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Information on EC 3.4.21.53 - Endopeptidase La and Organism(s) Mus musculus and UniProt Accession Q8CGK3
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3.4.21.53 Endopeptidase LaSpecify your search results
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- 3.4.21.53
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antiretroviral
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- plasminogen
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hiv-infected
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virological
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- metalloproteinase
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amyloid
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anticoagulant
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- sars-cov-2
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mast
- covid-19
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-
zymography
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thrombotic
- antithrombin
- papain
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urokinase-type
- pai-1
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fibrinolytic
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granzyme
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tissue-type
- tryptase
- medicine
- biotechnology
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The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
protease, serine protease, clpxp, lon protease, lonp1, protease la, atp-dependent lon protease, protease lon, aaa+ protease, ms-lon, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ATP-dependent Lon proteinase
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-
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ATP-dependent protease La
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ATP-dependent serine proteinase
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Escherichia coli proteinase La
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-
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Escherichia coli serine proteinase La
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-
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Gene lon protease
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-
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Gene lon proteins
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-
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Lon proteinase
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-
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PIM1 protease
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-
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PIM1 proteinase
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Protease La
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Proteinase La
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Proteinase, Escherichia coli serine, La
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Proteinase, La
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Proteins, gene lon
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Proteins, specific or class, gene lon
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Serine protease La
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CAS REGISTRY NUMBER
COMMENTARY
79818-35-2
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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
cytochrome c oxidase subunit IVi1 + H2O
?
the phosphorylated IVi1 protein is degraded, while the phosphorylation-resistant S52A mutant protein is not degraded
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-
?
cytochrome c oxidase subunit Vb + H2O
?
the phosphorylated Vb protein is degraded, while the phosphorylation-resistant S40A mutant protein is not degraded
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-
?
additional information
?
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three-dimensional modeling of cytochrome c oxidase (CcO)-Lon complex based on the X-ray crystal structures of bovine CcO complex and Escherichia coli Lon protein, interaction analysis, docking study
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?
additional information
?
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three-dimensional modeling of cytochrome c oxidase (CcO)-Lon complex based on the X-ray crystal structures of bovine CcO complex and Escherichia coli Lon protein, interaction analysis, docking study
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-
?
additional information
?
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mediates the degradation of misfolded, unassembled or oxidatively damaged polypeptides, not only degrades protein substrates but also binds DNA, specifically binds to single stranded but not to double-stranded DNA oligonucleotides
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?
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
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
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Lon protease expression and activity declines with age, steady-state levels of lon mRNA are ca. 4fold lower in 30-month-old mice than in young mice. 5fold decrease in protein levels and activity in old mice compared to young mice
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
Lon proteases can be divided into two subfamilies: LonA (found in eubacteria and eukarya) and LonB (found in archaea). LonA proteases are formed by three functional domains: the N-terminal, involved in substrate binding, the central AAA+ domain, and the C-terminal domain (named P domain), which containing the Ser-Lys catalytic dyad for proteolytic activity. LonB proteases are composed by an ATPase and a protease domain and a hydrophobic transmembrane region which anchors the protein to the internal face of cell membrane. In eukarya, two Lon proteases are present: a mitochondrial and a peroxisomal form, encoded by two different genes
malfunction
physiological function
malfunction
homozygous deletion of Lonp1 causes early embryonic lethality, whereas its haploinsufficiency protects against colorectal and skin tumors. LONP1 knockdown inhibits cellular proliferation and tumor and metastasis formation, phenotypes, overview. LONP1 is necessary for proliferation and metastasis of melanoma cells
malfunction
enzyme knockout is embryonically lethal in mice. Lon+/- mouse model, in which the expression of Lon is halved, is characterized by a lower tendency to develop cancer and a higher resistance to carcinogenic compounds than wild type counterparts. Accordingly, growth of Lon-silenced cancer cells in xenograft model is significantly reduced if compared to control cells, while cells overexpressing Lon grow more rapidly. In vivo, Lon overexpression favours glycolysis, facilitates proliferation, and capability to migrate and form metastasis of melanoma cells in nude mice
physiological function
the enzyme expression in reguated by HtrA2 serine protease, Lon1 protease is overexpressed in HtrA2-deficient cells, phenotype, overview. HtrA2 regulates mitochondrial proteins through its serine protease activity
physiological function
the enzyme plays a key role in metabolic reprogramming by remodeling OXPHOS complexes and protecting against senescence. The protease is a central regulator of mitochondrial activity in oncogenesis. Role of LONP1 in the regulation of mitochondrial function in cancer, overview
physiological function
Lon protease (Lonp1) is a nuclear encoded, mitochondrial ATP-dependent serine peptidase, which mediates the selective degradation of mutant and abnormal proteins in the organelle, and helps in the maintenance of mitochondrial homeostasis. Together with its proteolytic and chaperone activities, Lon ability to bind DNA is conserved from bacteria to mammalian mitochondria. Lon ability to bind to DNA needs conformational changes in Lon itself, and such changes are inhibited by ATP, and are stimulated by a protein substrate
physiological function
mitochondrial LON protease-dependent degradation of cytochrome c oxidase (CcO) subunits under hypoxia and myocardial ischemia. Lon is involved in the preferential turnover of phosphorylated CcO subunits under hypoxic/ischemic stress. Role of Lon in the degradation of phosphorylated subunits of CcO complex and importance of phosphorylation sites S40 of Vb and T52 of IVi1 subunits in Lon mediated degradation
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). LONM_MOUSE
949
0
105843
Swiss-Prot
Mitochondrion (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His6-tagged enzyme, solubilized from Escherichia coli strain BL21(DE3) Codon Plus (RIL) inclusion bodies, by nickel affinity chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene LONP1, recombinant expression of His6-tagged enzyme in Escherichia coli strain BL21(DE3) Codon Plus (RIL) in inclusion bodies
Lon cDNA cloned and expressed in yeast strain PIM1, complementing a LON deletion, also overexpressed in COS-7 cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
in muscle creatine kinase mouse heart model for Friedreich ataxia, a rare hereditary neurodegenerative disease characterized by progressive ataxia and cardiomyopathy, there is a clear progressive increase in protein levels of mitochondrial ATP-dependent proteases, Lon and ClpP, in the hearts of muscle creatine kinase mutants. Lon and ClpP upregulation, which is triggered at a mid-stage of the disease through separate pathways, is accompanied by an increase in proteolytic activity.
