PSMA1

UniProt ID: P25786
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

PSMA1 encodes proteasome subunit alpha type-1, a non-catalytic alpha-ring component of the human 20S core proteasome. It contributes to the architecture and gated entry surface of the 20S core, thereby supporting proteasomal protein catabolism in cytosolic and nuclear proteasome complexes.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005634 nucleus
IBA
GO_REF:0000033
ACCEPT
Summary: nucleus is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IBA
GO_REF:0000033
ACCEPT
Summary: proteasome-mediated ubiquitin-dependent protein catabolic process captures the proteasome-mediated protein catabolism process supported for this subunit as part of the proteasome.
Reason: The gene product is a core 20S proteasome subunit, so proteasomal protein catabolism is an appropriate core biological-process context.
Supporting Evidence:
file:human/PSMA1/PSMA1-deep-research-falcon.md
PSMA1 is thus part of the **execution machinery** for UPS-mediated proteolysis by enabling regulated access to catalytic sites.
GO:0019773 proteasome core complex, alpha-subunit complex
IBA
GO_REF:0000033
ACCEPT
Summary: proteasome core complex, alpha-subunit complex is the appropriate core-complex membership annotation for PSMA1.
Reason: Structural studies and UniProt summaries place the protein in the 20S proteasome core; this complex-membership annotation is central to the gene product role.
Supporting Evidence:
file:human/PSMA1/PSMA1-deep-research-falcon.md
PSMA1 is one of PSMA1-7 forming the outer Ξ± rings that regulate access to the proteolytic chamber.
GO:0005634 nucleus
IEA
GO_REF:0000044
ACCEPT
Summary: nucleus is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005737 cytoplasm
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: cytoplasm is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0005829 cytosol
IEA
GO_REF:0000117
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005839 proteasome core complex
IEA
GO_REF:0000120
ACCEPT
Summary: proteasome core complex is the appropriate core-complex membership annotation for PSMA1.
Reason: Structural studies and UniProt summaries place the protein in the 20S proteasome core; this complex-membership annotation is central to the gene product role.
Supporting Evidence:
file:human/PSMA1/PSMA1-deep-research-falcon.md
The 20S CP is a barrel made of **four stacked heteroheptameric rings** arranged **Ξ±1–7 Ξ²1–7 Ξ²1–7 Ξ±1–7**; the **two outer Ξ± rings** act as a **gate** that restricts access to the proteolytic chamber.
GO:0006511 ubiquitin-dependent protein catabolic process
IEA
GO_REF:0000002
MODIFY
Summary: ubiquitin-dependent protein catabolic process is directionally related to the proteasome role but is less specific than the supported proteasome term.
Reason: Replace the broad annotation with proteasome-mediated ubiquitin-dependent protein catabolic process, which better captures the gene product role supported by proteasome literature and existing specific GOA annotations.
GO:0019773 proteasome core complex, alpha-subunit complex
IEA
GO_REF:0000002
ACCEPT
Summary: proteasome core complex, alpha-subunit complex is the appropriate core-complex membership annotation for PSMA1.
Reason: Structural studies and UniProt summaries place the protein in the 20S proteasome core; this complex-membership annotation is central to the gene product role.
GO:0030163 protein catabolic process
IEA
GO_REF:0000002
MODIFY
Summary: protein catabolic process is directionally related to the proteasome role but is less specific than the supported proteasome term.
Reason: Replace the broad annotation with proteasomal protein catabolic process, which better captures the gene product role supported by proteasome literature and existing specific GOA annotations.
GO:0005515 protein binding
IPI
PMID:12376572
Mapping and structural dissection of human 20 S proteasome u...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:14733938
Protein-protein interactions among human 20S proteasome subu...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:15225636
The alpha4 and alpha7 subunits and assembly of the 20S prote...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:16189514
Towards a proteome-scale map of the human protein-protein in...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:17948026
The proteasome maturation protein POMP facilitates major ste...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:19060904
An empirical framework for binary interactome mapping.
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:21516116
Next-generation sequencing to generate interactome datasets.
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:21988832
Toward an understanding of the protein interaction network o...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network.
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:25599644
Crystal structure of the human 20S proteasome in complex wit...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:29568061
An AP-MS- and BioID-compatible MAC-tag enables comprehensive...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:29636472
Structural mechanism for nucleotide-driven remodeling of the...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:29892012
An interactome perturbation framework prioritizes damaging m...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:31473102
Characterization of Fully Recombinant Human 20S and 20S-PA20...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:31515488
Extensive disruption of protein interactions by genetic vari...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:34702852
The 20S as a stand-alone proteasome in cells can degrade the...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human ce...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:35858375
Structural insights into the human PA28-20S proteasome enabl...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0005515 protein binding
IPI
PMID:37776851
Analysis of proteome-wide degradation dynamics in ALS SOD1 i...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0000502 proteasome complex
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: proteasome complex is true complex membership but broader or more context-specific than the core 20S subunit identity.
Reason: The core review should emphasize the specific 20S core subcomplex membership; broader proteasome or spermatoproteasome membership can be retained as non-core context.
GO:0001530 lipopolysaccharide binding
IEA
GO_REF:0000107
REMOVE
Summary: Lipopolysaccharide binding is not supported as a human PSMA1 core function.
Reason: This is an automated computational projection and is not supported by the human PSMA1 UniProt functional summary or the proteasome structural literature reviewed here.
GO:0002862 negative regulation of inflammatory response to antigenic stimulus
IEA
GO_REF:0000107
MARK AS OVER ANNOTATED
Summary: negative regulation of inflammatory response to antigenic stimulus is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0140756 structural constituent of proteasome
IDA
PMID:27493187
The inhibition mechanism of human 20S proteasomes enables ne...
ACCEPT
Summary: PSMA1 is a non-catalytic alpha-ring subunit whose core molecular role is structural contribution to the 20S proteasome.
Reason: Human proteasome structures and reviews support alpha subunits as structural components of the 20S core; PSMA1 should receive structural constituent/complex membership, not catalytic protease activity.
Supporting Evidence:
file:human/PSMA1/PSMA1-deep-research-falcon.md
PSMA1’s primary function is to serve as an essential **structural subunit of the 20S Ξ± ring**, contributing to:
file:human/PSMA1/PSMA1-deep-research-falcon.md
Importantly, **PSMA1 is not a catalytic peptidase active site**; proteolysis occurs at catalytic **Ξ² subunits**.
GO:0000502 proteasome complex
NAS
PMID:29636472
Structural mechanism for nucleotide-driven remodeling of the...
KEEP AS NON CORE
Summary: proteasome complex is true complex membership but broader or more context-specific than the core 20S subunit identity.
Reason: The core review should emphasize the specific 20S core subcomplex membership; broader proteasome or spermatoproteasome membership can be retained as non-core context.
GO:0000502 proteasome complex
NAS
PMID:33729481
Proteasome in action: substrate degradation by the 26S prote...
KEEP AS NON CORE
Summary: proteasome complex is true complex membership but broader or more context-specific than the core 20S subunit identity.
Reason: The core review should emphasize the specific 20S core subcomplex membership; broader proteasome or spermatoproteasome membership can be retained as non-core context.
GO:0000502 proteasome complex
NAS
PMID:37228199
An abundance of free regulatory (19S) proteasome particles r...
KEEP AS NON CORE
Summary: proteasome complex is true complex membership but broader or more context-specific than the core 20S subunit identity.
Reason: The core review should emphasize the specific 20S core subcomplex membership; broader proteasome or spermatoproteasome membership can be retained as non-core context.
GO:0005829 cytosol
NAS
PMID:12032076
Properties of the hybrid form of the 26S proteasome containi...
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0008021 synaptic vesicle
NAS
PMID:37228199
An abundance of free regulatory (19S) proteasome particles r...
KEEP AS NON CORE
Summary: synaptic vesicle is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0010498 proteasomal protein catabolic process
NAS
PMID:33729481
Proteasome in action: substrate degradation by the 26S prote...
ACCEPT
Summary: proteasomal protein catabolic process captures the proteasome-mediated protein catabolism process supported for this subunit as part of the proteasome.
Reason: The gene product is a core 20S proteasome subunit, so proteasomal protein catabolism is an appropriate core biological-process context.
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
NAS
PMID:19489727
Recognition and processing of ubiquitin-protein conjugates b...
ACCEPT
Summary: proteasome-mediated ubiquitin-dependent protein catabolic process captures the proteasome-mediated protein catabolism process supported for this subunit as part of the proteasome.
Reason: The gene product is a core 20S proteasome subunit, so proteasomal protein catabolism is an appropriate core biological-process context.
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
NAS
PMID:33729481
Proteasome in action: substrate degradation by the 26S prote...
ACCEPT
Summary: proteasome-mediated ubiquitin-dependent protein catabolic process captures the proteasome-mediated protein catabolism process supported for this subunit as part of the proteasome.
Reason: The gene product is a core 20S proteasome subunit, so proteasomal protein catabolism is an appropriate core biological-process context.
GO:0061136 regulation of proteasomal protein catabolic process
NAS
PMID:12032076
Properties of the hybrid form of the 26S proteasome containi...
MARK AS OVER ANNOTATED
Summary: regulation of proteasomal protein catabolic process is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0000502 proteasome complex
NAS
PMID:30104634
The immunoproteasome and thymoproteasome: functions, evoluti...
KEEP AS NON CORE
Summary: proteasome complex is true complex membership but broader or more context-specific than the core 20S subunit identity.
Reason: The core review should emphasize the specific 20S core subcomplex membership; broader proteasome or spermatoproteasome membership can be retained as non-core context.
GO:0000502 proteasome complex
IPI
PMID:31283222
Design and Evaluation of Highly Selective Human Immunoprotea...
KEEP AS NON CORE
Summary: proteasome complex is true complex membership but broader or more context-specific than the core 20S subunit identity.
Reason: The core review should emphasize the specific 20S core subcomplex membership; broader proteasome or spermatoproteasome membership can be retained as non-core context.
GO:0000502 proteasome complex
NAS
PMID:32134919
Cryo-EM structures of the human PA200 and PA200-20S complex ...
KEEP AS NON CORE
Summary: proteasome complex is true complex membership but broader or more context-specific than the core 20S subunit identity.
Reason: The core review should emphasize the specific 20S core subcomplex membership; broader proteasome or spermatoproteasome membership can be retained as non-core context.
GO:0000502 proteasome complex
IPI
PMID:34702852
The 20S as a stand-alone proteasome in cells can degrade the...
KEEP AS NON CORE
Summary: proteasome complex is true complex membership but broader or more context-specific than the core 20S subunit identity.
Reason: The core review should emphasize the specific 20S core subcomplex membership; broader proteasome or spermatoproteasome membership can be retained as non-core context.
GO:0000502 proteasome complex
IPI
PMID:35714770
Proteasome activator 28Ξ³ (PA28Ξ³) allosterically activates tr...
KEEP AS NON CORE
Summary: proteasome complex is true complex membership but broader or more context-specific than the core 20S subunit identity.
Reason: The core review should emphasize the specific 20S core subcomplex membership; broader proteasome or spermatoproteasome membership can be retained as non-core context.
GO:0000502 proteasome complex
IPI
PMID:35858375
Structural insights into the human PA28-20S proteasome enabl...
KEEP AS NON CORE
Summary: proteasome complex is true complex membership but broader or more context-specific than the core 20S subunit identity.
Reason: The core review should emphasize the specific 20S core subcomplex membership; broader proteasome or spermatoproteasome membership can be retained as non-core context.
GO:0002376 immune system process
NAS
PMID:33019542
Adaptation of Proteasomes and Lysosomes to Cellular Environm...
MARK AS OVER ANNOTATED
Summary: immune system process is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0005634 nucleus
NAS
PMID:32134919
Cryo-EM structures of the human PA200 and PA200-20S complex ...
ACCEPT
Summary: nucleus is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005634 nucleus
NAS
PMID:33019542
Adaptation of Proteasomes and Lysosomes to Cellular Environm...
ACCEPT
Summary: nucleus is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005634 nucleus
NAS
PMID:35858375
Structural insights into the human PA28-20S proteasome enabl...
ACCEPT
Summary: nucleus is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005737 cytoplasm
NAS
PMID:35858375
Structural insights into the human PA28-20S proteasome enabl...
KEEP AS NON CORE
Summary: cytoplasm is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0005839 proteasome core complex
IPI
PMID:34702852
The 20S as a stand-alone proteasome in cells can degrade the...
ACCEPT
Summary: proteasome core complex is the appropriate core-complex membership annotation for PSMA1.
Reason: Structural studies and UniProt summaries place the protein in the 20S proteasome core; this complex-membership annotation is central to the gene product role.
GO:0006281 DNA repair
NAS
PMID:32134919
Cryo-EM structures of the human PA200 and PA200-20S complex ...
MARK AS OVER ANNOTATED
Summary: DNA repair is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0006915 apoptotic process
NAS
PMID:32935661
Role of oncogenic REGΞ³ in cancer.
MARK AS OVER ANNOTATED
Summary: apoptotic process is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0006974 DNA damage response
NAS
PMID:32134919
Cryo-EM structures of the human PA200 and PA200-20S complex ...
MARK AS OVER ANNOTATED
Summary: DNA damage response is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0006979 response to oxidative stress
IDA
PMID:34702852
The 20S as a stand-alone proteasome in cells can degrade the...
MARK AS OVER ANNOTATED
Summary: response to oxidative stress is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0006979 response to oxidative stress
NAS
PMID:35858375
Structural insights into the human PA28-20S proteasome enabl...
MARK AS OVER ANNOTATED
Summary: response to oxidative stress is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0007283 spermatogenesis
NAS
PMID:23706739
Acetylation-mediated proteasomal degradation of core histone...
MARK AS OVER ANNOTATED
Summary: spermatogenesis is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0010498 proteasomal protein catabolic process
NAS
PMID:23569244
Thymoproteasome subunit-Ξ²5T generates peptide-MHC complexes ...
ACCEPT
Summary: proteasomal protein catabolic process captures the proteasome-mediated protein catabolism process supported for this subunit as part of the proteasome.
Reason: The gene product is a core 20S proteasome subunit, so proteasomal protein catabolism is an appropriate core biological-process context.
GO:0010498 proteasomal protein catabolic process
NAS
PMID:23706739
Acetylation-mediated proteasomal degradation of core histone...
ACCEPT
Summary: proteasomal protein catabolic process captures the proteasome-mediated protein catabolism process supported for this subunit as part of the proteasome.
Reason: The gene product is a core 20S proteasome subunit, so proteasomal protein catabolism is an appropriate core biological-process context.
GO:0010498 proteasomal protein catabolic process
NAS
PMID:30104634
The immunoproteasome and thymoproteasome: functions, evoluti...
ACCEPT
Summary: proteasomal protein catabolic process captures the proteasome-mediated protein catabolism process supported for this subunit as part of the proteasome.
Reason: The gene product is a core 20S proteasome subunit, so proteasomal protein catabolism is an appropriate core biological-process context.
GO:0010498 proteasomal protein catabolic process
IDA
PMID:34702852
The 20S as a stand-alone proteasome in cells can degrade the...
ACCEPT
Summary: proteasomal protein catabolic process captures the proteasome-mediated protein catabolism process supported for this subunit as part of the proteasome.
Reason: The gene product is a core 20S proteasome subunit, so proteasomal protein catabolism is an appropriate core biological-process context.
