Information on EC 3.4.25.1 - proteasome endopeptidase complex and Organism(s) Homo sapiens

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The taxonomic range for the selected organisms is: Homo sapiens

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.4.25.1
-
RECOMMENDED NAME
GeneOntology No.
proteasome endopeptidase complex
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
cleavage of peptide bonds with very broad specificity
show the reaction diagram
ATPase activity
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
140879-24-9
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acetyl-DPSD-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
cleaved by the beta1 subunit of the 20S proteasome
-
-
?
acetyl-EPFD-7-amido-4-carbamoylcoumarin + H2O
?
show the reaction diagram
-
-
-
?
acetyl-HHSL-7-amido-4-carbamoylcoumarin + H2O
?
show the reaction diagram
-
-
-
?
acetyl-norleucine-Arg-norleucine-Arg-7-amido-4-carbamoylcoumarin + H2O
?
show the reaction diagram
-
-
-
?
acetyl-YWTQ-7-amido-4-carbamoylcoumarin + H2O
?
show the reaction diagram
-
-
-
?
benzoyl-LRR-4-methyl-7-amido-coumarin + H2O
benzoyl-LRR + 4-methyl-7-amino-coumarin
show the reaction diagram
Boc-Leu-Arg-Arg-7-amido-4-methylcoumarin + H2O
Boc-Leu-Arg-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
trypsin-like activity
-
-
?
Bz-Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
Bz-DL-Arg-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
Bz-VGR-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
DBC2 protein + H2O
?
show the reaction diagram
-
-
-
-
?
ERM transcription factor + H2O
?
show the reaction diagram
-
-
-
-
?
IGF-1 + H2O
?
show the reaction diagram
-
-
-
-
?
N-methoxysuccinyl-Glu-Val-Lys-Met-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
N-succinyl-LLVY-7-amido-4-methylcoumarin + H2O
N-succinyl-LLVY + 7-amino-4-methylcoumarin
show the reaction diagram
N-succinyl-LLVY-aminoluciferin + H2O
?
show the reaction diagram
-
-
-
-
?
ovalbumin + H2O
?
show the reaction diagram
-
-
-
-
?
oxidized insulin B chain + H2O
?
show the reaction diagram
-
-
-
-
?
p27(KIP1) + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-LLVY-aminoluciferin + H2O
succinyl-LLVY + aminoluciferin
show the reaction diagram
-
chymotrypsin-like proteasome activity
-
-
?
ubiquitinylated proteins
?
show the reaction diagram
-
individual substrates unknown
-
-
-
unstable green fluorescence protein + H2O
?
show the reaction diagram
-
artificial substrate for the proteasome. The model proteasomal substrate is stabilized by the carboxyl-terminal half of S5a, S5aC
-
-
?
Z-LLE-2-naphthylamide + H2O
Z-LLE + 2-naphthylamine
show the reaction diagram
-
post-acidic proteasome activity
-
-
?
Z-LLE-4-methyl-7-amido-coumarin + H2O
Z-LLE + 4-methyl-7-amino-coumarin
show the reaction diagram
Z-LLE-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
Z-LRR-aminoluciferin + H2O
?
show the reaction diagram
-
-
-
-
?
Z-nLPnLD-aminoluciferin + 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
ubiquitinylated proteins
?
