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Information on EC 3.4.24.64 - mitochondrial processing peptidase and Organism(s) Homo sapiens and UniProt Accession O75439
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3.4.24.64 mitochondrial processing peptidaseSpecify your search results
Word Map
- 3.4.24.64
- presequence
-
nuclear-encoded
- preproteins
-
intermembrane
- frataxin
- metalloendopeptidase
-
friedreich
-
matrix-targeting
-
hxxeh
- mas1
- plumbaginifolia
-
nuclearly
-
matrix-localized
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intermediate-sized
- agriculture
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
mitochondrial processing peptidase, beta-mpp, alpha-mpp, processing peptidase, matrix processing peptidase, atp23, mitochondrial processing protease, processing enhancing protein, general mitochondrial processing peptidase, pmpca, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Alpha-MPP
-
-
-
-
Beta-MPP
-
-
-
-
General mitochondrial processing peptidase
-
-
-
-
HA1523
-
-
-
-
Matrix peptidase
-
-
-
-
Matrix processing peptidase
-
-
-
-
Matrix processing proteinase
-
-
-
-
Mitochondrial chelator-sensitive protease
-
-
-
-
Mitochondrial protein precursor-processing proteinase
-
-
-
-
MPP
P-52
-
-
-
-
P-55
-
-
-
-
Processing enhancing peptidase
-
-
-
-
Proteinase, mitochondrial protein precursor-processing
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-
-
-
MPP
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
86280-61-7
-
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
Abz-FRSGQPLQNKVQLQ-ED(Dnp) + H2O
Abz-FRSGQPLQ + NKVQLQ-ED(Dnp)
-
-
-
?
Abz-MTAALKTK(Dnp)-NH2 + H2O
Abz-MT + AALK + TK(Dnp)-NH2
cleavage sites: 2-aminobenzoyl-MT-/-AALK-/-TK-(N-(2,4-dinitrophenyl)-ethylenediamine)-NH2
-
-
?
Abz-TTKLKAAK(Dnp)-NH2 + H2O
Abz-TTKL + L-Lys + L-Ala + AK(Dnp)-NH2
cleavage sites: 2-aminobenzoyl-TTKL-/-K-/-A-/-AK-(N-(2,4-dinitrophenyl)-ethylenediamine)-NH2
-
-
?
Abz-VRNFRSGQPLQNKVQ-ED(Dnp) + H2O
Abz-VRNFRSGQPLQ + NKVQ-ED(Dnp)
-
-
-
?
frataxin + H2O
mature frataxin 56-210 + prepeptide
-
removal of the N-terminal peptide, MPP cleavage site between residues 55 and 56
the N-terminus of MPP-processed frataxin shows a unique high-affinity iron site, and this iron center appears to mediate a self-cleavage reaction, overview
-
?
additional information
?
-
-
the mitochondrial processing peptidase removes leader peptides of preproteins after import into the mitochondrial matrix space to increase protein stability, enzyme inhibition leads to degradation of the unprocessed preproteins in the mitochondrial matrix space, overview
-
-
?
additional information
?
-
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binding of the iron-promoted binding of the iron-sulfur cluster assembly scaffold partner protein, ISU, overview
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-
?
additional information
?
-
-
the enzyme specifically cleaves off presequences from mitochondrial precursor proteins
-
-
?
additional information
?
-
the enzyme shows a preference for uncharged polar residues at positions P1 and P1 and nonpolar residues at the substrate P3, P2, P2' and P3' positions
-
-
?
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
additional information
?
-
-
the mitochondrial processing peptidase removes leader peptides of preproteins after import into the mitochondrial matrix space to increase protein stability, enzyme inhibition leads to degradation of the unprocessed preproteins in the mitochondrial matrix space, overview
-
-
?
additional information
?