Supporting Evidence:
file:human/PSMA1/PSMA1-deep-research-falcon.md
Identified substrates are enriched for intrinsically disordered RNA- and DNA-binding proteins, especially nuclear and stress-granule proteins.
GO:0010499 proteasomal ubiquitin-independent protein catabolic process
NAS
PMID:31473102
Characterization of Fully Recombinant Human 20S and 20S-PA20...
ACCEPT
Summary: proteasomal ubiquitin-independent protein catabolic process captures the proteasome-mediated protein catabolism process supported for this subunit as part of the proteasome. Falcon deep research reinforces this, noting that about half of cellular proteasomes exist as free 20S complexes that degrade substrates (especially intrinsically disordered, nuclear, and stress-granule proteins) independently of ubiquitin, and PSMA1 is a constitutive alpha-ring subunit of these free 20S cores.
Reason: The gene product is a core 20S proteasome subunit, so proteasomal protein catabolism is an appropriate core biological-process context. Ubiquitin-independent degradation by free 20S is now a systematically characterized pathway in which PSMA1-containing cores participate.
Supporting Evidence:
file:human/PSMA1/PSMA1-deep-research-falcon.md
Pepelnjak et al. (2024) emphasize that **~half of cellular proteasomes** can exist as **free 20S complexes**, enabling ubiquitin-independent turnover of certain substratesβ€”especially proteins with **intrinsically disordered regions (IDRs)** and enrichment among **nuclear and stress granule proteins**.
GO:0030317 flagellated sperm motility
NAS
PMID:23706739
Acetylation-mediated proteasomal degradation of core histone...
MARK AS OVER ANNOTATED
Summary: flagellated sperm motility is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0030317 flagellated sperm motility
NAS
PMID:27003159
Proteasome activators, PA28Ξ³ and PA200, play indispensable r...
MARK AS OVER ANNOTATED
Summary: flagellated sperm motility is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0032729 positive regulation of type II interferon production
NAS
PMID:30104634
The immunoproteasome and thymoproteasome: functions, evoluti...
MARK AS OVER ANNOTATED
Summary: positive regulation of type II interferon production is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0032743 positive regulation of interleukin-2 production
NAS
PMID:30104634
The immunoproteasome and thymoproteasome: functions, evoluti...
MARK AS OVER ANNOTATED
Summary: positive regulation of interleukin-2 production is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0032760 positive regulation of tumor necrosis factor production
NAS
PMID:30104634
The immunoproteasome and thymoproteasome: functions, evoluti...
MARK AS OVER ANNOTATED
Summary: positive regulation of tumor necrosis factor production is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0034341 response to type II interferon
NAS
PMID:30104634
The immunoproteasome and thymoproteasome: functions, evoluti...
MARK AS OVER ANNOTATED
Summary: response to type II interferon is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0034515 proteasome storage granule
NAS
PMID:31380390
Regulation of Proteasome Activity by (Post-)transcriptional ...
KEEP AS NON CORE
Summary: proteasome storage granule is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:34702852
The 20S as a stand-alone proteasome in cells can degrade the...
ACCEPT
Summary: proteasome-mediated ubiquitin-dependent protein catabolic process captures the proteasome-mediated protein catabolism process supported for this subunit as part of the proteasome.
Reason: The gene product is a core 20S proteasome subunit, so proteasomal protein catabolism is an appropriate core biological-process context.
GO:0043374 CD8-positive, alpha-beta T cell differentiation
NAS
PMID:33019542
Adaptation of Proteasomes and Lysosomes to Cellular Environm...
MARK AS OVER ANNOTATED
Summary: CD8-positive, alpha-beta T cell differentiation is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0045061 thymic T cell selection
NAS
PMID:30650357
Restricted Expression of the Thymoproteasome Is Required for...
MARK AS OVER ANNOTATED
Summary: thymic T cell selection is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0045063 T-helper 1 cell differentiation
NAS
PMID:30104634
The immunoproteasome and thymoproteasome: functions, evoluti...
MARK AS OVER ANNOTATED
Summary: T-helper 1 cell differentiation is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0045590 negative regulation of regulatory T cell differentiation
NAS
PMID:30104634
The immunoproteasome and thymoproteasome: functions, evoluti...
MARK AS OVER ANNOTATED
Summary: negative regulation of regulatory T cell differentiation is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0051321 meiotic cell cycle
NAS
PMID:23706739
Acetylation-mediated proteasomal degradation of core histone...
MARK AS OVER ANNOTATED
Summary: meiotic cell cycle is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0061136 regulation of proteasomal protein catabolic process
IDA
PMID:35714770
Proteasome activator 28Ξ³ (PA28Ξ³) allosterically activates tr...
MARK AS OVER ANNOTATED
Summary: regulation of proteasomal protein catabolic process is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0061136 regulation of proteasomal protein catabolic process
NAS
PMID:35714770
Proteasome activator 28Ξ³ (PA28Ξ³) allosterically activates tr...
MARK AS OVER ANNOTATED
Summary: regulation of proteasomal protein catabolic process is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0071357 cellular response to type I interferon
NAS
PMID:31380390
Regulation of Proteasome Activity by (Post-)transcriptional ...
MARK AS OVER ANNOTATED
Summary: cellular response to type I interferon is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0072539 T-helper 17 cell differentiation
NAS
PMID:30104634
The immunoproteasome and thymoproteasome: functions, evoluti...
MARK AS OVER ANNOTATED
Summary: T-helper 17 cell differentiation is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0160165 CD8-positive, alpha-beta T cell homeostasis
NAS
PMID:33815406
The Role of Proteasomes in the Thymus.
MARK AS OVER ANNOTATED
Summary: CD8-positive, alpha-beta T cell homeostasis is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:1990111 spermatoproteasome complex
NAS
PMID:35377789
Proteasome complexes experience profound structural and func...
KEEP AS NON CORE
Summary: spermatoproteasome complex is true complex membership but broader or more context-specific than the core 20S subunit identity.
Reason: The core review should emphasize the specific 20S core subcomplex membership; broader proteasome or spermatoproteasome membership can be retained as non-core context.
GO:2000045 regulation of G1/S transition of mitotic cell cycle
NAS
PMID:32935661
Role of oncogenic REGΞ³ in cancer.
MARK AS OVER ANNOTATED
Summary: regulation of G1/S transition of mitotic cell cycle is a pathway- or physiology-level consequence of proteasome activity rather than a specific function of PSMA1.
Reason: These annotations are largely projected from whole proteasome complexes or specialized proteasome variants; they should not be interpreted as individual subunit core functions.
GO:0005654 nucleoplasm
IDA
GO_REF:0000052
KEEP AS NON CORE
Summary: nucleoplasm is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0016604 nuclear body
IDA
GO_REF:0000052
KEEP AS NON CORE
Summary: nuclear body is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0005634 nucleus
EXP
PMID:12181345
Clastosome: a subtype of nuclear body enriched in 19S and 20...
ACCEPT
Summary: nucleus is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
Supporting Evidence:
file:human/PSMA1/PSMA1-deep-research-falcon.md
Proteasomes exist in both the **cytoplasm and nucleus**.
file:human/PSMA1/PSMA1-deep-research-falcon.md
Under PSMD1 knockdown (reducing intact 26S), the authors observed that β€œβ€˜free’ 20S CPs remained nuclear, whereas the 19S RP accumulated in the cytoplasm,” indicating compartment-specific dynamics of PSMA1-containing cores versus 19S components.
GO:0005737 cytoplasm
EXP
PMID:12181345
Clastosome: a subtype of nuclear body enriched in 19S and 20...
KEEP AS NON CORE
Summary: cytoplasm is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1168640
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1234159
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1236970
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1504193
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-174105
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-174202
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-174203
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-174255
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-180573
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-180603
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-209061
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-2130282
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-264458
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-353125
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-3640874
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-450466
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-4608855
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-4641256
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-4641260
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5362448
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5387392
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5607724
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5607731
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5610754
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5610758
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5610760
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5635868
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5658430
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5665854
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5665871
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5668481
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5668520
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5687112
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5689539
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-68948
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-69016
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-75825
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8850992
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8852354
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8854044
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8854071
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8866553
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8866858
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8932355
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8956140
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8956184
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8957265
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9755303
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9755306
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9766223
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-983150
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9907898
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9907912
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9907919
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9907925
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9907928
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9907940
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9907941
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9908052
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9908069
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9908101
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9908178
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9908709
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9908721
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9912636
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9912655
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9912747
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9912751
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9929352
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9929486
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9931314
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9934893
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9954728
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-NUL-212917
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-NUL-5610751
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
TAS
Reactome:R-NUL-9011324
ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005634 nucleus
IDA
PMID:34711951
AKIRIN2 controls the nuclear import of proteasomes in verteb...
ACCEPT
Summary: nucleus is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005737 cytoplasm
IDA
PMID:34711951
AKIRIN2 controls the nuclear import of proteasomes in verteb...
KEEP AS NON CORE
Summary: cytoplasm is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0005839 proteasome core complex
IDA
PMID:34711951
AKIRIN2 controls the nuclear import of proteasomes in verteb...
ACCEPT
Summary: proteasome core complex is the appropriate core-complex membership annotation for PSMA1.
Reason: Structural studies and UniProt summaries place the protein in the 20S proteasome core; this complex-membership annotation is central to the gene product role.
GO:0005515 protein binding
IPI
PMID:29804830
ZFAND1 Recruits p97 and the 26S Proteasome to Promote the Cl...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0000502 proteasome complex
IDA
PMID:17323924
Mass spectrometric characterization of the affinity-purified...
KEEP AS NON CORE
Summary: proteasome complex is true complex membership but broader or more context-specific than the core 20S subunit identity.
Reason: The core review should emphasize the specific 20S core subcomplex membership; broader proteasome or spermatoproteasome membership can be retained as non-core context.
GO:0070062 extracellular exosome
HDA
PMID:23533145
In-depth proteomic analyses of exosomes isolated from expres...
KEEP AS NON CORE
Summary: extracellular exosome is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0005634 nucleus
HDA
PMID:21630459
Proteomic characterization of the human sperm nucleus.
ACCEPT
Summary: nucleus is a core cellular context for the assembled proteasome containing PSMA1.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0070062 extracellular exosome
HDA
PMID:19056867
Large-scale proteomics and phosphoproteomics of urinary exos...
KEEP AS NON CORE
Summary: extracellular exosome is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0070062 extracellular exosome
HDA
PMID:20458337
MHC class II-associated proteins in B-cell exosomes and pote...
KEEP AS NON CORE
Summary: extracellular exosome is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-174058
KEEP AS NON CORE
Summary: nucleoplasm is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-187574
KEEP AS NON CORE
Summary: nucleoplasm is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-188191
KEEP AS NON CORE
Summary: nucleoplasm is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5635854
KEEP AS NON CORE
Summary: nucleoplasm is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-68825
KEEP AS NON CORE
Summary: nucleoplasm is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-69600
KEEP AS NON CORE
Summary: nucleoplasm is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8939801
KEEP AS NON CORE
Summary: nucleoplasm is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8952408
KEEP AS NON CORE
Summary: nucleoplasm is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9762096
KEEP AS NON CORE
Summary: nucleoplasm is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0005654 nucleoplasm
TAS
Reactome:R-NUL-9604648
KEEP AS NON CORE
Summary: nucleoplasm is a supported localization or active-location annotation for proteasomes but not the gene-specific core function.
Reason: Proteasomes operate in cytosolic and nuclear compartments; localization annotations should be retained as context without replacing the core catalytic/structural role.
GO:0005839 proteasome core complex
ISS
GO_REF:0000024
ACCEPT
Summary: proteasome core complex is the appropriate core-complex membership annotation for PSMA1.
Reason: Structural studies and UniProt summaries place the protein in the 20S proteasome core; this complex-membership annotation is central to the gene product role.
GO:0005515 protein binding
IPI
PMID:17292860
Conserved signal peptide of Notch3 inhibits interaction with...
MARK AS OVER ANNOTATED
Summary: The interaction evidence may show physical association, but generic protein binding is too low-information for the reviewed function of this proteasome subunit.
Reason: For proteasome subunits, the informative annotations are catalytic activity, structural constituent activity, complex membership, and proteasomal protein catabolism; generic protein binding should not be treated as a core function.
GO:0019773 proteasome core complex, alpha-subunit complex
ISS
GO_REF:0000024
ACCEPT
Summary: proteasome core complex, alpha-subunit complex is the appropriate core-complex membership annotation for PSMA1.
Reason: Structural studies and UniProt summaries place the protein in the 20S proteasome core; this complex-membership annotation is central to the gene product role.
GO:0000502 proteasome complex
TAS
PMID:8811196
Structure and functions of the 20S and 26S proteasomes.
KEEP AS NON CORE
Summary: proteasome complex is true complex membership but broader or more context-specific than the core 20S subunit identity.
Reason: The core review should emphasize the specific 20S core subcomplex membership; broader proteasome or spermatoproteasome membership can be retained as non-core context.

