):e0158386. doi: 10.1371/journal.pone.0158386. eCollection 2016.
• [15] High expression FUT1 and B3GALT5 is an independent predictor of postoperative recurrence and survival in hepatocellular carcinoma.Sci Rep. 2017 Sep 7;7(1):10750. doi: 10.1038/s41598-017-11136-w.
• [16] Genotoxicity of retroviral hematopoietic stem cell gene therapy.Expert Opin Biol Ther. 2011 May;11(5):581-93. doi: 10.1517/14712598.2011.562496. Epub 2011 Mar 7.
• [17] An Improved Patient-Derived Xenograft Humanized Mouse Model for Evaluation of Lung Cancer Immune Responses.Cancer Immunol Res. 2019 Aug;7(8):1267-1279. doi: 10.1158/2326-6066.CIR-18-0874. Epub 2019 Jun 11.
• [18] Role of activation-induced cytidine deaminase in the development of oral squamous cell carcinoma.PLoS One. 2013 Apr 25;8(4):e62066. doi: 10.1371/journal.pone.0062066. Print 2013.
• [19] Correction to: miR-140-5p/miR-149 Affects Chondrocyte Proliferation, Apoptosis, and Autophagy by Targeting FUT1 in Osteoarthritis.Inflammation. 2019 Aug;42(4):1515-1516. doi: 10.1007/s10753-019-01001-5.
• [20] Fancd2-deficient hematopoietic stem and progenitor cells depend on augmented mitochondrial translation for survival and proliferation.Stem Cell Res. 2019 Oct;40:101550. doi: 10.1016/j.scr.2019.101550. Epub 2019 Aug 23.
• [21] Engraftment of gene-marked hematopoietic progenitors in myeloma patients after transplant of autologous long-term marrow cultures.Hum Gene Ther. 1999 Aug 10;10(12):1953-64. doi: 10.1089/10430349950017310.
• [22] Arsenic but not all-trans retinoic acid overcomes the aberrant stem cell capacity of PML/RARalpha-positive leukemic stem cells.Haematologica. 2007 Mar;92(3):323-31. doi: 10.3324/haematol.10541.
• [23] A spliced form of CD44 expresses the unique glycan that is recognized by the prostate cancer specific antibody F77.Oncotarget. 2017 Dec 16;9(3):3631-3640. doi: 10.18632/oncotarget.23341. eCollection 2018 Jan 9.
• [24] Silver nanoparticles Clinacanthus Nutans leaves extract induced apoptosis towards oral squamous cell carcinoma cell lines.Artif Cells Nanomed Biotechnol. 2018;46(sup2):131-139. doi: 10.1080/21691401.2018.1452750. Epub 2018 Mar 21.
• [25] Stem cell selection in vivo using foamy vectors cures canine pyruvate kinase deficiency.PLoS One. 2012;7(9):e45173. doi: 10.1371/journal.pone.0045173. Epub 2012 Sep 13.
• [26] Lentiviral Gene Therapy in HSCs Restores Lineage-Specific Foxp3 Expression and Suppresses Autoimmunity in a Mouse Model of IPEX Syndrome.Cell Stem Cell. 2019 Feb 7;24(2):309-317.e7. doi: 10.1016/j.stem.2018.12.003. Epub 2019 Jan 10.
• [27] Tamoxifen inhibits the proliferation of nonmelanoma skin cancer cells by increasing intracellular calcium concentration.Int J Oncol. 2018 Nov;53(5):2157-2166. doi: 10.3892/ijo.2018.4548. Epub 2018 Aug 31.
• [28] Decrease of hepatic stellate cells in rats with enhanced sensitivity to clofibrate-induced hepatocarcinogenesis. Cancer Sci. 2011 Apr;102(4):735-41. doi: 10.1111/j.1349-7006.2011.01856.x. Epub 2011 Feb 10.
• [29] Coreceptor-Based Hematopoietic Stem Cell Gene Therapy for HIV Disease.Curr Stem Cell Res Ther. 2019;14(7):591-597. doi: 10.2174/1574888X14666190523094556.
• [30] Clinical features and outcome of hepatosplenic fungal infections in children with haematological malignancies.Mycoses. 2020 Jan;63(1):30-37. doi: 10.1111/myc.13002. Epub 2019 Nov 13.
• [31] miR-181b promotes hepatic stellate cells proliferation by targeting p27 and is elevated in the serum of cirrhosis patients.Biochem Biophys Res Commun. 2012 Apr 27;421(1):4-8. doi: 10.1016/j.bbrc.2012.03.025. Epub 2012 Mar 13.
• [32] Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge.Nat Commun. 2018 Dec 6;9(1):5206. doi: 10.1038/s41467-018-07548-5.
• [33] Targeting a Pre-existing Anti-transgene T Cell Response for Effective Gene Therapy of MPS-I in the Mouse Model of the Disease.Mol Ther. 2019 Jul 3;27(7):1215-1227. doi: 10.1016/j.ymthe.2019.04.014. Epub 2019 Apr 19.
• [34] Parachuting in the epigenome: the biology of gene vector insertion profiles in the context of clinical trials.EMBO Mol Med. 2011 Feb;3(2):75-7. doi: 10.1002/emmm.201000110. Epub 2011 Jan 21.
• [35] Role of HIF-1-activated Epac1 on HSC-mediated neuroplasticity in stroke model.Neurobiol Dis. 2013 Oct;58:76-91. doi: 10.1016/j.nbd.2013.05.006. Epub 2013 May 20.
• [36] A key role for Fut1-regulated angiogenesis and ICAM-1 expression in K/BxN arthritis.Ann Rheum Dis. 2015 Jul;74(7):1459-66. doi: 10.1136/annrheumdis-2013-204814. Epub 2014 Mar 24.
• [37] A retinoid responsive cytokine gene, MK, is preferentially expressed in the proximal tubules of the kidney and human tumor cell lines.Am J Pathol. 1993 Feb;142(2):425-31.
• [38] High-Efficiency Lentiviral Transduction of Human CD34(+) Cells in High-Density Culture with Poloxamer and Prostaglandin E2.Mol Ther Methods Clin Dev. 2019 Jan 25;13:187-196. doi: 10.1016/j.omtm.2019.01.005. eCollection 2019 Jun 14.
• [39] 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.
• [40] Development of a forward-oriented therapeutic lentiviral vector for hemoglobin disorders.Nat Commun. 2019 Oct 2;10(1):4479. doi: 10.1038/s41467-019-12456-3.
• [41] 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.
• [42] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [43] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [44] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [45] 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.
• [46] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [47] Differently expressed long noncoding RNAs and mRNAs in TK6 cells exposed to low dose hydroquinone. Oncotarget. 2017 Oct 4;8(56):95554-95567. doi: 10.18632/oncotarget.21481. eCollection 2017 Nov 10.
• [48] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [49] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [50] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [51] 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.
• [52] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [53] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [54] Genomic analysis of pterostilbene predicts its antiproliferative effects against pancreatic cancer in vitro and in vivo. J Gastrointest Surg. 2012 Jun;16(6):1136-43. doi: 10.1007/s11605-012-1869-7. Epub 2012 Mar 27.
• [55] Alterations in the glycolipid composition and cellular properties of ovarian carcinoma-derived RMG-1 cells on transfection of the alpha1,2-fucosyltransferase gene. Cancer Sci. 2005 Jan;96(1):26-30. doi: 10.1111/j.1349-7006.2005.00005.x.