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Information on EC 3.4.25.1 - proteasome endopeptidase complex and Organism(s) Saccharomyces cerevisiae and UniProt Accession P38624
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3.4.25.1 proteasome endopeptidase complexSpecify your search results
Word Map
- 3.4.25.1
- bortezomib
- myeloma
-
polyubiquitinated
- neurodegenerative
-
misfolded
- lysosomal
- histone
-
chymotrypsin-like
- ligases
- leukemia
-
relapsed
- nf-kappab
-
immunomodulatory
- parkinsonism
- lymphoma
- deacetylase
-
ubiquitin-dependent
- alzheimer
- cyclins
- hematologic
-
caspase
-
histocompatibility
-
proteostasis
-
ubiquitin-like
- dexamethasone
- hsp90
-
deubiquitinating
-
ubiquitin-conjugating
- calpains
-
autologous
- inclusions
-
incurable
-
cyclin-dependent
-
short-lived
-
mantle
-
trypsin-like
-
progression-free
- thalidomide
-
ubiquitin-mediated
-
polyglutamine
- ikappab
- mcl-1
-
multisubunit
- mdm2
- ikappabalpha
- parkin
- rituximab
- alpha-synuclein
-
single-agent
- p27kip1
- synthesis
- medicine
- degradation
- analysis
- drug development
- biotechnology
The taxonomic range for the selected organisms is: Saccharomyces cerevisiae
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
proteasome, 26s proteasome, 20s proteasome, 26 s proteasome, multicatalytic proteinase, 20 s proteasome, multicatalytic protease, 26s proteasome complex, prosome, proteasome 20s, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
20S CP
26S protease
-
-
-
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27 kDa prosomal protein
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-
-
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30 kDa prosomal protein
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-
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Component Y8
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-
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GPRO-28
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-
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HsBPROS26
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-
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HSN3
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-
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ingensin
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-
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large multicatalytic protease
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-
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macropain
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-
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multicatalytic endopeptidase complex
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-
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Multicatalytic endopeptidase complex C7
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-
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multicatalytic protease
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-
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multicatalytic proteinase
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-
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p27K
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-
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PROS-27
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-
-
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PROS-30
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-
-
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PROS-Dm25
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-
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PROS-Dm28.1
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-
-
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PROS-Dm29
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-
-
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PROS-Dm35
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-
-
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prosome
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-
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proteasome
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-
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Proteasome component C13
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-
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Proteasome component C2
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-
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Proteasome component C3
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-
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Proteasome component C5
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-
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Proteasome component C8
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-
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Proteasome component C9
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-
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Proteasome component DD4
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Proteasome component DD5
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-
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Proteasome component pts1
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RING12 protein
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-
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RN3
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-
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SCL1 suppressor protein
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-
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TAS-F22/FAFP98
-
-
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TAS-G64
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-
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TCPR29
-
-
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tricorn protease
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-
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tricorn proteinase
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-
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XC3
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-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cleavage of peptide bonds with very broad specificity
ATPase activity
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
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CAS REGISTRY NUMBER
COMMENTARY
140879-24-9
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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
acetyl-Ala-Pro-norleucine-Leu-Leu-7-amido-4-methylcoumarin + H2O
acetyl-Ala-Pro-norleucine-Leu-Leu + 7-amino-4-methylcoumarin
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-
-
?
acetyl-GPLD-7-amido-4-methylcoumarin + H2O
acetyl-GPLD + 7-amino-4-methylcoumarin
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-
-
?
acetyl-GPLE-7-amido-4-methylcoumarin + H2O
acetyl-GPLE + 7-amino-4-methylcoumarin
-
-
-
?
acetyl-GPLL-7-amido-4-methylcoumarin + H2O
acetyl-GPLL + 7-amino-4-methylcoumarin
-
-
-
?
acetyl-norleucine-Leu-Pro-norleucine-Leu-YVAD-7-amido-4-methylcoumarin + H2O
acetyl-norleucine-Leu-Pro-norleucine-Leu-YVAD + 7-amino-4-methylcoumarin
-
-
-
?
acetyl-YVAD-7-amido-4-methylcoumarin + H2O
acetyl-YVAD + 7-amino-4-methylcoumarin
-
-
-
?
benzyloxycarbonyl-Ala-Arg-Arg-Arg-7-amido-4-methylcoumarin + H2O
?
