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PROSITE documentation PDOC51154 [for PROSITE entry PS51154]

Macro domain profile





Description

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 [1]. 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 [4]. The human macroH2A1.1 Macro domain binds an NAD metabolite O-acetyl-ADP-ribose [5]. 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:

  • Mammalian histone macro-H2A.1 and macro-H2A.2, the latter with an alternatively spliced Macro domain. These histones are enriched in the chromatin of inactive X-chromosomes and appear to have a role in transcriptional silencing [3,5].
  • Mammalian B aggressive lymphoma protein (BAL), which is a highly expressed risk factor in some agressive lymphomas.
  • Mammalian PARP-14 and PARP-15 proteins, with predicted PARP activity.
  • Yeast YBR022W protein, which catalyzes the hydrolyzation of Appr-1''-P, a metabolite from tRNA splicing, to ADP-ribose and Pi.
  • Archaeoglobus fulgidus AF1521 and related archaeal and bacterial proteins.
  • Coronaviral papain-like proteinase (nsp3), in replicase polyprotein 1ab, which is responsible for cleavages at the N-terminus of replicase polyprotein.
  • Rubella virus protease p150.
  • Hepatitis E virus non-structural polyprotein.
  • αvirus non-structural protein 3.

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.

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Technical section

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

MACRO, PS51154; Macro domain profile  (MATRIX)


References

1AuthorsMartzen M.R. McCraith S.M. Spinelli S.L. Torres F.M. Fields S. Grayhack E.J. Phizicky E.M.
TitleA biochemical genomics approach for identifying genes by the activity of their products.
SourceScience 286:1153-1155(1999).
PubMed ID10550052

2AuthorsAravind L.
TitleThe WWE domain: a common interaction module in protein ubiquitination and ADP ribosylation.
SourceTrends Biochem. Sci. 26:273-275(2001).
PubMed ID11343911

3AuthorsAllen M.D. Buckle A.M. Cordell S.C. Lowe J. Bycroft M.
TitleThe crystal structure of AF1521 a protein from Archaeoglobus fulgidus with homology to the non-histone domain of macroH2A.
SourceJ. Mol. Biol. 330:503-511(2003).
PubMed ID12842467

4AuthorsKarras G.I. Kustatscher G. Buhecha H.R. Allen M.D. Pugieux C. Sait F. Bycroft M. Ladurner A.G.
TitleThe macro domain is an ADP-ribose binding module.
SourceEMBO J. 24:1911-1920(2005).
PubMed ID15902274
DOI10.1038/sj.emboj.7600664

5AuthorsKustatscher G. Hothorn M. Pugieux C. Scheffzek K. Ladurner A.G.
TitleSplicing regulates NAD metabolite binding to histone macroH2A.
SourceNat. Struct. Mol. Biol. 12:624-625(2005).
PubMed ID15965484
DOI10.1038/nsmb956

6AuthorsEgloff M.P. Malet H. Putics A. Heinonen M. Dutartre H. Frangeul A. Gruez A. Campanacci V. Cambillau C. Ziebuhr J. Ahola T. Canard B.
TitleStructural and functional basis for ADP-ribose and poly(ADP-ribose) binding by viral macro domains.
SourceJ. Virol. 80:8493-8502(2006).
PubMed ID16912299
DOI10.1128/JVI.00713-06



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