Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB2W7DW)

• DOT Name: Galactokinase (GALK1)
• Synonyms: EC 2.7.1.6; Galactose kinase
• Gene Name: GALK1
• Related Disease: Galactokinase deficiency
• UniProt ID: GALK1_HUMAN
• PDB ID: 1WUU; 6GR2; 6Q3W; 6Q3X; 6Q8Z; 6Q90; 6Q91; 6QJE; 6ZFH; 6ZGV; 6ZGW; 6ZGX; 6ZGY; 6ZGZ; 6ZH0; 7OZX; 7RCL; 7RCM; 7S49; 7S4C
• EC Number: 2.7.1.6
• Pfam ID: PF10509 ; PF08544 ; PF00288
• Sequence:
  MAALRQPQVAELLAEARRAFREEFGAEPELAVSAPGRVNLIGEHTDYNQGLVLPMALELM
  TVLVGSPRKDGLVSLLTTSEGADEPQRLQFPLPTAQRSLEPGTPRWANYVKGVIQYYPAA
  PLPGFSAVVVSSVPLGGGLSSSASLEVATYTFLQQLCPDSGTIAARAQVCQQAEHSFAGM
  PCGIMDQFISLMGQKGHALLIDCRSLETSLVPLSDPKLAVLITNSNVRHSLASSEYPVRR
  RQCEEVARALGKESLREVQLEELEAARDLVSKEGFRRARHVVGEIRRTAQAAAALRRGDY
  RAFGRLMVESHRSLRDDYEVSCPELDQLVEAALAVPGVYGSRMTGGGFGGCTVTLLEASA
  APHAMRHIQEHYGGTATFYLSQAADGAKVLCL
• Function: Catalyzes the transfer of a phosphate from ATP to alpha-D-galactose and participates in the first committed step in the catabolism of galactose.
• KEGG Pathway:
  Galactose metabolism (hsa00052)
  Amino sugar and nucleotide sugar metabolism (hsa00520)
  Metabolic pathways (hsa01100)
  Biosynthesis of nucleotide sugars (hsa01250)
• Reactome Pathway:
  Galactose catabolism (R-HSA-70370)
  Defective GALK1 causes GALCT2 (R-HSA-5609976)
• BioCyc Pathway: MetaCyc:HS03112-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Galactokinase deficiency	DISEB0V4	Definitive	Autosomal recessive	[1]

11 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 Galactokinase (GALK1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Galactokinase (GALK1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Galactokinase (GALK1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Galactokinase (GALK1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Galactokinase (GALK1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Galactokinase (GALK1).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Galactokinase (GALK1).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Galactokinase (GALK1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Galactokinase (GALK1).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Galactokinase (GALK1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Galactokinase (GALK1).	[3]

2 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 Galactokinase (GALK1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Galactokinase (GALK1).	[13]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] 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.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] 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.
• [9] Proteomic and functional analyses reveal a dual molecular mechanism underlying arsenic-induced apoptosis in human multiple myeloma cells. J Proteome Res. 2009 Jun;8(6):3006-19.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [13] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.