show the reaction diagram
-
individual substrates unknown
-
-
-
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ATP
-
dependent on
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
-
enhanced by low concentrations of Mg2+ (5-15 mM)
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(-)-epigallocatechin-3-gallate
-
i.e. EGCG, inhibits the proteasomal chymotrypsin-like activity
(2E)-3-(4-tert-butylphenyl)-1-[4-(4-nitrophenyl)piperazin-1-yl]prop-2-en-1-one
-
-
(2R,3S)-1,2,3,4-tetrahydronaphthalene-2,3-diyl bis(3,4,5-triethoxybenzoate)
-
inhibits 48% of MDA-MB-231 cell proliferation at 0.05 mM
(2R,3S)-1,2,3,4-tetrahydronaphthalene-2,3-diyl bis(3,4,5-trihydroxybenzoate)
-
-
(2R,3S)-1,2,3,4-tetrahydronaphthalene-2,3-diyl bis(3,5-diethoxybenzoate)
-
70-79% inhibition in MDA-MB-231 cells at 0.025-0.050 mM
(2R,3S)-1,2,3,4-tetrahydronaphthalene-2,3-diyl bis(3,5-dihydroxybenzoate)
-
-
(acetato-kappaO)[2,4-diiodo-6-({[(pyridin-2-yl-kappaN)methyl]amino-kappaN}methyl)phenolato-kappaO]copper
-
a copper complex, causes selective 20S proteasomal inhibition and apoptosis induction in several lines of cancer cells
1-[1-(1-[(2,4-dioxoimidazolidin-1-ylimino)-methyl]-2-phenyl-ethylcarbamoyl)-2-(1H-indol-3-yl)-ethylcarbamoyl]-2-(1H-indol)
-
i.e. S-2209, potently inhibits chymotrypsin-like proteasome activity of the human 20S proteasome. S-2209 targets NFkappaB activity, overview. S-2209 inhibits cell growth and induces apoptosis in human multiple myeloma cells, mechanisms, overview
2-(2-bromo-4-tert-butylphenoxy)-1-[4-(4-nitrophenyl)piperazin-1-yl]ethanone
-
-
2-(2-chlorophenyl)-N-[4-(1,3-thiazol-2-ylsulfamoyl)phenyl]quinoline-4-carboxamide
-
-
2-(4-tert-butylphenoxy)-1-[4-(4-methoxy-2-nitrophenyl)piperazin-1-yl]ethanone
-
-
2-methyl-5-[4-(phenylamino)phthalazin-1-yl]-N-(tetrahydrofuran-2-ylmethyl)benzenesulfonamide
-
-
3,4-dichloroisocoumarin
-
-
4-(4-methoxyphenyl)-N-(4-nitrophenyl)piperazine-1-carbothioamide
-
-
4-tert-butyl-N-[4-(diethylsulfamoyl)phenyl]benzamide
-
-
4-tert-butyl-N-[4-(dipropylsulfamoyl)phenyl]benzamide
-
-
4-tert-butyl-N-[4-[di(prop-2-en-1-yl)sulfamoyl]phenyl]benzamide
-
-
acetyl-DPSD-CHO
-
-
ALLN
-
-
antipain
-
-
belactosin A
-
isolated from a Streptomyces sp. strain
Belactosin C
-
isolated from a Streptomyces sp. strain
bortezomib
Ca2+
-
-
carbobenzoxy-L-leucyl-L-leucyl-leucinal
-
MG-132
carfilzomib
CEP-18770
-
reversible
chloro[2,4-diiodo-6-({[(pyridin-2-yl-kappaN)methyl]amino-kappaN}methyl)phenolato-kappaO]copper
-
a copper complex, causes selective 20S proteasomal inhibition and apoptosis induction in several lines of cancer cells
chymostatin
-
-
c[Ala-Leu-Leu-Glu(Leu-vinyl ester)]
-
-
c[Gly-Leu-Leu-Glu(Leu-vinyl ester)]
-
-
c[Ser-Leu-Leu-Glu(Leu-vinyl ester)]
-
-
c[Val-Leu-Leu-Glu(Leu-vinyl ester)]
-
-
epoxomicin
epoxomycin
-
effect on mRNA and protein abundance in HeLa cells, overview
ethanol
-
ethanol-induced proteasome inhibition in liver cells
glial fibrillary acidic protein
-
human recombinant GFP-tagged, accumulation of the intermediate filament protein, glial fibrillary acidic protein, GFAP, in astrocytes of Alexander disease impairs proteasome function in astrocytes, also oligomers of R239C mutant GFAP inhibit the proteasome system in Alexander disease astrocytes to an even higher extent compared to the wild-type GFAP. The small heat shock protein chaperone alphaB-crystallin reverses the inhibition by shifting the size of the mutant protein from larger oligomers to smaller oligomers and monomers. The proteasome cannot efficiently degrade unassembled R239C GFAP, and the interaction of R239C GFAP with proteasomes actually inhibits proteasomal protease activity in a non-competitive manner, detailed overview
