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

PARG (Q86W56) - Overview - Molecular Target Synopsis

Protein


PARG, Poly(ADP-ribose) glycohydrolase
Enzyme Classification 3.2.1.143
UniProt Q86W56

Also Known as PARG_HUMAN, PARG

Poly(ADP-ribose) glycohydrolase that degrades poly(ADP-ribose) by hydrolyzing the ribose-ribose bonds present in poly(ADP-ribose) (PubMed:21892188, PubMed:23102699, PubMed:23474714). PARG acts both as an endo- and exoglycosidase, releasing poly(ADP-ribose) of different length as well as ADP-ribose monomers (PubMed:23102699, PubMed:23481255). 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 (PubMed:21892188, PubMed:23474714). Poly(ADP-ribose) is synthesized after DNA damage is only present transiently and is rapidly degraded by PARG (PubMed:23102699). Required to prevent detrimental accumulation of poly(ADP-ribose) upon prolonged replicative stress, while it is not required for recovery from transient replicative stress (PubMed:24906880). 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 (PubMed:23102699). Involved in the synthesis of ATP in the nucleus, together with PARP1, NMNAT1 and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257). Interacts with PCNA (PubMed:21398629). Interacts with NUDT5 (PubMed:27257257).

6HH6
HUMAN POLY(ADP-RIBOSE) GLYCOHYDROLASE IN COMPLEX WITH ADP-HPM
RCSB/PDB
Inspect Structure
See all 3D Structures for PARG

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
976Q86W56-1
894Q86W56-2
868Q86W56-3
527Q86W56-4
491ENSG00000227345ENST00000402038ENSP00000384408
475Q86W56-5

Sub-cellular localization


UniProt: PARG is active in the following subcellular-locations: cytoplasm, mitochondrion, mitochondrion matrix, nucleus.
GO terms: PARG is active in the following subcellular-locations: cytoplasm, cytosol, intracellular membrane-bounded organelle, mitochondrial matrix, nucleoplasm, nucleus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PARG has gain in 2 cell-lines, loss in 1 cell-lines and no signal in 1002 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: PC_3, SW_620, SK_MEL_2

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: PC-3, SK-N-FI, KYSE-70

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, HSMM, SK-N-SH_RA

(see details)

3D Structures


For PARG there are:
12 structures (12 chains) solved
10 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PARG has been screened with 30 compounds (34 bioactivities), 1 compounds have bioactivities that show binding affinity of <= 500nM (1 bioactivities). (see details)