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-S-x-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
The MPN domain is composed of a five-stranded mixed β-sheet with strand
order 21345 sanwiched between two α-helices. There is a second smaller
three-stranded parallel β-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
- 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.
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