Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ5DB06)

DOT Name Phosphoglycerate mutase 1 (PGAM1)
Synonyms EC 5.4.2.11; EC 5.4.2.4; BPG-dependent PGAM 1; Phosphoglycerate mutase isozyme B; PGAM-B
Gene Name PGAM1
Related Disease
Carcinoma ( )
Malaria ( )
Adenocarcinoma ( )
Advanced cancer ( )
Anemia ( )
Astrocytoma ( )
Bipolar disorder ( )
Bladder cancer ( )
Bone osteosarcoma ( )
Breast cancer ( )
Breast carcinoma ( )
Creutzfeldt Jacob disease ( )
Gastric cancer ( )
Gastric neoplasm ( )
Glioblastoma multiforme ( )
Glioma ( )
Hepatocellular carcinoma ( )
Hereditary diffuse gastric adenocarcinoma ( )
Lung cancer ( )
Non-small-cell lung cancer ( )
Oligospermia ( )
Osteosarcoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Osteoarthritis ( )
Squamous cell carcinoma ( )
Undifferentiated carcinoma ( )
Colorectal carcinoma ( )
Matthew-Wood syndrome ( )
Neoplasm ( )
UniProt ID
PGAM1_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1YFK; 1YJX; 4GPI; 4GPZ; 5Y2I; 5Y2U; 5Y35; 5Y64; 5Y65; 5ZRM; 5ZS8; 6ISN; 7XB7; 7XB8; 7XB9
EC Number
5.4.2.11; 5.4.2.4
Pfam ID
PF00300
Sequence
MAAYKLVLIRHGESAWNLENRFSGWYDADLSPAGHEEAKRGGQALRDAGYEFDICFTSVQ
KRAIRTLWTVLDAIDQMWLPVVRTWRLNERHYGGLTGLNKAETAAKHGEAQVKIWRRSYD
VPPPPMEPDHPFYSNISKDRRYADLTEDQLPSCESLKDTIARALPFWNEEIVPQIKEGKR
VLIAAHGNSLRGIVKHLEGLSEEAIMELNLPTGIPIVYELDKNLKPIKPMQFLGDEETVR
KAMEAVAAQGKAKK
Function
Catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglyceratea crucial step in glycolysis, by using 2,3-bisphosphoglycerate. Also catalyzes the interconversion of (2R)-2,3-bisphosphoglycerate and (2R)-3-phospho-glyceroyl phosphate.
Tissue Specificity Expressed in the liver and brain. Not found in the muscle.
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
Glycolysis (R-HSA-70171 )
Gluconeogenesis (R-HSA-70263 )
Neutrophil degranulation (R-HSA-6798695 )
BioCyc Pathway
MetaCyc:HS10286-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Carcinoma DISH9F1N Definitive Biomarker [1]
Malaria DISQ9Y50 Definitive Biomarker [2]
Adenocarcinoma DIS3IHTY Strong Biomarker [3]
Advanced cancer DISAT1Z9 Strong Biomarker [4]
Anemia DISTVL0C Strong Biomarker [5]
Astrocytoma DISL3V18 Strong Altered Expression [6]
Bipolar disorder DISAM7J2 Strong Biomarker [7]
Bladder cancer DISUHNM0 Strong Biomarker [8]
Bone osteosarcoma DIST1004 Strong Biomarker [9]
Breast cancer DIS7DPX1 Strong Biomarker [10]
Breast carcinoma DIS2UE88 Strong Biomarker [10]
Creutzfeldt Jacob disease DISCB6RX Strong Biomarker [11]
Gastric cancer DISXGOUK Strong Biomarker [3]
Gastric neoplasm DISOKN4Y Strong Biomarker [3]
Glioblastoma multiforme DISK8246 Strong Biomarker [12]
Glioma DIS5RPEH Strong Biomarker [13]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [14]
Hereditary diffuse gastric adenocarcinoma DISUIBYS Strong Biomarker [3]
Lung cancer DISCM4YA Strong Biomarker [15]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [16]
Oligospermia DIS6YJF3 Strong Altered Expression [17]
Osteosarcoma DISLQ7E2 Strong Biomarker [9]
Prostate cancer DISF190Y Strong Biomarker [18]
Prostate carcinoma DISMJPLE Strong Biomarker [18]
Urinary bladder cancer DISDV4T7 Strong Biomarker [8]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [8]
Osteoarthritis DIS05URM moderate Biomarker [19]
Squamous cell carcinoma DISQVIFL moderate Biomarker [20]
Undifferentiated carcinoma DISIAZST Disputed Biomarker [1]
Colorectal carcinoma DIS5PYL0 Limited Altered Expression [21]
Matthew-Wood syndrome DISA7HR7 Limited Biomarker [22]
Neoplasm DISZKGEW Limited Biomarker [4]
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⏷ Show the Full List of 32 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
16 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 Phosphoglycerate mutase 1 (PGAM1). [23]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Phosphoglycerate mutase 1 (PGAM1). [24]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Phosphoglycerate mutase 1 (PGAM1). [25]
Quercetin DM3NC4M Approved Quercetin increases the expression of Phosphoglycerate mutase 1 (PGAM1). [26]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of Phosphoglycerate mutase 1 (PGAM1). [27]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Phosphoglycerate mutase 1 (PGAM1). [28]
Ibuprofen DM8VCBE Approved Ibuprofen increases the expression of Phosphoglycerate mutase 1 (PGAM1). [29]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of Phosphoglycerate mutase 1 (PGAM1). [30]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Phosphoglycerate mutase 1 (PGAM1). [31]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of Phosphoglycerate mutase 1 (PGAM1). [33]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Phosphoglycerate mutase 1 (PGAM1). [34]
chloropicrin DMSGBQA Investigative chloropicrin decreases the expression of Phosphoglycerate mutase 1 (PGAM1). [35]
Phencyclidine DMQBEYX Investigative Phencyclidine decreases the expression of Phosphoglycerate mutase 1 (PGAM1). [36]
AHPN DM8G6O4 Investigative AHPN decreases the expression of Phosphoglycerate mutase 1 (PGAM1). [37]
PP-242 DM2348V Investigative PP-242 decreases the expression of Phosphoglycerate mutase 1 (PGAM1). [38]
(E)-4-(3,5-dimethoxystyryl)phenol DMYXI2V Investigative (E)-4-(3,5-dimethoxystyryl)phenol decreases the expression of Phosphoglycerate mutase 1 (PGAM1). [39]
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⏷ Show the Full List of 16 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of Phosphoglycerate mutase 1 (PGAM1). [32]
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References

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9 S1P/S1PR3 axis promotes aerobic glycolysis by YAP/c-MYC/PGAM1 axis in osteosarcoma.EBioMedicine. 2019 Feb;40:210-223. doi: 10.1016/j.ebiom.2018.12.038. Epub 2018 Dec 23.
