|PROSITE documentation PDOC50249 [for PROSITE entry PS50249]|
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 [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:
The profile we developed covers the entire MPN domain.Last update:
June 2017 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Maytal-Kivity V. Reis N. Hofmann K. Glickman M.H.|
|Title||MPN+, a putative catalytic motif found in a subset of MPN domain proteins from eukaryotes and prokaryotes, is critical for Rpn11 function.|
|Source||BMC Biochem. 3:28-28(2002).|
|2||Authors||Tran H.J.T.T. Allen M.D. Loewe J. Bycroft M.|
|Title||Structure of the Jab1/MPN domain and its implications for proteasome function.|
|3||Authors||Ambroggio X.I. Rees D.C. Deshaies R.J.|
|Title||JAMM: a metalloprotease-like zinc site in the proteasome and signalosome.|
|Source||PLoS Biol. 2:E2-E2(2004).|
|4||Authors||Grainger R.J. Beggs J.D.|
|Title||Prp8 protein: at the heart of the spliceosome.|
|5||Authors||Patterson-Fortin J. Shao G. Bretscher H. Messick T.E. Greenberg R.A.|
|Title||Differential regulation of JAMM domain deubiquitinating enzyme activity within the RAP80 complex.|
|Source||J. Biol. Chem. 285:30971-30981(2010).|
|6||Authors||Birol M. Echalier A.|
|Title||Structure and function of MPN (Mpr1/Pad1 N-terminal) domain-containing proteins.|
|Source||Curr. Protein Pept. Sci. 15:504-517(2014).|
|7||Authors||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.|
|Title||Higher-Order Assembly of BRCC36-KIAA0157 Is Required for DUB Activity and Biological Function.|
|Source||Mol. Cell 59:970-983(2015).|