Information on EC 3.4.24.59 - mitochondrial intermediate peptidase

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The expected taxonomic range for this enzyme is: Opisthokonta

EC NUMBER
COMMENTARY
3.4.24.59
-
RECOMMENDED NAME
GeneOntology No.
mitochondrial intermediate peptidase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
release of an N-terminal octapeptide as second stage of processing of some proteins imported into the mitochondrion
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hMIP
-
-
MIP
-
-
-
-
MIPEP
-
-
mitochondrial intermediate peptidase
-
putative homologue of the Schizophyllum commune mitochondrial intermediate peptidase gene detected
mitochondrial intermediate peptidase
-
-
Proteinase, mitochondrial intermediate precursor-processing
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-
-
-
CAS REGISTRY NUMBER
COMMENTARY
136447-30-8
-
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
cleavage of Notch recptor at the S5 site is abolished in MIEP knockout cells
physiological function
-
Notch function can be modulated by MIPEP-mediated cleavage. Results show that S5 site proteolysis represents a novel regulatory component of Notch signaling
physiological function
-
the stability of intermediate and mature forms of Oct1 substrate proteins in organello and in vivo is compared. Oct1 cleavage increases the half-life of its substrate proteins, most likely by re-moving destabilizing amino acids at the intermediate's N-terminus. Oct1 converts unstable precursor intermediates generated by mitochondrial processing peptidase (MPP) into stable mature proteins. Oct1 acts as a quality control system for MPP-processed preproteins
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Abz-GFSPFRQ-EDDnp + H2O
Abz-GF + SPFRQ-EDDnp
show the reaction diagram
-
-
-
-
?
Abz-RPPGFSPFRQ-EDDnp + H2O
Abz-RPPGF + SPFRQ-EDDnp
show the reaction diagram
-
-
-
-
?
Bradykinin + H2O
?
show the reaction diagram
-
-
-
-
?
cytochrome c oxidase 4 precursor protein + H2O
mature cytochrome c oxidase + propeptide
show the reaction diagram
-
enzyme inhibition leads to prevention of the normal processing of the precursor of cytochrome c oxidase, i.e. COX, subunit 4 and induced COX degradation, overview, identification of the MIP recognition site, overview
-
-
?
Mitochondrial intermediate proteins + H2O
?
show the reaction diagram
-
-
-
-
-
Mitochondrial intermediate proteins + H2O
?
show the reaction diagram
-
respiratory components, including subunits of electron transport chain and tricarboxylic acid cycle enzymes, and components of the mitochondrial genetic machinery, including ribosomal proteins, translation factors, and proteins required for mitochondrial DNA metabolism
-
-
-
Mitochondrial intermediate proteins + H2O
?
show the reaction diagram
-
with the amino-terminal octapeptide Phe/Ile/Leu-Xaa-Xaa-Ser/Thr/Gly-Xaa-Xaa-Xaa-Xaa
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-
-
Notch receptor + H2O
?
show the reaction diagram
-
Notch is proteolysed at the S5 site which is 8 amino acids downstream of the S3 site, generating a DELTA NICD (Notch intracellular domain) fragment
-
-
?
Precursor proteins that have already been processed by mitochondrial processing peptidase + H2O
?
show the reaction diagram
-
-
-
-
-
Precursor proteins that have already been processed by mitochondrial processing peptidase + H2O
?
show the reaction diagram
-
required step for a subgroup of nuclear-encoded mitochondrial precursors
-
-
-
Precursor proteins that have already been processed by mitochondrial processing peptidase + H2O
?
show the reaction diagram
-
a new component of the yeast mitochondrial import machinery
-
-
-
Proteins with the octapeptide Phe-Xaa-Xaa-Ser-Xaa-Xaa-Xaa-Xaa at the amino termini + H2O
Protein + Phe-Xaa-Xaa-Ser-Xaa-Xaa-Xaa-Xaa
show the reaction diagram
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amino-terminal octapeptide can be cleaved only within the structural context of twice-cleaved precursors
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-
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Ygr031w/Imo32 + H2O
?
show the reaction diagram
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Ygr031w/Imo32 encodes an Oct1 substrate protein with an unusual sequence motif
-
-
?
