PSMB5

UniProt ID: P28074
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

PSMB5 encodes proteasome subunit beta type-5, the constitutive beta5 catalytic subunit of the human 20S proteasome core. After removal of its N-terminal propeptide, the mature chain begins with Thr60, the nucleophilic active-site residue that supports chymotrypsin-like threonine endopeptidase activity. PSMB5 therefore carries catalytic protease function as a member of the 20S/26S proteasome, in contrast to non-catalytic structural subunits such as PSMA1.

Existing Annotations Review

GO Term Evidence Action Reason
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.
GO:0005634 nucleus
IBA
GO_REF:0000033 		ACCEPT
Summary: nucleus is a core cellular context for the assembled proteasome containing PSMB5.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0005829 cytosol
IBA
GO_REF:0000033 		ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMB5.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
GO:0004175 endopeptidase activity
IBA
GO_REF:0000033 		MODIFY
Summary: endopeptidase activity is directionally related to the proteasome role but is less specific than the supported proteasome term.
Reason: Replace the broad annotation with threonine-type endopeptidase activity, which better captures the gene product role supported by proteasome literature and existing specific GOA annotations.
Supporting Evidence:
file:human/PSMB5/PSMB5-deep-research-falcon.md
Within the 20S Ξ² rings, Ξ²1, Ξ²2, and Ξ²5 are the three catalytically active Ξ²-subunits. Ξ²5 (PSMB5) is assigned the CT-L activity, which preferentially cleaves peptide bonds after hydrophobic residues.
GO:0019774 proteasome core complex, beta-subunit complex
IBA
GO_REF:0000033 		ACCEPT
Summary: proteasome core complex, beta-subunit complex is the appropriate core-complex membership annotation for PSMB5.
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/PSMB5/PSMB5-deep-research-falcon.md
In the standard/constitutive proteasome, Ξ²5 is one of three catalytically active Ξ²-subunits (Ξ²1, Ξ²2, Ξ²5) and is responsible for the chymotrypsin-like (CT-L) activity.
GO:0004298 threonine-type endopeptidase activity
IEA
GO_REF:0000002 		ACCEPT
Summary: PSMB5 is the beta5 catalytic subunit of the constitutive 20S proteasome and carries the threonine-type endopeptidase active site.
Reason: The mature PSMB5 chain begins at Thr60, annotated as the nucleophilic active-site residue, and structural/activity studies support beta5 chymotrypsin-like proteasome activity.
Supporting Evidence:
file:human/PSMB5/PSMB5-deep-research-falcon.md
Proteasome catalytic Ξ² subunits operate via an N-terminal nucleophile mechanism centered on the N-terminal threonine (Thr1). Mechanistically, Thr1 attacks the scissile peptide bond carbonyl to form an acyl-enzyme intermediate, which is subsequently hydrolyzed to release products and regenerate the catalytic threonine.
GO:0005634 nucleus
IEA
GO_REF:0000044 		ACCEPT
Summary: nucleus is a core cellular context for the assembled proteasome containing PSMB5.
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:0005839 proteasome core complex
IEA
GO_REF:0000120 		ACCEPT
Summary: proteasome core complex is the appropriate core-complex membership annotation for PSMB5.
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/PSMB5/PSMB5-deep-research-falcon.md
The target gene PSMB5 (proteasome 20S subunit beta 5) encodes the constitutive catalytic Ξ²5 subunit of the 20S proteasome core particle (CP), which forms the proteolytic core of the 26S proteasome.
GO:0010498 proteasomal protein catabolic process
IEA
GO_REF:0000117 		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/PSMB5/PSMB5-deep-research-falcon.md
The eukaryotic 26S proteasome is the principal executor of ubiquitin–proteasome system (UPS) protein degradation.
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: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:15231747
A protein interaction framework for human mRNA degradation. 		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:20723761
Immunoproteasomes preserve protein homeostasis upon interfer... 		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:28514442
Architecture of the human interactome defines protein commun... 		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: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: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: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:40205054
Multimodal cell maps as a foundation for structural and func... 		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:0008233 peptidase activity
IEA
GO_REF:0000120 		MODIFY
Summary: peptidase activity is directionally related to the proteasome role but is less specific than the supported proteasome term.
Reason: Replace the broad annotation with threonine-type endopeptidase activity, which better captures the gene product role supported by proteasome literature and existing specific GOA annotations.
GO:0004298 threonine-type endopeptidase activity
IDA
PMID:27493187
The inhibition mechanism of human 20S proteasomes enables ne... 		ACCEPT
Summary: PSMB5 is the beta5 catalytic subunit of the constitutive 20S proteasome and carries the threonine-type endopeptidase active site.
Reason: The mature PSMB5 chain begins at Thr60, annotated as the nucleophilic active-site residue, and structural/activity studies support beta5 chymotrypsin-like proteasome activity.
Supporting Evidence:
file:human/PSMB5/PSMB5-deep-research-falcon.md