-
glidobactin A
-
GlbA
H-Ala-Leu-Leu-Glu(Leu-vinyl ester)-NH2
-
-
H-Gly-Leu-Leu-Glu(Leu-vinyl ester)-NH2
-
-
H-Ser-Leu-Leu-Glu(Leu-vinyl ester)-NH2
-
-
H-Val-Leu-Leu-Glu(Leu-vinyl ester)-NH2
-
-
lactacystin
leupeptin
-
-
marizomib
-
-
MG-132
MG132
MLN9708
-
an N-capped dipeptidyl leucine boronic acid, a potent inhibitor of the proteasome in tumor cells
mutant huntingtin
-
mutant huntingtin filamentous aggregates can inhibit 26S proteasome activity, but only when not recruited inclusion bodies
-
N,N'-bis(4-methoxyphenyl)tricyclo[3.3.1.13,7]decane-1,3-dicarboxamide
-
-
N-(1-hydroxy-2-methylpropan-2-yl)-5-[4-[(3-hydroxyphenyl)amino]phthalazin-1-yl]-2-methylbenzenesulfonamide
-
-
N-(3-hydroxy-2-oxopropyl)-5-[4-[(3-hydroxyphenyl)amino]phthalazin-1-yl]-2-methylbenzenesulfonamide
-
-
N-(4-methoxyphenyl)-3-(4-methylphenyl)tricyclo[3.3.1.13,7]decane-1-carboxamide
-
-
N-(tert-butoxycarbonyl)-L-alanyl-N5-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-N1-(naphthalen-2-ylmethyl)-L-glutamamide
-
-
N-(tert-butoxycarbonyl)-L-alanyl-N6-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-N-(naphthalen-2-ylmethyl)-6-oxo-L-lysinamide
-
-
N-(tert-butoxycarbonyl)-L-isoleucyl-N5-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-N1-(naphthalen-2-ylmethyl)-L-glutamamide
-
-
N-(tert-butoxycarbonyl)-L-phenylalanyl-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-O-methyl-L-tyrosinamide
-
60.06% inhibition at 0.01 mM
N-(tert-butoxycarbonyl)-L-phenylalanyl-N5-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-N1-(naphthalen-2-ylmethyl)-L-glutamamide
-
-
N-(tert-butoxycarbonyl)-O-methyl-L-tyrosyl-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-tyrosinamide
-
89.7% inhibition at 0.01 mM
N-(tert-butoxycarbonyl)-O-methyl-L-tyrosyl-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-O-methyl-L-tyrosinamide
-
69.7% inhibition at 0.01 mM
N-(tert-butoxycarbonyl)glycyl-N1-benzyl-N5-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-L-glutamamide
-
shows significant inhibition of 20S proteasome chymotrypsin-like, b5 activity
N-(tert-butoxycarbonyl)glycyl-N5-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-N1-(naphthalen-2-ylmethyl)-L-glutamamide
-
shows significant inhibition of 20S proteasome chymotrypsin-like, b5 activity
N-(tert-butoxycarbonyl)glycyl-N6-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-N-(naphthalen-2-ylmethyl)-6-oxo-L-lysinamide
-
-
N-acetyl-Leu-Leu-norleucinal
-
-
N-carbobenzoxy-L-leucyl-L-norvalinal
-
-
N-methoxysuccinyl-Glu-Val-Lys-Phe-H
-
modified
N-tert-butyl-5-[4-[(3-hydroxyphenyl)amino]phthalazin-1-yl]-2-methylbenzenesulfonamide
-
-
N-tosylphenylalanylchloromethylketone
-
-
N-[(1S)-1-benzyl-2-[[(1S)-1-(furan-2-ylcarbonyl)-3-methylbutyl]amino]-2-oxoethyl]-Na-(tert-butoxycarbonyl)-L-phenylalaninamide
-
inhibits chymotrypsin-like activity of the 26S proteasome
N-[(benzyloxy)carbonyl]-L-leucyl-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-phenylalaninamide
-
58.5% inhibition at 0.01 mM
N-[(benzyloxy)carbonyl]-L-leucyl-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-O-methyl-L-tyrosinamide
-
73.4% inhibition at 0.01 mM
N-[(benzyloxy)carbonyl]-L-phenylalanyl-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-O-methyl-L-tyrosinamide
-
82.2% inhibition at 0.01 mM
N-[4-(acetylsulfamoyl)phenyl]-2-(4-ethoxyphenyl)quinoline-4-carboxamide