Core Functions

PSMA1 is a structural alpha-ring subunit of the 20S proteasome core. It does not provide the catalytic threonine nucleophile; instead, it helps form the alpha-ring architecture and gated entry/regulator-binding surface that allows the assembled proteasome to carry out protein catabolism.

Supporting Evidence:
  • PMID:23495936
    barrel-shaped proteolytic 20S core particle (CP) of 28 subunits
  • PMID:23495936
    the outer rings consist of seven different Ξ± subunits
  • PMID:23495936
    The Ξ²1, Ξ²2, and Ξ²5 subunits contain the proteolytic active sites
  • file:human/PSMA1/PSMA1-deep-research-falcon.md
    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.
  • file:human/PSMA1/PSMA1-deep-research-falcon.md
    PSMA1 contributes to forming these Ξ±-ring interfaces and pockets that receive regulatory tails.

References

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-Ξ²5T 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, PA28Ξ³ 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 REGΞ³ 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 28Ξ³ (PA28Ξ³) allosterically activates trypsin-like proteolysis by binding to the Ξ±-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.
Reactome:R-HSA-1168640
Ubiquitinated IkB is degraded
Reactome:R-HSA-1234159
Proteasome proteolyzes ub-HIF-alpha
Reactome:R-HSA-1236970
Proteasomal clevage of exogenous antigen (26S proteasome catalyst)
Reactome:R-HSA-1504193
Ubiquitinated DVL is degraded by the proteasome
Reactome:R-HSA-174058
Degradation of multiubiquitinated Cdh1
Reactome:R-HSA-174105
Degradation of multiubiquitinated cell cycle proteins
Reactome:R-HSA-174202
Degradation of multiubiquitinated Securin
Reactome:R-HSA-174203
SCF-mediated degradation of Emi1
Reactome:R-HSA-174255
Degradation multiubiquitinated Cyclin A
Reactome:R-HSA-180573
Degradation of ubiquitinated CD4
Reactome:R-HSA-180603
Proteosome-mediated degradation of APOBEC3G
Reactome:R-HSA-187574
Degradation of ubiquitinated p27/p21 by the 26S proteasome
Reactome:R-HSA-188191
APC/C:Cdh1-mediated degradation of Skp2
Reactome:R-HSA-209061
Ubiquitinated and phosphorylated IKBA binds to and is degraded by the proteasome complex
Reactome:R-HSA-2130282
Degradation of ubiquitinated beta catenin by the proteasome
Reactome:R-HSA-264458
Proteasome mediated degradation of COP1
Reactome:R-HSA-353125
26S proteosome degrades ODC holoenzyme complex
Reactome:R-HSA-3640874
Ub-RibC-AXIN is degraded by the proteasome
Reactome:R-HSA-450466
AUF1:mRNA complex is degraded
Reactome:R-HSA-4608855
PRICKLE1 is degraded by the proteasome
Reactome:R-HSA-4641256
Ubiquitinated AXIN is degraded by the proteasome
Reactome:R-HSA-4641260
Ubiquitinated DVL1 is degraded by the proteasome
Reactome:R-HSA-5362448
Hh C-terminal fragments are degraded by the proteasome
Reactome:R-HSA-5387392
processing defective Hh variants are degraded by the proteasome
Reactome:R-HSA-5607724
26S proteasome processes K48PolyUb-K21,22-p-S32,36-IkBA:NF-kB complex to form NF-kB complex
Reactome:R-HSA-5607731
26S proteasome processes p-7S-p100:RELB to form p52:RELB
Reactome:R-HSA-5610754
GLI3 is partially degraded by the proteasome to yield the GLI3 repressor
Reactome:R-HSA-5610758
GLI1 is degraded by the proteasome after ubiquitination by beta-TrCP
Reactome:R-HSA-5610760
GLI1 is degraded by the proteasome after ubiquitination by ITCH
Reactome:R-HSA-5635854
GLI2,3 are degraded by the proteasome
Reactome:R-HSA-5635868
ub-GLI is degraded by the proteasome
Reactome:R-HSA-5658430
NF1 is degraded by the proteasome
Reactome:R-HSA-5665854
ADRM1:26S proteaseome binds UCHL5
Reactome:R-HSA-5665871
ADRM1 binds 26S proteasome
Reactome:R-HSA-5668481
Protesomal degradation of K48polyUb-TRAF3
Reactome:R-HSA-5668520
26Sproteasome degrades K48polyUb-NIK
Reactome:R-HSA-5687112
MAPK6 is degraded by the 26S proteasome
Reactome:R-HSA-5689539
ADRM1:26S proteaseome binds USP14
Reactome:R-HSA-68825
Ubiquitinated geminin is degraded by the proteasome
Reactome:R-HSA-68948
Ubiquitinated Orc1 is degraded by the proteasome
Reactome:R-HSA-69016
Ubiquitinated Cdc6 is degraded by the proteasome
Reactome:R-HSA-69600
Proteolytic degradation of ubiquitinated-Cdc25A
Reactome:R-HSA-75825
Proteasome mediated degradation of Cyclin D1
Reactome:R-HSA-8850992
Proteasome degrades polyubiquitinated PTEN
Reactome:R-HSA-8852354
GTSE1 facilitates proteasome-mediated degradation of TP53
Reactome:R-HSA-8854044
Proteasome degrades AURKA ubiquitinated by SCF-FBXL7
Reactome:R-HSA-8854071
Proteasome-mediated degradation of PolyUb-FBXL7
Reactome:R-HSA-8866553
misfolded CFTR is degraded by the 26S proteasome
Reactome:R-HSA-8866858
CFTR F508del is degraded by the 26S proteasome
Reactome:R-HSA-8932355
26S proteasome degrades Ub-NFE2L2
Reactome:R-HSA-8939801
26S proteasome degrades PolyUb-RUNX2
Reactome:R-HSA-8952408
Polyubiquitinated RUNX3 is degraded by the proteasome
Reactome:R-HSA-8956140
NEDD8 and UBD bind NUB1 and the 26S proteasome
Reactome:R-HSA-8956184
26S- and NUB1-mediated degradation of NEDD8, UBD and their conjugates
Reactome:R-HSA-8957265
26S proteasome degrades TP73 polyubiquitinated by ITCH
Reactome:R-HSA-9755303
26S proteasome degrades HIFalpha
Reactome:R-HSA-9755306
ub UBXN7 is degraded by the 26S proteasome
Reactome:R-HSA-9762096
Ub,pS335,S338,T NFE2L2 is degraded
Reactome:R-HSA-9766223
Proteasome-dependent degradation of ubiquitinated CDH1
Reactome:R-HSA-983150
Proteasomal cleavage of substrate
Reactome:R-HSA-9907898
Formation of the inner ring of the 20S core particle of the 26S proteasome
Reactome:R-HSA-9907912
Formation of the outer ring of the 20S core particle
Reactome:R-HSA-9907919
Formation of the preholoproteasome
Reactome:R-HSA-9907925
Formation of the inner ring of the 20S immunoproteasome core particle
Reactome:R-HSA-9907928
Formation of the inner ring of the 20S thymoproteasome core particle
Reactome:R-HSA-9907940
Formation of the preholothymoproteasome
Reactome:R-HSA-9907941
Fromation of the preholoimmunoproteasome
Reactome:R-HSA-9908052
PSMG1:PSMG2 dimer binds the 20S core particle outer ring
Reactome:R-HSA-9908069
POMP binds the 20S core particle outer ring
Reactome:R-HSA-9908101
Maturation of the canonical 20S core particle
Reactome:R-HSA-9908178
Formation of the 26S proteasome
Reactome:R-HSA-9908709
Formation of the PA28-alpha-beta-20S proteasome
Reactome:R-HSA-9908721
Formation of the PA28gamma-20S proteasome
Reactome:R-HSA-9912636
Proteasomal cleavage of intracellular substrate (PA28-alpha-beta-20S proteasome catalyst)
Reactome:R-HSA-9912655
Proteasomal cleavage of intracellular substrate (immunoproteasome catalyst)
Reactome:R-HSA-9912747
Proteasomal clevage of exogenous antigen (immunoproteasome catalyst)
Reactome:R-HSA-9912751
Proteasomal cleavage of partially digested antigen (immunoproteasome catalyst)
Reactome:R-HSA-9929352
Ubiquitinated CD274 is degraded by the 26S proteasome
Reactome:R-HSA-9929486
SPOP-mediated degradation of CD274 by 26S Proteosome
Reactome:R-HSA-9931314
Proteasomal degradation of polyUb-p-S195-CD274
Reactome:R-HSA-9934893
Proteolysis of K48polyUb-K,p-S-PER1,2,3
Reactome:R-HSA-9954728
The proteasome degrades the K48-polyubiquitinated alanine-tailed nascent peptide
Reactome:R-NUL-212917
Proteasome mediated degradation of PAK-2p34
Reactome:R-NUL-5610751
Gli2is degraded by the proteasome
Reactome:R-NUL-9011324
Proteasome degrades SAX-3 ubiquitinated by EBAX-1
Reactome:R-NUL-9604648
Proteasome degrades ubiquitinated mouse NICD4
Molecular architecture and assembly of the eukaryotic proteasome.
file:human/PSMA1/PSMA1-deep-research-falcon.md
Falcon deep research report on PSMA1
  • 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 **Ξ² subunits**."
  • 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 **Ξ±1–7 Ξ²1–7 Ξ²1–7 Ξ±1–7**; the **two outer Ξ± rings** act as a **gate** that restricts access to the proteolytic chamber. PSMA1 is one of the **non-catalytic Ξ± subunits** contributing to this gate architecture."
  • 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."
  • 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 Ξ± 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."
  • 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 Ξ± subunits** to promote **CP gate opening**. As an Ξ± subunit, PSMA1 contributes to forming these Ξ±-ring interfaces and pockets that receive regulatory tails."
  • 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 **Ξ± ring** assisted by **PAC1/2 and PAC3/4**, followed by sequential Ξ² incorporation to form **half-CPs** that fuse; activation requires cleavage of Ξ² propeptides."
  • 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."
  • 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 β€œβ€˜free’ 20S CPs remained nuclear, whereas the 19S RP accumulated in the cytoplasm,” indicating compartment-specific dynamics of PSMA1-containing cores versus 19S components."
  • 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 substratesβ€”especially proteins with **intrinsically disordered regions (IDRs)** and enrichment among **nuclear and stress granule proteins**."
  • 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 Ξ² subunits** (especially Ξ²5), rather than Ξ± subunits like PSMA1. This frames PSMA1 more as a biomarker/proteasome-state indicator than a direct pharmacologic target."

Suggested Questions for Experts

Q: Should non-catalytic proteasome alpha subunits use contributes_to for complex-level protease activity, or should GO curation prefer structural constituent of proteasome plus part_of complex annotations?

Suggested experts: Tomko RJ Jr, Hochstrasser M

Suggested Experiments

Experiment: Use purified proteasome complexes or separation-of-function PSMA1 mutants at alpha-ring/regulator interfaces, then measure assembly, gate opening, substrate entry, and beta-subunit peptidase activity separately.

Hypothesis: PSMA1 contributes structurally to alpha-ring gating/regulator docking but does not directly catalyze peptide bond hydrolysis.

Type: structure-guided mutagenesis with proteasome activity and assembly assays

Deep Research

Falcon

(PSMA1-deep-research-falcon.md)
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 26 citations 2 artifacts 2026-05-30T00:05:34.284456

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research report: Human PSMA1 (UniProt P25786) – functional annotation

1) Target verification (critical disambiguation)

PSMA1 (proteasome 20S subunit alpha 1; UniProt P25786) is a proteasome Ξ±-ring subunit and should not be confused with the acronym PSMA used in oncology for prostate-specific membrane antigen (gene FOLH1). The sources synthesized here explicitly use PSMA1 in the context of the 20S/26S proteasome Ξ±-ring (PSMA1–PSMA7), consistent with UniProt P25786. (xiong2024thecoherencebetween pages 6-7, larsson2022pancanceranalysisof pages 1-2, steinberger2023methodofmonitoring pages 1-2)

2) Key concepts and definitions (current understanding)

2.1 The proteasome and where PSMA1 fits

The eukaryotic proteasome comprises a 20S core particle (CP) that performs proteolysis and regulatory particles (e.g., 19S) that recognize substrates and control entry. The 20S CP is a barrel made of four stacked heteroheptameric rings arranged Ξ±1–7 Ξ²1–7 Ξ²1–7 Ξ±1–7; the two outer Ξ± rings act as a gate that restricts access to the proteolytic chamber. PSMA1 is one of the non-catalytic Ξ± subunits contributing to this gate architecture. (larsson2022pancanceranalysisof pages 1-2, steinberger2023methodofmonitoring pages 1-2)

Importantly, PSMA1 is not a catalytic peptidase active site; proteolysis occurs at catalytic Ξ² subunits. Structural/functional descriptions emphasize that active sites are sequestered inside the CP and are only accessible through the Ξ±-ring pore. (adolf2024visualizingchaperonemediatedmultistep pages 1-2, larsson2022pancanceranalysisof pages 1-2)

2.2 β€œGate opening” and PSMA1’s structural role

Gate opening is a regulated conformational transition in which the Ξ±-ring pore becomes permissive for substrate entry. Multiple sources describe a key mechanism: C-terminal HbYX motifs of proteasome regulators (e.g., the 19S RP) insert into pockets between adjacent Ξ± subunits to promote CP gate opening. As an Ξ± subunit, PSMA1 contributes to forming these Ξ±-ring interfaces and pockets that receive regulatory tails. (adolf2024visualizingchaperonemediatedmultistep pages 1-2, xiong2024thecoherencebetween pages 6-7)

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. (steinberger2023methodofmonitoring pages 1-2)

3) Molecular function, substrate specificity, and pathways

3.1 Primary function: structural component of the proteasome Ξ± ring

PSMA1’s primary function is to serve as an essential structural subunit of the 20S Ξ± 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. (xiong2024thecoherencebetween pages 6-7, steinberger2023methodofmonitoring pages 1-2)

Because PSMA1 is non-catalytic, β€œsubstrate specificity” is not attributable to PSMA1 as an enzyme active site. Instead, substrate routing and selectivity emerge from (i) which regulatory caps engage the Ξ± ring (e.g., 19S, PA28, PA200), and (ii) properties of substrates, including ubiquitin dependence and structural disorder. (xiong2024thecoherencebetween pages 6-7)

3.2 Canonical UPS pathway (26S proteasome)

In canonical ubiquitin-proteasome system (UPS) degradation, substrates are polyubiquitylated and recognized by the 19S; the 19S base includes six AAA ATPases (PSMC1–PSMC6) that unfold substrates and translocate them into the 20S core, with Ξ±-ring gating serving as the entry control point. PSMA1 is thus part of the execution machinery for UPS-mediated proteolysis by enabling regulated access to catalytic sites. (xiong2024thecoherencebetween pages 6-7)

