Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Properties of the hybrid form of the 26S proteasome containing both 19S and PA28 complexes.
Clastosome: a subtype of nuclear body enriched in 19S and 20S proteasomes, ubiquitin, and protein substrates of proteasome.
Mapping and structural dissection of human 20 S proteasome using proteomic approaches.
Protein-protein interactions among human 20S proteasome subunits and proteassemblin.
The alpha4 and alpha7 subunits and assembly of the 20S proteasome.
Towards a proteome-scale map of the human protein-protein interaction network.
Conserved signal peptide of Notch3 inhibits interaction with proteasome.
Mass spectrometric characterization of the affinity-purified human 26S proteasome complex.
The proteasome maturation protein POMP facilitates major steps of 20S proteasome formation at the endoplasmic reticulum.
Large-scale proteomics and phosphoproteomics of urinary exosomes.
An empirical framework for binary interactome mapping.
Recognition and processing of ubiquitin-protein conjugates by the proteasome.
MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
Next-generation sequencing to generate interactome datasets.
Proteomic characterization of the human sperm nucleus.
Toward an understanding of the protein interaction network of the human liver.
In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
Thymoproteasome subunit-β5T generates peptide-MHC complexes specialized for positive selection.
Acetylation-mediated proteasomal degradation of core histones during DNA repair and spermatogenesis.
A proteome-scale map of the human interactome network.
Crystal structure of the human 20S proteasome in complex with carfilzomib.
Proteasome activators, PA28γ and PA200, play indispensable roles in male fertility.
The inhibition mechanism of human 20S proteasomes enables next-generation inhibitor design.
An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations.
Structural mechanism for nucleotide-driven remodeling of the AAA-ATPase unfoldase in the activated human 26S proteasome.
ZFAND1 Recruits p97 and the 26S Proteasome to Promote the Clearance of Arsenite-Induced Stress Granules.
An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders.
The immunoproteasome and thymoproteasome: functions, evolution and human disease.
Restricted Expression of the Thymoproteasome Is Required for Thymic Selection and Peripheral Homeostasis of CD8(+) T Cells.
Design and Evaluation of Highly Selective Human Immunoproteasome Inhibitors Reveal a Compensatory Process That Preserves Immune Cell Viability.
Regulation of Proteasome Activity by (Post-)transcriptional Mechanisms.
Characterization of Fully Recombinant Human 20S and 20S-PA200 Proteasome Complexes.
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
Cryo-EM structures of the human PA200 and PA200-20S complex reveal regulation of proteasome gate opening and two PA200 apertures.
A reference map of the human binary protein interactome.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
Role of oncogenic REGγ in cancer.
Adaptation of Proteasomes and Lysosomes to Cellular Environments.
Proteasome in action: substrate degradation by the 26S proteasome.
The Role of Proteasomes in the Thymus.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
The 20S as a stand-alone proteasome in cells can degrade the ubiquitin tag.
AKIRIN2 controls the nuclear import of proteasomes in vertebrates.
OpenCell: Endogenous tagging for the cartography of human cellular organization.
Proteasome complexes experience profound structural and functional rearrangements throughout mammalian spermatogenesis.
Proteasome activator 28γ (PA28γ) allosterically activates trypsin-like proteolysis by binding to the α-ring of the 20S proteasome.
Structural insights into the human PA28-20S proteasome enabled by efficient tagging and purification of endogenous proteins.
An abundance of free regulatory (19S) proteasome particles regulates neuronal synapses.
Analysis of proteome-wide degradation dynamics in ALS SOD1 iPSC-derived patient neurons reveals disrupted VCP homeostasis.
Structure and functions of the 20S and 26S proteasomes.