Ξ²5 (PSMB5) is assigned the CT-L activity, which preferentially cleaves peptide bonds after hydrophobic residues.
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 PSMB5.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
Supporting Evidence:
file:human/PSMB5/PSMB5-deep-research-falcon.md
The active sites are located on the inner surface of the 20S core, sequestered in the central catalytic chamber; access is controlled by Ξ±-ring gating and by association with regulatory particles such as the 19S cap (forming the 26S proteasome).
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 PSMB5.
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: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: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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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: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
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.
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.
Reason: The gene product is a core 20S proteasome subunit, so proteasomal protein catabolism is an appropriate core biological-process context.
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 PSMB5.
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 PSMB5.
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.
Supporting Evidence:
file:human/PSMB5/PSMB5-deep-research-falcon.md
Its 20S core particle is a barrel-like complex of four stacked heptameric rings (Ξ±/Ξ²/Ξ²/Ξ±). The active sites are located on the inner surface of the 20S core, sequestered in the central catalytic chamber.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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:0010499 proteasomal ubiquitin-independent protein catabolic process
TAS
Reactome:R-HSA-9912633 		ACCEPT
Summary: proteasomal ubiquitin-independent 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:0043248 proteasome assembly
TAS
Reactome:R-HSA-9907900 		KEEP AS NON CORE
Summary: PSMB5 maturation and incorporation are relevant to proteasome biogenesis, but assembly is not the mature subunit catalytic function.
Reason: Retain proteasome assembly as non-core context because PSMB5 has a propeptide and assembly dependencies, while the reviewed core function is beta5 proteolysis in the mature 20S core.
Supporting Evidence:
file:human/PSMB5/PSMB5-deep-research-falcon.md
Catalytic Ξ² subunits are synthesized with N-terminal propeptides that are removed by autolysis after correct assembly. The propeptides are described as being autolyzed between a glycine residue and a threonine residue, yielding the mature catalytic subunit with Thr1 at the N-terminus; Ξ²5 propeptides also contribute to proteasome assembly.
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 PSMB5.
Reason: The reviewed core function occurs in cytosolic and nuclear proteasome pools, supported by proteasome localization and nuclear-import evidence.
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:0004175 endopeptidase activity
TAS
Reactome:R-HSA-9912636 		MODIFY
Summary: endopeptidase activity is directionally related to the proteasome role but is less specific than the supported proteasome term.
Reason: Replace the broad annotation with threonine-type endopeptidase activity, which better captures the gene product role supported by proteasome literature and existing specific GOA annotations.
GO:0004175 endopeptidase activity
TAS
Reactome:R-HSA-9908101 		MODIFY
Summary: endopeptidase activity is directionally related to the proteasome role but is less specific than the supported proteasome term.
Reason: Replace the broad annotation with threonine-type endopeptidase activity, which better captures the gene product role supported by proteasome literature and existing specific GOA annotations.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1168640 		ACCEPT
Summary: cytosol is a core cellular context for the assembled proteasome containing PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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 PSMB5.
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:0006508 proteolysis
IDA
PMID:17540904
Regulation of CD8+ T cell development by thymus-specific pro... 		MODIFY
Summary: proteolysis 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:0008233 peptidase activity
IDA
PMID:17540904
Regulation of CD8+ T cell development by thymus-specific pro... 		MODIFY
Summary: peptidase activity is directionally related to the proteasome role but is less specific than the supported proteasome term.
Reason: Replace the broad annotation with threonine-type endopeptidase activity, which better captures the gene product role supported by proteasome literature and existing specific GOA annotations.
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: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 PSMB5.
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: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 PSMB5.
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:0019774 proteasome core complex, beta-subunit complex
ISS
GO_REF:0000024 		ACCEPT
Summary: proteasome core complex, beta-subunit complex is the appropriate core-complex membership annotation for PSMB5.
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

PSMB5 is the beta5 active-site subunit of the mature 20S proteasome core. Its N-terminal propeptide is removed during maturation, exposing Thr60 as the catalytic nucleophile. In the assembled proteasome, PSMB5 provides the chymotrypsin-like threonine endopeptidase activity used for proteasomal protein catabolism.