3.3 Non-canonical ubiquitin-independent degradation by free 20S

A major recent development is the systematic characterization of ubiquitin-independent degradation by free 20S particles. Pepelnjak et al. (2024) emphasize that ~half of cellular proteasomes can exist as free 20S complexes, enabling ubiquitin-independent turnover of certain substratesβ€”especially proteins with intrinsically disordered regions (IDRs) and enrichment among nuclear and stress granule proteins. This provides a pathway-level context in which PSMA1-containing 20S cores contribute to proteostasis beyond classical ubiquitin-dependent 26S degradation. (monika2024systematicidentificationof pages 1-1, monika2024systematicidentificationof pages 1-2)

Pepelnjak et al. developed a proteomics workflow (PiP-MS) and reported 280 candidate 20S substrates supported by 2,180 peptides marking proteasome-cleaved regions, and also used cellular perturbations consistent with ubiquitin-independent turnover for selected proteins. (monika2024systematicidentificationof pages 5-6)

4) Subcellular localization: where PSMA1-containing complexes act

4.1 Basal localization and stress-induced nuclear proteasome granules

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. (steinberger2023methodofmonitoring pages 1-2, steinberger2023methodofmonitoring pages 6-8)

4.2 Compartment-specific behavior of free 20S vs 19S material

The same 2023 study provided direct evidence for subcellular segregation when 26S integrity is disrupted. Under PSMD1 knockdown (reducing intact 26S), the authors observed that β€œβ€˜free’ 20S CPs remained nuclear, whereas the 19S RP accumulated in the cytoplasm,” indicating compartment-specific dynamics of PSMA1-containing cores versus 19S components. (steinberger2023methodofmonitoring pages 2-4, steinberger2023methodofmonitoring pages 8-11)

5) Recent developments and latest research (prioritizing 2023–2024)

5.1 2024: Human 20S proteasome assembly pathway visualized by cryo-EM

Adolf et al. (Apr 2024, Nature Structural & Molecular Biology) presented cryo-EM reconstructions of multiple human 20S assembly intermediates and summarized key quantitative and mechanistic features of 20S biogenesis:
- 20S CP is a ~700 kDa barrel, with active sites sequestered inside and accessed via the Ξ±-ring gated pore. (adolf2024visualizingchaperonemediatedmultistep pages 1-2)
- Assembly begins with formation of a complete Ξ± ring assisted by PAC1/2 and PAC3/4, followed by sequential Ξ² incorporation to form half-CPs that fuse; activation requires cleavage of Ξ² propeptides. (adolf2024visualizingchaperonemediatedmultistep pages 1-2)
- Quantitatively, they estimated ~3,000 CPs/min are produced in proliferating HeLa cells and a CP copy number of ~4Γ—10^6 per cell. (adolf2024visualizingchaperonemediatedmultistep pages 1-2)

These results strengthen mechanistic understanding of how PSMA1-containing Ξ± rings form early and set the stage for catalytic maturation of the CP. (adolf2024visualizingchaperonemediatedmultistep pages 1-2)

A cropped figure from Adolf et al. explicitly labels the Ξ±1–α7 subunits forming the Ξ± ring and shows the gate/pore, providing structural context for PSMA1 as Ξ±1. (adolf2024visualizingchaperonemediatedmultistep media 190794a0, adolf2024visualizingchaperonemediatedmultistep media 67df21f7)

5.2 2024: Systematic identification of free-20S substrates

Pepelnjak et al. (Jan 2024, Molecular Systems Biology) broadened the substrate landscape for PSMA1-containing 20S cores by mapping ubiquitin-independent substrates enriched for nuclear/stress-granule and IDR-containing proteins and identifying 280 candidates. (monika2024systematicidentificationof pages 5-6, monika2024systematicidentificationof pages 1-2)

5.3 2024: Alzheimer’s disease bioinformatics linking Ξ±-ring module (PSMA1–7) with PSMC6

Xiong et al. (Jan 2024, Frontiers in Molecular Neuroscience) analyzed transcriptomic datasets using Ξ±-ring genes PSMA1–PSMA7 as a module together with PSMC6, reporting computational associations between coordinated downregulation of these subunits and Alzheimer’s disease progression/risk; the authors explicitly caution that these results require experimental validation. (xiong2024thecoherencebetween pages 1-2)

6) Current applications and real-world implementations

6.1 PSMA1 as a prognostic biomarker candidate in cancer

A lung squamous cell carcinoma (LUSC) study (Liu et al., Feb 2023, Disease Markers) reported that PSMA1 is overexpressed in tumors relative to normal tissue in TCGA (Normal n=52 vs Primary tumor n=503) and is associated with worse survival:
- Overall survival: HR 1.33 (95% CI 1.05–1.69), log-rank P=0.017. (liu2023psma1apoor pages 5-7)
- First progression: HR 1.6 (95% CI 0.93–2.74), P=0.087. (liu2023psma1apoor pages 5-7)

In a clinical tissue cohort (30 patients; 15 low vs 15 high PSMA1), high PSMA1 expression associated with TNM stage (P=0.02) and pathological grading (P=0.046). (liu2023psma1apoor pages 7-9)

The same study provided in vitro functional evidence that PSMA1 knockdown reduces viability and clonogenicity and increases apoptosis, while overexpression shows the opposite trends, supporting PSMA1 as a potential tumor-promoting factor in LUSC (though mechanistic pathways remain unresolved). (liu2023psma1apoor pages 1-2, liu2023psma1apoor pages 11-12)

6.2 Proteasome inhibitors: clinical relevance but not PSMA1-specific targeting

Pan-cancer analysis emphasizes that proteasome genes (including PSMA1) are often upregulated and prognostically informative, but also highlights that clinically used proteasome inhibitors (e.g., bortezomib) act on catalytic Ξ² subunits (especially Ξ²5), rather than Ξ± subunits like PSMA1. This frames PSMA1 more as a biomarker/proteasome-state indicator than a direct pharmacologic target. (larsson2022pancanceranalysisof pages 1-2)

6.3 Evidence platform linkages

Open Targets lists PSMA1 associations spanning neoplasm and hematologic malignancies (e.g., multiple myeloma), reflecting the broader clinical relevance of proteasome biology and inhibition; these entries should be interpreted cautiously as pathway/target-family evidence rather than proof PSMA1 is the direct drug target. (OpenTargets Search: -PSMA1)

7) Expert analysis and synthesis

1) Functional core concept: PSMA1’s most defensible β€œprimary function” is structuralβ€”forming part of the Ξ± ring gate and regulator-binding interfaces. Multiple sources converge on the Ξ±-subunit N-termini as gate-forming elements and regulator tail insertion (HbYX) as a conserved activation mechanism. (steinberger2023methodofmonitoring pages 1-2, adolf2024visualizingchaperonemediatedmultistep pages 1-2)

2) Emerging view (2023–2024): The proteasome system should be conceptualized as a dynamic set of proteolytic states, including abundant free 20S particles executing ubiquitin-independent degradation, particularly of nuclear/IDR proteins and stress-granule biologyβ€”areas where PSMA1 is mechanistically implicated by virtue of being a constitutive Ξ±-ring subunit. (monika2024systematicidentificationof pages 1-1, monika2024systematicidentificationof pages 5-6)

3) Compartmentalization as regulation: Nuclear granule formation and the observation that free 20S cores can remain nuclear while 19S material accumulates cytoplasmically upon 26S destabilization suggests compartmental regulation of proteasome forms that could influence which substrates are accessible, especially under stress. (steinberger2023methodofmonitoring pages 8-11, steinberger2023methodofmonitoring pages 2-4)

4) Translational angle: Cancer studies support PSMA1 expression as prognostic in specific contexts (e.g., LUSC with HR~1.33 for OS), and pan-cancer analyses suggest broad prognostic relevance across cancer types. However, because PSMA1 is non-catalytic, direct therapeutic targeting is less straightforward than targeting Ξ² active sites; PSMA1 likely reflects proteasome abundance/assembly state and tumor proteostasis dependence. (liu2023psma1apoor pages 5-7, larsson2022pancanceranalysisof pages 1-2)

8) Evidence summary table

The following table consolidates key findings, statistics, dates, and URLs across the main sources.

Topic Key findings (1-2 sentences) Quantitative/statistical details Source (author year journal) Publication date (month year) URL Evidence context id(s)
Identity / complex role PSMA1 (UniProt P25786) is the human proteasome 20S subunit alpha 1, a non-catalytic Ξ±-ring subunit of the 20S core particle; the catalytic protease active sites reside in Ξ² subunits, not PSMA1. In the 20S/26S architecture, PSMA1 is one of PSMA1-7 forming the outer Ξ± rings that regulate access to the proteolytic chamber. 20S core is arranged as Ξ±1-7 Ξ²1-7 Ξ²1-7 Ξ±1-7; the PSM family comprises 49 genes including 19 20S Ξ±/Ξ² ring subunits. Larsson et al. 2022 BMC Cancer Sep 2022 https://doi.org/10.1186/s12885-022-10079-4 (larsson2022pancanceranalysisof pages 1-2)
Gate / structure PSMA1 belongs to the Ξ± ring that forms the gated pore of the 20S core; Ξ±-subunit N termini create the gate controlling substrate entry, whereas proteolysis is executed by Ξ² catalytic subunits. Activator docking and gate opening occur through interactions at Ξ±-ring pockets, linking PSMA1 structurally to proteasome regulation rather than catalysis. Ξ±-ring surface binds regulators such as PA700/19S, PA28, and PA200; gate opening is mediated by C-terminal HbYX motifs from regulators inserting between adjacent Ξ± subunits. Xiong et al. 2024 Frontiers in Molecular Neuroscience; Steinberger et al. 2023 Biomolecules Jan 2024; Jun 2023 https://doi.org/10.3389/fnmol.2023.1330853; https://doi.org/10.3390/biom13060992 (xiong2024thecoherencebetween pages 6-7, steinberger2023methodofmonitoring pages 1-2)
Assembly / biogenesis Human 20S biogenesis begins with formation of a complete Ξ± ring assisted by PAC1/2 and PAC3/4, followed by ordered Ξ²-subunit addition, half-core formation, half-core fusion, and Ξ²-propeptide cleavage. These structural studies are directly relevant to PSMA1 because it is one of the Ξ±-ring building blocks assembled before catalytic maturation of Ξ² sites. ~3,000 core particles/min are produced in proliferating HeLa cells; total CP copy number is ~4 Γ— 10^6. Five immature intermediates were resolved by cryo-EM at 2.67-2.95 Γ…; mature CP superimposed with r.m.s.d. 0.703 Γ…. Adolf et al. 2024 Nature Structural & Molecular Biology Apr 2024 https://doi.org/10.1038/s41594-024-01268-9 (adolf2024visualizingchaperonemediatedmultistep pages 1-2, adolf2024visualizingchaperonemediatedmultistep media 190794a0)
Localization Proteasomes are present in both cytoplasm and nucleus, and stress can drive formation of nuclear proteasome granules containing 26S complexes. When 26S integrity is perturbed, free 20S-containing complexes remain predominantly nuclear while liberated 19S material accumulates in the cytoplasm, supporting compartment-specific behavior of PSMA1-containing cores. Under osmotic/salt stress, nuclear 26S granules appear within minutes and peak at ~4-12 min. PSMD1 knockdown causes marked loss of intact 26S and increase in 20S signal; PSMD1-depleted cells die after 4-5 days of doxycycline treatment. Steinberger et al. 2023 Biomolecules Jun 2023 https://doi.org/10.3390/biom13060992 (steinberger2023methodofmonitoring pages 8-11, steinberger2023methodofmonitoring pages 1-2, steinberger2023methodofmonitoring pages 6-8, steinberger2023methodofmonitoring pages 2-4)
Free 20S substrates / pathway context PSMA1-containing free 20S particles represent a major proteasome pool and can degrade proteins independently of ubiquitin/26S. Identified substrates are enriched for intrinsically disordered RNA- and DNA-binding proteins, especially nuclear and stress-granule proteins, highlighting a pathway context in stress responses and non-canonical proteostasis. Approximately half of cellular proteasomes are free 20S; PiP-MS identified 280 candidate 20S substrates from 2,180 cleavage-informative peptides. About 20% of proteins in the proteomic analysis had at least three peptides indicative of 20S cleavage. Pepelnjak et al. 2024 Molecular Systems Biology Jan 2024 https://doi.org/10.1038/s44320-024-00015-y (monika2024systematicidentificationof pages 1-1, monika2024systematicidentificationof pages 5-6, monika2024systematicidentificationof pages 1-2, monika2024systematicidentificationof pages 12-13)
Disease / cancer association Across TCGA pan-cancer data, PSMA1 expression is frequently elevated in tumors and is associated with worse prognosis in many cancer types, suggesting biomarker value rather than direct catalytic druggability. This aligns with proteasome dependence in cancer, although approved proteasome inhibitors primarily target catalytic Ξ² subunits (especially PSMB5), not PSMA1. ~11,000 TCGA samples across 33 cancer types were analyzed; PSMA1 and PSMD11 were linked to unfavorable OS and PFI in β‰₯30% of cancer types. Larsson et al. 2022 BMC Cancer Sep 2022 https://doi.org/10.1186/s12885-022-10079-4 (larsson2022pancanceranalysisof pages 1-2)
Disease / cancer association In lung squamous cell carcinoma (LUSC), PSMA1 is overexpressed in tumors and behaves as a poor prognostic factor; functional perturbation shows PSMA1 promotes proliferation and suppresses apoptosis in vitro. The study supports PSMA1 as a candidate prognostic biomarker, while noting mechanism remains unresolved. TCGA comparison used normal n = 52 vs primary tumor n = 503. Survival: OS HR = 1.33 (95% CI 1.05-1.69), log-rank P = 0.017; first progression HR = 1.6 (95% CI 0.93-2.74), P = 0.087. Clinical cohort: 30 patients split into 15 low vs 15 high PSMA1; high expression associated with TNM stage (P = 0.02) and pathological grading (P = 0.046). Liu et al. 2023 Disease Markers Feb 2023 https://doi.org/10.1155/2023/5386635 (liu2023psma1apoor pages 1-2, liu2023psma1apoor pages 5-7, liu2023psma1apoor pages 7-9)
AD bioinformatics In Alzheimer disease transcriptomic analyses, PSMA1 was analyzed as part of the Ξ±-ring module (PSMA1-7) together with the ATPase subunit PSMC6. The study suggests coordinated downregulation of Ξ±-ring genes and PSMC6 tracks AD progression, but these are computational associations requiring biological validation. PCA/SVM analyses used GSE1297 and GSE5281; no PSMA1-specific effect size or AUC was provided in the extracted evidence. The authors report decreased total proteasome numbers with progression but inferred compensatory coordination/activity in remaining complexes. Xiong et al. 2024 Frontiers in Molecular Neuroscience Jan 2024 https://doi.org/10.3389/fnmol.2023.1330853 (xiong2024thecoherencebetween pages 6-7, xiong2024thecoherencebetween pages 1-2)
Clinical / evidence-platform associations Open Targets lists PSMA1 disease associations largely reflecting the broader therapeutic relevance of proteasome inhibition in oncology and related disorders; these associations should be interpreted as pathway-level/target-family evidence, not proof that PSMA1 itself is the direct pharmacologic target. Reported disease associations include neoplasm (score 0.6318), multiple myeloma (0.5999), mantle cell lymphoma (0.5023), HIV infection (0.4771), and amyloidosis (0.3992); evidence rows include approval/Phase 4 records. Open Targets Platform Accessed in current session https://platform.opentargets.org/target/ENSG00000129084 (OpenTargets Search: -PSMA1)

Table: This table summarizes key evidence for human PSMA1/P25786 across structural biology, localization, free-20S proteostasis, and disease-association studies. It is useful for distinguishing PSMA1’s structural non-catalytic role in the proteasome from the catalytic functions of proteasomal beta subunits and for highlighting recent 2023-2024 findings.