Ubiquitinated IkB is degraded
Proteasome proteolyzes ub-HIF-alpha
Proteasomal clevage of exogenous antigen (26S proteasome catalyst)
Ubiquitinated DVL is degraded by the proteasome
Degradation of multiubiquitinated Cdh1
Degradation of multiubiquitinated cell cycle proteins
Degradation of multiubiquitinated Securin
SCF-mediated degradation of Emi1
Degradation multiubiquitinated Cyclin A
Degradation of ubiquitinated CD4
Proteosome-mediated degradation of APOBEC3G
Degradation of ubiquitinated p27/p21 by the 26S proteasome
APC/C:Cdh1-mediated degradation of Skp2
Ubiquitinated and phosphorylated IKBA binds to and is degraded by the proteasome complex
Degradation of ubiquitinated beta catenin by the proteasome
Proteasome mediated degradation of COP1
26S proteosome degrades ODC holoenzyme complex
Ub-RibC-AXIN is degraded by the proteasome
AUF1:mRNA complex is degraded
PRICKLE1 is degraded by the proteasome
Ubiquitinated AXIN is degraded by the proteasome
Ubiquitinated DVL1 is degraded by the proteasome
Hh C-terminal fragments are degraded by the proteasome
processing defective Hh variants are degraded by the proteasome
26S proteasome processes K48PolyUb-K21,22-p-S32,36-IkBA:NF-kB complex to form NF-kB complex
26S proteasome processes p-7S-p100:RELB to form p52:RELB
GLI3 is partially degraded by the proteasome to yield the GLI3 repressor
GLI1 is degraded by the proteasome after ubiquitination by beta-TrCP
GLI1 is degraded by the proteasome after ubiquitination by ITCH
GLI2,3 are degraded by the proteasome
ub-GLI is degraded by the proteasome
NF1 is degraded by the proteasome
ADRM1:26S proteaseome binds UCHL5
ADRM1 binds 26S proteasome
Protesomal degradation of K48polyUb-TRAF3
26Sproteasome degrades K48polyUb-NIK
MAPK6 is degraded by the 26S proteasome
ADRM1:26S proteaseome binds USP14
Ubiquitinated geminin is degraded by the proteasome
Ubiquitinated Orc1 is degraded by the proteasome
Ubiquitinated Cdc6 is degraded by the proteasome
Proteolytic degradation of ubiquitinated-Cdc25A
Proteasome mediated degradation of Cyclin D1
Proteasome degrades polyubiquitinated PTEN
GTSE1 facilitates proteasome-mediated degradation of TP53
Proteasome degrades AURKA ubiquitinated by SCF-FBXL7
Proteasome-mediated degradation of PolyUb-FBXL7
misfolded CFTR is degraded by the 26S proteasome
CFTR F508del is degraded by the 26S proteasome
26S proteasome degrades Ub-NFE2L2
26S proteasome degrades PolyUb-RUNX2
Polyubiquitinated RUNX3 is degraded by the proteasome
NEDD8 and UBD bind NUB1 and the 26S proteasome
26S- and NUB1-mediated degradation of NEDD8, UBD and their conjugates
26S proteasome degrades TP73 polyubiquitinated by ITCH
26S proteasome degrades HIFalpha
ub UBXN7 is degraded by the 26S proteasome
Ub,pS335,S338,T NFE2L2 is degraded
Proteasome-dependent degradation of ubiquitinated CDH1
Proteasomal cleavage of substrate
Formation of the inner ring of the 20S core particle of the 26S proteasome
Formation of the outer ring of the 20S core particle
Formation of the preholoproteasome
Formation of the inner ring of the 20S immunoproteasome core particle
Formation of the inner ring of the 20S thymoproteasome core particle
Formation of the preholothymoproteasome
Fromation of the preholoimmunoproteasome
PSMG1:PSMG2 dimer binds the 20S core particle outer ring
POMP binds the 20S core particle outer ring
Maturation of the canonical 20S core particle
Formation of the 26S proteasome
Formation of the PA28-alpha-beta-20S proteasome
Formation of the PA28gamma-20S proteasome
Proteasomal cleavage of intracellular substrate (PA28-alpha-beta-20S proteasome catalyst)
Proteasomal cleavage of intracellular substrate (immunoproteasome catalyst)
Proteasomal clevage of exogenous antigen (immunoproteasome catalyst)
Proteasomal cleavage of partially digested antigen (immunoproteasome catalyst)
Ubiquitinated CD274 is degraded by the 26S proteasome
SPOP-mediated degradation of CD274 by 26S Proteosome
Proteasomal degradation of polyUb-p-S195-CD274
Proteolysis of K48polyUb-K,p-S-PER1,2,3
The proteasome degrades the K48-polyubiquitinated alanine-tailed nascent peptide
Proteasome mediated degradation of PAK-2p34
Gli2is degraded by the proteasome
Proteasome degrades SAX-3 ubiquitinated by EBAX-1
Proteasome degrades ubiquitinated mouse NICD4
Molecular architecture and assembly of the eukaryotic proteasome.
Falcon deep research report on PSMA1
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PSMA1 (UniProt P25786) is a non-catalytic alpha subunit of the 20S proteasome
core particle; the catalytic protease active sites reside in beta subunits, not
in PSMA1.
