{PDOC51977} {PS51977; WGR} {BEGIN} ********************** * WGR domain profile * ********************** 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 ) with various domains like zinc finger (see ), BRCT (see ), SAM (see ), SAP (see , ankyrin (see ) and macro domain (see ). 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 beta sheet and the alpha helix of WGR (see ) [6]. The profile we developed covers the entire WGR domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: June 2021 / First entry. [ 1] Jubin T., Kadam A., Jariwala M., Bhatt S., Sutariya S., Gani A.R., Gautam S., Begum R. "The PARP family: insights into functional aspects of poly (ADP-ribose) polymerase-1 in cell growth and survival." Cell. Prolif. 49:421-437(2016). PubMed=27329285; DOI=10.1111/cpr.12268 [ 2] Obaji E., Haikarainen T., Lehtioe L. "Structural basis for DNA break recognition by ARTD2/PARP2." Nucleic. Acids. Res. 46:12154-12165(2018). PubMed=30321391; DOI=10.1093/nar/gky927 [ 3] Langelier M.-F., Riccio A.A., Pascal J.M. "PARP-2 and PARP-3 are selectively activated by 5' phosphorylated DNA breaks through an allosteric regulatory mechanism shared with PARP-1." Nucleic. Acids. Res. 42:7762-7775(2014). PubMed=24928857; DOI=10.1093/nar/gku474 [ 4] Dawicki-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. "PARP-1 Activation Requires Local Unfolding of an Autoinhibitory Domain." Mol. Cell. 60:755-768(2015). PubMed=26626480; DOI=10.1016/j.molcel.2015.10.013 [ 5] Altmeyer M., Messner S., Hassa P.O., Fey M., Hottiger M.O. "Molecular mechanism of poly(ADP-ribosyl)ation by PARP1 and identification of lysine residues as ADP-ribose acceptor sites." Nucleic. Acids. Res. 37:3723-3738(2009). PubMed=19372272; DOI=10.1093/nar/gkp229 [ 6] Langelier M.-F., Planck J.L., Roy S., Pascal J.M. "Structural basis for DNA damage-dependent poly(ADP-ribosyl)ation by human PARP-1." Science 336:728-732(2012). PubMed=22582261; DOI=10.1126/science.1216338 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}