Molecular Function:
threonine-type endopeptidase activity
Directly Involved In:
proteasomal protein catabolic process proteasome-mediated ubiquitin-dependent protein catabolic process proteasomal ubiquitin-independent protein catabolic process
Cellular Locations:
cytosol nucleus
In Complex:
proteasome core complex, beta-subunit complex
Supporting Evidence:
  • PMID:23495936
    The Ξ²1, Ξ²2, and Ξ²5 subunits contain the proteolytic active sites
  • PMID:27176742
    The proteasome is a multicatalytic protease responsible for the degradation of misfolded proteins.
  • PMID:18565852
    marked changes in chymotrypsin-like proteasome activity
  • file:human/PSMB5/PSMB5-deep-research-falcon.md
    PSMB5 encodes the constitutive Ξ²5 catalytic subunit of the 20S proteasome core, providing the chymotrypsin-like proteolytic activity that preferentially cleaves after hydrophobic residues. Catalysis is mediated by an N-terminal Thr1 nucleophile exposed by propeptide autolysis during proteasome assembly. Ξ²5 resides within the interior catalytic chamber of the 20S/26S proteasome, functioning centrally in the UPS.

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:12032076
Properties of the hybrid form of the 26S proteasome containing both 19S and PA28 complexes.
PMID:12181345
Clastosome: a subtype of nuclear body enriched in 19S and 20S proteasomes, ubiquitin, and protein substrates of proteasome.
PMID:14733938
Protein-protein interactions among human 20S proteasome subunits and proteassemblin.
PMID:15231747
A protein interaction framework for human mRNA degradation.
PMID:17323924
Mass spectrometric characterization of the affinity-purified human 26S proteasome complex.
PMID:17540904
Regulation of CD8+ T cell development by thymus-specific proteasomes.
PMID:17948026
The proteasome maturation protein POMP facilitates major steps of 20S proteasome formation at the endoplasmic reticulum.
PMID:19056867
Large-scale proteomics and phosphoproteomics of urinary exosomes.
PMID:19489727
Recognition and processing of ubiquitin-protein conjugates by the proteasome.
PMID:20723761
Immunoproteasomes preserve protein homeostasis upon interferon-induced oxidative stress.
PMID:21630459
Proteomic characterization of the human sperm nucleus.
PMID:23706739
Acetylation-mediated proteasomal degradation of core histones during DNA repair and spermatogenesis.
PMID:27003159
Proteasome activators, PA28Ξ³ and PA200, play indispensable roles in male fertility.
PMID:27493187
The inhibition mechanism of human 20S proteasomes enables next-generation inhibitor design.
PMID:28514442
Architecture of the human interactome defines protein communities and disease networks.
PMID:29636472
Structural mechanism for nucleotide-driven remodeling of the AAA-ATPase unfoldase in the activated human 26S proteasome.
PMID:31380390
Regulation of Proteasome Activity by (Post-)transcriptional Mechanisms.
PMID:31473102
Characterization of Fully Recombinant Human 20S and 20S-PA200 Proteasome Complexes.
PMID:32134919
Cryo-EM structures of the human PA200 and PA200-20S complex reveal regulation of proteasome gate opening and two PA200 apertures.
PMID:32296183
A reference map of the human binary protein interactome.
PMID:32935661
Role of oncogenic REGΞ³ in cancer.
PMID:33729481
Proteasome in action: substrate degradation by the 26S proteasome.
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
PMID:34702852
The 20S as a stand-alone proteasome in cells can degrade the ubiquitin tag.
PMID:34711951
AKIRIN2 controls the nuclear import of proteasomes in vertebrates.
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human cellular organization.
PMID:35377789
Proteasome complexes experience profound structural and functional rearrangements throughout mammalian spermatogenesis.
PMID:35714770
Proteasome activator 28Ξ³ (PA28Ξ³) allosterically activates trypsin-like proteolysis by binding to the Ξ±-ring of the 20S proteasome.
PMID:35858375
Structural insights into the human PA28-20S proteasome enabled by efficient tagging and purification of endogenous proteins.
PMID:37228199
An abundance of free regulatory (19S) proteasome particles regulates neuronal synapses.
PMID:40205054
Multimodal cell maps as a foundation for structural and functional genomics.
PMID:8811196
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-9907900
Proteasome assembly
