Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0JGZPO)

• DOT Name: Glycerol kinase 2 (GK2)
• Synonyms: GK 2; Glycerokinase 2; EC 2.7.1.30; ATP:glycerol 3-phosphotransferase 2; Glycerol kinase, testis specific 2
• Gene Name: GK2
• Related Disease: Tourette syndrome
• UniProt ID: GLPK2_HUMAN
• EC Number: 2.7.1.30
• Pfam ID: PF02782 ; PF00370
• Sequence:
  MAAPKTAAVGPLVGAVVQGTNSTRFLVFNSKTAELLSHHKVELTQEFPKEGWVEQDPKEI
  LQSVYECIARTCEKLDELNIDISNIKAVGVSNQRETTVIWDKLTGEPLYNAVVWLDLRTQ
  TTVEDLSKKIPGNSNFVKSKTGLPLSTYFSAVKLRWMLDNVRNVQKAVEEGRALFGTIDS
  WLIWSLTGGVNGGVHCTDVTNASRTMLFNIHSLEWDKELCDFFEIPMDLLPNVFSSSEIY
  GLIKTGALEGVPISGCLGDQCAALVGQMCFQEGQAKNTYGTGCFLLCNTGRKCVFSEHGL
  LTTVAYKLGREKPAYYALEGSVAIAGAVIRWLRDNLGIIETSGDIERLAKEVGTSYGCYF
  VPAFSGLYAPYWEPSARGILCGLTQFTNKCHIAFAALEAVCFQTREILEAMNRDCGIPLR
  HLQVDGGMTNNKVLMQLQADILHIPVIKPFMPETTALGAAMAAGAAEGVSVWSLEPQALS
  VLRMERFEPQIQATESEIRYATWKKAVMKSMGWVTSQSPEGGDPSIFSSLPLGFFIVSSM
  VMLIGARYISGVP
• Function: Key enzyme in the regulation of glycerol uptake and metabolism. Essential for male fertility and sperm mitochondrial sheath formation. Required for proper arrangement of crescent-like mitochondria to form the mitochondrial sheath during spermatogenesis. Can induce mitochondrial clustering through interactions with PLD6 and up-regulation of phosphatidic acid synthesis in the mitochondria.
• Tissue Specificity: Testis-specific . Expressed in the midpiece of spermatozoa .
• KEGG Pathway:
  Glycerolipid metabolism (hsa00561)
  Metabolic pathways (hsa01100)
  PPAR sig.ling pathway (hsa03320)
• Reactome Pathway: Triglyceride biosynthesis (R-HSA-75109)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Tourette syndrome	DISX9D54	No Known	Unknown	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Glycerol kinase 2 (GK2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Glycerol kinase 2 (GK2).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Glycerol kinase 2 (GK2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Glycerol kinase 2 (GK2).	[4]

References

• [1] De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Neuron. 2017 May 3;94(3):486-499.e9. doi: 10.1016/j.neuron.2017.04.024.
• [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] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.