{PDOC51154}
{PS51154; MACRO}
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* Macro domain profile *
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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 alpha/beta fold of a mixed
beta  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 [3-6].

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.
 - Alphavirus non-structural protein 3.

The  profile we developed covers the entire Macro domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Note:  The  Macro  domain  has  also  been called A1pp, the X domain, ADRP or
 macro-H2A domain.

-Last update: May 2007 / Text revised.

[ 1] Martzen M.R., McCraith S.M., Spinelli S.L., Torres F.M., Fields S.,
     Grayhack E.J., Phizicky E.M.
     "A biochemical genomics approach for identifying genes by the activity
     of their products."
     Science 286:1153-1155(1999).
     PubMed=10550052
[ 2] Aravind L.
     "The WWE domain: a common interaction module in protein ubiquitination
     and ADP ribosylation."
     Trends Biochem. Sci. 26:273-275(2001).
     PubMed=11343911
[ 3] Allen M.D., Buckle A.M., Cordell S.C., Lowe J., Bycroft M.
     "The crystal structure of AF1521 a protein from Archaeoglobus fulgidus
     with homology to the non-histone domain of macroH2A."
     J. Mol. Biol. 330:503-511(2003).
     PubMed=12842467
[ 4] Karras G.I., Kustatscher G., Buhecha H.R., Allen M.D., Pugieux C.,
     Sait F., Bycroft M., Ladurner A.G.
     "The macro domain is an ADP-ribose binding module."
     EMBO J. 24:1911-1920(2005).
     PubMed=15902274; DOI=10.1038/sj.emboj.7600664
[ 5] Kustatscher G., Hothorn M., Pugieux C., Scheffzek K., Ladurner A.G.
     "Splicing regulates NAD metabolite binding to histone macroH2A."
     Nat. Struct. Mol. Biol. 12:624-625(2005).
     PubMed=15965484; DOI=10.1038/nsmb956
[ 6] 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.
     "Structural and functional basis for ADP-ribose and poly(ADP-ribose)
     binding by viral macro domains."
     J. Virol. 80:8493-8502(2006).
     PubMed=16912299; DOI=10.1128/JVI.00713-06

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