9) Key figure (proteasome architecture / Ξ±-ring placement)

Cropped images from Adolf et al. 2024 provide a labeled view of the Ξ± ring (Ξ±1–α7) and a stepwise assembly schematic, supporting the mapping of PSMA1 to the Ξ±1 position and its gate-related role. (adolf2024visualizingchaperonemediatedmultistep media 190794a0, adolf2024visualizingchaperonemediatedmultistep media 67df21f7)

References (URLs and publication dates)

  • Adolf F. et al. β€œVisualizing chaperone-mediated multistep assembly of the human 20S proteasome.” Nat Struct Mol Biol (Apr 2024). https://doi.org/10.1038/s41594-024-01268-9 (adolf2024visualizingchaperonemediatedmultistep pages 1-2)
  • Pepelnjak M. et al. β€œSystematic identification of 20S proteasome substrates.” Mol Syst Biol (Jan 2024). https://doi.org/10.1038/s44320-024-00015-y (monika2024systematicidentificationof pages 5-6)
  • Xiong J. et al. β€œThe coherence between PSMC6 and Ξ±-ring in the 26S proteasome is associated with Alzheimer’s disease.” Front Mol Neurosci (Jan 2024). https://doi.org/10.3389/fnmol.2023.1330853 (xiong2024thecoherencebetween pages 1-2)
  • Steinberger S. et al. β€œMethod of Monitoring 26S Proteasome in Cells Revealed the Crucial Role of PSMA3 C-Terminus in 26S Integrity.” Biomolecules (Jun 2023). https://doi.org/10.3390/biom13060992 (steinberger2023methodofmonitoring pages 1-2)
  • Liu Z. et al. β€œPSMA1, a Poor Prognostic Factor, Promotes Tumor Growth in Lung Squamous Cell Carcinoma.” Disease Markers (Feb 2023). https://doi.org/10.1155/2023/5386635 (liu2023psma1apoor pages 5-7)
  • Larsson P. et al. β€œPan-cancer analysis of genomic and transcriptomic data reveals the prognostic relevance of human proteasome genes in different cancer types.” BMC Cancer (Sep 2022). https://doi.org/10.1186/s12885-022-10079-4 (larsson2022pancanceranalysisof pages 1-2)
  • Open Targets Platform: PSMA1 (ENSG00000129084). Accessed in-session. https://platform.opentargets.org/target/ENSG00000129084 (OpenTargets Search: -PSMA1)

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Artifacts

Citations

  1. steinberger2023methodofmonitoring pages 1-2
  2. xiong2024thecoherencebetween pages 6-7
  3. monika2024systematicidentificationof pages 5-6
  4. adolf2024visualizingchaperonemediatedmultistep pages 1-2
  5. xiong2024thecoherencebetween pages 1-2
  6. larsson2022pancanceranalysisof pages 1-2
  7. monika2024systematicidentificationof pages 1-1
  8. monika2024systematicidentificationof pages 1-2
  9. steinberger2023methodofmonitoring pages 6-8
  10. steinberger2023methodofmonitoring pages 2-4
  11. steinberger2023methodofmonitoring pages 8-11
  12. monika2024systematicidentificationof pages 12-13
  13. https://doi.org/10.1186/s12885-022-10079-4
  14. https://doi.org/10.3389/fnmol.2023.1330853;
  15. https://doi.org/10.3390/biom13060992
  16. https://doi.org/10.1038/s41594-024-01268-9
  17. https://doi.org/10.1038/s44320-024-00015-y
  18. https://doi.org/10.1155/2023/5386635
  19. https://doi.org/10.3389/fnmol.2023.1330853
  20. https://platform.opentargets.org/target/ENSG00000129084
  21. https://doi.org/10.3389/fnmol.2023.1330853,
  22. https://doi.org/10.1186/s12885-022-10079-4,
  23. https://doi.org/10.3390/biom13060992,
  24. https://doi.org/10.1038/s41594-024-01268-9,
  25. https://doi.org/10.1038/s44320-024-00015-y,
  26. https://doi.org/10.1155/2023/5386635,

πŸ“š Additional Documentation

Notes

(PSMA1-notes.md)

PSMA1 notes

PSMA1 encodes proteasome subunit alpha type-1, a non-catalytic alpha-ring component
of the 20S core proteasome. The key curation distinction is that PSMA1 is a
structural constituent of the proteasome, not an executor of the beta-subunit
threonine protease chemistry.

Evidence summary:

  • The eukaryotic 26S proteasome contains a 20S core particle of 28 subunits capped
    by 19S regulatory particles PMID:23495936.
  • The 20S core has alpha outer rings and beta inner rings; beta1, beta2, and beta5
    contain the proteolytic active sites PMID:23495936.
  • Human structural studies of the 20S proteasome support the assembled complex context
    for PSMA1 PMID:27493187.
  • Proteasomes are found in cytoplasmic and nuclear contexts, including clastosomes
    enriched for 19S and 20S proteasomes PMID:12181345.
  • AKIRIN2 binds fully assembled 20S proteasomes and mediates nuclear import, supporting
    nuclear active-location annotations for proteasome subunits PMID:34711951.

Curation decisions:

  • Accept structural constituent of proteasome and specific 20S alpha/core complex
    membership as the core PSMA1 annotations.
  • Keep cytosol, cytoplasm, nucleus, nucleoplasm, nuclear body, and other localization
    annotations as non-core context.
  • Accept proteasome-mediated protein catabolism process annotations only when they
    stay at the proteasome-process level.
  • Avoid annotating PSMA1 as independently enabling protease activity; the reviewed
    evidence supports a non-catalytic alpha-ring structural role, while proteolytic
    chemistry occurs at beta subunits.
  • Mark generic protein binding as over-annotated. The interactions may be real, but
    the term does not distinguish PSMA1's proteasome-specific role.
  • Mark immune, DNA repair, apoptosis, spermatogenesis, cell-cycle, and similar
    pathway-level process exports as over-annotated for the individual PSMA1 subunit.
  • Remove the automated lipopolysaccharide binding annotation because it is not
    supported as a human PSMA1 function by the proteasome evidence reviewed here.

