Poly(ADP-ribose) glycohydrolase (PARG) is the major enzyme responsible for the catabolism of poly(ADP-ribose), a reversible covalent-modifier of chromosomal proteins. The protein is found in many tissues and may be subject to proteolysis generating smaller, active products. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSe... See more...

Aliases for PARG Gene

Aliases for PARG Gene

  • Poly(ADP-Ribose) Glycohydrolase 2 3 4 5
  • EC 3.2.1.143 4 51
  • Poly(ADP-Ribose) Glycohydrolase 60 KDa Isoform 3
  • Mitochondrial Poly(ADP-Ribose) Glycohydrolase 3
  • PARG99 3
  • PARG 5

External Ids for PARG Gene

Previous GeneCards Identifiers for PARG Gene

  • GC10P050148
  • GC10M049974
  • GC10M050918
  • GC10M050371
  • GC10M050572
  • GC10P051293
  • GC10M051026
  • GC10M045291

Summaries for PARG Gene

Entrez Gene Summary for PARG Gene

  • Poly(ADP-ribose) glycohydrolase (PARG) is the major enzyme responsible for the catabolism of poly(ADP-ribose), a reversible covalent-modifier of chromosomal proteins. The protein is found in many tissues and may be subject to proteolysis generating smaller, active products. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]

GeneCards Summary for PARG Gene

PARG (Poly(ADP-Ribose) Glycohydrolase) is a Protein Coding gene. Diseases associated with PARG include Arthrogryposis, Renal Dysfunction, And Cholestasis 1 and Osebold-Remondini Syndrome. Among its related pathways are Telomere C-strand (Lagging Strand) Synthesis and Chromatin Regulation / Acetylation. Gene Ontology (GO) annotations related to this gene include poly(ADP-ribose) glycohydrolase activity.

UniProtKB/Swiss-Prot Summary for PARG Gene

  • 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).

Gene Wiki entry for PARG Gene

Additional gene information for PARG Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PARG Gene

Genomics for PARG Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for PARG Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PARG on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PARG

Top Transcription factor binding sites by QIAGEN in the PARG gene promoter:
  • Cart-1
  • E47
  • FAC1
  • FOXC1
  • Pax-2
  • Pax-2a
  • SRY
  • YY1

Genomic Locations for PARG Gene

Genomic Locations for PARG Gene
chr10:49,818,274-49,970,203
(GRCh38/hg38)
Size:
151,930 bases
Orientation:
Minus strand
chr10:51,026,325-51,371,331
(GRCh37/hg19)
Size:
345,007 bases
Orientation:
Minus strand

Genomic View for PARG Gene

Genes around PARG on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PARG Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PARG Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PARG Gene

Proteins for PARG Gene

  • Protein details for PARG Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q86W56-PARG_HUMAN
    Recommended name:
    Poly(ADP-ribose) glycohydrolase
    Protein Accession:
    Q86W56
    Secondary Accessions:
    • A5YBK3
    • B2RC24
    • B4DIU5
    • B4DYR4
    • I6RUV3
    • Q6E4P6
    • Q6E4P7
    • Q7Z742
    • Q9Y4W7

    Protein attributes for PARG Gene

    Size:
    976 amino acids
    Molecular mass:
    111110 Da
    Quaternary structure:
    • Interacts with PCNA (PubMed:21398629). Interacts with NUDT5 (PubMed:27257257).
    Miscellaneous:
    • [Isoform 4]: Catalytically inactive.
    • [Isoform 5]: Catalytically inactive.

    Three dimensional structures from OCA and Proteopedia for PARG Gene

    Alternative splice isoforms for PARG Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PARG Gene

Selected DME Specific Peptides for PARG Gene

Q86W56:
  • KLYPFIYHA
  • KDLWDNKHVKMPCSEQNLYPVEDENGER
  • PDINFNRL
  • TEIVAIDALHFRRYLDQFVPEK
  • CTFPRRN
  • SCQDSEADEE
  • SKENNNTR
  • VATGNWGCG
  • RDNQQFLT
  • AGSRWELIQTALLN
  • SRLFTEVLDHNECLIITGTEQYSEYTGYAETYRW

Post-translational modifications for PARG Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for PARG Gene

Gene Families for PARG Gene

Human Protein Atlas (HPA):
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for PARG Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for PARG Gene

GenScript: Design optimal peptide antigens:
  • Poly(ADP-ribose) glycohydrolase 60 kDa isoform (A5YBK3_HUMAN)
  • Poly(ADP-ribose) glycohydrolase (PARG_HUMAN)
  • Poly (ADP-ribose) glycohydrolase (Q0MQR4_HUMAN)
  • Poly (ADP-ribose) glycohydrolase (Q5SQP4_HUMAN)
  • Poly (ADP-ribose) glycohydrolase (Q5SQP5_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q86W56

