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PROSITE documentation PDOC51977 [for PROSITE entry PS51977]

WGR domain profile





Description

Poly (ADP-ribose) polymerase (PARP) enzymes are a family of proteins involved in a number of cellular processes including gene regulation, chromatin remodeling, DNA repair and apoptosis. These enzymes are present in all eukaryotes except yeast. PARPs can either transfer a single unit of (ADP-ribose) or more than one (ADP-ribose) moieties from NAD(+) onto substrates yielding poly (ADP-ribose) (PAR) chains, which can be of varying length and branch content. The PARP superfamily is composed of 17 members that have a conserved catalytic (CAT) domain (see <PDOC51059>) with various domains like zinc finger (see <PDOC00360>), BRCT (see <PDOC50172>), SAM (see <PDOC50105>), SAP (see <PDOC50800>, ankyrin (see <PDOC50088>) and macro domain (see <PDOC51154>). PARP-1, PARP-2 and PARP-3 are DNA-dependent PARPs that localize to DNA damage, synthesize PAR covalently attached to target proteins including themselves, and thereby recruit repair factors to DNA breaks to increase repair efficiency. PARP-1, PARP-2 and PARP-3 have in common two C-terminal domains, an 80-90 amino acid long tryptophane-, glycine-, arginine-rich (WGR) domain and the CAT domain. The WGR domain participates in binding DNA near the 5' terminus and mediates domain-domain contacts essential for DNA-dependent activity. The CAT domain, which is responsible for binding the substrate NAD(+) and for the synthesis of PAR,contains two subdomains: a helical domain (HD) that is conserved in DNA damage-dependent PARPs 1, 2, and 3, and the ADP-ribosyltransferase (ART) domain that contains the active site and a fold that is conserved in all PARP family members [1,2,3,4,5,6].

WGR binds to the 5'-terminus of one DNA strand, holding the DNA backbone between the central β sheet and the α helix of WGR (see <PDB:4DQY>) [6].

The profile we developed covers the entire WGR domain.

Last update:

June 2021 / First entry.

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Technical section

PROSITE method (with tools and information) covered by this documentation:

WGR, PS51977; WGR domain profile  (MATRIX)


References

1AuthorsJubin T. Kadam A. Jariwala M. Bhatt S. Sutariya S. Gani A.R. Gautam S. Begum R.
TitleThe PARP family: insights into functional aspects of poly (ADP-ribose) polymerase-1 in cell growth and survival.
SourceCell. Prolif. 49:421-437(2016).
PubMed ID27329285
DOI10.1111/cpr.12268

2AuthorsObaji E. Haikarainen T. Lehtioe L.
TitleStructural basis for DNA break recognition by ARTD2/PARP2.
SourceNucleic. Acids. Res. 46:12154-12165(2018).
PubMed ID30321391
DOI10.1093/nar/gky927

3AuthorsLangelier M.-F. Riccio A.A. Pascal J.M.
TitlePARP-2 and PARP-3 are selectively activated by 5' phosphorylated DNA breaks through an allosteric regulatory mechanism shared with PARP-1.
SourceNucleic. Acids. Res. 42:7762-7775(2014).
PubMed ID24928857
DOI10.1093/nar/gku474

4AuthorsDawicki-McKenna J.M. Langelier M.-F. DeNizio J.E. Riccio A.A. Cao C.D. Karch K.R. McCauley M. Steffen J.D. Black B.E. Pascal J.M.
TitlePARP-1 Activation Requires Local Unfolding of an Autoinhibitory Domain.
SourceMol. Cell. 60:755-768(2015).
PubMed ID26626480
DOI10.1016/j.molcel.2015.10.013

5AuthorsAltmeyer M. Messner S. Hassa P.O. Fey M. Hottiger M.O.
TitleMolecular mechanism of poly(ADP-ribosyl)ation by PARP1 and identification of lysine residues as ADP-ribose acceptor sites.
SourceNucleic. Acids. Res. 37:3723-3738(2009).
PubMed ID19372272
DOI10.1093/nar/gkp229

6AuthorsLangelier M.-F. Planck J.L. Roy S. Pascal J.M.
TitleStructural basis for DNA damage-dependent poly(ADP-ribosyl)ation by human PARP-1.
SourceScience 336:728-732(2012).
PubMed ID22582261
DOI10.1126/science.1216338



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