πŸ“„ View Raw YAML

id: P25786
gene_symbol: PSMA1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 'PSMA1 encodes proteasome subunit alpha type-1, a non-catalytic alpha-ring
  component of the human 20S core proteasome. It contributes to the architecture and
  gated entry surface of the 20S core, thereby supporting proteasomal protein catabolism
  in cytosolic and nuclear proteasome complexes.'
alternative_products:
- name: Short
  id: P25786-1
- name: Long
  id: P25786-2
  sequence_note: VSP_005279
existing_annotations:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: nucleus is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: is_active_in
- term:
    id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: proteasome-mediated ubiquitin-dependent protein catabolic process captures
      the proteasome-mediated protein catabolism process supported for this subunit
      as part of the proteasome.
    action: ACCEPT
    reason: The gene product is a core 20S proteasome subunit, so proteasomal protein
      catabolism is an appropriate core biological-process context.
    additional_reference_ids:
    - file:human/PSMA1/PSMA1-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/PSMA1/PSMA1-deep-research-falcon.md
      supporting_text: PSMA1 is thus part of the **execution machinery** for UPS-mediated
        proteolysis by enabling regulated access to catalytic sites.
  qualifier: involved_in
- term:
    id: GO:0019773
    label: proteasome core complex, alpha-subunit complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: proteasome core complex, alpha-subunit complex is the appropriate core-complex
      membership annotation for PSMA1.
    action: ACCEPT
    reason: Structural studies and UniProt summaries place the protein in the 20S
      proteasome core; this complex-membership annotation is central to the gene product
      role.
    additional_reference_ids:
    - file:human/PSMA1/PSMA1-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/PSMA1/PSMA1-deep-research-falcon.md
      supporting_text: PSMA1 is one of PSMA1-7 forming the outer Ξ± rings that regulate
        access to the proteolytic chamber.
  qualifier: part_of
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: nucleus is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: cytoplasm is a supported localization or active-location annotation for
      proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005839
    label: proteasome core complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: proteasome core complex is the appropriate core-complex membership annotation
      for PSMA1.
    action: ACCEPT
    reason: Structural studies and UniProt summaries place the protein in the 20S
      proteasome core; this complex-membership annotation is central to the gene product
      role.
    additional_reference_ids:
    - file:human/PSMA1/PSMA1-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/PSMA1/PSMA1-deep-research-falcon.md
      supporting_text: The 20S CP is a barrel made of **four stacked heteroheptameric
        rings** arranged **Ξ±1–7 Ξ²1–7 Ξ²1–7 Ξ±1–7**; the **two outer Ξ± rings** act as
        a **gate** that restricts access to the proteolytic chamber.
  qualifier: part_of
- term:
    id: GO:0006511
    label: ubiquitin-dependent protein catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: ubiquitin-dependent protein catabolic process is directionally related
      to the proteasome role but is less specific than the supported proteasome term.
    action: MODIFY
    reason: Replace the broad annotation with proteasome-mediated ubiquitin-dependent
      protein catabolic process, which better captures the gene product role supported
      by proteasome literature and existing specific GOA annotations.
    proposed_replacement_terms:
    - id: GO:0043161
      label: proteasome-mediated ubiquitin-dependent protein catabolic process
  qualifier: involved_in
- term:
    id: GO:0019773
    label: proteasome core complex, alpha-subunit complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: proteasome core complex, alpha-subunit complex is the appropriate core-complex
      membership annotation for PSMA1.
    action: ACCEPT
    reason: Structural studies and UniProt summaries place the protein in the 20S
      proteasome core; this complex-membership annotation is central to the gene product
      role.
  qualifier: part_of
- term:
    id: GO:0030163
    label: protein catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: protein catabolic process is directionally related to the proteasome
      role but is less specific than the supported proteasome term.
    action: MODIFY
    reason: Replace the broad annotation with proteasomal protein catabolic process,
      which better captures the gene product role supported by proteasome literature
      and existing specific GOA annotations.
    proposed_replacement_terms:
    - id: GO:0010498
      label: proteasomal protein catabolic process
  qualifier: involved_in
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12376572
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14733938
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15225636
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16189514
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17948026
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19060904
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21516116
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21988832
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25599644
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29568061
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29636472
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29892012
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31473102
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34702852
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35858375
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37776851
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0000502
    label: proteasome complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: proteasome complex is true complex membership but broader or more context-specific
      than the core 20S subunit identity.
    action: KEEP_AS_NON_CORE
    reason: The core review should emphasize the specific 20S core subcomplex membership;
      broader proteasome or spermatoproteasome membership can be retained as non-core
      context.
  qualifier: part_of
- term:
    id: GO:0001530
    label: lipopolysaccharide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Lipopolysaccharide binding is not supported as a human PSMA1 core function.
    action: REMOVE
    reason: This is an automated computational projection and is not supported by
      the human PSMA1 UniProt functional summary or the proteasome structural literature
      reviewed here.
  qualifier: enables
- term:
    id: GO:0002862
    label: negative regulation of inflammatory response to antigenic stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of inflammatory response to antigenic stimulus is
      a pathway- or physiology-level consequence of proteasome activity rather than
      a specific function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0140756
    label: structural constituent of proteasome
  evidence_type: IDA
  original_reference_id: PMID:27493187
  review:
    summary: PSMA1 is a non-catalytic alpha-ring subunit whose core molecular role
      is structural contribution to the 20S proteasome.
    action: ACCEPT
    reason: Human proteasome structures and reviews support alpha subunits as structural
      components of the 20S core; PSMA1 should receive structural constituent/complex
      membership, not catalytic protease activity.
    additional_reference_ids:
    - file:human/PSMA1/PSMA1-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/PSMA1/PSMA1-deep-research-falcon.md
      supporting_text: |-
        PSMA1’s primary function is to serve as an essential **structural subunit of the 20S Ξ± ring**, contributing to:
    - reference_id: file:human/PSMA1/PSMA1-deep-research-falcon.md
      supporting_text: Importantly, **PSMA1 is not a catalytic peptidase active site**;
        proteolysis occurs at catalytic **Ξ² subunits**.
  qualifier: enables
- term:
    id: GO:0000502
    label: proteasome complex
  evidence_type: NAS
  original_reference_id: PMID:29636472
  review:
    summary: proteasome complex is true complex membership but broader or more context-specific
      than the core 20S subunit identity.
    action: KEEP_AS_NON_CORE
    reason: The core review should emphasize the specific 20S core subcomplex membership;
      broader proteasome or spermatoproteasome membership can be retained as non-core
      context.
  qualifier: part_of
- term:
    id: GO:0000502
    label: proteasome complex
  evidence_type: NAS
  original_reference_id: PMID:33729481
  review:
    summary: proteasome complex is true complex membership but broader or more context-specific
      than the core 20S subunit identity.
    action: KEEP_AS_NON_CORE
    reason: The core review should emphasize the specific 20S core subcomplex membership;
      broader proteasome or spermatoproteasome membership can be retained as non-core
      context.
  qualifier: part_of
- term:
    id: GO:0000502
    label: proteasome complex
  evidence_type: NAS
  original_reference_id: PMID:37228199
  review:
    summary: proteasome complex is true complex membership but broader or more context-specific
      than the core 20S subunit identity.
    action: KEEP_AS_NON_CORE
    reason: The core review should emphasize the specific 20S core subcomplex membership;
      broader proteasome or spermatoproteasome membership can be retained as non-core
      context.
  qualifier: part_of
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: NAS
  original_reference_id: PMID:12032076
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0008021
    label: synaptic vesicle
  evidence_type: NAS
  original_reference_id: PMID:37228199
  review:
    summary: synaptic vesicle is a supported localization or active-location annotation
      for proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0010498
    label: proteasomal protein catabolic process
  evidence_type: NAS
  original_reference_id: PMID:33729481
  review:
    summary: proteasomal protein catabolic process captures the proteasome-mediated
      protein catabolism process supported for this subunit as part of the proteasome.
    action: ACCEPT
    reason: The gene product is a core 20S proteasome subunit, so proteasomal protein
      catabolism is an appropriate core biological-process context.
  qualifier: involved_in
- term:
    id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  evidence_type: NAS
  original_reference_id: PMID:19489727
  review:
    summary: proteasome-mediated ubiquitin-dependent protein catabolic process captures
      the proteasome-mediated protein catabolism process supported for this subunit
      as part of the proteasome.
    action: ACCEPT
    reason: The gene product is a core 20S proteasome subunit, so proteasomal protein
      catabolism is an appropriate core biological-process context.
  qualifier: involved_in
- term:
    id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  evidence_type: NAS
  original_reference_id: PMID:33729481
  review:
    summary: proteasome-mediated ubiquitin-dependent protein catabolic process captures
      the proteasome-mediated protein catabolism process supported for this subunit
      as part of the proteasome.
    action: ACCEPT
    reason: The gene product is a core 20S proteasome subunit, so proteasomal protein
      catabolism is an appropriate core biological-process context.
  qualifier: involved_in
- term:
    id: GO:0061136
    label: regulation of proteasomal protein catabolic process
  evidence_type: NAS
  original_reference_id: PMID:12032076
  review:
    summary: regulation of proteasomal protein catabolic process is a pathway- or
      physiology-level consequence of proteasome activity rather than a specific function
      of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0000502
    label: proteasome complex
  evidence_type: NAS
  original_reference_id: PMID:30104634
  review:
    summary: proteasome complex is true complex membership but broader or more context-specific
      than the core 20S subunit identity.
    action: KEEP_AS_NON_CORE
    reason: The core review should emphasize the specific 20S core subcomplex membership;
      broader proteasome or spermatoproteasome membership can be retained as non-core
      context.
  qualifier: part_of
- term:
    id: GO:0000502
    label: proteasome complex
  evidence_type: IPI
  original_reference_id: PMID:31283222
  review:
    summary: proteasome complex is true complex membership but broader or more context-specific
      than the core 20S subunit identity.
    action: KEEP_AS_NON_CORE
    reason: The core review should emphasize the specific 20S core subcomplex membership;
      broader proteasome or spermatoproteasome membership can be retained as non-core
      context.
  qualifier: part_of
- term:
    id: GO:0000502
    label: proteasome complex
  evidence_type: NAS
  original_reference_id: PMID:32134919
  review:
    summary: proteasome complex is true complex membership but broader or more context-specific
      than the core 20S subunit identity.
    action: KEEP_AS_NON_CORE
    reason: The core review should emphasize the specific 20S core subcomplex membership;
      broader proteasome or spermatoproteasome membership can be retained as non-core
      context.
  qualifier: part_of
- term:
    id: GO:0000502
    label: proteasome complex
  evidence_type: IPI
  original_reference_id: PMID:34702852
  review:
    summary: proteasome complex is true complex membership but broader or more context-specific
      than the core 20S subunit identity.
    action: KEEP_AS_NON_CORE
    reason: The core review should emphasize the specific 20S core subcomplex membership;
      broader proteasome or spermatoproteasome membership can be retained as non-core
      context.
  qualifier: part_of
- term:
    id: GO:0000502
    label: proteasome complex
  evidence_type: IPI
  original_reference_id: PMID:35714770
  review:
    summary: proteasome complex is true complex membership but broader or more context-specific
      than the core 20S subunit identity.
    action: KEEP_AS_NON_CORE
    reason: The core review should emphasize the specific 20S core subcomplex membership;
      broader proteasome or spermatoproteasome membership can be retained as non-core
      context.
  qualifier: part_of
- term:
    id: GO:0000502
    label: proteasome complex
  evidence_type: IPI
  original_reference_id: PMID:35858375
  review:
    summary: proteasome complex is true complex membership but broader or more context-specific
      than the core 20S subunit identity.
    action: KEEP_AS_NON_CORE
    reason: The core review should emphasize the specific 20S core subcomplex membership;
      broader proteasome or spermatoproteasome membership can be retained as non-core
      context.
  qualifier: part_of
- term:
    id: GO:0002376
    label: immune system process
  evidence_type: NAS
  original_reference_id: PMID:33019542
  review:
    summary: immune system process is a pathway- or physiology-level consequence of
      proteasome activity rather than a specific function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: NAS
  original_reference_id: PMID:32134919
  review:
    summary: nucleus is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: NAS
  original_reference_id: PMID:33019542
  review:
    summary: nucleus is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: NAS
  original_reference_id: PMID:35858375
  review:
    summary: nucleus is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: NAS
  original_reference_id: PMID:35858375
  review:
    summary: cytoplasm is a supported localization or active-location annotation for
      proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0005839
    label: proteasome core complex
  evidence_type: IPI
  original_reference_id: PMID:34702852
  review:
    summary: proteasome core complex is the appropriate core-complex membership annotation
      for PSMA1.
    action: ACCEPT
    reason: Structural studies and UniProt summaries place the protein in the 20S
      proteasome core; this complex-membership annotation is central to the gene product
      role.
  qualifier: part_of
- term:
    id: GO:0006281
    label: DNA repair
  evidence_type: NAS
  original_reference_id: PMID:32134919
  review:
    summary: DNA repair is a pathway- or physiology-level consequence of proteasome
      activity rather than a specific function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: NAS
  original_reference_id: PMID:32935661
  review:
    summary: apoptotic process is a pathway- or physiology-level consequence of proteasome
      activity rather than a specific function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: NAS
  original_reference_id: PMID:32134919
  review:
    summary: DNA damage response is a pathway- or physiology-level consequence of
      proteasome activity rather than a specific function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0006979
    label: response to oxidative stress
  evidence_type: IDA
  original_reference_id: PMID:34702852
  review:
    summary: response to oxidative stress is a pathway- or physiology-level consequence
      of proteasome activity rather than a specific function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0006979
    label: response to oxidative stress
  evidence_type: NAS
  original_reference_id: PMID:35858375
  review:
    summary: response to oxidative stress is a pathway- or physiology-level consequence
      of proteasome activity rather than a specific function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0007283
    label: spermatogenesis
  evidence_type: NAS
  original_reference_id: PMID:23706739
  review:
    summary: spermatogenesis is a pathway- or physiology-level consequence of proteasome
      activity rather than a specific function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0010498
    label: proteasomal protein catabolic process
  evidence_type: NAS
  original_reference_id: PMID:23569244
  review:
    summary: proteasomal protein catabolic process captures the proteasome-mediated
      protein catabolism process supported for this subunit as part of the proteasome.
    action: ACCEPT
    reason: The gene product is a core 20S proteasome subunit, so proteasomal protein
      catabolism is an appropriate core biological-process context.
  qualifier: involved_in
- term:
    id: GO:0010498
    label: proteasomal protein catabolic process
  evidence_type: NAS
  original_reference_id: PMID:23706739
  review:
    summary: proteasomal protein catabolic process captures the proteasome-mediated
      protein catabolism process supported for this subunit as part of the proteasome.
    action: ACCEPT
    reason: The gene product is a core 20S proteasome subunit, so proteasomal protein
      catabolism is an appropriate core biological-process context.
  qualifier: involved_in
- term:
    id: GO:0010498
    label: proteasomal protein catabolic process
  evidence_type: NAS
  original_reference_id: PMID:30104634
  review:
    summary: proteasomal protein catabolic process captures the proteasome-mediated
      protein catabolism process supported for this subunit as part of the proteasome.
    action: ACCEPT
    reason: The gene product is a core 20S proteasome subunit, so proteasomal protein
      catabolism is an appropriate core biological-process context.
  qualifier: involved_in
- term:
    id: GO:0010498
    label: proteasomal protein catabolic process
  evidence_type: IDA
  original_reference_id: PMID:34702852
  review:
    summary: proteasomal protein catabolic process captures the proteasome-mediated
      protein catabolism process supported for this subunit as part of the proteasome.
    action: ACCEPT
    reason: The gene product is a core 20S proteasome subunit, so proteasomal protein
      catabolism is an appropriate core biological-process context.
    additional_reference_ids:
    - file:human/PSMA1/PSMA1-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/PSMA1/PSMA1-deep-research-falcon.md
      supporting_text: Identified substrates are enriched for intrinsically disordered
        RNA- and DNA-binding proteins, especially nuclear and stress-granule proteins.
  qualifier: involved_in
- term:
    id: GO:0010499
    label: proteasomal ubiquitin-independent protein catabolic process
  evidence_type: NAS
  original_reference_id: PMID:31473102
  review:
    summary: >-
      proteasomal ubiquitin-independent protein catabolic process captures the
