Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEAS7OC)

• DOT Name: Phosphoglucomutase-like protein 5 (PGM5)
• Synonyms: Aciculin; Phosphoglucomutase-related protein; PGM-RP
• Gene Name: PGM5
• Related Disease:
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
  Bladder cancer
  Juvenile idiopathic arthritis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Colorectal carcinoma
• UniProt ID: PGM5_HUMAN
• PDB ID: 7U21
• Pfam ID: PF02878 ; PF02879 ; PF02880
• Sequence:
  MEGSPIPVLTVPTAPYEDQRPAGGGGLRRPTGLFEGQRNYLPNFIQSVLSSIDLRDRQGC
  TMVVGSDGRYFSRTAIEIVVQMAAANGIGRLIIGQNGILSTPAVSCIIRKIKAAGGIILT
  ASHCPGGPGGEFGVKFNVANGGPAPDVVSDKIYQISKTIEEYAICPDLRIDLSRLGRQEF
  DLENKFKPFRVEIVDPVDIYLNLLRTIFDFHAIKGLLTGPSQLKIRIDAMHGVMGPYVRK
  VLCDELGAPANSAINCVPLEDFGGQHPDPNLTYATTLLEAMKGGEYGFGAAFDADGDRYM
  ILGQNGFFVSPSDSLAIIAANLSCIPYFRQMGVRGFGRSMPTSMALDRVAKSMKVPVYET
  PAGWRFFSNLMDSGRCNLCGEESFGTGSDHLREKDGLWAVLVWLSIIAARKQSVEEIVRD
  HWAKFGRHYYCRFDYEGLDPKTTYYIMRDLEALVTDKSFIGQQFAVGSHVYSVAKTDSFE
  YVDPVDGTVTKKQGLRIIFSDASRLIFRLSSSSGVRATLRLYAESYERDPSGHDQEPQAV
  LSPLIAIALKISQIHERTGRRGPTVIT
• Function: Component of adherens-type cell-cell and cell-matrix junctions. Has no phosphoglucomutase activity in vitro.
• Tissue Specificity: Detected in smooth and cardiac muscle at high levels and in skeletal muscle at low level. Present in other tissues due to vascular or other smooth muscle component. Low levels are present in liver, kidney, skin and brain (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Definitive	Biomarker	[1]
Liver cancer	DISDE4BI	Definitive	Biomarker	[1]
Bladder cancer	DISUHNM0	Strong	Biomarker	[2]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[3]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[2]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[4]

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 Phosphoglucomutase-like protein 5 (PGM5).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Phosphoglucomutase-like protein 5 (PGM5).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Phosphoglucomutase-like protein 5 (PGM5).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Phosphoglucomutase-like protein 5 (PGM5).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Phosphoglucomutase-like protein 5 (PGM5).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Phosphoglucomutase-like protein 5 (PGM5).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Phosphoglucomutase-like protein 5 (PGM5).	[10]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Phosphoglucomutase-like protein 5 (PGM5).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Phosphoglucomutase-like protein 5 (PGM5).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Phosphoglucomutase-like protein 5 (PGM5).	[14]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Phosphoglucomutase-like protein 5 (PGM5).	[15]

References

• [1] PGM5: a novel diagnostic and prognostic biomarker for liver cancer.PeerJ. 2019 Jun 11;7:e7070. doi: 10.7717/peerj.7070. eCollection 2019.
• [2] Transcriptomic analysis of high-throughput sequencing about circRNA, lncRNA and mRNA in bladder cancer.Gene. 2018 Nov 30;677:189-197. doi: 10.1016/j.gene.2018.07.041. Epub 2018 Jul 17.
• [3] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
• [4] Comprehensive analysis of the long noncoding RNA expression profile and construction of the lncRNA-mRNA co-expression network in colorectal cancer.Cancer Biol Ther. 2020;21(2):157-169. doi: 10.1080/15384047.2019.1673098. Epub 2019 Oct 16.
• [5] 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.
• [6] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] 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.
• [9] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [10] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [11] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [12] 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.
• [13] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [14] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [15] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.