Information on EC 3.4.24.B18 - m-AAA protease

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.4.24.B18
preliminary BRENDA-supplied EC number
RECOMMENDED NAME
GeneOntology No.
m-AAA protease
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
proteolytic degradation of proteins
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
CAS REGISTRY NUMBER
COMMENTARY hide
213390-44-4
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
enzyme belongs to the AAA protease family
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
alpha-casein + H2O
?
show the reaction diagram
-
best substrate
-
-
?
apocytochrome P450scc + H2O
?
show the reaction diagram
-
bovine protein substrate from adrenal cortex mitochondrial inner membrane, imported in vitro into isolated yeast mitochondrial membrane, due to an N-terminal fusion to a heterologous transmembrane region
-
?
beta-casein + H2O
?
show the reaction diagram
-
-
-
-
?
carbonylated membrane proteins + H2O
?
show the reaction diagram
-
-
-
-
?
cytochrome c peroxidase + H2O
?
show the reaction diagram
cytochrome c peroxidase 1 + H2O
?
show the reaction diagram
HMG1-phosphorylated mitochondrial transcription factor A + H2O
?
show the reaction diagram
-
-
-
-
?
hybrid protein + H2O
2 peptide fragments f2 and f3
show the reaction diagram
-
hybrid protein of subunit 2 of cytochrome oxidase residues 1-74, mouse dihydrofolate reductase, and mitochondrial presequence, residues 1-66, of subunit 9 of the ATPase of Neurospora crassa, in vitro import into the mitochondrion
product characterization
?
kappa-casein + H2O
?
show the reaction diagram
-
-
-
-
?
mitochondrial integral inner membrane protein Yme2p + H2O
?
show the reaction diagram
MrpL32 + H2O
?
show the reaction diagram
protein + H2O
peptides
show the reaction diagram
protein Atp7 + H2O
?
show the reaction diagram
-
subunit of F1Fo-ATP synthase, peripheral membrane protein
-
-
?
protein Cob + H2O
?
show the reaction diagram
-
degradation of membrane proteins, essentially required as a membrane-integrated quality control
-
?
protein Cox1 + H2O
?
show the reaction diagram
-
degradation of membrane proteins, essentially required as a membrane-integrated quality control
-
?
protein Cox3 + H2O
?
show the reaction diagram
-
degradation of membrane proteins, essentially required as a membrane-integrated quality control
-
?
protein F0 subunit 6 + H2O
?
show the reaction diagram
-
degradation of membrane proteins, essentially required as a membrane-integrated quality control
-
?
protein F0 subunit 8 + H2O
?
show the reaction diagram
-
degradation of membrane proteins, essentially required as a membrane-integrated quality control
-
?
protein F0 subunit 9 + H2O
?
show the reaction diagram
-
degradation of membrane proteins, essentially required as a membrane-integrated quality control
-
?
protein OAP1 + H2O
?
show the reaction diagram
-
homo-oligomeric m-AAA protease complexes composed of murine Afg3l1, Afg3l2, or human AFG3L2 subunits cleave OPA1 with higher efficiency than paraplegin-containing m-AAA proteases
-
-
?
residues 1-74 of subunit 2 of cytochrome oxidase + H2O
?
show the reaction diagram
-
two-step procedure, in vitro import into the mitochondrion
-
?
rhodamine 110, bis-(Cbz-L-alanyl-L-alanine amide) + H2O
?
show the reaction diagram
-
-
-
-
?
unassembled cytochrome oxidase 2 + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
carbonylated membrane proteins + H2O
?
show the reaction diagram
-
-
-
-
?
cytochrome c peroxidase + H2O
?
show the reaction diagram
-
the m-AAA protease is enriched in the inner boundary membrane of mitochondria. The membrane-anchored precursor form of cytochrome c peroxidase (pCcp1) is preferentially localized in this subdomain of the inner membrane. On processing by the m-AAA protease and rhomboid protease Pcp1, the mature Ccp1 is released and moves into the cristae space
-
-
?
cytochrome c peroxidase 1 + H2O
?
show the reaction diagram
HMG1-phosphorylated mitochondrial transcription factor A + H2O
?
show the reaction diagram
-
-
-
-
?