      proteasome-mediated protein catabolism process supported for this subunit
      as part of the proteasome. Falcon deep research reinforces this, noting that
      about half of cellular proteasomes exist as free 20S complexes that degrade
      substrates (especially intrinsically disordered, nuclear, and stress-granule
      proteins) independently of ubiquitin, and PSMA1 is a constitutive alpha-ring
      subunit of these free 20S cores.
    action: ACCEPT
    reason: >-
      The gene product is a core 20S proteasome subunit, so proteasomal protein
      catabolism is an appropriate core biological-process context. Ubiquitin-independent
      degradation by free 20S is now a systematically characterized pathway in which
      PSMA1-containing cores participate.
    additional_reference_ids:
    - file:human/PSMA1/PSMA1-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/PSMA1/PSMA1-deep-research-falcon.md
      supporting_text: |-
        Pepelnjak et al. (2024) emphasize that **~half of cellular proteasomes** can exist as **free 20S complexes**, enabling ubiquitin-independent turnover of certain substratesβ€”especially proteins with **intrinsically disordered regions (IDRs)** and enrichment among **nuclear and stress granule proteins**.
  qualifier: involved_in
- term:
    id: GO:0030317
    label: flagellated sperm motility
  evidence_type: NAS
  original_reference_id: PMID:23706739
  review:
    summary: flagellated sperm motility is a pathway- or physiology-level consequence
      of proteasome activity rather than a specific function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0030317
    label: flagellated sperm motility
  evidence_type: NAS
  original_reference_id: PMID:27003159
  review:
    summary: flagellated sperm motility is a pathway- or physiology-level consequence
      of proteasome activity rather than a specific function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0032729
    label: positive regulation of type II interferon production
  evidence_type: NAS
  original_reference_id: PMID:30104634
  review:
    summary: positive regulation of type II interferon production is a pathway- or
      physiology-level consequence of proteasome activity rather than a specific function
      of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0032743
    label: positive regulation of interleukin-2 production
  evidence_type: NAS
  original_reference_id: PMID:30104634
  review:
    summary: positive regulation of interleukin-2 production is a pathway- or physiology-level
      consequence of proteasome activity rather than a specific function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0032760
    label: positive regulation of tumor necrosis factor production
  evidence_type: NAS
  original_reference_id: PMID:30104634
  review:
    summary: positive regulation of tumor necrosis factor production is a pathway-
      or physiology-level consequence of proteasome activity rather than a specific
      function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0034341
    label: response to type II interferon
  evidence_type: NAS
  original_reference_id: PMID:30104634
  review:
    summary: response to type II interferon is a pathway- or physiology-level consequence
      of proteasome activity rather than a specific function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0034515
    label: proteasome storage granule
  evidence_type: NAS
  original_reference_id: PMID:31380390
  review:
    summary: proteasome storage granule is a supported localization or active-location
      annotation for proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  evidence_type: IDA
  original_reference_id: PMID:34702852
  review:
    summary: proteasome-mediated ubiquitin-dependent protein catabolic process captures
      the proteasome-mediated protein catabolism process supported for this subunit
      as part of the proteasome.
    action: ACCEPT
    reason: The gene product is a core 20S proteasome subunit, so proteasomal protein
      catabolism is an appropriate core biological-process context.
  qualifier: involved_in
- term:
    id: GO:0043374
    label: CD8-positive, alpha-beta T cell differentiation
  evidence_type: NAS
  original_reference_id: PMID:33019542
  review:
    summary: CD8-positive, alpha-beta T cell differentiation is a pathway- or physiology-level
      consequence of proteasome activity rather than a specific function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0045061
    label: thymic T cell selection
  evidence_type: NAS
  original_reference_id: PMID:30650357
  review:
    summary: thymic T cell selection is a pathway- or physiology-level consequence
      of proteasome activity rather than a specific function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0045063
    label: T-helper 1 cell differentiation
  evidence_type: NAS
  original_reference_id: PMID:30104634
  review:
    summary: T-helper 1 cell differentiation is a pathway- or physiology-level consequence
      of proteasome activity rather than a specific function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0045590
    label: negative regulation of regulatory T cell differentiation
  evidence_type: NAS
  original_reference_id: PMID:30104634
  review:
    summary: negative regulation of regulatory T cell differentiation is a pathway-
      or physiology-level consequence of proteasome activity rather than a specific
      function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0051321
    label: meiotic cell cycle
  evidence_type: NAS
  original_reference_id: PMID:23706739
  review:
    summary: meiotic cell cycle is a pathway- or physiology-level consequence of proteasome
      activity rather than a specific function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0061136
    label: regulation of proteasomal protein catabolic process
  evidence_type: IDA
  original_reference_id: PMID:35714770
  review:
    summary: regulation of proteasomal protein catabolic process is a pathway- or
      physiology-level consequence of proteasome activity rather than a specific function
      of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0061136
    label: regulation of proteasomal protein catabolic process
  evidence_type: NAS
  original_reference_id: PMID:35714770
  review:
    summary: regulation of proteasomal protein catabolic process is a pathway- or
      physiology-level consequence of proteasome activity rather than a specific function
      of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0071357
    label: cellular response to type I interferon
  evidence_type: NAS
  original_reference_id: PMID:31380390
  review:
    summary: cellular response to type I interferon is a pathway- or physiology-level
      consequence of proteasome activity rather than a specific function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0072539
    label: T-helper 17 cell differentiation
  evidence_type: NAS
  original_reference_id: PMID:30104634
  review:
    summary: T-helper 17 cell differentiation is a pathway- or physiology-level consequence
      of proteasome activity rather than a specific function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0160165
    label: CD8-positive, alpha-beta T cell homeostasis
  evidence_type: NAS
  original_reference_id: PMID:33815406
  review:
    summary: CD8-positive, alpha-beta T cell homeostasis is a pathway- or physiology-level
      consequence of proteasome activity rather than a specific function of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:1990111
    label: spermatoproteasome complex
  evidence_type: NAS
  original_reference_id: PMID:35377789
  review:
    summary: spermatoproteasome complex is true complex membership but broader or
      more context-specific than the core 20S subunit identity.
    action: KEEP_AS_NON_CORE
    reason: The core review should emphasize the specific 20S core subcomplex membership;
      broader proteasome or spermatoproteasome membership can be retained as non-core
      context.
  qualifier: part_of
- term:
    id: GO:2000045
    label: regulation of G1/S transition of mitotic cell cycle
  evidence_type: NAS
  original_reference_id: PMID:32935661
  review:
    summary: regulation of G1/S transition of mitotic cell cycle is a pathway- or
      physiology-level consequence of proteasome activity rather than a specific function
      of PSMA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: These annotations are largely projected from whole proteasome complexes
      or specialized proteasome variants; they should not be interpreted as individual
      subunit core functions.
  qualifier: involved_in
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: nucleoplasm is a supported localization or active-location annotation
      for proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0016604
    label: nuclear body
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: nuclear body is a supported localization or active-location annotation
      for proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:12181345
  review:
    summary: nucleus is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
    additional_reference_ids:
    - file:human/PSMA1/PSMA1-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/PSMA1/PSMA1-deep-research-falcon.md
      supporting_text: Proteasomes exist in both the **cytoplasm and nucleus**.
    - reference_id: file:human/PSMA1/PSMA1-deep-research-falcon.md
      supporting_text: 'Under PSMD1 knockdown (reducing intact 26S), the authors observed
        that β€œβ€˜free’ 20S CPs remained nuclear, whereas the 19S RP accumulated in the
        cytoplasm,” indicating compartment-specific dynamics of PSMA1-containing cores
        versus 19S components.'
  qualifier: located_in
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:12181345
  review:
    summary: cytoplasm is a supported localization or active-location annotation for
      proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1168640
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1234159
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1236970
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1504193
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-174105
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-174202
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-174203
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-174255
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-180573
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-180603
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-209061
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2130282
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-264458
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-353125
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3640874
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-450466
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4608855
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4641256
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4641260
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5362448
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5387392
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5607724
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5607731
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5610754
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5610758
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5610760
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5635868
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5658430
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5665854
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5665871
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5668481
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5668520
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5687112
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5689539
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-68948
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-69016
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-75825
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8850992
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8852354
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8854044
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8854071
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8866553
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8866858
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8932355
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8956140
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8956184
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8957265
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9755303
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9755306
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9766223
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-983150
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9907898
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9907912
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9907919
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9907925
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9907928
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9907940
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9907941
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9908052
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9908069
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9908101
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9908178
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9908709
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9908721
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9912636
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9912655
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9912747
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9912751
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9929352
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9929486
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9931314
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9934893
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9954728
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-212917
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-5610751
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-9011324
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:34711951
  review:
    summary: nucleus is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: is_active_in
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:34711951
  review:
    summary: cytoplasm is a supported localization or active-location annotation for
      proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: is_active_in
- term:
    id: GO:0005839
    label: proteasome core complex
  evidence_type: IDA
  original_reference_id: PMID:34711951
  review:
    summary: proteasome core complex is the appropriate core-complex membership annotation
      for PSMA1.
    action: ACCEPT
    reason: Structural studies and UniProt summaries place the protein in the 20S
      proteasome core; this complex-membership annotation is central to the gene product
      role.
  qualifier: part_of
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29804830
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0000502
    label: proteasome complex
  evidence_type: IDA
  original_reference_id: PMID:17323924
  review:
    summary: proteasome complex is true complex membership but broader or more context-specific
      than the core 20S subunit identity.
    action: KEEP_AS_NON_CORE
    reason: The core review should emphasize the specific 20S core subcomplex membership;
      broader proteasome or spermatoproteasome membership can be retained as non-core
      context.
  qualifier: part_of
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  review:
    summary: extracellular exosome is a supported localization or active-location
      annotation for proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: HDA
  original_reference_id: PMID:21630459
  review:
    summary: nucleus is a core cellular context for the assembled proteasome containing
      PSMA1.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
  qualifier: located_in
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19056867
  review:
    summary: extracellular exosome is a supported localization or active-location
      annotation for proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:20458337
  review:
    summary: extracellular exosome is a supported localization or active-location
      annotation for proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-174058
  review:
    summary: nucleoplasm is a supported localization or active-location annotation
      for proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-187574
  review:
    summary: nucleoplasm is a supported localization or active-location annotation
      for proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-188191
  review:
    summary: nucleoplasm is a supported localization or active-location annotation
      for proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5635854
  review:
    summary: nucleoplasm is a supported localization or active-location annotation
      for proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-68825
  review:
    summary: nucleoplasm is a supported localization or active-location annotation
      for proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-69600
  review:
    summary: nucleoplasm is a supported localization or active-location annotation
      for proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8939801
  review:
    summary: nucleoplasm is a supported localization or active-location annotation
      for proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8952408
  review:
    summary: nucleoplasm is a supported localization or active-location annotation
      for proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9762096
  review:
    summary: nucleoplasm is a supported localization or active-location annotation
      for proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-9604648
  review:
    summary: nucleoplasm is a supported localization or active-location annotation
      for proteasomes but not the gene-specific core function.
    action: KEEP_AS_NON_CORE
    reason: Proteasomes operate in cytosolic and nuclear compartments; localization
      annotations should be retained as context without replacing the core catalytic/structural
      role.
  qualifier: located_in
- term:
    id: GO:0005839
    label: proteasome core complex
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: proteasome core complex is the appropriate core-complex membership annotation
      for PSMA1.
    action: ACCEPT
    reason: Structural studies and UniProt summaries place the protein in the 20S
      proteasome core; this complex-membership annotation is central to the gene product
      role.
  qualifier: part_of
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17292860
  review:
    summary: The interaction evidence may show physical association, but generic protein
      binding is too low-information for the reviewed function of this proteasome
      subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: For proteasome subunits, the informative annotations are catalytic activity,
      structural constituent activity, complex membership, and proteasomal protein
      catabolism; generic protein binding should not be treated as a core function.
  qualifier: enables
- term:
    id: GO:0019773
    label: proteasome core complex, alpha-subunit complex
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: proteasome core complex, alpha-subunit complex is the appropriate core-complex
      membership annotation for PSMA1.
    action: ACCEPT
    reason: Structural studies and UniProt summaries place the protein in the 20S
      proteasome core; this complex-membership annotation is central to the gene product
      role.
  qualifier: part_of
- term:
    id: GO:0000502
    label: proteasome complex
  evidence_type: TAS
  original_reference_id: PMID:8811196
  review:
    summary: proteasome complex is true complex membership but broader or more context-specific
      than the core 20S subunit identity.
    action: KEEP_AS_NON_CORE
    reason: The core review should emphasize the specific 20S core subcomplex membership;
      broader proteasome or spermatoproteasome membership can be retained as non-core
      context.
  qualifier: part_of
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:12032076