-
-
-
-
?
benzyloxycarbonyl-Gly-Gly-Leu-7-amido-4-methylcoumarin + H2O
?
-
-
-
-
?
benzyloxycarbonyl-Leu-Leu-Glu-beta-naphthylamide + H2O
?
-
-
-
-
?
succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin + H2O
?
-
-
-
-
?
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
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
occupancy of the caspase-like sites stimulates the trypsin-like activity of the proteasomes
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
ubiquitin C-terminal hydrolase Ubp6 binds to the regulatory particle non-ATPase (Rpn) 1 via its N-terminal ubiquitin-like domain, whereas its catalytic ubiquitin-specific protease domain is positioned variably. Addition of ubiquitin aldehyde stabilizes the binding of the ubiquitin-specific protease domain in a position where it bridges the proteasome subunits Rpn1 and the regulatory particle triple-A ATPase (Rpt) 1. The ubiquitin-specific protease domain binds to Rpt1 in the immediate vicinity of the Ubp6 active site. The catalytic triad is positioned in proximity to the mouth of the ATPase module and to the deubiquitylating enzyme Rpn11. On the proteasome side, binding of Ubp6 favors conformational switching of the 26S proteasome into an intermediate-energy conformational state, in particular upon the addition of ubiquitin aldehyde
physiological function
additional information
physiological function
-
the 26S proteasome plays an essential role in the process of ATP-dependent protein degradation. The 26S proteasome is also involved in many non-proteolytic cellular activities, which are often mediated by subunits in its 19S regulatory complex. Unlike the entire 26S proteasome, the 20S CP performs a relative simple protease function and is biochemically very stable
physiological function
-
proteasomal substrates usually are tagged by a substrate-anchored polyubiquitin chain, while some proteins are degraded following monoubiquitination. For randomly sampled representative substrates, monoubiquitinated substrates are smaller than the polyubiquitinated ones, are enriched in specific pathways
additional information
-
development of an integrated proteomic approach, QTAX, for quantitative analysis of tandem affinity purified in vivo cross-linked protein complexes to capture protein interactions of all natures in a single analysis, overview. Investigation of cell cycle specific proteasome interaction networks
additional information
-
structures of the 26S proteasome, e.g. the 19S subunits of 26S proteasome, including proteasomal ATPases, ubiquitin receptors, deubiquitinating enzymes and subunits that contain PCI domain, or the molecular structures of the barrel-shaped 20S protease core particle, 20S CP, detailed overview
PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
polymer
additional information
-
three-dimensional structures of the 26S proteasome, e.g. the 19S subunits of 26S proteasome, including proteasomal ATPases, ubiquitin receptors, deubiquitinating enzymes and subunits that contain PCI domain, or the molecular structures of the barrel-shaped 20S protease core particle, detailed overview. Simple assembly process of the 20S proteasome. The 20S proteasome shows a hollow barrel-shaped structure with C2 symmetry composed of four stacked rings: two inner beta rings and two outer alpha rings. The eukaryotic alpha and beta rings are each composed of seven distinct homologous subunits, which form a pseudo 7fold symmetrical structure of alpha17beta17beta17alpha17, with proteolytic active sites located at the N-termini of three subunits, beta1, beta2 and beta5, of each beta-ring
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
