A1pp Appr-1"-p processing enzyme
SMART ACC:	SM000506
Description:	Function determined by Martzen et al. Extended family detected by reciprocal PSI-BLAST searches (unpublished results, and Pehrson & Fuji).
InterPro ACC:	IPR002589
InterPro abstract:	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 [ PUBMED:16959969 ]: in certain cases it is believed to bind non-covalently [ PUBMED:18983849 … expand 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 [ PUBMED:16959969 ]: in certain cases it is believed to bind non-covalently [ PUBMED:18983849 ]; 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 [ PUBMED:18172500 ]. The domain was described originally in association with ADP-ribose 1''-phosphate (Appr-1''-P) processing activity (A1pp) of the yeast YBR022W protein [ PUBMED:10550052 ]. The domain is also called Macro domain as it is the C-terminal domain of mammalian core histone macro-H2A [ PUBMED:11343911 PUBMED:12842467 ]. Macro domain proteins can be found in eukaryotes, in (mostly pathogenic) bacteria, in archaea and in ssRNA viruses, such as coronaviruses [ PUBMED:21525212 PUBMED:31095648 ], 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 [ PUBMED:15902274 ]. The human macroH2A1.1 Macro domain binds an NAD metabolite O-acetyl-ADP-ribose [ PUBMED:15965484 ]. 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 SARS-CoV Macro domain has a mixed α/β fold consisting of a central seven-stranded twisted mixed β-sheet sandwiched between two α-helices on one face, and three on the other. The final α-helix, located on the edge of the central β-sheet, forms the C terminus of the protein [ PUBMED:16912299 ]. The crystal structure of AF1521 (a Macro domain-only protein from Archaeoglobus fulgidus) has also been reported and compared with other Macro domain containing proteins. Several Macro domain only proteins are shorter than AF1521, and appear to lack either the first strand of the β-sheet or the C-terminal helix 5. Well conserved residues form a hydrophobic cleft and cluster around the AF1521-ADP-ribose binding site [ PUBMED:12842467 PUBMED:15902274 PUBMED:15965484 PUBMED:16912299 ]. collapse
Family alignment:	View the Family alignment or the Alignment consensus sequence
There are 16 662 A1pp domains in 14 754 proteins in SMART's NRDB database.

Taxonomic distribution of proteins containing A1pp domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing A1pp domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Relevant references for this domain

Primary literature for the A1pp domain is listed below. Automatically-derived, secondary literature is also available.

KEGG pathways involving proteins which contain this domain

This information is based on the mapping of SMART genomic protein database to KEGG orthologous groups. Percentages are related to the number of proteins containing a A1pp domain which could be assigned to a KEGG orthologous group, and not all proteins containing A1pp domains. Please note that proteins can be included in multiple pathways, ie. the numbers below will not add to 100%.

KEGG pathways

Some of these pathways are included in the interactive Pathways Explorer overview maps. Select an overview map and click the button below to highlight them in iPath.

KEGG orthologous groups

Some of these KOs are included in the interactive Pathways Explorer overview maps. Select an overview map and click the button below to highlight them in iPath.

3D structures in PDB containing this domain

Links to other resources describing this domain

InterPro	IPR002589