Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT10JTIO)

• DOT Name: Poly(ADP-ribose) glycohydrolase (PARG)
• Synonyms: EC 3.2.1.143
• Gene Name: PARG
• UniProt ID: PARG_HUMAN
• PDB ID: 4A0D; 4B1G; 4B1H; 4B1I; 4B1J; 5A7R; 5LHB; 6HH6; 6HMK; 6HML; 6HMM; 6HMN; 6O9X; 6O9Y; 6OA0; 6OA1; 6OA3; 6OAK; 6OAL; 7KFP; 7KG0; 7KG1; 7KG6; 7KG7; 7KG8
• EC Number: 3.2.1.143
• Pfam ID: PF05028 ; PF20811
• Sequence:
  MNAGPGCEPCTKRPRWGAATTSPAASDARSFPSRQRRVLDPKDAHVQFRVPPSSPACVPG
  RAGQHRGSATSLVFKQKTITSWMDTKGIKTAESESLDSKENNNTRIESMMSSVQKDNFYQ
  HNVEKLENVSQLSLDKSPTEKSTQYLNQHQTAAMCKWQNEGKHTEQLLESEPQTVTLVPE
  QFSNANIDRSPQNDDHSDTDSEENRDNQQFLTTVKLANAKQTTEDEQAREAKSHQKCSKS
  CDPGEDCASCQQDEIDVVPESPLSDVGSEDVGTGPKNDNKLTRQESCLGNSPPFEKESEP
  ESPMDVDNSKNSCQDSEADEETSPGFDEQEDGSSSQTANKPSRFQARDADIEFRKRYSTK
  GGEVRLHFQFEGGESRTGMNDLNAKLPGNISSLNVECRNSKQHGKKDSKITDHFMRLPKA
  EDRRKEQWETKHQRTERKIPKYVPPHLSPDKKWLGTPIEEMRRMPRCGIRLPLLRPSANH
  TVTIRVDLLRAGEVPKPFPTHYKDLWDNKHVKMPCSEQNLYPVEDENGERTAGSRWELIQ
  TALLNKFTRPQNLKDAILKYNVAYSKKWDFTALIDFWDKVLEEAEAQHLYQSILPDMVKI
  ALCLPNICTQPIPLLKQKMNHSITMSQEQIASLLANAFFCTFPRRNAKMKSEYSSYPDIN
  FNRLFEGRSSRKPEKLKTLFCYFRRVTEKKPTGLVTFTRQSLEDFPEWERCEKPLTRLHV
  TYEGTIEENGQGMLQVDFANRFVGGGVTSAGLVQEEIRFLINPELIISRLFTEVLDHNEC
  LIITGTEQYSEYTGYAETYRWSRSHEDGSERDDWQRRCTEIVAIDALHFRRYLDQFVPEK
  MRRELNKAYCGFLRPGVSSENLSAVATGNWGCGAFGGDARLKALIQILAAAAAERDVVYF
  TFGDSELMRDIYSMHIFLTERKLTVGDVYKLLLRYYNEECRNCSTPGPDIKLYPFIYHAV
  ESCAETADHSGQRTGT
• Function: Poly(ADP-ribose) glycohydrolase that degrades poly(ADP-ribose) by hydrolyzing the ribose-ribose bonds present in poly(ADP-ribose). PARG acts both as an endo- and exoglycosidase, releasing poly(ADP-ribose) of different length as well as ADP-ribose monomers. It is however unable to cleave the ester bond between the terminal ADP-ribose and ADP-ribosylated residues, leaving proteins that are mono-ADP-ribosylated. Poly(ADP-ribose) is synthesized after DNA damage is only present transiently and is rapidly degraded by PARG. Required to prevent detrimental accumulation of poly(ADP-ribose) upon prolonged replicative stress, while it is not required for recovery from transient replicative stress. Responsible for the prevalence of mono-ADP-ribosylated proteins in cells, thanks to its ability to degrade poly(ADP-ribose) without cleaving the terminal protein-ribose bond. Required for retinoid acid-dependent gene transactivation, probably by removing poly(ADP-ribose) from histone demethylase KDM4D, allowing chromatin derepression at RAR-dependent gene promoters. Involved in the synthesis of ATP in the nucleus, together with PARP1, NMNAT1 and NUDT5. Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway: Base excision repair (hsa03410)
• Reactome Pathway: POLB-Dependent Long Patch Base Excision Repair (R-HSA-110362)

Molecular Interaction Atlas (MIA) of This DOT

4 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 Poly(ADP-ribose) glycohydrolase (PARG).	[1]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Poly(ADP-ribose) glycohydrolase (PARG).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Poly(ADP-ribose) glycohydrolase (PARG).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Poly(ADP-ribose) glycohydrolase (PARG).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Poly(ADP-ribose) glycohydrolase (PARG).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Poly(ADP-ribose) glycohydrolase (PARG).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Poly(ADP-ribose) glycohydrolase (PARG).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Poly(ADP-ribose) glycohydrolase (PARG).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Poly(ADP-ribose) glycohydrolase (PARG).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Poly(ADP-ribose) glycohydrolase (PARG).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Poly(ADP-ribose) glycohydrolase (PARG).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Poly(ADP-ribose) glycohydrolase (PARG).	[10]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Poly(ADP-ribose) glycohydrolase (PARG).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Poly(ADP-ribose) glycohydrolase (PARG).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Poly(ADP-ribose) glycohydrolase (PARG).	[13]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Poly(ADP-ribose) glycohydrolase (PARG).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Poly(ADP-ribose) glycohydrolase (PARG).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Poly(ADP-ribose) glycohydrolase (PARG).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Poly(ADP-ribose) glycohydrolase (PARG).	[17]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Poly(ADP-ribose) glycohydrolase (PARG).	[18]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Poly(ADP-ribose) glycohydrolase (PARG).	[19]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID decreases the activity of Poly(ADP-ribose) glycohydrolase (PARG).	[20]
Myricetin	DMTV4L0	Investigative	Myricetin decreases the activity of Poly(ADP-ribose) glycohydrolase (PARG).	[20]
ROSMARINIC ACID	DMQ6SJT	Investigative	ROSMARINIC ACID decreases the activity of Poly(ADP-ribose) glycohydrolase (PARG).	[20]

References

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