cryo-EM structures of the actively ATP-hydrolyzing, substrate-engaged 26S proteasome with four distinct motor conformations. Structures suggest a ubiquitin capture mechanism, in which mechanical pulling on the substrate by the AAA+ motor delivers ubiquitin modifications directly into the Rpn11 catalytic groove and accelerates isopeptide cleavage for efficient, cotranslocational deubiquitination. The substrate polypeptide traverses from the Rpn11 deubiquitinase, through the AAA+ motor, and into the core peptidase. The proteasomal motor thereby adopts staircase arrangements with five substrate-engaged subunits and one disengaged subunit. Four of the substrate-engaged subunits are ATP bound, whereas the subunit at the bottom of the staircase and the disengaged subunit are bound to ADP
enzyme core particle with the alpha7DELTAN mutation, hanging drop vapor diffusion method, using 0.1 M MES (pH 6.5), 50 mM magnesium acetate, and 14% (v/v) 2-methyl-2,4-pentanediol
hanging drop vapour diffusion method, structure of the 20S proteasome/TMC-95A complex
-
in complex with bortezomib, hanging drop vapour diffusion method at 24°C in 30 mM MgOAc, 100 mM MES (pH 7.2), and 10% 2-methyl-2,4-pentanediol
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purified 20S protease core, X-ray diffraction structure determination and analysis
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
development of an integrated proteomic approach, QTAX, for quantitative analysis of tandem affinity purified in vivo cross-linked protein complexes to capture protein interactions of all natures in a single analysis, overview. Investigation of cell cycle specific proteasome interaction networks. Wild-type and RPN11-HBH cells are synchronized in three phases (G1, S, and M) before cross-linking and tandem affinity purification
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
the HEAT repeat protein 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
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
development of an integrated proteomic approach, QTAX, for quantitative analysis of tandem affinity purified in vivo cross-linked protein complexes to capture protein interactions of all natures in a single analysis, overview. Investigation of cell cycle specific proteasome interaction networks. Wild-type and RPN11-HBH cells are synchronized in three phases (G1, S, and M) before cross-linking and tandem affinity purification using nickel affinity resin and streptavidin beads after lysis using buffer containing 8 M urea, 300 mM NaCl, 50 mM NaH2PO4, 0.5% Igepal, 20 mM imidazole, and 1 mM PMSF, pH 8.5
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Seufert, W.; Jentsch, S.
In vivo function of the proteasome in the ubiquitin pathway
EMBO J.
11
3077-3080
1992
Saccharomyces cerevisiae
Groll, M.; Ditzel, L.; Loewe, J.; Stock, D.; Bochtler, M.; Bartunik, H.D.; Huber, R.
Structure of 20S proteasomes from yeast at 2.4 A resolution
Nature
386
463-471
1997
Saccharomyces cerevisiae
Hilt, W.; Heinemeyer, W.; Wolf, D.H.
Studies on the yeast proteasome uncover its basic structural features and multiple in vivo functions
Enzyme Protein
47
189-201
1994
Saccharomyces cerevisiae, Oryctolagus cuniculus, Drosophila melanogaster, Homo sapiens, Schizosaccharomyces pombe, Thermoplasma acidophilum, Xenopus laevis
Dick, T.P.; Nussbaum, A.K.; Deeg, M.; Heinemeyer, W.; Groll, M.; Schirle, M.; Keilholz, W.; Stevanovic, S.; Wolf, D.H.; Huber, R.; Rammensee, H.G.; Schild, H.
Contribution of proteasomal beta-subunits to the cleavage of peptide substrates analyzed with yeast mutants
J. Biol. Chem.
273
25637-25646
1998
Saccharomyces cerevisiae
Rivett, J.
Proteasomes: Multicatalytic proteinase complexes
Biochem. J.
291
1-10
1993
Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Thermoplasma acidophilum, Xenopus laevis
-
Coux, O.; Tanaka, K.; Goldberg, A.L.
Structure and functions of the 20S and 26S proteasomes
Annu. Rev. Biochem.
65
801-847
1996
Saccharomyces cerevisiae, Escherichia coli, Homo sapiens, Rattus norvegicus, Rhodococcus sp., Spinacia oleracea, Thermoplasma acidophilum
Wojcikiewicz, R.J.H.; Xu, Q.; Webster, J.M.; Alzayady, K.; Gao, C.
Ubiquitination and proteasomal degrdn. of endogenous and exogenous inositol 1,4,5-trisphosphate receptors in aT3-1 anterior pituitary cells
J. Biol. Chem.
278
940-947
2003
Saccharomyces cerevisiae, Oryctolagus cuniculus
Groll, M.; Koguchi, Y.; Huber, R.; Kohno, J.