"Importantly, **PSMA1 is not a catalytic peptidase active site**; proteolysis occurs at catalytic **β subunits**."
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The 20S core particle is a barrel of four stacked heteroheptameric rings
(alpha1-7 beta1-7 beta1-7 alpha1-7); the two outer alpha rings act as a gate
restricting access to the proteolytic chamber, and PSMA1 is one of the
non-catalytic alpha subunits contributing to this gate architecture.
"The 20S CP is a barrel made of **four stacked heteroheptameric rings** arranged **α1–7 β1–7 β1–7 α1–7**; the **two outer α rings** act as a **gate** that restricts access to the proteolytic chamber. PSMA1 is one of the **non-catalytic α subunits** contributing to this gate architecture."
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The N-terminal regions of PSMA1-PSMA7 form the gate controlling access to the
proteolytic chamber, defining PSMA1's primary molecular function as structural
regulation of substrate access rather than catalysis.
"A 2023 cell-biological study reiterates that **PSMA1–PSMA7 N-terminal regions form the gate controlling access to the proteolytic chamber**, situating PSMA1’s primary molecular function as **structural regulation of substrate access** rather than catalysis."
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PSMA1's primary function is to serve as an essential structural subunit of the
20S alpha ring, contributing to the gated entry pore and to binding interfaces
for regulators that activate or cap the core particle.
"PSMA1’s primary function is to serve as an essential **structural subunit of the 20S α ring**, contributing to:
1) **formation of the gated entry pore** (N-termini-based barrier), and
2) **binding interfaces** for regulators that activate or cap the core particle."
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Gate opening is driven by C-terminal HbYX motifs of proteasome regulators (e.g.
the 19S RP) inserting into pockets between adjacent alpha subunits; as an alpha
subunit PSMA1 contributes to forming these alpha-ring interfaces and pockets.
"**C-terminal HbYX motifs of proteasome regulators** (e.g., the 19S RP) insert into **pockets between adjacent α subunits** to promote **CP gate opening**. As an α subunit, PSMA1 contributes to forming these α-ring interfaces and pockets that receive regulatory tails."
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Human 20S biogenesis begins with formation of a complete alpha ring assisted by
the assembly chaperones PAC1/2 and PAC3/4, followed by sequential beta-subunit
incorporation; PSMA1 is one of the alpha-ring building blocks assembled before
catalytic maturation.
"Assembly begins with formation of a complete **α ring** assisted by **PAC1/2 and PAC3/4**, followed by sequential β incorporation to form **half-CPs** that fuse; activation requires cleavage of β propeptides."
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Proteasomes are present in both the cytoplasm and nucleus, and osmotic/salt
stress induces rapid formation of nuclear proteasome granules containing 26S
proteasomes.
"Proteasomes exist in both the **cytoplasm and nucleus**. In a 2023 imaging and tagging study, osmotic/salt stress induced rapid formation of **nuclear proteasome granules** containing 26S proteasomes (positive for both a 20S marker and a 19S marker), consistent with regulated nuclear proteasome compartmentalization."
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When 26S integrity is disrupted (PSMD1 knockdown), free 20S core particles
remain nuclear while the 19S regulatory particle accumulates in the cytoplasm,
indicating compartment-specific dynamics of PSMA1-containing cores.
"Under PSMD1 knockdown (reducing intact 26S), the authors observed that “‘free’ 20S CPs remained nuclear, whereas the 19S RP accumulated in the cytoplasm,” indicating compartment-specific dynamics of PSMA1-containing cores versus 19S components."
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About half of cellular proteasomes can exist as free 20S complexes that carry
out ubiquitin-independent turnover, especially of substrates with intrinsically
disordered regions and of nuclear and stress-granule proteins.
"Pepelnjak et al. (2024) emphasize that **~half of cellular proteasomes** can exist as **free 20S complexes**, enabling ubiquitin-independent turnover of certain substrates—especially proteins with **intrinsically disordered regions (IDRs)** and enrichment among **nuclear and stress granule proteins**."
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Approved proteasome inhibitors act on the catalytic beta subunits (especially
beta5), not on alpha subunits like PSMA1, framing PSMA1 as a biomarker/
proteasome-state indicator rather than a direct pharmacologic target.
"clinically used proteasome inhibitors (e.g., bortezomib) act on **catalytic β subunits** (especially β5), rather than α subunits like PSMA1. This frames PSMA1 more as a biomarker/proteasome-state indicator than a direct pharmacologic target."