Reactome:R-HSA-9907919
Formation of the preholoproteasome
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-9912633
Antigen processing: Ub, ATP-independent proteasomal degradation
Reactome:R-HSA-9912636
Proteasomal cleavage of intracellular substrate (PA28-alpha-beta-20S proteasome 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
PMID:23495936
Molecular architecture and assembly of the eukaryotic proteasome.
PMID:27176742
Human 20S proteasome activity towards fluorogenic peptides of various chain lengths.
PMID:18565852
Molecular basis of bortezomib resistance: proteasome subunit beta5 (PSMB5) gene mutation and overexpression of PSMB5 protein.
PMID:18502982
Point mutation of the proteasome beta5 subunit gene is an important mechanism of bortezomib resistance in bortezomib-selected variants of Jurkat T cell lymphoblastic lymphoma/leukemia line.
file:human/PSMB5/PSMB5-deep-research-falcon.md
Falcon deep research on PSMB5 (Edison Scientific Literature)
  • PSMB5 encodes the constitutive catalytic beta5 subunit of the 20S proteasome core particle, one of the three catalytically active beta subunits (beta1, beta2, beta5) and part of the 26S proteasome; it provides the chymotrypsin-like (CT-L) activity.
    "The target gene PSMB5 (proteasome 20S subunit beta 5) encodes the constitutive catalytic Ξ²5 subunit of the 20S proteasome core particle (CP), which forms the proteolytic core of the 26S proteasome. In the standard/constitutive proteasome, Ξ²5 is one of three catalytically active Ξ²-subunits (Ξ²1, Ξ²2, Ξ²5) and is responsible for the chymotrypsin-like (CT-L) activity."
  • The CT-L activity of beta5 preferentially cleaves peptide bonds after hydrophobic residues.
    "Ξ²5 (PSMB5) is assigned the CT-L activity, which preferentially cleaves peptide bonds after hydrophobic residues."
  • Catalysis uses an N-terminal threonine (Thr1) nucleophile mechanism typical of Ntn hydrolases; Thr1 attacks the scissile peptide bond to form an acyl-enzyme intermediate that is then hydrolyzed.
    "Proteasome catalytic Ξ² subunits operate via an N-terminal nucleophile mechanism centered on the N-terminal threonine (Thr1). Mechanistically, Thr1 attacks the scissile peptide bond carbonyl to form an acyl-enzyme intermediate, which is subsequently hydrolyzed to release products and regenerate the catalytic threonine."
  • Catalytic beta subunits are made with N-terminal propeptides removed by autolysis between a glycine and a threonine residue, exposing the mature Thr1; beta5 propeptide also contributes to 20S assembly.
    "Catalytic Ξ² subunits are synthesized with N-terminal propeptides that are removed by autolysis after correct assembly. The propeptides are described as being autolyzed between a glycine residue and a threonine residue, yielding the mature catalytic subunit with Thr1 at the N-terminus; Ξ²5 propeptides also contribute to proteasome assembly."
  • The beta5 active sites are buried inside the central catalytic chamber of the barrel-shaped 20S core (alpha-beta-beta-alpha arrangement); the 26S proteasome degrades ubiquitin-tagged cytosolic proteins with access controlled by regulatory caps and gates.
    "The active sites are located on the inner surface of the 20S core, sequestered in the central catalytic chamber; access is controlled by Ξ±-ring gating and by association with regulatory particles such as the 19S cap (forming the 26S proteasome)."
  • Proteasome proteolysis contributes to MHC class I antigen presentation; proteasome subtype composition shifts cleavage preferences and the peptide repertoire loaded onto MHC I.
    "proteasome proteolysis contributes to MHC class I antigen presentation by generating peptides that can be transported into the ER and loaded onto MHC I. Proteasome subtype composition (standard vs immunoproteasome and intermediates) shifts cleavage preferences."
  • PSMB5/beta5 is the dominant catalytic drug target; clinically successful proteasome inhibitors (bortezomib, carfilzomib, ixazomib) largely exploit the beta5/CT-L site, and resistance includes beta5 active-site mutations (A49T, A50V, C52F) and non-mutational rewiring such as PSMB5 upregulation and compensatory autophagy.
    "Clinically successful proteasome inhibitors largely exploit the Ξ²5/CT-L site... PI resistance can also arise through PSMB5 upregulation/subunit replacement and compensatory autophagy."

