|PROSITE documentation PDOC51154 [for PROSITE entry PS51154]|
The Macro or A1pp domain is a module of ~180 amino acids which can bind ADP-ribose, an NAD metabolite or related ligands. The domain was described originally in association with ADP-ribose 1''-phosphate (Appr-1''-P) processing activity (A1pp) of the yeast YBR022W protein . The domain is also called Macro domain as it is the C-terminal domain of mammalian core histone macro-H2A [2,3]. Macro domain proteins can be found in eukaryotes, in (mostly pathogenic) bacteria, in archaea and in ssRNA viruses, such as coronaviruses, Rubella and Hepatitis E viruses. In vertebrates the domain occurs e.g. in histone macroH2A, in predicted poly-ADP-ribose polymerases (PARPs) and in B aggressive lymphoma (BAL) protein. The macro domain can be associated with catalytic domains, such as PARP (see <PDOC51059>), or sirtuin (See <PDOC50305>). The Macro domain can recognize ADP-ribose or in some cases poly-ADP-ribose, which can be involved in ADP-ribosylation reactions that occur in important processes, such as chromatin biology, DNA repair and transcription regulation . The human macroH2A1.1 Macro domain binds an NAD metabolite O-acetyl-ADP-ribose . The Macro domain has been suggested to play a regulatory role in ADP-ribosylation, which is involved in inter- and intracellular signaling, transcriptional regulation, DNA repair pathways and maintenance of genomic stability, telomere dynamics, cell differentiation and proliferation, and necrosis and apoptosis.
The 3D structure of the Macro domain has a mixed α/β fold of a mixed β sheet sandwiched between four helices (see <PDB:2BFQ>). Several Macro domain only domains are shorter than the structure of AF1521 and lack either the first strand or the C-terminal helix 5. Well conserved residues form a hydrophobic cleft and cluster around the AF1521-ADP-ribose binding site [3,4,5,6].
Some proteins known to contain a Macro domain:
The profile we developed covers the entire Macro domain.Note:
The Macro domain has also been called A1pp, the X domain, ADRP or macro-H2A domain.Last update:
May 2007 / Text revised.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Martzen M.R. McCraith S.M. Spinelli S.L. Torres F.M. Fields S. Grayhack E.J. Phizicky E.M.|
|Title||A biochemical genomics approach for identifying genes by the activity of their products.|
|Title||The WWE domain: a common interaction module in protein ubiquitination and ADP ribosylation.|
|Source||Trends Biochem. Sci. 26:273-275(2001).|
|3||Authors||Allen M.D. Buckle A.M. Cordell S.C. Lowe J. Bycroft M.|
|Title||The crystal structure of AF1521 a protein from Archaeoglobus fulgidus with homology to the non-histone domain of macroH2A.|
|Source||J. Mol. Biol. 330:503-511(2003).|
|4||Authors||Karras G.I. Kustatscher G. Buhecha H.R. Allen M.D. Pugieux C. Sait F. Bycroft M. Ladurner A.G.|
|Title||The macro domain is an ADP-ribose binding module.|
|Source||EMBO J. 24:1911-1920(2005).|
|5||Authors||Kustatscher G. Hothorn M. Pugieux C. Scheffzek K. Ladurner A.G.|
|Title||Splicing regulates NAD metabolite binding to histone macroH2A.|
|Source||Nat. Struct. Mol. Biol. 12:624-625(2005).|
|6||Authors||Egloff M.P. Malet H. Putics A. Heinonen M. Dutartre H. Frangeul A. Gruez A. Campanacci V. Cambillau C. Ziebuhr J. Ahola T. Canard B.|
|Title||Structural and functional basis for ADP-ribose and poly(ADP-ribose) binding by viral macro domains.|
|Source||J. Virol. 80:8493-8502(2006).|