Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOPGL9M)

• DOT Name: 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase FUT5 (FUT5)
• Synonyms: EC 2.4.1.152; 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase FUT5; EC 2.4.1.65; Fucosyltransferase 5; Fucosyltransferase V; Fuc-TV; FucT-V; Galactoside 3-L-fucosyltransferase
• Gene Name: FUT5
• Related Disease:
  Colorectal carcinoma
  Gastric cancer
  Hepatocellular carcinoma
  Lung cancer
  Prostate neoplasm
  Stomach cancer
  Inherited retinal dystrophy
  Lung carcinoma
  Colon adenocarcinoma
• UniProt ID: FUT5_HUMAN
• EC Number: 2.4.1.152; 2.4.1.65
• Pfam ID: PF17039 ; PF00852
• Sequence:
  MDPLGPAKPQWLWRRCLAGLLFQLLVAVCFFSYLRVSRDDATGSPRPGLMAVEPVTGAPN
  GSRCQDSMATPAHPTLLILLWTWPFNTPVALPRCSEMVPGAADCNITADSSVYPQADAVI
  VHHWDIMYNPSANLPPPTRPQGQRWIWFSMESPSNCRHLEALDGYFNLTMSYRSDSDIFT
  PYGWLEPWSGQPAHPPLNLSAKTELVAWAVSNWKPDSARVRYYQSLQAHLKVDVYGRSHK
  PLPKGTMMETLSRYKFYLAFENSLHPDYITEKLWRNALEAWAVPVVLGPSRSNYERFLPP
  DAFIHVDDFQSPKDLARYLQELDKDHARYLSYFHWRETLRPRSFSWALAFCKACWKLQQE
  SRYQTVRSIAAWFT
• Function: Catalyzes preferentially the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl-beta-D-glucosamine (GlcNAc) of an N-acetyllactosamine unit (type 2 chain) of an oligosaccharide, or a glycoprotein- and a glycolipid-linked N-acetyllactosamine unit via an alpha (1,3) linkage and participates in the surface expression of VIM-2, Lewis X/SSEA-1 and sialyl Lewis X antigens. Preferentially transfers fucose to the GlcNAc of an internal N-acetyllactosamine unit of a poly-N-acetyllactosamine chain acceptor substrate. Also catalyzes to a lesser extend the transfer of L-fucose to the GlcNAc of a type 1 (beta-D-galactosyl-(1->3)-N-acetyl-beta-D-glucosaminyl) or H-type 1 (alpha-L-Fuc-(1->2)-beta-D-Gal-(1->3)-D-GlcNAc) chain oligosaccharide via an alpha (1,4) linkage. Preferentially catalyzes sialylated type 2 oligosaccharide acceptors over neutral type 2 or H type 2 (alpha-L-Fuc-(1->2)-beta-D-Gal-(1->4)-D-GlcNAc) oligosaccharide acceptors. Lactose-based structures are also acceptor substrates.
• Tissue Specificity: Liver, colon and testis and trace amounts in T-cells and brain.
• KEGG Pathway:
  Glycosphingolipid biosynthesis - lacto and neolacto series (hsa00601)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Lewis blood group biosynthesis (R-HSA-9037629)
• BioCyc Pathway: MetaCyc:HS05379-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Lung cancer	DISCM4YA	Strong	Biomarker	[4]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[5]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[2]
Inherited retinal dystrophy	DISGGL77	moderate	Biomarker	[6]
Lung carcinoma	DISTR26C	moderate	Biomarker	[7]
Colon adenocarcinoma	DISDRE0J	Limited	Altered Expression	[8]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase FUT5 (FUT5).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase FUT5 (FUT5).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase FUT5 (FUT5).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase FUT5 (FUT5).	[11]
Marinol	DM70IK5	Approved	Marinol decreases the expression of 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase FUT5 (FUT5).	[12]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase FUT5 (FUT5).	[13]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase FUT5 (FUT5).	[11]

References

• [1] miR-125a-3p/FUT5-FUT6 axis mediates colorectal cancer cell proliferation, migration, invasion and pathological angiogenesis via PI3K-Akt pathway.Cell Death Dis. 2017 Aug 3;8(8):e2968. doi: 10.1038/cddis.2017.352.
• [2] 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.
• [3] alpha-1,3-Fucosyltransferase-VII stimulates the growth of hepatocarcinoma cells via the cyclin-dependent kinase inhibitor p27Kip1.Cell Mol Life Sci. 2005 Jan;62(2):171-8. doi: 10.1007/s00018-004-4349-8.
• [4] Expression of alpha-1,3-fucosyltransferase type IV and VII genes is related to poor prognosis in lung cancer.Cancer Res. 1996 Jan 15;56(2):325-9.
• [5] Gene transfer of alpha1,3-fucosyltransferase increases tumor growth of the PC-3 human prostate cancer cell line through enhanced adhesion to prostatic stromal cells.Int J Cancer. 2003 Dec 20;107(6):949-57. doi: 10.1002/ijc.11513.
• [6] Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.Am J Hum Genet. 2017 Jan 5;100(1):75-90. doi: 10.1016/j.ajhg.2016.12.003. Epub 2016 Dec 29.
• [7] alpha-2,3-Sialyltransferase type 3N and alpha-1,3-fucosyltransferase type VII are related to sialyl Lewis(x) synthesis and patient survival from lung carcinoma.Cancer. 1997 May 1;79(9):1678-85. doi: 10.1002/(sici)1097-0142(19970501)79:9<1678::aid-cncr7>3.0.co;2-8.
• [8] Elevation of an alpha(1,3)fucosyltransferase activity correlated with apoptosis in the human colon adenocarcinoma cell line, HT-29.Glycoconj J. 1996 Dec;13(6):1021-9. doi: 10.1007/BF01053198.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [12] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [13] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [14] 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.