-
-
N-[4-(acetylsulfamoyl)phenyl]-2-(4-ethylphenyl)quinoline-4-carboxamide
-
-
N-[4-(azepan-1-ylsulfonyl)phenyl]-4-tert-butylbenzamide
-
-
N-[4-(benzylsulfamoyl)phenyl]-2-methylbenzamide
-
-
N-[4-(benzylsulfamoyl)phenyl]-2-[4-(thiophen-2-yl)phenyl]quinoline-4-carboxamide
-
-
N2-(decylcarbamoyl)-N-[(3E,5S,8S,9E)-2,7-dioxo-5-(propan-2-yl)-1,6-diazacyclododeca-3,9-dien-8-yl]-L-valinamide
-
rational design and synthesis of a syringolin A-based lipophilic derivative, which proves to be a very potent syrbactin-based proteasome inhibitor
N2-(tert-butoxycarbonyl)-N-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-3-[(naphthalen-2-ylmethyl)amino]-3-oxo-D-alaninamide
-
-
N2-(tert-butoxycarbonyl)-N5-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-N1-(naphthalen-2-ylmethyl)-L-glutamamide
-
-
N2-(tert-butoxycarbonyl)-N6-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-N-(naphthalen-2-ylmethyl)-6-oxo-L-lysinamide
-
-
Nalpha-(tert-butoxycarbonyl)-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-phenylalaninamide
-
7.7% inhibition at 0.01 mM
Nalpha-(tert-butoxycarbonyl)-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-tyrosinamide
-
16.5% inhibition at 0.01 mM
Nalpha-(tert-butoxycarbonyl)-N-[(2S)-1-[[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-O-methyl-L-tyrosinamide
-
73% inhibition at 0.01 mM
Nalpha-[(2S)-2-[2-(tert-butoxycarbonyl)hydrazinyl]-4-phenylbutanoyl]-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-phenylalaninamide
-
-
Nalpha-[(2S)-2-[[(benzyloxy)carbonyl]amino]-4-(4-methoxyphenyl)butanoyl]-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-tyrosinamide
-
84.8% inhibition at 0.01 mM
Nalpha-[(2S)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-phenylalaninamide
-
47.5% inhibition at 0.01 mM
Nalpha-[(2S)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-tyrosinamide
-
67.1% inhibition at 0.01 mM
Nalpha-[(2S)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-O-methyl-L-tyrosinamide
-
14.9% inhibition at 0.01 mM
Nalpha-[(benzyloxy)carbonyl]-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-phenylalaninamide
-
5.7% inhibition at 0.01 mM
Nalpha-[(benzyloxy)carbonyl]-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-tyrosinamide
-
13.6% inhibition at 0.01 mM
Nalpha-[(benzyloxy)carbonyl]-N-[(2S)-1-[[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]amino]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]-O-methyl-L-tyrosinamide
-
60.5% inhibition at 0.01 mM
Nalpha-[(benzyloxy)carbonyl]-N-[(2S)-1-[[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-O-methyl-L-tyrosinamide
-
36.4% inhibition at 0.01 mM
NH4+
-
-
NLVS
-
irreversible inhibitor
NPI-0052
-
irreversible
ONX0912
-
a selective, irreversible inhibitor of the chymotrypsin-like activity of constitutive proteasome 20S and immunoproteasome 20S. ONX0912 exerts toxicity in Waldenstroem macroglobulinemia cells, by reducing bone marrow-derived interleukin-6 and insulin-like growth factor 1 secretion, thus inhibiting BM-induced p-Akt and phosphorylated extracellular signal-related kinase activation in Waldenstroem macroglobulinemia cells, overview. ONX0912 acts synergistically with bortezomib
Pentamidine
-
-
prion protein
-
