Target Information
| Target General Information | Top | |||||
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| Target ID |
T17228
(Former ID: TTDI03472)
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| Target Name |
Poly [ADP-ribose] polymerase 3 (PARP3)
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| 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
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| Gene Name |
PARP3
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| Target Type |
Patented-recorded target
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[1] | ||||
| 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.
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| BioChemical Class |
Glycosyltransferases
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| UniProt ID | ||||||
| EC Number |
EC 2.4.2.-
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| Sequence |
MAPKPKPWVQTEGPEKKKGRQAGREEDPFRSTAEALKAIPAEKRIIRVDPTCPLSSNPGT
QVYEDYNCTLNQTNIENNNNKFYIIQLLQDSNRFFTCWNRWGRVGEVGQSKINHFTRLED AKKDFEKKFREKTKNNWAERDHFVSHPGKYTLIEVQAEDEAQEAVVKVDRGPVRTVTKRV QPCSLDPATQKLITNIFSKEMFKNTMALMDLDVKKMPLGKLSKQQIARGFEALEALEEAL KGPTDGGQSLEELSSHFYTVIPHNFGHSQPPPINSPELLQAKKDMLLVLADIELAQALQA VSEQEKTVEEVPHPLDRDYQLLKCQLQLLDSGAPEYKVIQTYLEQTGSNHRCPTLQHIWK VNQEGEEDRFQAHSKLGNRKLLWHGTNMAVVAAILTSGLRIMPHSGGRVGKGIYFASENS KSAGYVIGMKCGAHHVGYMFLGEVALGREHHINTDNPSLKSPPPGFDSVIARGHTEPDPT QDTELELDGQQVVVPQGQPVPCPEFSSSTFSQSEYLIYQESQCRLRYLLEVHL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: KU-0058948 | Ligand Info | |||||
| Structure Description | Human poly(ADP-ribose) polymerase 3, catalytic fragment in complex with an inhibitor KU0058948 | PDB:3C49 | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [3] |
| PDB Sequence |
SMKRVQPCSL
185 DPATQKLITN195 IFSKEMFKNT205 MALMDLDVKK215 MPLGKLSKQQ225 IARGFEALEA 235 LEEALKGPTD245 GGQSLEELSS255 HFYTVIPHNF265 GHSQPPPINS275 PELLQAKKDM 285 LLVLADIELA295 QALQAVSEQE305 KTVEEVPHPL315 DRDYQLLKCQ325 LQLLDSGAPE 335 YKVIQTYLEQ345 TGSNHRCPTL355 QHIWKVNQEG365 EEDRFQAHSK375 LGNRKLLWHG 385 TNMAVVAAIL395 TSGLRIMPHS405 GGRVGKGIYF415 ASENSKSAGY425 VIGMKCGAHH 435 VGYMFLGEVA445 LGREHHINTD455 NPSLKSPPPG465 FDSVIARGHT475 EPDPTQDTEL 485 ELDGQQVVVP495 QGQPVPCPEF505 SSSTFSQSEY515 LIYQESQCRL525 RYLLEVH |
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| Ligand Name: PJ34 | Ligand Info | |||||
| Structure Description | Human poly(ADP-ribose) polymerase 3, catalytic fragment in complex with an inhibitor PJ34 | PDB:3CE0 | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [3] |
| PDB Sequence |
KRVQPCSLDP
187 ATQKLITNIF197 SKEMFKNTMA207 LMDLDVKKMP217 LGKLSKQQIA227 RGFEALEALE 237 EALKDGGQSL250 EELSSHFYTV260 IPHNFGHSQP270 PPINSPELLQ280 AKKDMLLVLA 290 DIELAQALQA300 VSEQEKTVEE310 VPHPLDRDYQ320 LLKCQLQLLD330 SGAPEYKVIQ 340 TYLEQTGSNH350 RCPTLQHIWK360 VNQEGEEDRF370 QAHSKLGNRK380 LLWHGTNMAV 390 VAAILTSGLR400 IMPHSGGRVG410 KGIYFASENS420 KSAGYVIGMK430 CGAHHVGYMF 440 LGEVALGREH450 HINTDNPSLK460 SPPPGFDSVI470 ARGHTEPDPT480 QDTELELDGQ 490 QVVVPQGQPV500 PCPEFSSSTF510 SQSEYLIYQE520 SQCRLRYLLE530 VH |
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Human Similarity Proteins
Human Pathway Affiliation
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There is no similarity protein (E value < 0.005) for this target
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Base excision repair | hsa03410 | Affiliated Target |
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| Class: Genetic Information Processing => Replication and repair | Pathway Hierarchy | ||
| Apoptosis | hsa04210 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| References | Top | |||||
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| REF 1 | PARP inhibitors as antitumor agents: a patent update (2013-2015).Expert Opin Ther Pat. 2017 Mar;27(3):363-382. | |||||
| REF 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. | |||||
| REF 3 | Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3. J Med Chem. 2009 May 14;52(9):3108-11. | |||||
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