<p>The Macro or A1pp domain is a module of about 180 amino acids which can bind ADP-ribose, an NAD metabolite or related ligands. Binding to ADP-ribose could be either covalent or non-covalent [<cite idref="PUB00052327"/>]: in certain cases it is believed to bind non-covalently [<cite idref="PUB00052325"/>]; while in other cases (such as Aprataxin) it appears to bind both non-covalently through a zinc finger motif, and covalently through a separate region of the protein [<cite idref="PUB00052328"/>]. The domain was described originally in association with ADP-ribose 1''-phosphate (Appr-1''-P) processing activity (A1pp) of the yeast YBR022W protein [<cite idref="PUB00019075"/>]. The domain is also called Macro domain as it is the C-terminal domain of mammalian core histone macro-H2A [<cite idref="PUB00018391"/>, <cite idref="PUB00021744"/>]. 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, or sirtuin. The Macro domain can recognise 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 [<cite idref="PUB00021032"/>]. The human macroH2A1.1 Macro domain binds an NAD metabolite O-acetyl-ADP-ribose [<cite idref="PUB00033734"/>]. 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. </p><p>The 3D structure of the Macro domain has a mixed alpha/beta fold of a mixed beta sheet sandwiched between four helices. 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 [<cite idref="PUB00021744"/>, <cite idref="PUB00021032"/>, <cite idref="PUB00033734"/>, <cite idref="PUB00043976"/>]. </p> Appr-1-p processing