Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTD8MEH)

• DTT Name: Poly [ADP-ribose] polymerase 3 (PARP3)
• Synonyms: pADPRT-3; hPARP-3; Protein mono-ADP-ribosyltransferase PARP3; Poly[ADP-ribose] synthase 3; PARP-3; NAD(+) ADP-ribosyltransferase 3; IRT1; DNA ADP-ribosyltransferase PARP3; ARTD3; ADPRTL3; ADPRT3; ADPRT-3; ADP-ribosyltransferase diphtheria toxin-like 3
• Gene Name: PARP3
• DTT Type: Patented-recorded target; [1]
• BioChemical Class: Glycosyltransferases
• UniProt ID: PARP3_HUMAN
• TTD ID: T17228
• EC Number: EC 2.4.2.-
• Sequence:
  MAPKPKPWVQTEGPEKKKGRQAGREEDPFRSTAEALKAIPAEKRIIRVDPTCPLSSNPGT
  QVYEDYNCTLNQTNIENNNNKFYIIQLLQDSNRFFTCWNRWGRVGEVGQSKINHFTRLED
  AKKDFEKKFREKTKNNWAERDHFVSHPGKYTLIEVQAEDEAQEAVVKVDRGPVRTVTKRV
  QPCSLDPATQKLITNIFSKEMFKNTMALMDLDVKKMPLGKLSKQQIARGFEALEALEEAL
  KGPTDGGQSLEELSSHFYTVIPHNFGHSQPPPINSPELLQAKKDMLLVLADIELAQALQA
  VSEQEKTVEEVPHPLDRDYQLLKCQLQLLDSGAPEYKVIQTYLEQTGSNHRCPTLQHIWK
  VNQEGEEDRFQAHSKLGNRKLLWHGTNMAVVAAILTSGLRIMPHSGGRVGKGIYFASENS
  KSAGYVIGMKCGAHHVGYMFLGEVALGREHHINTDNPSLKSPPPGFDSVIARGHTEPDPT
  QDTELELDGQQVVVPQGQPVPCPEFSSSTFSQSEYLIYQESQCRLRYLLEVHL
• Function: Mediates mono-ADP-ribosylation of glutamate, aspartate or lysine residues on target proteins. In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation. Associates with a number of DNA repair factors and is involved in the response to exogenous and endogenous DNA strand breaks. Together with APLF, promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ). Cooperates with the XRRC6-XRCC5 (Ku70-Ku80) heterodimer to limit end-resection thereby promoting accurate NHEJ. Involved in DNA repair by mediating mono-ADP-ribosylation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism, such as XRRC5 and XRCC6. ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. May link the DNA damage surveillance network to the mitotic fidelity checkpoint. In addition to proteins, also able to ADP-ribosylate DNA: mediates DNA mono-ADP-ribosylation of DNA strand break termini via covalent addition of a single ADP-ribose moiety to a 5'- or 3'-terminal phosphate residues in DNA containing multiple strand breaks. Acts as a negative regulator of immunoglobulin class switch recombination, probably by controlling the level of AICDA /AID on the chromatin. Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins and plays a key role in the response to DNA damage.
• KEGG Pathway:
  Base excision repair (hsa03410)
  Apoptosis (hsa04210)

Molecular Interaction Atlas (MIA) of This DTT

1 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
3-phenyl isoquinolin-1(2H) derivative 1	DMB40HC	N. A.	N. A.	Patented	[1]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ME0328	DMCLT1V	Discovery agent	N.A.	Investigative	[2]

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Poly [ADP-ribose] polymerase 3 (PARP3) DME Info
• Gene Name: PARP3

1 Investigative Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
agmatine	DMSBZ29	Discovery agent	N.A.	Investigative	[3]

References

• [1] PARP inhibitors as antitumor agents: a patent update (2013-2015).Expert Opin Ther Pat. 2017 Mar;27(3):363-382.
• [2] Chemical probes to study ADP-ribosylation: synthesis and biochemical evaluation of inhibitors of the human ADP-ribosyltransferase ARTD3/PARP3. J Med Chem. 2013 Dec 12;56(23):9556-68.
• [3] Mono-ADP-ribosylation catalyzed by arginine-specific ADP-ribosyltransferases. Methods Mol Biol. 2018;1813:149-165.