recombinant mouse aggregated beta-PrP binds directly to human 20S and 26S proteasomes, i.e. its 20S core particle, overview. Conversion of cellular prion protein, PrPC, to toxic beta-sheet isoforms, PrPSc, which inhibit the ubiquitin-proteasome system and lead to accumulation of the system substrates, are associated with the prion diseases. PrP aggregates inhibit by stabilising the closed conformation of the substrate entry channel. The 20S proteasome is not inhibited when the gate in the alpha-ring is open due to a truncation mutation or by association with PA26/PA28. Modelling of location of aggregated beta-sheet rich PrP binding to the 20S proteasome and inhibition mechanism, detailed overview
-
pro-epigallocatechin-3-gallate
-
i.e. pro-EGCG, inhibitory efficacy is greatly improved from 42% inhibition to 89% inhibition when combined with 3,5-dinitrocatechol
PS-341
syringolin A
-
SylA, synthesis and inhibitory potency, overview
syringolin A methyl ester
-
-
-
syringolin B
-
SylB, synthesis and inhibitory potency, overview
Yu101
-
-
Z-b-Ala-Val-Ser-Leu-vinyl ester
-
-
Z-beta-Ala-Leu-Leu-Leu-vinyl ester
-
-
Z-Gly-Leu-Leu-Leu-vinyl ester
-
-
Z-Gly-Val-Ser-Leu-vinyl ester
-
-
Z-NH-(CH2)3-CO-Leu-Leu-Leu-vinyl ester
-
-
Z-NH-(CH2)3-CO-Val-Ser-Leu-vinyl ester
-
-
Z-NH-(CH2)4-CO-Leu-Leu-Leu-vinyl ester
-
-
Z-NH-(CH2)4-CO-Val-Ser-Leu-vinyl ester
-
-
Z-NH-(CH2)5-CO-Leu-Leu-Leu-vinyl ester
-
-
Z-NH-(CH2)5-CO-Val-Ser-Leu-vinyl ester
-
-
Z-NH-(CH2)6-CO-Leu-Leu-Leu-vinyl ester
-
-
Z-NH-(CH2)6-CO-Val-Ser-Leu-vinyl ester
-
-
Z-NH-(CH2)7-CO-Leu-Leu-Leu-vinyl ester
-
-
Z-NH-(CH2)7-CO-Val-Ser-Leu-vinyl ester
-
-
[Au(ESDT)]2
-
i.e. AUL15, a gold(I)-dithiocarbamato species, inhibits the chymotrypsin-like activity of purified 20S proteasome and 26S proteasome in breast cancer cells
[AuBr2(ESDT)]
-
i.e. AUL12, a gold(III)-dithiocarbamato species, inhibits the chymotrypsin-like activity of purified 20S proteasome and 26S proteasome in breast cancer cells
[Cu(HLI)(LI)]OAc
-
a copper complex, HLI is the ligand 2,4-diiodo-6-((pyridine-2-ylmethylamino)methyl)phenol, causes selective 20S proteasomal inhibition and apoptosis induction in several lines of cancer cells
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
19S regulatory complex
-
represents the major proteasome activator
-
doxorubicin
-
apoptosis inductor doxorubicin increases enzymatic activities, regulates subunit composition, and phosphorylation state of 26S proteasomes
nuclear factor erythroid-derived 2-related factor 1
-
i.e. Nrf1, a transcription factor of the cap and collar basic leucine zipper family, but not the related Nrf2, is necessary for induced proteasome gene transcription in cancer cell lines, overview
-
Rpt2
-
the 19S ATPase subunits, Rpt2 and Rpt5, bind ATP, their C-termini dock into intersubunit pockets in the 20S particle alpha-ring and induce gate opening, activating the protease activity. A conserved HbYX motif in the C-terminus is required
-
Rpt5
-
the 19S ATPase subunits, Rpt2 and Rpt5, bind ATP, their C-termini dock into intersubunit pockets in the 20S particle alpha-ring and induce gate opening, activating the protease activity. A conserved HbYX motif in the C-terminus is required
-
additional information
-
immediate early gene-X-1 may essentially modulate signalling pathways related to 26S proteasome activity
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.032
acetyl-EPFD-7-amido-4-carbamoylcoumarin
-
pH 7.8, 25°C
0.36
acetyl-HHSL-7-amido-4-carbamoylcoumarin
-
pH 7.5, 25°C
0.11
acetyl-norleucine-Arg-norleucine-Arg-7-amido-4-carbamoylcoumarin
-
pH 7.8, 25°C
0.027
acetyl-YWTQ-7-amido-4-carbamoylcoumarin
-
pH 7.8, 25°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.97
acetyl-EPFD-7-amido-4-carbamoylcoumarin
-
pH 7.8, 25°C
36.3
