Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMD662Q)

• DOT Name: Phosphoglycerate kinase 2 (PGK2)
• Synonyms: EC 2.7.2.3; Phosphoglycerate kinase, testis specific
• Gene Name: PGK2
• Related Disease:
  Azoospermia
  Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation
  Cryptorchidism
• UniProt ID: PGK2_HUMAN
• EC Number: 2.7.2.3
• Pfam ID: PF00162
• Sequence:
  MSLSKKLTLDKLDVRGKRVIMRVDFNVPMKKNQITNNQRIKASIPSIKYCLDNGAKAVVL
  MSHLGRPDGVPMPDKYSLAPVAVELKSLLGKDVLFLKDCVGAEVEKACANPAPGSVILLE
  NLRFHVEEEGKGQDPSGKKIKAEPDKIEAFRASLSKLGDVYVNDAFGTAHRAHSSMVGVN
  LPHKASGFLMKKELDYFAKALENPVRPFLAILGGAKVADKIQLIKNMLDKVNEMIIGGGM
  AYTFLKVLNNMEIGASLFDEEGAKIVKDIMAKAQKNGVRITFPVDFVTGDKFDENAQVGK
  ATVASGISPGWMGLDCGPESNKNHAQVVAQARLIVWNGPLGVFEWDAFAKGTKALMDEIV
  KATSKGCITVIGGGDTATCCAKWNTEDKVSHVSTGGGASLELLEGKILPGVEALSNM
• Function: Essential for sperm motility and male fertility. Not required for the completion of spermatogenesis.
• Tissue Specificity: Mainly found in round spermatids. Localized on the principle piece in the sperm (at protein level). Testis-specific. Expression significantly decreased in the testis of elderly men.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Biosynthesis of amino acids (hsa01230)
  HIF-1 sig.ling pathway (hsa04066)
• Reactome Pathway:
  Gluconeogenesis (R-HSA-70263)
  Glycolysis (R-HSA-70171)
• BioCyc Pathway: MetaCyc:HS10215-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Azoospermia	DIS94181	Strong	Biomarker	[1]
Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation	DIS56JR8	Moderate	Autosomal recessive	[2]
Cryptorchidism	DISYUD2P	Limited	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Phosphoglycerate kinase 2 (PGK2).	[4]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Phosphoglycerate kinase 2 (PGK2).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Phosphoglycerate kinase 2 (PGK2).	[4]

2 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 Phosphoglycerate kinase 2 (PGK2).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Phosphoglycerate kinase 2 (PGK2).	[7]

References

• [1] Carnitine/organic cation transporter 2 (OCTN2) contributes to rat epididymal epithelial cell growth and proliferation.Biomed Pharmacother. 2017 Sep;93:444-450. doi: 10.1016/j.biopha.2017.06.057. Epub 2017 Jun 27.
• [2] A genomics approach to male infertility. Genet Med. 2020 Dec;22(12):1967-1975. doi: 10.1038/s41436-020-0916-0. Epub 2020 Jul 28.
• [3] Association between RNA-binding protein Ptbp2 and germ cell injury in an experimentally-induced unilateral cryptorchidism murine model.PLoS One. 2017 Oct 18;12(10):e0186654. doi: 10.1371/journal.pone.0186654. eCollection 2017.
• [4] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [5] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [6] 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.
• [7] 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.