  title: Properties of the hybrid form of the 26S proteasome containing both 19S and
    PA28 complexes.
  findings: []
- id: PMID:12181345
  title: 'Clastosome: a subtype of nuclear body enriched in 19S and 20S proteasomes,
    ubiquitin, and protein substrates of proteasome.'
  findings: []
- id: PMID:12376572
  title: Mapping and structural dissection of human 20 S proteasome using proteomic
    approaches.
  findings: []
- id: PMID:14733938
  title: Protein-protein interactions among human 20S proteasome subunits and proteassemblin.
  findings: []
- id: PMID:15225636
  title: The alpha4 and alpha7 subunits and assembly of the 20S proteasome.
  findings: []
- id: PMID:16189514
  title: Towards a proteome-scale map of the human protein-protein interaction network.
  findings: []
- id: PMID:17292860
  title: Conserved signal peptide of Notch3 inhibits interaction with proteasome.
  findings: []
- id: PMID:17323924
  title: Mass spectrometric characterization of the affinity-purified human 26S proteasome
    complex.
  findings: []
- id: PMID:17948026
  title: The proteasome maturation protein POMP facilitates major steps of 20S proteasome
    formation at the endoplasmic reticulum.
  findings: []
- id: PMID:19056867
  title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
  findings: []
- id: PMID:19060904
  title: An empirical framework for binary interactome mapping.
  findings: []
- id: PMID:19489727
  title: Recognition and processing of ubiquitin-protein conjugates by the proteasome.
  findings: []
- id: PMID:20458337
  title: MHC class II-associated proteins in B-cell exosomes and potential functional
    implications for exosome biogenesis.
  findings: []
- id: PMID:21516116
  title: Next-generation sequencing to generate interactome datasets.
  findings: []
- id: PMID:21630459
  title: Proteomic characterization of the human sperm nucleus.
  findings: []
- id: PMID:21988832
  title: Toward an understanding of the protein interaction network of the human liver.
  findings: []
- id: PMID:23533145
  title: In-depth proteomic analyses of exosomes isolated from expressed prostatic
    secretions in urine.
  findings: []
- id: PMID:23569244
  title: Thymoproteasome subunit-Ξ²5T generates peptide-MHC complexes specialized for
    positive selection.
  findings: []
- id: PMID:23706739
  title: Acetylation-mediated proteasomal degradation of core histones during DNA
    repair and spermatogenesis.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:25599644
  title: Crystal structure of the human 20S proteasome in complex with carfilzomib.
  findings: []
- id: PMID:27003159
  title: Proteasome activators, PA28Ξ³ and PA200, play indispensable roles in male
    fertility.
  findings: []
- id: PMID:27493187
  title: The inhibition mechanism of human 20S proteasomes enables next-generation
    inhibitor design.
  findings: []
- id: PMID:29568061
  title: An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein
    interactions and subcellular localizations.
  findings: []
- id: PMID:29636472
  title: Structural mechanism for nucleotide-driven remodeling of the AAA-ATPase unfoldase
    in the activated human 26S proteasome.
  findings: []
- id: PMID:29804830
  title: ZFAND1 Recruits p97 and the 26S Proteasome to Promote the Clearance of Arsenite-Induced
    Stress Granules.
  findings: []
- id: PMID:29892012
  title: An interactome perturbation framework prioritizes damaging missense mutations
    for developmental disorders.
  findings: []
- id: PMID:30104634
  title: 'The immunoproteasome and thymoproteasome: functions, evolution and human
    disease.'
  findings: []
- id: PMID:30650357
  title: Restricted Expression of the Thymoproteasome Is Required for Thymic Selection
    and Peripheral Homeostasis of CD8(+) T Cells.
  findings: []
- id: PMID:31283222
  title: Design and Evaluation of Highly Selective Human Immunoproteasome Inhibitors
    Reveal a Compensatory Process That Preserves Immune Cell Viability.
  findings: []
- id: PMID:31380390
  title: Regulation of Proteasome Activity by (Post-)transcriptional Mechanisms.
  findings: []
- id: PMID:31473102
  title: Characterization of Fully Recombinant Human 20S and 20S-PA200 Proteasome
    Complexes.
  findings: []
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the
    allele frequency spectrum in human populations.
  findings: []
- id: PMID:32134919
  title: Cryo-EM structures of the human PA200 and PA200-20S complex reveal regulation
    of proteasome gate opening and two PA200 apertures.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:32935661
  title: Role of oncogenic REGΞ³ in cancer.
  findings: []
- id: PMID:33019542
  title: Adaptation of Proteasomes and Lysosomes to Cellular Environments.
  findings: []
- id: PMID:33729481
  title: 'Proteasome in action: substrate degradation by the 26S proteasome.'
  findings: []
- id: PMID:33815406
  title: The Role of Proteasomes in the Thymus.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:34702852
  title: The 20S as a stand-alone proteasome in cells can degrade the ubiquitin tag.
  findings: []
- id: PMID:34711951
  title: AKIRIN2 controls the nuclear import of proteasomes in vertebrates.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:35377789
  title: Proteasome complexes experience profound structural and functional rearrangements
    throughout mammalian spermatogenesis.
  findings: []
- id: PMID:35714770
  title: Proteasome activator 28Ξ³ (PA28Ξ³) allosterically activates trypsin-like proteolysis
    by binding to the Ξ±-ring of the 20S proteasome.
  findings: []
- id: PMID:35858375
  title: Structural insights into the human PA28-20S proteasome enabled by efficient
    tagging and purification of endogenous proteins.
  findings: []
- id: PMID:37228199
  title: An abundance of free regulatory (19S) proteasome particles regulates neuronal
    synapses.
  findings: []
- id: PMID:37776851
  title: Analysis of proteome-wide degradation dynamics in ALS SOD1 iPSC-derived patient
    neurons reveals disrupted VCP homeostasis.
  findings: []
- id: PMID:8811196
  title: Structure and functions of the 20S and 26S proteasomes.
  findings: []
- id: Reactome:R-HSA-1168640
  title: Ubiquitinated IkB is degraded
  findings: []
- id: Reactome:R-HSA-1234159
  title: Proteasome proteolyzes ub-HIF-alpha
  findings: []
- id: Reactome:R-HSA-1236970
  title: Proteasomal clevage of exogenous antigen (26S proteasome catalyst)
  findings: []
- id: Reactome:R-HSA-1504193
  title: Ubiquitinated DVL is degraded by the proteasome
  findings: []
- id: Reactome:R-HSA-174058
  title: Degradation of multiubiquitinated Cdh1
  findings: []
- id: Reactome:R-HSA-174105
  title: Degradation of multiubiquitinated cell cycle proteins
  findings: []
- id: Reactome:R-HSA-174202
  title: Degradation of multiubiquitinated Securin
  findings: []
- id: Reactome:R-HSA-174203
  title: SCF-mediated degradation of Emi1
  findings: []
- id: Reactome:R-HSA-174255
  title: Degradation multiubiquitinated Cyclin A
  findings: []
- id: Reactome:R-HSA-180573
  title: Degradation of ubiquitinated CD4
  findings: []
- id: Reactome:R-HSA-180603
  title: Proteosome-mediated degradation of APOBEC3G
  findings: []
- id: Reactome:R-HSA-187574
  title: Degradation of ubiquitinated p27/p21 by the 26S proteasome
  findings: []
- id: Reactome:R-HSA-188191
  title: APC/C:Cdh1-mediated degradation of Skp2
  findings: []
- id: Reactome:R-HSA-209061
  title: Ubiquitinated and phosphorylated IKBA binds to and is degraded by the proteasome
    complex
  findings: []
- id: Reactome:R-HSA-2130282
  title: Degradation of ubiquitinated beta catenin by the proteasome
  findings: []
- id: Reactome:R-HSA-264458
  title: Proteasome mediated degradation of COP1
  findings: []
- id: Reactome:R-HSA-353125
  title: 26S proteosome degrades ODC holoenzyme complex
  findings: []
- id: Reactome:R-HSA-3640874
  title: Ub-RibC-AXIN is degraded by the proteasome
  findings: []
- id: Reactome:R-HSA-450466
  title: AUF1:mRNA complex is degraded
  findings: []
- id: Reactome:R-HSA-4608855
  title: PRICKLE1 is degraded by the proteasome
  findings: []
- id: Reactome:R-HSA-4641256
  title: Ubiquitinated AXIN is degraded by the proteasome
  findings: []
- id: Reactome:R-HSA-4641260
  title: Ubiquitinated DVL1 is degraded by the proteasome
  findings: []
- id: Reactome:R-HSA-5362448
  title: Hh C-terminal fragments are degraded by the proteasome
  findings: []
- id: Reactome:R-HSA-5387392
  title: processing defective Hh variants are degraded by the proteasome
  findings: []
- id: Reactome:R-HSA-5607724
  title: 26S proteasome processes K48PolyUb-K21,22-p-S32,36-IkBA:NF-kB complex to
    form NF-kB complex
  findings: []
- id: Reactome:R-HSA-5607731
  title: 26S proteasome processes p-7S-p100:RELB to form p52:RELB
  findings: []
- id: Reactome:R-HSA-5610754
  title: GLI3 is partially degraded by the proteasome to yield the GLI3 repressor
  findings: []
- id: Reactome:R-HSA-5610758
  title: GLI1 is degraded by the proteasome after ubiquitination by beta-TrCP
  findings: []
- id: Reactome:R-HSA-5610760
  title: GLI1 is degraded by the proteasome after ubiquitination by ITCH
  findings: []
- id: Reactome:R-HSA-5635854
  title: GLI2,3 are degraded by the proteasome
  findings: []
- id: Reactome:R-HSA-5635868
  title: ub-GLI is degraded by the proteasome
  findings: []
- id: Reactome:R-HSA-5658430
  title: NF1 is degraded by the proteasome
  findings: []
- id: Reactome:R-HSA-5665854
  title: ADRM1:26S proteaseome binds UCHL5
  findings: []
- id: Reactome:R-HSA-5665871
  title: ADRM1 binds 26S proteasome
  findings: []
- id: Reactome:R-HSA-5668481
  title: Protesomal degradation of K48polyUb-TRAF3
  findings: []
- id: Reactome:R-HSA-5668520
  title: 26Sproteasome degrades K48polyUb-NIK
  findings: []
- id: Reactome:R-HSA-5687112
  title: MAPK6 is degraded by the 26S proteasome
  findings: []
- id: Reactome:R-HSA-5689539
  title: ADRM1:26S proteaseome binds USP14
  findings: []
- id: Reactome:R-HSA-68825
  title: Ubiquitinated geminin is degraded by the proteasome
  findings: []
- id: Reactome:R-HSA-68948
  title: Ubiquitinated Orc1 is degraded by the proteasome
  findings: []
- id: Reactome:R-HSA-69016
  title: Ubiquitinated Cdc6 is degraded by the proteasome
  findings: []
- id: Reactome:R-HSA-69600
  title: Proteolytic degradation of ubiquitinated-Cdc25A
  findings: []
- id: Reactome:R-HSA-75825
  title: Proteasome mediated degradation of Cyclin D1
  findings: []
- id: Reactome:R-HSA-8850992
  title: Proteasome degrades polyubiquitinated PTEN
  findings: []
- id: Reactome:R-HSA-8852354
  title: GTSE1 facilitates proteasome-mediated degradation of TP53
  findings: []
- id: Reactome:R-HSA-8854044
  title: Proteasome degrades AURKA ubiquitinated by SCF-FBXL7
  findings: []
- id: Reactome:R-HSA-8854071
  title: Proteasome-mediated degradation of PolyUb-FBXL7
  findings: []
- id: Reactome:R-HSA-8866553
  title: misfolded CFTR is degraded by the 26S proteasome
  findings: []
- id: Reactome:R-HSA-8866858
  title: CFTR F508del is degraded by the 26S proteasome
  findings: []
- id: Reactome:R-HSA-8932355
  title: 26S proteasome degrades Ub-NFE2L2
  findings: []
- id: Reactome:R-HSA-8939801
  title: 26S proteasome degrades PolyUb-RUNX2
  findings: []
- id: Reactome:R-HSA-8952408
  title: Polyubiquitinated RUNX3 is degraded by the proteasome
  findings: []
- id: Reactome:R-HSA-8956140
  title: NEDD8 and UBD bind NUB1 and the 26S proteasome
  findings: []
- id: Reactome:R-HSA-8956184
  title: 26S- and NUB1-mediated degradation of NEDD8, UBD and their conjugates
  findings: []
- id: Reactome:R-HSA-8957265
  title: 26S proteasome degrades TP73 polyubiquitinated by ITCH
  findings: []
- id: Reactome:R-HSA-9755303
  title: 26S proteasome degrades HIFalpha
  findings: []
- id: Reactome:R-HSA-9755306
  title: ub UBXN7 is degraded by the 26S proteasome
  findings: []
- id: Reactome:R-HSA-9762096
  title: Ub,pS335,S338,T NFE2L2 is degraded
  findings: []
- id: Reactome:R-HSA-9766223
  title: Proteasome-dependent degradation of ubiquitinated CDH1
  findings: []
- id: Reactome:R-HSA-983150
  title: Proteasomal cleavage of substrate
  findings: []
- id: Reactome:R-HSA-9907898
  title: Formation of the inner ring of the 20S core particle of the 26S proteasome
  findings: []
- id: Reactome:R-HSA-9907912
  title: Formation of the outer ring of the 20S core particle
  findings: []
- id: Reactome:R-HSA-9907919
  title: Formation of the preholoproteasome
  findings: []
- id: Reactome:R-HSA-9907925
  title: Formation of the inner ring of the 20S immunoproteasome core particle
  findings: []
- id: Reactome:R-HSA-9907928
  title: Formation of the inner ring of the 20S thymoproteasome core particle
  findings: []
- id: Reactome:R-HSA-9907940
  title: Formation of the preholothymoproteasome
  findings: []
- id: Reactome:R-HSA-9907941
  title: Fromation of the preholoimmunoproteasome
  findings: []
- id: Reactome:R-HSA-9908052
  title: PSMG1:PSMG2 dimer binds the 20S core particle outer ring
  findings: []
- id: Reactome:R-HSA-9908069
  title: POMP binds the 20S core particle outer ring
  findings: []
- id: Reactome:R-HSA-9908101
  title: Maturation of the canonical 20S core particle
  findings: []
- id: Reactome:R-HSA-9908178
  title: Formation of the 26S proteasome
  findings: []
- id: Reactome:R-HSA-9908709
  title: Formation of the PA28-alpha-beta-20S proteasome
  findings: []
- id: Reactome:R-HSA-9908721
  title: Formation of the PA28gamma-20S proteasome
  findings: []
- id: Reactome:R-HSA-9912636
  title: Proteasomal cleavage of intracellular substrate (PA28-alpha-beta-20S proteasome
    catalyst)
  findings: []
- id: Reactome:R-HSA-9912655
  title: Proteasomal cleavage of intracellular substrate (immunoproteasome catalyst)
  findings: []
- id: Reactome:R-HSA-9912747
  title: Proteasomal clevage of exogenous antigen (immunoproteasome catalyst)
  findings: []
- id: Reactome:R-HSA-9912751
  title: Proteasomal cleavage of partially digested antigen (immunoproteasome catalyst)
  findings: []
- id: Reactome:R-HSA-9929352
  title: Ubiquitinated CD274 is degraded by the 26S proteasome
  findings: []
- id: Reactome:R-HSA-9929486
  title: SPOP-mediated degradation of CD274 by 26S Proteosome
  findings: []
- id: Reactome:R-HSA-9931314
  title: Proteasomal degradation of polyUb-p-S195-CD274
  findings: []
- id: Reactome:R-HSA-9934893
  title: Proteolysis of K48polyUb-K,p-S-PER1,2,3
  findings: []
- id: Reactome:R-HSA-9954728
  title: The proteasome degrades the K48-polyubiquitinated alanine-tailed nascent
    peptide
  findings: []
- id: Reactome:R-NUL-212917
  title: Proteasome mediated degradation of PAK-2p34
  findings: []
- id: Reactome:R-NUL-5610751
  title: Gli2is degraded by the proteasome
  findings: []
- id: Reactome:R-NUL-9011324
  title: Proteasome degrades SAX-3 ubiquitinated by EBAX-1
  findings: []
- id: Reactome:R-NUL-9604648
  title: Proteasome degrades ubiquitinated mouse NICD4
  findings: []
- id: PMID:23495936
  title: Molecular architecture and assembly of the eukaryotic proteasome.
  findings: []
- id: file:human/PSMA1/PSMA1-deep-research-falcon.md
  title: Falcon deep research report on PSMA1
  findings:
  - statement: |
      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.
    supporting_text: |-
      Importantly, **PSMA1 is not a catalytic peptidase active site**; proteolysis occurs at catalytic **Ξ² subunits**.
    reference_section_type: RESULTS
  - statement: |
      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.
    supporting_text: |-
      The 20S CP is a barrel made of **four stacked heteroheptameric rings** arranged **Ξ±1–7 Ξ²1–7 Ξ²1–7 Ξ±1–7**; the **two outer Ξ± rings** act as a **gate** that restricts access to the proteolytic chamber. PSMA1 is one of the **non-catalytic Ξ± subunits** contributing to this gate architecture.
    reference_section_type: RESULTS
  - statement: |
      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.
    supporting_text: |-
      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.
    reference_section_type: RESULTS
  - statement: |
      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.
    supporting_text: |-
      PSMA1’s primary function is to serve as an essential **structural subunit of the 20S Ξ± 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.
    reference_section_type: RESULTS
  - statement: |
      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.
    supporting_text: |-
      **C-terminal HbYX motifs of proteasome regulators** (e.g., the 19S RP) insert into **pockets between adjacent Ξ± subunits** to promote **CP gate opening**. As an Ξ± subunit, PSMA1 contributes to forming these Ξ±-ring interfaces and pockets that receive regulatory tails.
    reference_section_type: RESULTS
  - statement: |
      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.
    supporting_text: |-
      Assembly begins with formation of a complete **Ξ± ring** assisted by **PAC1/2 and PAC3/4**, followed by sequential Ξ² incorporation to form **half-CPs** that fuse; activation requires cleavage of Ξ² propeptides.
    reference_section_type: RESULTS
  - statement: |
      Proteasomes are present in both the cytoplasm and nucleus, and osmotic/salt
      stress induces rapid formation of nuclear proteasome granules containing 26S
      proteasomes.
    supporting_text: |-
      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.
    reference_section_type: RESULTS
  - statement: |
      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.
    supporting_text: |-
      Under PSMD1 knockdown (reducing intact 26S), the authors observed that β€œβ€˜free’ 20S CPs remained nuclear, whereas the 19S RP accumulated in the cytoplasm,” indicating compartment-specific dynamics of PSMA1-containing cores versus 19S components.
    reference_section_type: RESULTS
  - statement: |
      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.
    supporting_text: |-
      Pepelnjak et al. (2024) emphasize that **~half of cellular proteasomes** can exist as **free 20S complexes**, enabling ubiquitin-independent turnover of certain substratesβ€”especially proteins with **intrinsically disordered regions (IDRs)** and enrichment among **nuclear and stress granule proteins**.
    reference_section_type: RESULTS
  - statement: |
      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.
    supporting_text: |-
      clinically used proteasome inhibitors (e.g., bortezomib) act on **catalytic Ξ² subunits** (especially Ξ²5), rather than Ξ± subunits like PSMA1. This frames PSMA1 more as a biomarker/proteasome-state indicator than a direct pharmacologic target.
    reference_section_type: DISCUSSION
core_functions:
- molecular_function:
    id: GO:0140756
    label: structural constituent of proteasome
  contributes_to_molecular_function:
    id: GO:0004298
    label: threonine-type endopeptidase activity
  directly_involved_in:
  - id: GO:0010498
    label: proteasomal protein catabolic process
  - id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0005634
    label: nucleus
  in_complex:
    id: GO:0019773
    label: proteasome core complex, alpha-subunit complex
  description: PSMA1 is a structural alpha-ring subunit of the 20S proteasome core.
    It does not provide the catalytic threonine nucleophile; instead, it helps form
    the alpha-ring architecture and gated entry/regulator-binding surface that allows
    the assembled proteasome to carry out protein catabolism.
  supported_by:
  - reference_id: PMID:23495936
    supporting_text: barrel-shaped proteolytic 20S core particle (CP) of 28 subunits
  - reference_id: PMID:23495936
    supporting_text: the outer rings consist of seven different Ξ± subunits
  - reference_id: PMID:23495936
    supporting_text: The Ξ²1, Ξ²2, and Ξ²5 subunits contain the proteolytic active sites
  - reference_id: file:human/PSMA1/PSMA1-deep-research-falcon.md
    supporting_text: |-
      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.
  - reference_id: file:human/PSMA1/PSMA1-deep-research-falcon.md
    supporting_text: |-
      PSMA1 contributes to forming these Ξ±-ring interfaces and pockets that receive regulatory tails.
suggested_questions:
- question: Should non-catalytic proteasome alpha subunits use contributes_to for
    complex-level protease activity, or should GO curation prefer structural constituent
    of proteasome plus part_of complex annotations?
  experts:
  - Tomko RJ Jr
  - Hochstrasser M
suggested_experiments:
- hypothesis: PSMA1 contributes structurally to alpha-ring gating/regulator docking
    but does not directly catalyze peptide bond hydrolysis.
  description: Use purified proteasome complexes or separation-of-function PSMA1 mutants
    at alpha-ring/regulator interfaces, then measure assembly, gate opening, substrate
    entry, and beta-subunit peptidase activity separately.
  experiment_type: structure-guided mutagenesis with proteasome activity and assembly
    assays