acetyl-HHSL-7-amido-4-carbamoylcoumarin
-
pH 7.5, 25°C
3.3 - 5.34
acetyl-norleucine-Arg-norleucine-Arg-7-amido-4-carbamoylcoumarin
0.27
acetyl-YWTQ-7-amido-4-carbamoylcoumarin
-
pH 7.8, 25°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000086 - 0.000194
(-)-epigallocatechin-3-gallate
Homo sapiens;
-
inhibition of the chymotrypsin-like activity of the proteasome in vitro, pH not specified in the publication, temperature not specified in the publication
0.019
(2R,3S)-1,2,3,4-tetrahydronaphthalene-2,3-diyl bis(3,4,5-trihydroxybenzoate)
Homo sapiens;
-
for the chymotrypsin-like activity, pH 7.5, 37°C
0.029
(2R,3S)-1,2,3,4-tetrahydronaphthalene-2,3-diyl bis(3,5-dihydroxybenzoate)
Homo sapiens;
-
for the chymotrypsin-like activity, pH 7.5, 37°C
0.00022
1-[1-(1-[(2,4-dioxoimidazolidin-1-ylimino)-methyl]-2-phenyl-ethylcarbamoyl)-2-(1H-indol-3-yl)-ethylcarbamoyl]-2-(1H-indol)
Homo sapiens;
-
pH 7.5, 30°C
0.000049 - 0.002
glidobactin A
0.0000373
MG-132
Homo sapiens;
-
in 10 mM HEPES (pH 7.6), at 37°C
0.00084 - 0.01
N-(tert-butoxycarbonyl)-L-alanyl-N5-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-N1-(naphthalen-2-ylmethyl)-L-glutamamide
0.00428 - 0.01
N-(tert-butoxycarbonyl)-L-alanyl-N6-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-N-(naphthalen-2-ylmethyl)-6-oxo-L-lysinamide
0.0015 - 0.01
N-(tert-butoxycarbonyl)-L-isoleucyl-N5-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-N1-(naphthalen-2-ylmethyl)-L-glutamamide
0.00942
N-(tert-butoxycarbonyl)-L-phenylalanyl-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-O-methyl-L-tyrosinamide
Homo sapiens;
-
in 10 mM HEPES (pH 7.6), at 37°C
0.00147 - 0.01
N-(tert-butoxycarbonyl)-L-phenylalanyl-N5-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-N1-(naphthalen-2-ylmethyl)-L-glutamamide
0.00164
N-(tert-butoxycarbonyl)-O-methyl-L-tyrosyl-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-tyrosinamide
Homo sapiens;
-
in 10 mM HEPES (pH 7.6), at 37°C
0.00815
N-(tert-butoxycarbonyl)-O-methyl-L-tyrosyl-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-O-methyl-L-tyrosinamide
Homo sapiens;
-
in 10 mM HEPES (pH 7.6), at 37°C
0.00054 - 0.01
N-(tert-butoxycarbonyl)glycyl-N1-benzyl-N5-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-L-glutamamide
0.00028 - 0.01
N-(tert-butoxycarbonyl)glycyl-N5-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-N1-(naphthalen-2-ylmethyl)-L-glutamamide
0.00274 - 0.01
N-(tert-butoxycarbonyl)glycyl-N6-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-N-(naphthalen-2-ylmethyl)-6-oxo-L-lysinamide
0.00785
N-[(1S)-1-benzyl-2-[[(1S)-1-(furan-2-ylcarbonyl)-3-methylbutyl]amino]-2-oxoethyl]-Na-(tert-butoxycarbonyl)-L-phenylalaninamide
Homo sapiens;
-
-
0.00756
N-[(benzyloxy)carbonyl]-L-leucyl-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-phenylalaninamide
Homo sapiens;
-
in 10 mM HEPES (pH 7.6), at 37°C
0.00585
N-[(benzyloxy)carbonyl]-L-leucyl-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-O-methyl-L-tyrosinamide
Homo sapiens;
-
in 10 mM HEPES (pH 7.6), at 37°C
0.00262
N-[(benzyloxy)carbonyl]-L-phenylalanyl-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-O-methyl-L-tyrosinamide
Homo sapiens;
-
in 10 mM HEPES (pH 7.6), at 37°C
0.00000865 - 0.0000796
N2-(decylcarbamoyl)-N-[(3E,5S,8S,9E)-2,7-dioxo-5-(propan-2-yl)-1,6-diazacyclododeca-3,9-dien-8-yl]-L-valinamide
0.00451 - 0.01
N2-(tert-butoxycarbonyl)-N-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-3-[(naphthalen-2-ylmethyl)amino]-3-oxo-D-alaninamide
0.00723 - 0.01
