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Information on EC 5.6.1.5 - proteasome ATPase

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EC Tree
IUBMB Comments
Belongs to the AAA-type superfamily and, like EC 5.6.1.4 (minus-end-directed kinesin ATPase), is involved in channel gating and polypeptide unfolding before proteolysis in the proteasome. Six ATPase subunits are present in the regulatory particle (RP) of 26S proteasome.
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UNIPROT: P9WQN5
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Word Map
  • 5.6.1.5
  • atpases
  • ubiquitin-proteasome
  • subcomplexes
  • misfolded
  • hexameric
  • polyubiquitinated
  • disassembly
  • hslu
  • ubiquitin-dependent
  • non-atpase
  • ubiquitin-like
  • er-associated
  • multisubunit
  • deubiquitinase
  • reticulum-associated
  • proteotoxic
  • retrotranslocation
  • proteasome-mediated
  • escrts
  • deubiquitylating
  • valosin-containing
  • immunoproteasome
  • katanin
  • proteasome-associated
  • zellweger
  • escrt-iii
  • spastin
  • medicine
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
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=
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unfolded polypeptide
Synonyms
aaa atpase, pa700, 19s regulatory particle, 19s proteasome, hslvu, tbp-1, 19s rp, rpt2a, psmc5, 26s-proteasome, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mtb proteasomal ATPase
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proteasomal ATPase Mpa
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RP triphosphatase
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-
-
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RP triple-A protein
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-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
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-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (polypeptide-degrading)
Belongs to the AAA-type superfamily and, like EC 5.6.1.4 (minus-end-directed kinesin ATPase), is involved in channel gating and polypeptide unfolding before proteolysis in the proteasome. Six ATPase subunits are present in the regulatory particle (RP) of 26S proteasome.
CAS REGISTRY NUMBER
COMMENTARY hide
9000-83-3
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
proteasome-mediated protein turnover in all domains of life is an energy-dependent process that requires ATPase activity. Mycobacterium tuberculosis possesses an ubiquitin-like proteasome pathway that plays an essential role in its resistance to killing by products of host macrophages
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
ARC_MYCTU
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
609
0
67401
Swiss-Prot
-
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
100000
gel filtration, suggesting that Mpa-ID oligomerized in solution as a hexamer
16600
6 * 20000, SDS-PAGE, 6 * 16600, predicted
20000
6 * 20000, SDS-PAGE, 6 * 16600, predicted
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dodecamer
Mpa-ID forms hexamers in the crystal structure, two hexamers stack end to end, forming a dodecamer, being the packing unit in the crystal structure
hexamer
monomer
Mpa is a monomer of 67000 Da that assembles into a hexameric ring. Each monomer consists of three main regions, an N-terminal coiled-coil domain (CC, residues 1-98), an interdomain (ID, residues 99-216) and an ATPase domain of the AAA-type (residues 217-609). The N-terminal coiled-coil domain of Mpa specifically interacts with Pub-decorated beads, indicating that it mediates the binding to pupylated substrates
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
characterization of the structural determinants of Pup (mybacterial ubiquitin-like protein) and its interaction witrh Mpa. The N-terminal coiled-coil domain of Mpa makes extensive contacts along the central region (residues 21-58) of Pup leaving its N-terminal uncontrained and available for other functional interactions
of the conserved interdomain shows a five stranded double beta barrel structure containing a Greek key motif, 2.0 A resolution. Structure and mutational analysis indicate a major role of the interdomain for Mpa hexamerization. The central in the Mpa hexamer is involved in protein substrate translocation and degradation. Mpa is a multidomain structure, with an N-terminal coiled coil domain, a 150 amino acid interdomain (Mpa-ID) that is unique to the proteasome-associated ATPases, a canonical AAA (ATPase associated with various activities) domain, and a small C-terminal domain. The Mpa-ID forms a tightly packed ring-shaped hexamer in the crystal structure as well as in solution. In fact, two hexamers stack end to end, forming a dodecamer, being the packiung unit in the crystal structure
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
R173E/W187A/K235E
triple mutant disrupts the salt-bridges and the hydrophobic interaction during hexamerization. In gel filtration the triple mutant Mpa-ID elutes as monomeric
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
full length protein, the interdomain Mpa-ID and the mutant forms
Mpa fragments are purified as N-terminal fusions with His6-tagged maltose-binding protein followed by a TEV cleavage site, producing the folowing fragments: Mpa-wt (residues 1-609), Mpa-CC (residues 1-98), Mpa-ID (99-216), and Mpa-CC-ID (1-216)
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sutter, M.; Striebel, F.; Damberger, F.F.; Allain, F.H.; Weber-Ban, E.
A distinct structural region of the prokaryotic ubiquitin-like protein (Pup) is recognized by the N-terminal domain of the proteasomal ATPase Mpa
FEBS Lett.
583
3151-3157
2009
Mycobacterium tuberculosis (P9WQN5), Mycobacterium tuberculosis H37Rv (P9WQN5)
Manually annotated by BRENDA team
Wang, T.; Li, H.; Lin, G.; Tang, C.; Li, D.; Nathan, C.; Darwin, K.H.; Li, H.
Structural insights on the Mycobacterium tuberculosis proteasomal ATPase Mpa
Structure
17
1377-1385
2009
Mycobacterium tuberculosis (P9WQN5), Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv (P9WQN5)
Manually annotated by BRENDA team