-
-
the enzyme specifically cleaves off presequences from mitochondrial precursor proteins
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
-
the N-terminus of MPP-processed frataxin shows a unique high-affinity iron site, and this iron center appears to mediate a self-cleavage reaction, the N-terminus blocks previously defined iron-binding sites located on the carboxylate-rich surface defined by the helix alpha1 and the beta-sheet beta1, most likely through electrostatic contact with the carboxylate-rich surface on the core protein, as well as inhibiting iron-promoted binding of the iron-sulfur cluster assembly scaffold partner protein, ISU, overview
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
o-phenanthroline
-
enzyme inhibition leads to degradation of the unprocessed preproteins in the mitochondrial matrix space
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Q10713: mitochondrial-processing peptidase subunit alpha, O75439: mitochondrial-processing peptidase subunit beta
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
-
the enzyme plays a role in phosphatase and tensin homologue-induced kinase 1 (PINK1) import and mitochondrial quality control via the PINK1-Parkin pathway
physiological function
malfunction
-
reducing enzyme activity induces phosphatase and tensin homologue-induced kinase 1 accumulation at the mitochondrial surface, leading to Parkin recruitment and mitophagy
malfunction
mutations in the substrate binding glycine-rich loop of the mitochondrial processing peptidase-alpha protein (PMPCA) cause a severe mitochondrial disease
physiological function
most important processing enzyme that acts on proteins directed to the inner membrane intermembrane space or mitochondrial matrix. Most of the proteins targeted to the mitochondrial matrix or inner membrane present a single cleavage by mitochondrial processing peptidase
physiological function
primary enzyme responsible for the maturation of the vast majority of nuclear-encoded mitochondrial proteins, which is necessary for life at the cellular level. Analysis of lymphoblastoid cells and fibroblasts from patients homozygous for the PMPCA p.Ala377Thr, a mutation in the alpha subunit of mitochondrial processing peptidase and carriers demonstrate that the mutation impacts both the level of the alpha subunit encoded by PMPCA and the function of mitochondrial processing peptidase. This mutation impacts the maturation process of frataxin, the protein which is depleted in Friedreich ataxia
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MPPB_HUMAN
489
0
54366
Swiss-Prot
Mitochondrion (Reliability: 1)
B3KM34_HUMAN
489
0
54386
TrEMBL
Mitochondrion (Reliability: 1)
G3V0E4_HUMAN
490
0
54192
TrEMBL
Mitochondrion (Reliability: 1)
A8K1E9_HUMAN
489
0
54250
TrEMBL
Mitochondrion (Reliability: 1)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
yeast malate dehydrogenase and human, yeast, or rat liver aldehyde dehydrogenases are mutated so that they would not be processed by the enzyme after import into the mitochondrial matrix space, the mutant nonprocessed enzymes are functional but instable, the nonprocessed precursors are degraded in the matrix space, expression in HeLa cells, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Mukhopadhyay, A.; Yang, C.S.; Wei, B.; Weiner, H.
Precursor protein is readily degraded in mitochondrial matrix space if the leader is not processed by mitochondrial processing peptidase
J. Biol. Chem.
282
37266-37275
2007
Homo sapiens, Saccharomyces cerevisiae
Yoon, T.; Dizin, E.; Cowan, J.A.
N-terminal iron-mediated self-cleavage of human frataxin: regulation of iron binding and complex formation with target proteins
J. Biol. Inorg. Chem.
12
535-542
2007
Homo sapiens
Teixeira, P.; Glaser, E.
Processing peptidases in mitochondria and chloroplasts
Biochim. Biophys. Acta
1833
360-370
2013
Homo sapiens
Greene, A.; Grenier, K.; Aguileta, M.; Muise, S.; Farazifard, R.; Haque, M.; McBride, H.; Park, D.; Fon, E.
Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment
EMBO Rep.
13
378-385
2012
Homo sapiens
Jobling, R.K.; Assoum, M.; Gakh, O.; Blaser, S.; Raiman, J.A.; Mignot, C.; Roze, E.; Duerr, A.; Brice, A.; Levy, N.; Prasad, C.; Paton, T.; Paterson, A.D.; Roslin, N.M.; Marshall, C.R.; Desvignes, J.P.; Roeckel-Trevisiol, N.; Scherer, S.W.; Rouleau, G.A.; Megarbane, A.; Isaya, G.; Delague, V.; Yoon, G.
PMPCA mutations cause abnormal mitochondrial protein processing in patients with non-progressive cerebellar ataxia
Brain
138
1505-1517
2015
Homo sapiens (Q10713 AND O75439), Homo sapiens
Joshi, M.; Anselm, I.; Shi, J.; Bale, T.A.; Towne, M.; Schmitz-Abe, K.; Crowley, L.; Giani, F.C.; Kazerounian, S.; Markianos, K.; Lidov, H.G.; Folkerth, R.; Sankaran, V.G.; Agrawal, P.B.
Mutations in the substrate binding glycine-rich loop of the mitochondrial processing peptidase-alpha protein (PMPCA) cause a severe mitochondrial disease
Cold Spring Harb. Mol. Case Stud.
2
a000786
2016
Homo sapiens (Q10713), Homo sapiens
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