N2-(tert-butoxycarbonyl)-N5-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-N1-(naphthalen-2-ylmethyl)-L-glutamamide
0.00068 - 0.01
N2-(tert-butoxycarbonyl)-N6-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-N-(naphthalen-2-ylmethyl)-6-oxo-L-lysinamide
0.01
Nalpha-(tert-butoxycarbonyl)-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-phenylalaninamide
Homo sapiens;
-
IC50 above 0.01 mM, in 10 mM HEPES (pH 7.6), at 37°C
0.01
Nalpha-(tert-butoxycarbonyl)-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-tyrosinamide
Homo sapiens;
-
IC50 above 0.01 mM, in 10 mM HEPES (pH 7.6), at 37°C
0.00682
Nalpha-(tert-butoxycarbonyl)-N-[(2S)-1-[[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-O-methyl-L-tyrosinamide
Homo sapiens;
-
in 10 mM HEPES (pH 7.6), at 37°C
0.00785
Nalpha-[(2S)-2-[2-(tert-butoxycarbonyl)hydrazinyl]-4-phenylbutanoyl]-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-phenylalaninamide
Homo sapiens;
-
in 10 mM HEPES (pH 7.6), at 37°C
0.00327
Nalpha-[(2S)-2-[[(benzyloxy)carbonyl]amino]-4-(4-methoxyphenyl)butanoyl]-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-tyrosinamide
Homo sapiens;
-
in 10 mM HEPES (pH 7.6), at 37°C
0.00839
Nalpha-[(2S)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-phenylalaninamide
Homo sapiens;
-
in 10 mM HEPES (pH 7.6), at 37°C
0.00642
Nalpha-[(2S)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-tyrosinamide
Homo sapiens;
-
in 10 mM HEPES (pH 7.6), at 37°C
0.01
Nalpha-[(2S)-2-[[(benzyloxy)carbonyl]amino]-4-phenylbutanoyl]-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-O-methyl-L-tyrosinamide
Homo sapiens;
-
IC50 above 0.01 mM, in 10 mM HEPES (pH 7.6), at 37°C
0.01
Nalpha-[(benzyloxy)carbonyl]-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-phenylalaninamide
Homo sapiens;
-
IC50 above 0.01 mM, in 10 mM HEPES (pH 7.6), at 37°C
0.01
Nalpha-[(benzyloxy)carbonyl]-N-[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]-L-tyrosinamide
Homo sapiens;
-
IC50 above 0.01 mM, in 10 mM HEPES (pH 7.6), at 37°C
0.00601
Nalpha-[(benzyloxy)carbonyl]-N-[(2S)-1-[[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]amino]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]-O-methyl-L-tyrosinamide
Homo sapiens;
-
in 10 mM HEPES (pH 7.6), at 37°C
0.01
Nalpha-[(benzyloxy)carbonyl]-N-[(2S)-1-[[(2S)-1-(furan-2-yl)-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-O-methyl-L-tyrosinamide
Homo sapiens;
-
IC50 above 0.01 mM, in 10 mM HEPES (pH 7.6), at 37°C
0.00102 - 0.0103
syringolin A
0.000757 - 0.0187
syringolin A methyl ester
-
0.00778 - 0.1078
syringolin B
additional information
additional information
Homo sapiens;
-
cell growth inhibition activities, overview
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
29
-
chymotrypsin-like activity, KG1a cells, pH 7.4, 22°C
71
-
chymotrypsin-like activity, U-937 cells, pH 7.4, 22°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2
-
assay at
7.3
-
assay at
7.4
-
assay at
8
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
primary cells, and cell lines
Manually annotated by BRENDA team
-
from subjects with Alexander disease
Manually annotated by BRENDA team
-
immortalized with Epstein Barr virus
Manually annotated by BRENDA team
-
primary Waldenstroem macroglobulinemia cells
Manually annotated by BRENDA team
-
localization in nuclei of neurons of the putamen and substantia nigra of Parkinson's disease patients, no nuclear localization is observed in the same areas of brains of controls
Manually annotated by BRENDA team