UniProtKB/Swiss-Prot:

PARG_HUMAN :
  • The PIP-box mediates interaction with PCNA and localization to replication foci.
  • Belongs to the poly(ADP-ribose) glycohydrolase family.
Domain:
  • The PIP-box mediates interaction with PCNA and localization to replication foci.
Family:
  • Belongs to the poly(ADP-ribose) glycohydrolase family.
genes like me logo Genes that share domains with PARG: view

Function for PARG Gene

Molecular function for PARG Gene

UniProtKB/Swiss-Prot Function:
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).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=[(1''->2')-ADP-alpha-D-ribose]n + H2O = [(1''->2')-ADP-alpha-D-ribose]n-1 + ADP-D-ribose; Xref=Rhea:RHEA:52216, Rhea:RHEA-COMP:15070, Rhea:RHEA-COMP:15071, ChEBI:CHEBI:15377, ChEBI:CHEBI:57967, ChEBI:CHEBI:142512; EC=3.2.1.143; Evidence={ECO:0000269|PubMed:21892188, ECO:0000269|PubMed:23481255};.
GENATLAS Biochemistry:
poly ADP-ribose glycohydrolase,responsible for rapid turnover for ADP-ribose polymer,immediately induced by DNA damage

Enzyme Numbers (IUBMB) for PARG Gene

Phenotypes From GWAS Catalog for PARG Gene

Gene Ontology (GO) - Molecular Function for PARG Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004649 poly(ADP-ribose) glycohydrolase activity TAS --
GO:0005515 protein binding IPI 27257257
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with PARG: view
genes like me logo Genes that share phenotypes with PARG: view

Animal Models for PARG Gene

MGI Knock Outs for PARG:
  • Parg Parg<tm2b(KOMP)Mbp>
  • Parg Parg<tm1Tmd>

Animal Model Products

  • Taconic Biosciences Mouse Models for PARG

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PARG

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PARG Gene

Localization for PARG Gene

Subcellular locations from UniProtKB/Swiss-Prot for PARG Gene

[Isoform 1]: Nucleus. Note=Colocalizes with PCNA at replication foci (PubMed:21398629). Relocalizes to the cytoplasm in response to DNA damage (PubMed:16460818). {ECO:0000269 PubMed:16460818, ECO:0000269 PubMed:21398629}.
[Isoform 2]: Cytoplasm. Note=Translocates to the nucleus in response to DNA damage. {ECO:0000269 PubMed:16460818}.
[Isoform 3]: Cytoplasm.
[Isoform 4]: Cytoplasm. Mitochondrion.
[Isoform 5]: Mitochondrion matrix.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PARG gene
Compartment Confidence
nucleus 5
cytosol 5
mitochondrion 4
plasma membrane 2
cytoskeleton 2
extracellular 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (3)
  • Cytosol (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PARG Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 9074616
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm TAS,IBA 21873635
GO:0005739 mitochondrion IEA --
GO:0005759 mitochondrial matrix IEA --
genes like me logo Genes that share ontologies with PARG: view

Pathways & Interactions for PARG Gene

genes like me logo Genes that share pathways with PARG: view

Gene Ontology (GO) - Biological Process for PARG Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005975 carbohydrate metabolic process IEA --
GO:0006282 regulation of DNA repair IBA 21873635
GO:0006974 cellular response to DNA damage stimulus IEA --
GO:0009225 nucleotide-sugar metabolic process IBA 21873635
GO:0031056 regulation of histone modification IBA 21873635
genes like me logo Genes that share ontologies with PARG: view

No data available for SIGNOR curated interactions for PARG Gene

Drugs & Compounds for PARG Gene

(1) Drugs for PARG Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(5) Additional Compounds for PARG Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist 58-64-0
genes like me logo Genes that share compounds with PARG: view

Transcripts for PARG Gene

mRNA/cDNA for PARG Gene

5 REFSEQ mRNAs :
20 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PARG

Alternative Splicing Database (ASD) splice patterns (SP) for PARG Gene

No ASD Table

Relevant External Links for PARG Gene

GeneLoc Exon Structure for
PARG

Expression for PARG Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PARG Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

  • Bone (Muscoskeletal System)

Protein differential expression in normal tissues from HIPED for PARG Gene

This gene is overexpressed in Breast (67.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for PARG Gene



Protein tissue co-expression partners for PARG Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PARG

SOURCE GeneReport for Unigene cluster for PARG Gene:

Hs.535298

mRNA Expression by UniProt/SwissProt for PARG Gene:

Q86W56-PARG_HUMAN
Tissue specificity: Ubiquitously expressed.

