PROSITE documentation PDOC50249

MPN domain profile

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 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 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.