-
colon cancer cell line
Manually annotated by BRENDA team
-
prostate cancer cell line
Manually annotated by BRENDA team
-
prostate cancer cell line
Manually annotated by BRENDA team
-
fibroblast
Manually annotated by BRENDA team
-
from peripheral blood
Manually annotated by BRENDA team
-
primary, multiple
Manually annotated by BRENDA team
-
localization in nuclei of neurons of the putamen and substantia nigra of Parkinson's disease patients, no nuclear localization is observed in the same areas of brains of controls
Manually annotated by BRENDA team
-
prostate cancer cell line
Manually annotated by BRENDA team
-
localization in nuclei of neurons of the putamen and substantia nigra of Parkinson's disease patients, no nuclear localization is observed in the same areas of brains of controls
Manually annotated by BRENDA team
-
osteosarcoma cell line
Manually annotated by BRENDA team
-
from subjects with Alexander disease, significantly decreased PGPH and chymotrypsin-like protease activities in white matter from Alexander disease patients expressing GFAP R239C, R416W, and R239H mutants
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
UNIPROT
ORGANISM
Homo sapiens;
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
heteromer
-
the 20S proteasomes are cylinder-shaped heteromeric dimers with a subunit configuration of alpha7, beta7, beta7, alpha7
multimer
-
7 * ? (20S alpha-type subunits) + 10 * ? (20S beta-type subnits) + 16 * ? (19S ATPase subunits) + 14 * ? (19S non-ATPase subunits)
tetramer
-
alpha5-subunit PSMA5 exists as tetramer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
acetylation
-
N-terminal acetylation of subunit alpha7
dephosphorylation
-
N-terminal dephosphorylation of subunit alpha7
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
in complex with carfilzomib, hanging drop vapor diffusion method, using 0.2 M sodium formate, 40% (w/v) 2-methyl-2,4-pentanediol, at 16°C
purified 20S protease core, X-ray diffraction structure determination and analysis
-
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
Blm10 (a large protein known to attach to the alpha ring surface of proteasomes), the 19S regulatory particles, and the Pre4 C-terminal extension have partly redundant functions in 20S catalytic core particle formation and maturation
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DEAE-Toyopearl 650S column chromatography and Superose 6 gel filtration
-
glutathione Sepharose 4B beads chromatography
-
HiTrap phenyl-Sepharose column chromatography
IgG-affinity resin chromatography
-
Ni2+ chelate chromatography
-
partially by preparation of erythrocytes, lysis, and differential centrifugation, determination of the subunits in proteasomal analysis, overview
-
Q-Sepharose HP chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in 293 cell line
-
expressed in Escherichia coli BL21 (DE3) cells and AH109 cells
-
expressed in Jurkat cells
-
PSMA5 is subcloned into the vector pET-22b(+) and expressed as inclusion bodies in Escherichia coli BL21
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
importance of antioxidant response elements in Nrf1-mediated upregulation of proteasome subunit genes
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
-
the proteasome is a target for inhibitor development and optimization, overview
medicine
additional information
-
peptide splicing is an intrinsic additional catalytic property of the proteasome, which may provide a qualitative peptide pool for immune selection