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Information on EC 3.4.24.B19 - i-AAA protease and Organism(s) Saccharomyces cerevisiae and UniProt Accession P32795
for references in articles please use BRENDA:EC3.4.24.B19preliminary BRENDA-supplied EC number
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3.4.24.B19 i-AAA proteaseSpecify your search results
The taxonomic range for the selected organisms is: Saccharomyces cerevisiae
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
iap-1, yme1p, ftsh4, i-aaa protease, osd1 protein, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
YME1
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
proteolytic degradation of proteins
conserved metal-binding site HEXXH, selective degradation, mechanism
-
proteolytic degradation of proteins
i-AAA protease shows overlapping substrate specificity with the m-AAA protease, enzyme degrades domains of substrate proteins exposed to the opposite membrane surface, active site contains the conserved motif HEXXH, a helical region is located at the extreme C-terminus of the subunit
-
proteolytic degradation of proteins
mechanism, model, degradation of hydrophobic membrane-spanning segments of misfolded mitochodrial membrane proteins
-
proteolytic degradation of proteins
substrate recognition mechanism model
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CAS REGISTRY NUMBER
COMMENTARY
405910-55-6
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
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 + H2O
4 peptide fragments f1-f4
-
in vitro import into the mitochondrion
product characterization
?
loosely folded Yta10(161)-dihydrofolate reductase + H2O
?
-
in vitro import into mitochondria, not intact wild-type dihydrofolate reductase
-
?
polynucleotide phosphorylase + H2O
?
-
Yme1 is required for PNPase assembly in the intermembrane space
-
-
?
protein Cox2 + H2O
?
-
degradation of membrane protein, essentially required as a membrane-integrated quality control
-
?
residues 1-74 of subunit 2 of cytochrome oxidase + H2O
?
-
two-step procedure, in vitro import into the mitochondrion
-
?
unassembled gamma subunit of mitochondrial ATP-synthase + H2O
?
-
i.e. Atp3p
-
?
unassembled subunit II of cytochrome oxidase + H2O
?
-
i.e. Cox2p
-
?
protein + H2O
peptides
-
ATP hydrolysis causes conformational changes, regulates the accessibility of the proteolytic sites and trigger unfolding of substrate polypeptides, substrate recognition and binding to the enzymes ATPase domain is crucial for proteolytic function against unfolded membrane protein substrates
product peptides are released directly into the intermembrane space
?
protein + H2O
peptides
-
enzyme probably forms a pore-like structure facilitating the transport of hydrophilic parts of the substrate protein during its extraction, limited substrate recognition, 25 amino acids of the substrate exposed to the solvent are sufficient for the enzyme to bind via its AAA domain
product peptides are released directly into the intermembrane space
?
protein + H2O
peptides
-
important role in the removal of non-assembled polypeptides from the inner membrane, inactivation of the enzyme is lethal, enzyme deficiency causes pleiotropic defects, including impaired respiration at high temperature and an aberrant mitochondrial morphology, required as a membrane-integrated quality control to facilitate protein folding and to ensure the selective removal of non-native polypeptides
-
?
protein + H2O
peptides
-
proteolytic activity of the i-AAA protease is required for the maintenance of mitochondrial function at high temperature, pointing to an important role in mitochondrial biogenesis
-
?
protein + H2O
peptides
-
the substrate binding region is mapped to the N-terminus of the AAA domain and is probably close to the membrane surface, degradation of membrane proteins, essentially required as a membrane-integrated quality control
-
?
additional information
?
-
Yme1 probably chaperones the folding and/or assembly of Oxa1-exported Cox2 (cytochrome c oxidase subunit) in the absence of Mrg1 or Mgr3
-
-
?
additional information
?
-
-
Yme1 probably chaperones the folding and/or assembly of Oxa1-exported Cox2 (cytochrome c oxidase subunit) in the absence of Mrg1 or Mgr3
-
-
?
additional information
?
-
-
shedding model for availability of water molecules: enzyme shed solvent exposed loops or domains from membrane-embedded polypeptides, pulling model: binding of unfolded substrate protein segments together with ATP-dependent conformational changes in the enzyme can provide a plling force on membrane proteins, with the enzyme being embedded in the bilayer
-
?
additional information
?
-
-
polynucleotide phosphorylase-dihydrofolate reductase is not a proteolytic substrate for Yme1
-
-
?
additional information
?