10 The diagnostic value and functional roles of phosphoglycerate mutase 1 in glioma.Oncol Rep. 2016 Oct;36(4):2236-44. doi: 10.3892/or.2016.5046. Epub 2016 Aug 25.
11 Global protein differential expression profiling of cerebrospinal fluid samples pooled from Chinese sporadic CJD and non-CJD patients.Mol Neurobiol. 2014 Feb;49(1):290-302. doi: 10.1007/s12035-013-8519-2. Epub 2013 Aug 4.
12 Decreased FBP1 expression rewires metabolic processes affecting aggressiveness of glioblastoma.Oncogene. 2020 Jan;39(1):36-49. doi: 10.1038/s41388-019-0974-4. Epub 2019 Aug 23.
13 A new potential anti-cancer beta-carboline derivative decreases the expression levels of key proteins involved in glioma aggressiveness: A proteomic investigation.Drug Dev Res. 2020 Feb;81(1):32-42. doi: 10.1002/ddr.21600. Epub 2019 Sep 9.
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15 Large meta-analysis of multiple cancers reveals a common, compact and highly prognostic hypoxia metagene.Br J Cancer. 2010 Jan 19;102(2):428-35. doi: 10.1038/sj.bjc.6605450.
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17 PGAM1 knockdown is associated with busulfaninduced hypospermatogenesis and spermatogenic cell apoptosis.Mol Med Rep. 2019 Apr;19(4):2497-2502. doi: 10.3892/mmr.2019.9930. Epub 2019 Feb 4.
18 Phosphoglycerate mutase 1 knockdown inhibits prostate cancer cell growth, migration, and invasion.Asian J Androl. 2018 Mar-Apr;20(2):178-183. doi: 10.4103/aja.aja_57_17.
19 Dysregulation of the NUDT7-PGAM1 axis is responsible for chondrocyte death during osteoarthritis pathogenesis.Nat Commun. 2018 Aug 24;9(1):3427. doi: 10.1038/s41467-018-05787-0.
20 Phosphoglycerate Mutase 1 Predicts the Poor Prognosis of Oral Squamous Cell Carcinoma and is Associated with Cell Migration.J Cancer. 2017 Jul 5;8(11):1943-1951. doi: 10.7150/jca.19278. eCollection 2017.
21 Proteomics identification of ITGB3 as a key regulator in reactive oxygen species-induced migration and invasion of colorectal cancer cells.Mol Cell Proteomics. 2011 Oct;10(10):M110.005397. doi: 10.1074/mcp.M110.005397. Epub 2011 May 27.
22 An allosteric PGAM1 inhibitor effectively suppresses pancreatic ductal adenocarcinoma.Proc Natl Acad Sci U S A. 2019 Nov 12;116(46):23264-23273. doi: 10.1073/pnas.1914557116. Epub 2019 Oct 29.
23 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.
24 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
25 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.
26 Differential protein expression of peroxiredoxin I and II by benzo(a)pyrene and quercetin treatment in 22Rv1 and PrEC prostate cell lines. Toxicol Appl Pharmacol. 2007 Apr 15;220(2):197-210. doi: 10.1016/j.taap.2006.12.030. Epub 2007 Jan 9.
27 Proteomic identification of differentially expressed proteins associated with the multiple drug resistance in methotrexate-resistant human breast cancer cells. Int J Oncol. 2014 Jul;45(1):448-58.
28 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.
29 Protein profile in neuroblastoma cells incubated with S- and R-enantiomers of ibuprofen by iTRAQ-coupled 2-D LC-MS/MS analysis: possible action of induced proteins on Alzheimer's disease. Proteomics. 2008 Apr;8(8):1595-607. doi: 10.1002/pmic.200700556.
30 Resveratrol-induced cell growth inhibition and apoptosis is associated with modulation of phosphoglycerate mutase B in human prostate cancer cells: two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometry evaluation. Cancer Detect Prev. 2004;28(6):443-52. doi: 10.1016/j.cdp.2004.08.009.
31 Gene expression changes in human prostate carcinoma cells exposed to genotoxic and nongenotoxic aryl hydrocarbon receptor ligands. Toxicol Lett. 2011 Oct 10;206(2):178-88.
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34 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
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