Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOA0UYT)

• DOT Name: Glycosaminoglycan xylosylkinase (FAM20B)
• Synonyms: EC 2.7.1.-; Xylose kinase
• Gene Name: FAM20B
• Related Disease:
  Ehlers-Danlos syndrome
  Psoriasis
  Desbuquois dysplasia
• UniProt ID: XYLK_HUMAN
• EC Number: 2.7.1.-
• Pfam ID: PF06702
• Sequence:
  MKLKQRVVLLAILLVIFIFTKVFLIDNLDTSAANREDQRAFHRMMTGLRVELAPKLDHTL
  QSPWEIAAQWVVPREVYPEETPELGAVMHAMATKKIIKADVGYKGTQLKALLILEGGQKV
  VFKPKRYSRDHVVEGEPYAGYDRHNAEVAAFHLDRILGFHRAPLVVGRFVNLRTEIKPVA
  TEQLLSTFLTVGNNTCFYGKCYYCRETEPACADGDIMEGSVTLWLPDVWPLQKHRHPWGR
  TYREGKLARWEYDESYCDAVKKTSPYDSGPRLLDIIDTAVFDYLIGNADRHHYESFQDDE
  GASMLILLDNAKSFGNPSLDERSILAPLYQCCIIRVSTWNRLNYLKNGVLKSALKSAMAH
  DPISPVLSDPHLDAVDQRLLSVLATVKQCTDQFGMDTVLVEDRMPLSHL
• Function: Responsible for the 2-O-phosphorylation of xylose in the glycosaminoglycan-protein linkage region of proteoglycans thereby regulating the amount of mature GAG chains. Sulfated glycosaminoglycans (GAGs), including heparan sulfate and chondroitin sulfate, are synthesized on the so-called common GAG-protein linkage region (GlcUAbeta1-3Galbeta1-3Galbeta1-4Xylbeta1-O-Ser) of core proteins, which is formed by the stepwise addition of monosaccharide residues by the respective specific glycosyltransferases. Xylose 2-O-phosphorylation may influence the catalytic activity of B3GAT3 (GlcAT-I) which completes the precursor tetrasaccharide of GAG-protein linkage regions on which the repeating disaccharide region is synthesized.
• Tissue Specificity: Widely expressed. Strongly expressed in pancreas, spleen and fetal liver.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ehlers-Danlos syndrome	DISSVBRR	Strong	Genetic Variation	[1]
Psoriasis	DIS59VMN	Strong	Biomarker	[2]
Desbuquois dysplasia	DISCBF04	Limited	Autosomal recessive	[3]

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 Glycosaminoglycan xylosylkinase (FAM20B).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glycosaminoglycan xylosylkinase (FAM20B).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glycosaminoglycan xylosylkinase (FAM20B).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Glycosaminoglycan xylosylkinase (FAM20B).	[7]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Glycosaminoglycan xylosylkinase (FAM20B).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Glycosaminoglycan xylosylkinase (FAM20B).	[10]

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 increases the methylation of Glycosaminoglycan xylosylkinase (FAM20B).	[9]

References

• [1] Xylose phosphorylation functions as a molecular switch to regulate proteoglycan biosynthesis.Proc Natl Acad Sci U S A. 2014 Nov 4;111(44):15723-8. doi: 10.1073/pnas.1417993111. Epub 2014 Oct 20.
• [2] Five regulatory genes detected by matching signatures of eQTL and GWAS in psoriasis.J Dermatol Sci. 2014 Nov;76(2):139-42. doi: 10.1016/j.jdermsci.2014.07.007. Epub 2014 Aug 13.
• [3] A novel gene (FAM20B encoding glycosaminoglycan xylosylkinase) for neonatal short limb dysplasia resembling Desbuquois dysplasia. Clin Genet. 2019 Jun;95(6):713-717. doi: 10.1111/cge.13530. Epub 2019 Apr 11.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [9] 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.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.