-
-
YME1L degradation involves the activity of the ATP-independent mitochondrial protease OMA1
-
-
?
additional information
?
-
-
primary function of Tim9 is to protect Tim10 from degradation by Yme1 via assembly into the Tim9-Tim10 complex
-
-
?
additional information
?
-
-
Yme1p degrades Tim10 more rapidly than Tim9, and loss of Tim10 is accelerated by disruption of conserved disulfide bonds within the substrate. An unstructured N-terminal region of Tim10 is necessary and sufficient to target the substrate to the protease through recognition of a short phenylalanine rich motif
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
protein Cox2 + H2O
?
-
degradation of membrane protein, essentially required as a membrane-integrated quality control
-
?
unassembled gamma subunit of mitochondrial ATP-synthase + H2O
?
-
i.e. Atp3p
-
?
unassembled subunit II of cytochrome oxidase + H2O
?
-
i.e. Cox2p
-
?
protein + H2O
peptides
-
important role in the removal of non-assembled polypeptides from the inner membrane, inactivation of the enzyme is lethal, enzyme deficiency causes pleiotropic defects, including impaired respiration at high temperature and an aberrant mitochondrial morphology, required as a membrane-integrated quality control to facilitate protein folding and to ensure the selective removal of non-native polypeptides
-
?
protein + H2O
peptides
-
proteolytic activity of the i-AAA protease is required for the maintenance of mitochondrial function at high temperature, pointing to an important role in mitochondrial biogenesis
-
?
protein + H2O
peptides
-
the substrate binding region is mapped to the N-terminus of the AAA domain and is probably close to the membrane surface, degradation of membrane proteins, essentially required as a membrane-integrated quality control
-
?
additional information
?
-
Yme1 probably chaperones the folding and/or assembly of Oxa1-exported Cox2 (cytochrome c oxidase subunit) in the absence of Mrg1 or Mgr3
-
-
?
additional information
?
-
-
Yme1 probably chaperones the folding and/or assembly of Oxa1-exported Cox2 (cytochrome c oxidase subunit) in the absence of Mrg1 or Mgr3
-
-
?
additional information
?
-
-
YME1L degradation involves the activity of the ATP-independent mitochondrial protease OMA1
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
no activity with beta-gamma-imidoadenosine 5'-phosphate, i.e. AMP-PNP
-
ATP
-
ATP binding is not necessary for enzyme assembly, enzyme contains conserved Walker-type ATPase domain of approximately 230 amino acids, dependent on, hydrolysis induces conformational changes
ATP
-
dependent on, enzyme contains an ATPase domain with a Walker-type P-loop typical for the AAA protease family, hydrolysis induces conformational changes of the AAA domain driving substrate unfolding and dislocation from the membrane
ATP
-
required, contains ATP-binding site spanning from residues 316 to 328, GVLLTGPPGTGKT
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
additional information
-
conserved metal-binding motif HEXGH at the proteolytic centre
Zn2+
-
dependent on, 2 zinc ligands are the conserved His540 and His546
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
methotrexate
-
inhibits binding of the protein substrate to the enzyme's AAA domain
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Mgr1p
Mgr3p and Mgr1p can bind substrate even in the absence of Yme1p, and both proteins are needed for maximal binding of an unfolded substrate by the i-AAA complex. Mgr3p and Mgr1p function together in an adaptor complex that seems to help target substrates to the i-AAA protease for degradation
-
Mgr3p
Mgr3p and Mgr1p can bind substrate even in the absence of Yme1p, and both proteins are needed for maximal binding of an unfolded substrate by the i-AAA complex. Mgr3p and Mgr1p function together in an adaptor complex that seems to help target substrates to the i-AAA protease for degradation
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
integral, a large domain is exposed to the intermembrane space
-
integral, catalytic site facing the intermembrane space
-
only subunit type Yme1p spans the membrane once, integral, catalytic site facing the inter membrane space
-
tightly associated with the inner mitochondrial membrane, oriented with the bulk of the protein facing the matrix
-
Yme1p is associated with the Mgr1 protein in mitochondria
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
mutations in the catalytic subunit of the i-AAA protease complex cause an elevated rate of mitochondrial turnover. Inactivation of the enzyme results in a slight increase in H2O2 sensitivity; while inactivation of both TAZ1 and YME1 together results in a dramatic increase in H2O2 sensitivity