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
recombinangt His-tagged enzyme from inclusion bodies in Escherichia coli strain BL21(DE3) Codon Plus (RIL) by solubilization in in 50 mM Tris-HCl, pH 8.0, containing 8 M urea. The urea solubilized protein is refolded by dialyzing the protein for 3 h in each of 50 mM Tris-HCl pH 8.0, 1 mM 2-mercaptoethanol buffer containing 6 M, 4 M, 2 M, 1 M, and 100 mM urea, respectively with 0.075% deoxycholate. Finally, the storage buffer (20 mM Tris-HCl, pH 8.0, 1 mM 2-mercaptoethanol, 10% glycerol, 0.075% deoxycholate) without urea is used for dialysis
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
in muscle creatine kinase mouse heart model for Friedreich ataxia, a rare hereditary neurodegenerative disease characterized by progressive ataxia and cardiomyopathy, there is a clear progressive increase in protein levels of mitochondrial ATP-dependent proteases, Lon and ClpP, in the hearts of muscle creatine kinase mutants. Lon and ClpP upregulation, which is triggered at a mid-stage of the disease through separate pathways, is accompanied by an increase in proteolytic activity. There is a simultaneous and significant progressive loss of mitochondrial Fe-S proteins with no substantial change in their mRNA level
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lu, B.; Liu, T.; Crosby, J.A.; Thomas-Wohlever, J.; Lee, I.; Suzuki, C.K.
The ATP-dependent Lon protease of Mus musculus is a DNA-binding protein that is functionally conserved between yeast and mammals
Gene
306
45-55
2003
Homo sapiens, Mus musculus
Ngo, J.K.; Davies, K.J.
Importance of the lon protease in mitochondrial maintenance and the significance of declining lon in aging
Ann. N. Y. Acad. Sci.
1119
78-87
2007
Homo sapiens, Mus musculus, Rattus norvegicus
Guillon, B.; Bulteau, A.L.; Wattenhofer-Donze, M.; Schmucker, S.; Friguet, B.; Puccio, H.; Drapier, J.C.; Bouton, C.
Frataxin deficiency causes upregulation of mitochondrial Lon and ClpP proteases and severe loss of mitochondrial Fe-S proteins
FEBS J.
276
1036-1047
2009
Mus musculus
Quiros, P.M.; Espanol, Y.; Acin-Perez, R.; Rodriguez, F.; Barcena, C.; Watanabe, K.; Calvo, E.; Loureiro, M.; Fernandez-Garcia, M.S.; Fueyo, A.; Vazquez, J.; Enriquez, J.A.; Lopez-Otin, C.
ATP-dependent Lon protease controls tumor bioenergetics by reprogramming mitochondrial activity
Cell Rep.
8
542-556
2014
Homo sapiens, Mus musculus (Q8CGK3)
Goo, H.G.; Rhim, H.; Kang, S.
HtrA2/Omi influences the stability of LON protease 1 and prohibitin, proteins involved in mitochondrial homeostasis
Exp. Cell Res.
328
456-465
2014
Homo sapiens (P36776), Mus musculus (Q8CGK3), Mus musculus
Pinti, M.; Gibellini, L.; Nasi, M.; De Biasi, S.; Bortolotti, C.A.; Iannone, A.; Cossarizza, A.
Emerging role of Lon protease as a master regulator of mitochondrial functions
Biochim. Biophys. Acta
1857
1300-1306
2016
Thermococcus onnurineus (B6YU74), Escherichia coli (P0A9M0), Saccharomyces cerevisiae (P36775), Homo sapiens (P36776), Mus musculus (Q8CGK3), Saccharomyces cerevisiae ATCC 204508 (P36775)
Sepuri, N.B.V.; Angireddy, R.; Srinivasan, S.; Guha, M.; Spear, J.; Lu, B.; Anandatheerthavarada, H.K.; Suzuki, C.K.; Avadhani, N.G.
Mitochondrial LON protease-dependent degradation of cytochrome c oxidase subunits under hypoxia and myocardial ischemia
Biochim. Biophys. Acta
1858
519-528
2017
Oryctolagus cuniculus (G1TBZ8), Oryctolagus cuniculus, Mus musculus (Q8CGK3), Mus musculus
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