Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4NTHYO)

• DOT Name: L-fucose kinase (FCSK)
• Synonyms: Fucokinase; EC 2.7.1.52
• Gene Name: FCSK
• Related Disease:
  Congenital disorder of glycosylation
  Intellectual disability
  Congenital disorder of glycosylation with defective fucosylation 2
• UniProt ID: FCSK_HUMAN
• EC Number: 2.7.1.52
• Pfam ID: PF07959 ; PF08544 ; PF00288
• Sequence:
  MEQPKGVDWTVIILTCQYKDSVQVFQRELEVRQKREQIPAGTLLLAVEDPEKRVGSGGAT
  LNALLVAAEHLSARAGFTVVTSDVLHSAWILILHMGRDFPFDDCGRAFTCLPVENPEAPV
  EALVCNLDCLLDIMTYRLGPGSPPGVWVCSTDMLLSVPANPGISWDSFRGARVIALPGSP
  AYAQNHGVYLTDPQGLVLDIYYQGTEAEIQRCVRPDGRVPLVSGVVFFSVETAERLLATH
  VSPPLDACTYLGLDSGARPVQLSLFFDILHCMAENVTREDFLVGRPPELGQGDADVAGYL
  QSARAQLWRELRDQPLTMAYVSSGSYSYMTSSASEFLLSLTLPGAPGAQIVHSQVEEQQL
  LAAGSSVVSCLLEGPVQLGPGSVLQHCHLQGPIHIGAGCLVTGLDTAHSKALHGRELRDL
  VLQGHHTRLHGSPGHAFTLVGRLDSWERQGAGTYLNVPWSEFFKRTGVRAWDLWDPETLP
  AEYCLPSARLFPVLHPSRELGPQDLLWMLDHQEDGGEALRAWRASWRLSWEQLQPCLDRA
  ATLASRRDLFFRQALHKARHVLEARQDLSLRPLIWAAVREGCPGPLLATLDQVAAGAGDP
  GVAARALACVADVLGCMAEGRGGLRSGPAANPEWMRPFSYLECGDLAAGVEALAQERDKW
  LSRPALLVRAARHYEGAGQILIRQAVMSAQHFVSTEQVELPGPGQWVVAECPARVDFSGG
  WSDTPPLAYELGGAVLGLAVRVDGRRPIGARARRIPEPELWLAVGPRQDEMTVKIVCRCL
  ADLRDYCQPHAPGALLKAAFICAGIVHVHSELQLSEQLLRTFGGGFELHTWSELPHGSGL
  GTSSILAGTALAALQRAAGRVVGTEALIHAVLHLEQVLTTGGGWQDQVGGLMPGIKVGRS
  RAQLPLKVEVEEVTVPEGFVQKLNDHLLLVYTGKTRLARNLLQDVLRSWYARLPAVVQNA
  HSLVRQTEECAEGFRQGSLPLLGQCLTSYWEQKKLMAPGCEPLTVRRMMDVLAPHVHGQS
  LAGAGGGGFLYLLTKEPQQKEALEAVLAKTEGLGNYSIHLVEVDTQGLSLKLLGTEASTC
  CPFP
• Function: Takes part in the salvage pathway for reutilization of fucose from the degradation of oligosaccharides.
• Tissue Specificity: Expressed in fibroblasts.
• KEGG Pathway:
  Fructose and mannose metabolism (hsa00051)
  Amino sugar and nucleotide sugar metabolism (hsa00520)
  Metabolic pathways (hsa01100)
  Biosynthesis of nucleotide sugars (hsa01250)
• Reactome Pathway: GDP-fucose biosynthesis (R-HSA-6787639)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital disorder of glycosylation	DIS400QP	moderate	Biomarker	[1]
Intellectual disability	DISMBNXP	moderate	Biomarker	[1]
Congenital disorder of glycosylation with defective fucosylation 2	DISKNQ0J	Limited	Unknown	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Progesterone	DMUY35B	Approved	L-fucose kinase (FCSK) affects the response to substance of Progesterone.	[9]

6 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 L-fucose kinase (FCSK).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of L-fucose kinase (FCSK).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of L-fucose kinase (FCSK).	[4]
Menadione	DMSJDTY	Approved	Menadione affects the expression of L-fucose kinase (FCSK).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of L-fucose kinase (FCSK).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of L-fucose kinase (FCSK).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of L-fucose kinase (FCSK).	[5]

References

• [1] Pathogenic Variants in Fucokinase Cause a Congenital Disorder of Glycosylation. Am J Hum Genet. 2018 Dec 6;103(6):1030-1037. doi: 10.1016/j.ajhg.2018.10.021. Epub 2018 Nov 29.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environ Health Perspect. 2015 May;123(5):458-66. doi: 10.1289/ehp.1408775. Epub 2015 Jan 13.