metabolism
-
constitutive OPA1 cleavage by YME1L and OMA1 at two distinct sites leads to the accumulation of both long and short forms of OPA1 and maintains mitochondrial fusion
physiological function
physiological function
-
stress-induced YME1L degradation attenuates protective regulation of mitochondrial proteostasis and promotes cellular death in response to oxidative stress
physiological function
-
the mitochondrial i-AAA protease Yme1 mediates Atg32 processing and is required for mitophagy. The enzyme regulates the Atg32-Atg11 interaction
physiological function
-
the protease Yme1 is required for efficient mitophagy in the absence of tafazzin. The catalytic subunit of the i-AAA protease complex is responsible for degradation of unfolded or misfolded mitochondrial gene products and also has a role in intermembrane space protein folding
physiological function
-
Yme1 has a folding assistant function for dihydrofolate reductase in the intermembrane space, in addition to its proteolytic function, in the protein homeostasis of mitochondria
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
ATP binding is not necessary for enzyme assembly
additional information
-
cooperative interactions between subunits might increase the affinity of assembled Yme1 in vivo
additional information
-
the enzyme consists of a AAA domain, providing chaperone-like properties and binding at its N-terminus to the unfolded, solvent-exposed domains of the substrate protein, a proteolytic doamin, and a Walker-type P-loop ATPase domain, single subunit type Yme1p contains 1 transmembrane segment
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E541Q
K327R
-
point mutation at the ATP-binding site, catalytically inactive
additional information
E541Q
-
site-directed mutagenesis, exchange in the active site, no complementation of deficient mutant cell DELTAyme1
additional information
-
construction of inactive mutant by site-directed mutagenesis in the ATP and Zn2+ binding domains, inactivation of the enzyme causes several distinct phenotypes: an increased rate of DNA escape from mitochondria, temperature-sensitive growth on nonfermentable carbon sources, extremely slow growth when mitochondrial DNA is completely absent from the cell, and altered morphology of the mitochondrial compartment
additional information
-
inactivation of the enzyme causes pleiotropic defects, including impaired respiration and aberrant mitochondrial morphology
additional information
-
N-terminal AAA-domain fragment, expressed in Escherichia coli, is sufficient for substrate binding, but the efficiency is reduced by 5fold compared to the wild-type enzyme
additional information
-
yme1delta mutant with Nde1p-HA turnover defect, mgr1delta yme1delta double mutant indistinguishable from the yme1delta mutant
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
YME1L is a stress-sensitive mitochondrial protease that is rapidly degraded in response to acute oxidative (0.2 mM H2O2) stress
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purification of recombinant GST-fusion AAA-domain N-terminal fragment from Escherichia coli
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of N-terminal residues 250-313 of the AAA domain as GST-fusion protein in Escherichia coli
-
expression of wild-type and mutant E41Q in deficient mutant cell DELTAyme1, complementation only by the wild-type
-
expression of wild-type enzyme in Escherichia coli strain DH5alpha, expression of deletion mutant in Escherichia coli strain BMH 71-18 mut S
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
Yme1p and Mgr1 are both members of the i-AAA-complex
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Boeckmann, B.; Bairoch, A.; Apweiler, R.; Blatter, M.C.; Estreicher, A.; Gasteiger, E.; Martin M.J.; Michoud, K.; O'Donovan, C.; Phan, I.; Pilbout, S.; Schneider, M.
The SWISS-PROT protein knowledgebase and its supplement TrEMBL
Nucleic Acids Res.
31
365-370
2003
Saccharomyces cerevisiae (P32795)
Langer, T.; Kaser, M.; Klanner, C.; Leonhard, K.
AAA proteases of mitochondria: quality control of membrane proteins and regulatory functions during mitochondrial biogenesis
Biochem. Soc. Trans.
29
431-436
2001
Neurospora crassa, Saccharomyces cerevisiae
Leonhard, K.; Herrmann, J.M.; Stuart, R.A.; Mannhaupt, G.; Neupert, W.; Langer, T.
AAA proteases with catalytic sites on opposite membrane surfaces comprise a proteolytic system for the ATP-dependent degradation of inner membrane proteins in mitochondria
EMBO J.
15
4218-4229
1996
Saccharomyces cerevisiae
Weber, E.R.; Hanekamp, T.; Thorsness, P.E.