Evidence on tissue expression from TISSUES for PARG Gene

  • Nervous system(4.8)
  • Liver(4.5)
  • Blood(4.5)
  • Skin(4.3)
  • Kidney(2.6)
  • Heart(2.5)
  • Muscle(2.4)
  • Lung(2.3)
  • Intestine(2.2)
  • Spleen(2.1)
genes like me logo Genes that share expression patterns with PARG: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for PARG Gene

Orthologs for PARG Gene

This gene was present in the common ancestor of animals.

Orthologs for PARG Gene

Organism Taxonomy Gene Similarity Type Details
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 96 (a)
OneToMany
-- 31
  • 83 (a)
OneToMany
-- 31
  • 82 (a)
OneToMany
-- 31
  • 18 (a)
OneToMany
Chimpanzee
(Pan troglodytes)
Mammalia PARG 31
  • 95 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia PARG 30 31
  • 91.82 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia PARG 30 31
  • 90.67 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Parg 30 17 31
  • 88.19 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Parg 30
  • 86.55 (n)
Oppossum
(Monodelphis domestica)
Mammalia PARG 31
  • 45 (a)
OneToOne
Chicken
(Gallus gallus)
Aves PARG 30 31
  • 69.75 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia PARG 31
  • 42 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia parg 30
  • 62.53 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.9949 30
Zebrafish
(Danio rerio)
Actinopterygii PARG 31
  • 46 (a)
OneToOne
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.9979 30
Fruit Fly
(Drosophila melanogaster)
Insecta Parg 30 31 32
  • 50.07 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000589 30
  • 47.16 (n)
Worm
(Caenorhabditis elegans)
Secernentea pme-4 31 32
  • 27 (a)
OneToMany
pme-3 31
  • 16 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 52 (a)
OneToOne
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.240 30
Species where no ortholog for PARG was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for PARG Gene

ENSEMBL:
Gene Tree for PARG (if available)
TreeFam:
Gene Tree for PARG (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PARG: view image

Paralogs for PARG Gene

Pseudogenes.org Pseudogenes for PARG Gene

genes like me logo Genes that share paralogs with PARG: view

No data available for Paralogs for PARG Gene

Variants for PARG Gene

Additional dbSNP identifiers (rs#s) for PARG Gene

Structural Variations from Database of Genomic Variants (DGV) for PARG Gene

Variant ID Type Subtype PubMed ID
esv23381 CNV loss 19812545
esv3623178 CNV gain 21293372
esv3623180 CNV loss 21293372
nsv1042677 CNV loss 25217958
nsv1069481 CNV deletion 25765185
nsv442181 CNV gain 18776908
nsv514557 CNV gain 21397061
nsv519934 CNV loss 19592680
nsv8640 CNV gain+loss 18304495
nsv8641 CNV gain 18304495
nsv947982 CNV duplication 23825009
nsv947983 CNV duplication 23825009
nsv947984 CNV duplication 23825009
nsv947985 CNV duplication 23825009
nsv947986 CNV duplication 23825009

Variation tolerance for PARG Gene

Gene Damage Index Score: 2.01; 36.99% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PARG Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
PARG

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PARG Gene

Disorders for PARG Gene

MalaCards: The human disease database

(3) MalaCards diseases for PARG Gene - From: DISEASES

Disorder Aliases PubMed IDs
arthrogryposis, renal dysfunction, and cholestasis 1
  • arcs1
osebold-remondini syndrome
  • brachymesophalangy with mesomelic short limbs and carpal and tarsal osseous abnormalities
hypercholesterolemia, familial, 4
  • fhcl4
- elite association - COSMIC cancer census association via MalaCards
Search PARG in MalaCards View complete list of genes associated with diseases

Additional Disease Information for PARG

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with PARG: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PARG Gene

Publications for PARG Gene

  1. Assignment of the poly(ADP-ribose) glycohydrolase gene (PARG) to human chromosome 10q11.23 and mouse chromosome 14B by in situ hybridization. (PMID: 10449915) Amé JC … Jacobson MK (Cytogenetics and cell genetics 1999) 2 3 4 23
  2. Two small enzyme isoforms mediate mammalian mitochondrial poly(ADP-ribose) glycohydrolase (PARG) activity. (PMID: 17509564) Meyer RG … Jacobson MK (Experimental cell research 2007) 3 4 23
  3. Human poly(ADP-ribose) glycohydrolase is expressed in alternative splice variants yielding isoforms that localize to different cell compartments. (PMID: 15212953) Meyer-Ficca ML … Jacobson MK (Experimental cell research 2004) 3 4 23
  4. Human poly(ADP-ribose) glycohydrolase (PARG) gene and the common promoter sequence it shares with inner mitochondrial membrane translocase 23 (TIM23). (PMID: 14527731) Meyer RG … Jacobson MK (Gene 2003) 3 4 23
  5. ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodeling. (PMID: 27257257) Wright RH … Beato M (Science (New York, N.Y.) 2016) 3 4

Products for PARG Gene

Sources for PARG Gene