Mitochondrial intermediate proteins + H2O
?
show the reaction diagram
-
with the amino-terminal octapeptide Phe/Ile/Leu-Xaa-Xaa-Ser/Thr/Gly-Xaa-Xaa-Xaa-Xaa
-
-
-
additional information
?
-
-
enzyme is involved in two-step processing of mitochondrial protein precursors
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-
?
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
cytochrome c oxidase 4 precursor protein + H2O
mature cytochrome c oxidase + propeptide
show the reaction diagram
-
enzyme inhibition leads to prevention of the normal processing of the precursor of cytochrome c oxidase, i.e. COX, subunit 4 and induced COX degradation, overview
-
-
?
Precursor proteins that have already been processed by mitochondrial processing peptidase + H2O
?
show the reaction diagram
-
-
-
-
-
Precursor proteins that have already been processed by mitochondrial processing peptidase + H2O
?
show the reaction diagram
-
required step for a subgroup of nuclear-encoded mitochondrial precursors
-
-
-
Precursor proteins that have already been processed by mitochondrial processing peptidase + H2O
?
show the reaction diagram
-
a new component of the yeast mitochondrial import machinery
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
1 mM, stimulates 2.2fold
Mg2+
-
1 mM, stimulates 4.8fold
Mn2+
-
1 mM, stimulates 4.5fold
additional information
-
activated by divalent cations
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1,10-phenanthroline
-
total inhibition at 10 mM
bestatin
-
significant inhibition
Captopril
-
-
Co2+
-
specific strong inhibition
DTT
-
inhibits enzymatic activity above to 0.1 mM
EDTA
-
90% inhibitiond by EDTA (10 mM)
iodoacetamide
-
-
iodoacetic acid
-
-
p-hydroxymercuribenzoate
-
-
Synthetic peptides
-
corresponding to the intermediate octapeptides of human ornithine transcarbamoylase and of Neurospora cytochrome c reductase Fe/S subunit
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Synthetic peptides
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-
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thiol-blocking agent
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-
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Thiol-blocking reagents
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-
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thiorphan
-
-
additional information
-
no inhibition by peptides lacking the amino-terminal hydrophobic residue, while substitution of such a residue by a polar amino acid causes a 10fold reduction in the efficiency of MIP inhibition
-
additional information
-
no inhibition by NaCl or KCl at concentrations up to 200 mM
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
DTT
-
activates enzymatic activity up to 0.1 mM
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.001
-
Abz-GFSPFRQ-EDDnp
-
pH 7.4, 37C, 0.1 mM DTT
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
40
-
Abz-GFSPFRQ-EDDnp
-
pH 7.4, 37C, 0.1 mM DTT
302677
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.057
-
Captopril
-
pH 7.4, 37C
0.007
-
JA-2
-
pH 7.4, 37C
0.0015
-
thiorphan
-
pH 7.4, 37C
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
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-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.4
-
-
assay at
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
27
-
-
assay at
37
-
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
initially MIP synthesized as a large precursor molecule carrying a mitochondrial leader peptide
Manually annotated by BRENDA team
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after import of MIP in mitochondrion, processing of the precursor to the mature form by MPP
Manually annotated by BRENDA team
-
encoding of MIP
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
74470
-
-
rat, calculation from amino acid sequence
75000
-
-
rat, gel filtration
78640
-
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mass spectroscopy
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
monomer
-
1 * 75000, rat, SDS-PAGE
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-70C, stable for at least 6 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
affinity chromatography using Ni-Sepharose resin and ion exchange chromatography with a Hi-trap resource Q column
-
recombinant MIPEP protein is purified from baculovirus-infected Sf9 cells
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purified 2250fold to homogeneity
-
affinity purified
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Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expressed in Escherichia coli as a His-tagged fusion protein
-
expressed in Saccharomyces cerevisiae
-
expressed in Saccharomyces cerevisiae
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cloned into vector pG-3
-
expressed in Saccharomyces cerevisiae
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
disruption of the mouse MIP gene results in early embryonic lethality
additional information
-
when MIP is genetically inactivated, the protein is no longer processed to the mature form, resulting in a complex respiratory-deficient phenotype with loss of mtDNA
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
MIP stimulates iron uptake by mitochondria