{PDOC50249}
{PS50249; MPN}
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* MPN domain profile *
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The MPN  (Mpr1,  Pad1 N-terminal) domain (also known as the Mov34, JAB, PAD-1,
or JAMM  (JAB1/MPN/Mov34 metalloenzyme) domain) is a widespread 120 amino acid
protein module  found  in  archaea, bacteria and eukaryotes. In eukaryotes the
MPN domain  is  found  in subunits of several multiprotein complexes including
the proteasome,  whereas  in eubacteria and archaea, the MPN domain is usually
found in single domain proteins [1,2,3,4,5,6,7].

Within the   MPN   domain   super-family,   two   main  subclasses  have  been
characterized: the  MPN+  and  MPN-  domain-containing  proteins. MPN+ domain-
containing proteins   are   classified   as   metalloenzymes  responsible  for
isopeptidase activity.  These proteins contain a conserved glutamate (E) and a
JAMM (Jab1/MPN/Mov34 metalloenzyme) motif, typically consisting of a canonical
sequence (H-x-H-x[7]-S-x[2]-D)  and  coordinating  a  zinc ion. The E and JAMM
motif specify  a  catalytic  center  essential  for  selective  hydrolysis  of
linkages, contained   between  ubiquitin/ubiquitin-like  proteins  and  target
proteins or  between ubiquitin monomers within a polymeric chain. MPN- domains
are recognizable by the absence of essential Zn(2+)-coordinating residues that
are required  for catalytic function. In protein complexes, an MPN+ domain can
associate with  MPN-  domains  for  purposes  that  are  not  well  understood
[1,3,6,7].

The MPN  domain  is  composed  of a five-stranded mixed beta-sheet with strand
order 21345  sanwiched  between  two  alpha-helices. There is a second smaller
three-stranded parallel  beta-sheet  formed by residues at the N and C termini
and in  the  loop  between  the  first  two  strands  of  the  main sheet (see
<PDB:1OI0>). MPN  domains  often  form  part  of  larger proteins. The N and C
termini of the structure are close in space, allowing it to be easily inserted
into a  multidomain  protein. The histidine and aspartate residues of the JAMM
motif coordinate a zinc ion [2,3,7].

Some proteins known to contain a MPN domain are listed below:

 - Eukaryotic COP9 signalosome complex subunit 5 (CSN5).
 - Eukaryotic COP9 signalosome complex subunit 6 (CSN6).
 - Eukaryotic 26S proteasome regulatory subunit RPN11.
 - Eukaryotic  26S  proteasome  non-ATPase  subunit  7  (PSMD7), also known as
   Mov34.
 - Eukaryotic AMSH (associated molecule with the SH3 domain of STAM) proteins,
   zinc metalloproteases that specifically cleave ubiquitin chains.
 - Eukaryotic  pre-mRNA-splicing  factor 8 (PRP8), a component of the U5 small
   nuclear RNA-protein (snRNP) complex.
 - Eukaryotic  translation  initiation  factor 3 (eIF3) subunits f and h (also
   known as subunits p47 and p40, respectively).
 - Animal BRCC36 family proteins, Lys-63-specific deubiquitinases.
 - Animal BRCA1-A complex subunit Abraxas.
 - Animal BRISC complex subunit Abro1.
 - Bacterial UPF0758 protein.
 - Bacteriophage lambda tail assembly protein 'K' (vtak).

The profile we developed covers the entire MPN domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: June 2017 / First entry.

[ 1] Maytal-Kivity V., Reis N., Hofmann K., Glickman M.H.
     "MPN+, a putative catalytic motif found in a subset of MPN domain
     proteins from eukaryotes and prokaryotes, is critical for Rpn11
     function."
     BMC Biochem. 3:28-28(2002).
     PubMed=12370088
[ 2] Tran H.J.T.T., Allen M.D., Loewe J., Bycroft M.
     "Structure of the Jab1/MPN domain and its implications for proteasome
     function."
     Biochemistry 42:11460-11465(2003).
     PubMed=14516197; DOI=10.1021/bi035033g
[ 3] Ambroggio X.I., Rees D.C., Deshaies R.J.
     "JAMM: a metalloprotease-like zinc site in the proteasome and
     signalosome."
     PLoS Biol. 2:E2-E2(2004).
     PubMed=14737182; DOI=10.1371/journal.pbio.0020002
[ 4] Grainger R.J., Beggs J.D.
     "Prp8 protein: at the heart of the spliceosome."
     RNA 11:533-557(2005).
     PubMed=15840809; DOI=10.1261/rna.2220705
[ 5] Patterson-Fortin J., Shao G., Bretscher H., Messick T.E.,
     Greenberg R.A.
     "Differential regulation of JAMM domain deubiquitinating enzyme
     activity within the RAP80 complex."
     J. Biol. Chem. 285:30971-30981(2010).
     PubMed=20656689; DOI=10.1074/jbc.M110.135319
[ 6] Birol M., Echalier A.
     "Structure and function of MPN (Mpr1/Pad1 N-terminal)
     domain-containing proteins."
     Curr. Protein Pept. Sci. 15:504-517(2014).
     PubMed=24555901
[ 7] Zeqiraj E., Tian L., Piggott C.A., Pillon M.C., Duffy N.M.,
     Ceccarelli D.F., Keszei A.F.A., Lorenzen K., Kurinov I., Orlicky S.,
     Gish G.D., Heck A.J.R., Guarne A., Greenberg R.A., Sicheri F.
     "Higher-Order Assembly of BRCC36-KIAA0157 Is Required for DUB Activity
     and Biological Function."
     Mol. Cell 59:970-983(2015).
     PubMed=26344097; DOI=10.1016/j.molcel.2015.07.028

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