Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PARP3 (Q9Y6F1) - Overview - Molecular Target Synopsis

Protein


PARP3, Protein mono-ADP-ribosyltransferase PARP3
Enzyme Classification 2.4.2.-
UniProt Q9Y6F1

Also Known as PARP3_HUMAN, PARP3, ADPRT3, ADPRTL3

Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins and plays a key role in the response to DNA damage (PubMed:16924674, PubMed:20064938, PubMed:21211721, PubMed:21270334, PubMed:25043379, PubMed:24598253). Mediates mono-ADP-ribosylation of glutamate, aspartate or lysine residues on target proteins (PubMed:20064938, PubMed:25043379). In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation (PubMed:25043379). Associates with a number of DNA repair factors and is involved in the response to exogenous and endogenous DNA strand breaks (PubMed:16924674, PubMed:21211721, PubMed:21270334). Together with APLF, promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ) (PubMed:21211721). Cooperates with the XRRC6-XRCC5 (Ku70-Ku80) heterodimer to limit end-resection thereby promoting accurate NHEJ (PubMed:24598253). 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 (PubMed:16924674, PubMed:24598253). ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks (PubMed:16924674, PubMed:21211721, PubMed:21270334). May link the DNA damage surveillance network to the mitotic fidelity checkpoint (PubMed:16924674). 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 (PubMed:29361132, PubMed:29520010). Acts as a negative regulator of immunoglobulin class switch recombination, probably by controlling the level of AICDA /AID on the chromatin. Interacts with PARP1; leading to activate PARP1 in absence of DNA (PubMed:16924674, PubMed:20064938). Interacts with PRKDC (PubMed:16924674). Interacts with XRCC5/Ku80; the interaction is dependent on nucleic acids (PubMed:16924674, PubMed:24598253). Interacts with XRCC6/Ku70; the interaction is dependent on nucleic acids (PubMed:16924674, PubMed:24598253). Interacts with EZH2, HDAC1, HDAC2, SUZ12, YY1, LRIG3 and LIG4 (PubMed:16924674).

4L70
HUMAN ARTD3 (PARP3) - CATALYTIC DOMAIN IN COMPLEX WITH INHIBITOR ME0352
RCSB/PDB
Inspect Structure
See all 3D Structures for PARP3

Isoforms / Transcripts (Protein Coding)


Drugs


PARP3 is targeted by Approved Drugs Olaparib, Rucaparib, Niraparib. (see details)
Olaparib
Rucaparib
Niraparib

Sub-cellular localization


UniProt: PARP3 is active in the following subcellular-locations: centriole, centrosome, chromosome, cytoplasm, cytoskeleton, microtubule organizing center, nucleus.
GO terms: PARP3 is active in the following subcellular-locations: centriole, nucleolus, nucleus, site of double-strand break.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PARP3 has gain in 0 cell-lines, loss in 7 cell-lines and no signal in 998 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SN12C, ACHN, SR

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: HCC364, NCI-H2373, SK-N-FI

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, BJ, HSMM

(see details)

3D Structures


For PARP3 there are:
16 structures (16 chains) solved
15 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PARP3 has been screened with compounds ( bioactivities). (see details)