Biochemical and functional analysis of the YME1 gene product, an ATP and zinc-dependent mitochondrial protease from S. cerevisiae
Mol. Biol. Cell
7
307-317
1996
Saccharomyces cerevisiae
Leonhard, K.; Stiegler, A.; Neupert, W.; Langer, T.
Chaperone-like activity of the AAA domain of the yeast Yme1 AAA protease
Nature
398
348-351
1999
Saccharomyces cerevisiae
Dunn, C.D.; Lee, M.S.; Spencer, F.A.; Jensen, R.E.
A genomewide screen for petite-negative yeast strains yields a new subunit of the i-AAA protease complex
Mol. Biol. Cell
17
213-226
2006
Saccharomyces cerevisiae
Arnold, I.; Wagner-Ecker, M.; Ansorge, W.; Langer, T.
Evidence for a novel mitochondria-to-nucleus signalling pathway in respiring cells lacking i-AAA protease and the ABC-transporter Mdl1
Gene
367
74-88
2006
Saccharomyces cerevisiae, Saccharomyces cerevisiae W303-1A
Song, Z.; Chen, H.; Fiket, M.; Alexander, C.; Chan, D.C.
OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L
J. Cell Biol.
178
749-755
2007
Saccharomyces cerevisiae
Rainey, R.N.; Glavin, J.D.; Chen, H.W.; French, S.W.; Teitell, M.A.; Koehler, C.M.
A new function in translocation for the mitochondrial i-AAA protease Yme1: import of polynucleotide phosphorylase into the intermembrane space
Mol. Cell. Biol.
26
8488-8497
2006
Saccharomyces cerevisiae
Graef, M.; Seewald, G.; Langer, T.
Substrate recognition by AAA+ ATPases: distinct substrate binding modes in ATP-dependent protease Yme1 of the mitochondrial intermembrane space
Mol. Cell. Biol.
27
2476-2485
2007
Saccharomyces cerevisiae, Neurospora crassa
Fiumera, H.L.; Dunham, M.J.; Saracco, S.A.; Butler, C.A.; Kelly, J.A.; Fox, T.D.
Translocation and assembly of mitochondrially coded Saccharomyces cerevisiae cytochrome c oxidase subunit Cox2 by Oxa1 and Yme1 in the absence of Cox18
Genetics
182
519-528
2009
Saccharomyces cerevisiae (P32795), Saccharomyces cerevisiae
Dunn, C.D.; Tamura, Y.; Sesaki, H.; Jensen, R.E.
Mgr3p and Mgr1p are adaptors for the mitochondrial i-AAA protease complex
Mol. Biol. Cell
19
5387-5397
2008
Saccharomyces cerevisiae (P32795), Saccharomyces cerevisiae
Wang, K.; Jin, M.; Liu, X.; Klionsky, D.J.
Proteolytic processing of Atg32 by the mitochondrial i-AAA protease Yme1 regulates mitophagy
Autophagy
9
1828-1836
2013
Saccharomyces cerevisiae
Rainbolt, T.K.; Saunders, J.M.; Wiseman, R.L.
YME1L degradation reduces mitochondrial proteolytic capacity during oxidative stress
EMBO Rep.
16
97-106
2015
Saccharomyces cerevisiae
Gaspard, G.J.; McMaster, C.R.
The mitochondrial quality control protein Yme1 is necessary to prevent defective mitophagy in a yeast model of Barth syndrome
J. Biol. Chem.
290
9284-9298
2015
Saccharomyces cerevisiae, Saccharomyces cerevisiae BY4741
Anand, R.; Wai, T.; Baker, M.J.; Kladt, N.; Schauss, A.C.; Rugarli, E.; Langer, T.
The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission
J. Cell Biol.
204
919-929
2014
Saccharomyces cerevisiae
Schreiner, B.; Westerburg, H.; Forne, I.; Imhof, A.; Neupert, W.; Mokranjac, D.
Role of the AAA protease Yme1 in folding of proteins in the intermembrane space of mitochondria
Mol. Biol. Cell
23
4335-4346
2012
Saccharomyces cerevisiae
Spiller, M.; Guo, L.; Wang, Q.; Tran, P.; Lu, H.
Mitochondrial Tim9 protects Tim10 from degradation by the protease Yme1
Biosci. Rep.
35
e00193
2015
Saccharomyces cerevisiae, Saccharomyces cerevisiae BY4742
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