Crystal structure of the 20 S proteasome:TMC-95A complex: a non-covalent proteasome inhibitor
J. Mol. Biol.
311
543-548
2001
Saccharomyces cerevisiae
Groll, M.; Huber, R.
Purification, crystallization, and X-ray analysis of the yeast 20S proteasome
Methods Enzymol.
398
329-336
2005
Saccharomyces cerevisiae
Marques, A.J.; Glanemann, C.; Ramos, P.C.; Dohmen, R.J.
The C-terminal extension of the beta7 subunit and activator complexes stabilize nascent 20 S proteasomes and promote their maturation
J. Biol. Chem.
282
34869-34876
2007
Saccharomyces cerevisiae, Homo sapiens
Iwanczyk, J.; Sadre-Bazzaz, K.; Ferrell, K.; Kondrashkina, E.; Formosa, T.; Hill, C.P.; Ortega, J.
Structure of the Blm10-20 S proteasome complex by cryo-electron microscopy. Insights into the mechanism of activation of mature yeast proteasomes
J. Mol. Biol.
363
648-659
2006
Saccharomyces cerevisiae
Isono, E.; Nishihara, K.; Saeki, Y.; Yashiroda, H.; Kamata, N.; Ge, L.; Ueda, T.; Kikuchi, Y.; Tanaka, K.; Nakano, A.; Toh-e, A.
The assembly pathway of the 19S regulatory particle of the yeast 26S proteasome
Mol. Biol. Cell
18
569-580
2007
Saccharomyces cerevisiae
Groll, M.; Berkers, C.R.; Ploegh, H.L.; Ovaa, H.
Crystal structure of the boronic acid-based proteasome inhibitor bortezomib in complex with the yeast 20S proteasome
Structure
14
451-456
2006
Saccharomyces cerevisiae
Kim, H.M.; Yu, Y.; Cheng, Y.
Structure characterization of the 26S proteasome
Biochim. Biophys. Acta
1809
67-79
2011
Saccharomyces cerevisiae, Escherichia coli, Homo sapiens, Methanocaldococcus jannaschii, Mycobacterium tuberculosis, Thermoplasma acidophilum
Kaake, R.M.; Milenkovic, T.; Przulj, N.; Kaiser, P.; Huang, L.
Characterization of cell cycle specific protein interaction networks of the yeast 26S proteasome complex by the QTAX strategy
J. Proteome Res.
9
2016-2029
2010
Saccharomyces cerevisiae
Yashiroda, H.; Toda, Y.; Otsu, S.; Takagi, K.; Mizushima, T.; Murata, S.
N-terminal alpha7 deletion of the proteasome 20S core particle substitutes for yeast PI31 function
Mol. Cell. Biol.
35
141-152
2015
Saccharomyces cerevisiae (P21243), Saccharomyces cerevisiae
Aufderheide, A.; Beck, F.; Stengel, F.; Hartwig, M.; Schweitzer, A.; Pfeifer, G.; Goldberg, A.L.; Sakata, E.; Baumeister, W.; Foerster, F.
Structural characterization of the interaction of Ubp6 with the 26S proteasome
Proc. Natl. Acad. Sci. USA
112
8626-8631
2015
Saccharomyces cerevisiae (P38624)
Braten, O.; Livneh, I.; Ziv, T.; Admon, A.; Kehat, I.; Caspi, L.; Gonen, H.; Bercovich, B.; Godzik, A.; Jahandideh, S.; Jaroszewski, L.; Sommer, T.; Kwon, Y.; Guharoy, M.; Tompa, P.; Ciechanover, A.
Numerous proteins with unique characteristics are degraded by the 26S proteasome following monoubiquitination
Proc. Natl. Acad. Sci. USA
113
E4639-E4647
2016
Saccharomyces cerevisiae, Homo sapiens
EXTERNAL LINKS (specific for EC-Number 3.4.25.1)
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