MrpL32 + H2O
?
show the reaction diagram
protein + H2O
peptides
show the reaction diagram
protein Atp7 + H2O
?
show the reaction diagram
-
subunit of F1Fo-ATP synthase, peripheral membrane protein
-
-
?
protein Cob + H2O
?
show the reaction diagram
-
degradation of membrane proteins, essentially required as a membrane-integrated quality control
-
?
protein Cox1 + H2O
?
show the reaction diagram
-
degradation of membrane proteins, essentially required as a membrane-integrated quality control
-
?
protein Cox3 + H2O
?
show the reaction diagram
-
degradation of membrane proteins, essentially required as a membrane-integrated quality control
-
?
protein F0 subunit 6 + H2O
?
show the reaction diagram
-
degradation of membrane proteins, essentially required as a membrane-integrated quality control
-
?
protein F0 subunit 8 + H2O
?
show the reaction diagram
-
degradation of membrane proteins, essentially required as a membrane-integrated quality control
-
?
protein F0 subunit 9 + H2O
?
show the reaction diagram
-
degradation of membrane proteins, essentially required as a membrane-integrated quality control
-
?
unassembled cytochrome oxidase 2 + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
metalloprotease complex
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
bortezomib
-
-
MG132
-
-
prohibitin
-
; located at the periphery of mitochondria at protein import sites, has a regulatory role, deletion of prohibitin leads to accelerated degradation of non-assembled membrane proteins by the m-AAA protease, overexpression of prohibitin stabilizes non-native polypeptides against degradation
-
additional information
-
not inhibited by epoxomicin
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000017
bortezomib
Homo sapiens
-
at 37°C, pH not specified in the publication
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
no activity at 25°C, unfolding of Yme2p at 37°C triggers its proteolytic breakdown
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
abnormal dysfunctional mitochondria in Purkinje cells of Spg7-/- Afg3l2Emv66/+ mice; abnormal dysfunctional mitochondria in Purkinje cells of Spg7-/- Afg3l2Emv66/+ mice
Manually annotated by BRENDA team
-
cell line 143B
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
the enzyme is part of a supercomplex in the inner mitochondrial membrane with a native MW of approximately 2000 kDa, assembling with the prohibitin complex
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 70000-80000, subunits Yta10 and Yta12 in equimolar amounts
heterooligomer
hexamer
homohexamer
paraplegin (SPG7) subunit, crystal structure and homology with FtsH
oligomer
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
AAA-domain of paraplegin bound to ADP, vapor diffusion method in sitting drops
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
HisTrap column chromatography
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immobilized metal ion affinity chromatography (Ni2+)
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immobilized metal ion affinity chromatography, gel filtration
metal chelating chromatography
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Ni-NTA agarose column chromatography and Superose 6 gel filtration
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Ni-NTA column chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
AFG3L2 and paraplegin expressed in yeast
expressed in Escherichia coli BL21 cells
-
expressed in Escherichia coli BL21 CodonPlus (DE3)-RIL cells
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His-tagged version expressed in Escherichia coli BL21(DE3)
paraplegin, AFG3L1 and AFG3L2, His-tagged versions expressed in yeast
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subunit AFG3L2, expressed in HEK-293 cell
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A510V
subunit paraplegin, function impaired, naturally occuring pathogenic mutation
E359A
-
the mutant lacks ATPase activity but retains casein lytic protease activity
E408Q
-
subunit AFG3L2, within Walker B motif, cells expressing AFG3L2 (E408Q) show a prominent reduction of their growth rate
G349S
subunit paraplegin, function impaired, naturally occuring pathogenic mutation
K354A
subunit AFG3L2, homo-oligomeric complex inactive
R688Q
subunit paraplegin, polymorphism, naturally occuring mutation
T503A
subunit paraplegin, polymorphism, naturally occuring mutation
W583C
subunit paraplegin, function impaired, naturally occuring pathogenic mutation
E567Q
-
catalytically inactive
E574Q
-
catalytically inactive
D634A
-
catalytically inactive
D689A
-
catalytically inactive
E388Q/E448Q
-
an ATP hydrolysis-deficient m-AAA protease variant. The mutant effectively traps ATP and keeps m-AAA protease subunits in one nucleotide conformation
E559Q/E614Q
-
inactive
additional information