Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9BE03I)

• DOT Name: Phosphoglycerate mutase 2 (PGAM2)
• Synonyms: EC 5.4.2.11; EC 5.4.2.4; BPG-dependent PGAM 2; Muscle-specific phosphoglycerate mutase; Phosphoglycerate mutase isozyme M; PGAM-M
• Gene Name: PGAM2
• Related Disease:
  Neoplasm
  Aarskog-Scott syndrome, X-linked
  Glycogen storage disease due to phosphoglycerate mutase deficiency
  Greig cephalopolysyndactyly syndrome
  Metabolic disorder
  Prostate cancer
  Prostate neoplasm
  Inherited fatty acid metabolism disorder
  Purine metabolism disease
  Disorder of glycogen metabolism
  Metabolic myopathy
  Myopathy
• UniProt ID: PGAM2_HUMAN
• EC Number: 5.4.2.11; 5.4.2.4
• Pfam ID: PF00300
• Sequence:
  MATHRLVMVRHGESTWNQENRFCGWFDAELSEKGTEEAKRGAKAIKDAKMEFDICYTSVL
  KRAIRTLWAILDGTDQMWLPVVRTWRLNERHYGGLTGLNKAETAAKHGEEQVKIWRRSFD
  IPPPPMDEKHPYYNSISKERRYAGLKPGELPTCESLKDTIARALPFWNEEIVPQIKAGKR
  VLIAAHGNSLRGIVKHLEGMSDQAIMELNLPTGIPIVYELNKELKPTKPMQFLGDEETVR
  KAMEAVAAQGKAK
• Function: Interconversion of 3- and 2-phosphoglycerate with 2,3-bisphosphoglycerate as the primer of the reaction. Can also catalyze the reaction of EC 5.4.2.4 (synthase), but with a reduced activity.
• Tissue Specificity: Expressed in the heart and muscle. Not found in the liver and brain.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Glycine, serine and threonine metabolism (hsa00260)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Biosynthesis of amino acids (hsa01230)
  Glucagon sig.ling pathway (hsa04922)
  Central carbon metabolism in cancer (hsa05230)
• Reactome Pathway:
  Gluconeogenesis (R-HSA-70263)
  Glycolysis (R-HSA-70171)
• BioCyc Pathway: MetaCyc:HS09121-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Aarskog-Scott syndrome, X-linked	DISNHV62	Strong	Biomarker	[2]
Glycogen storage disease due to phosphoglycerate mutase deficiency	DISC5WDN	Strong	Autosomal recessive	[3]
Greig cephalopolysyndactyly syndrome	DISBMUUT	Strong	Biomarker	[2]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[4]
Prostate cancer	DISF190Y	Strong	Biomarker	[5]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[5]
Inherited fatty acid metabolism disorder	DISOT51Y	moderate	Biomarker	[6]
Purine metabolism disease	DIS4B865	moderate	Biomarker	[6]
Disorder of glycogen metabolism	DISYGNOB	Limited	Biomarker	[7]
Metabolic myopathy	DISSE3BW	Limited	Biomarker	[7]
Myopathy	DISOWG27	Limited	Genetic Variation	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Phosphoglycerate mutase 2 (PGAM2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Phosphoglycerate mutase 2 (PGAM2).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Phosphoglycerate mutase 2 (PGAM2).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Phosphoglycerate mutase 2 (PGAM2).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Phosphoglycerate mutase 2 (PGAM2).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Phosphoglycerate mutase 2 (PGAM2).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Phosphoglycerate mutase 2 (PGAM2).	[15]

References

• [1] Oxidative stress activates SIRT2 to deacetylate and stimulate phosphoglycerate mutase.Cancer Res. 2014 Jul 1;74(13):3630-42. doi: 10.1158/0008-5472.CAN-13-3615. Epub 2014 May 1.
• [2] Molecular and cytogenetic analysis in two patients with microdeletions of 7p and Greig syndrome: hemizygosity for PGAM2 and TCRG genes.Genomics. 1990 Nov;8(3):487-91. doi: 10.1016/0888-7543(90)90035-s.
• [3] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [4] Myopathies Related to Glycogen Metabolism Disorders.Neurotherapeutics. 2018 Oct;15(4):915-927. doi: 10.1007/s13311-018-00684-2.
• [5] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [6] Exome sequencing in Jewish and Arab patients with rhabdomyolysis reveals single-gene etiology in 43% of cases.Pediatr Nephrol. 2017 Dec;32(12):2273-2282. doi: 10.1007/s00467-017-3755-8. Epub 2017 Aug 5.
• [7] Manifesting heterozygotes in a Japanese family with a novel mutation in the muscle-specific phosphoglycerate mutase (PGAM-M) gene.Neuromuscul Disord. 1999 Oct;9(6-7):399-402. doi: 10.1016/s0960-8966(99)00039-5.
• [8] Genomic analysis of five chromosome 7p deletion patients with Greig cephalopolysyndactyly syndrome (GCPS).Eur J Med Genet. 2006 Jul-Aug;49(4):338-45. doi: 10.1016/j.ejmg.2005.10.133. Epub 2005 Nov 28.
• [9] 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.
• [10] Functional cardiotoxicity assessment of cosmetic compounds using human-induced pluripotent stem cell-derived cardiomyocytes. Arch Toxicol. 2018 Jan;92(1):371-381.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] 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.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.