Suggested Questions for Experts

Q: When should broad peptidase annotations on catalytic proteasome beta subunits be replaced by threonine-type endopeptidase activity in GOA cleanup?

Suggested experts: Schrader J, Chari A, Drag M

Suggested Experiments

Experiment: Compare PSMB5 active-site or inhibitor-pocket mutants with PSMA1 alpha-ring interface mutants in matched cells or purified complexes, measuring chymotrypsin-like, caspase-like, and trypsin-like proteasome activities separately.

Hypothesis: PSMB5-specific perturbations should affect chymotrypsin-like proteasome activity more directly than non-catalytic alpha-ring subunit perturbations.

Type: comparative mutagenesis and proteasome activity profiling

Deep Research

Falcon

(PSMB5-deep-research-falcon.md)
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 40 citations 2 artifacts 2026-05-30T00:29:30.333812
Edison artifact artifact-00 (text/markdown)
## Context ID: pqac-00000011 The requested information can be found in Figures 1 and 2 of the document. Figure 1 (page 2) provides a schematic of the 20S protea (image/png)

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 PSMB5 (UniProt P28074)β€”functional annotation and translational relevance

Scope and identity verification

The target gene PSMB5 (proteasome 20S subunit beta 5) encodes the constitutive catalytic Ξ²5 subunit of the 20S proteasome core particle (CP), which forms the proteolytic core of the 26S proteasome. In the standard/constitutive proteasome, Ξ²5 is one of three catalytically active Ξ²-subunits (Ξ²1, Ξ²2, Ξ²5) and is responsible for the chymotrypsin-like (CT-L) activity. Older nomenclature includes the alias LMPX. (habib2022functionaldifferencesbetween pages 3-4, wang2025thedyt6dystonia pages 1-2, tychhon2023theprognosticvalue pages 1-2)

Note on UniProt cross-verification: The UniProt accession P28074 was provided by the user; the retrieved peer-reviewed sources in this run validate that human PSMB5 encodes the constitutive Ξ²5 proteasome catalytic subunit with the expected catalytic activities and maturation mechanism, but they do not explicitly cite the UniProt accession number. The functional identity is therefore verified by concordant molecular description rather than direct accession citation. (habib2022functionaldifferencesbetween pages 3-4, tychhon2023theprognosticvalue pages 1-2)

1) Key concepts and definitions (current understanding)

The proteasome and the Ξ²5 (PSMB5) catalytic site

The eukaryotic 26S proteasome is the principal executor of ubiquitin–proteasome system (UPS) protein degradation. Its 20S core particle is a barrel-like complex of four stacked heptameric rings (Ξ±/Ξ²/Ξ²/Ξ±). The active sites are located on the inner surface of the 20S core, sequestered in the central catalytic chamber; access is controlled by Ξ±-ring gating and by association with regulatory particles such as the 19S cap (forming the 26S proteasome). (nowak2024experimentalinvestigationson pages 23-27, pelon2024factorsdeterminingthe pages 1-2, habib2022functionaldifferencesbetween media d4ef57f2)

Within the 20S Ξ² rings, Ξ²1, Ξ²2, and Ξ²5 are the three catalytically active Ξ²-subunits. Ξ²5 (PSMB5) is assigned the CT-L activity, which preferentially cleaves peptide bonds after hydrophobic residues. (nowak2024experimentalinvestigationson pages 23-27, habib2022functionaldifferencesbetween pages 3-4, pelon2024factorsdeterminingthe pages 1-2)

A schematic depiction of the 20S architecture and the assignment of cleavage activities to Ξ²1/Ξ²2/Ξ²5 (including Ξ²5 = CT-L) is shown in the review figures retrieved from Habib et al. (Cells, 2022). (habib2022functionaldifferencesbetween media d4ef57f2, habib2022functionaldifferencesbetween media dbc3a546)

Catalytic mechanism: N-terminal threonine protease (Ntn hydrolase)

Proteasome catalytic Ξ² subunits operate via an N-terminal nucleophile mechanism centered on the N-terminal threonine (Thr1). Mechanistically, Thr1 attacks the scissile peptide bond carbonyl to form an acyl-enzyme intermediate, which is subsequently hydrolyzed to release products and regenerate the catalytic threonine. (habib2022functionaldifferencesbetween pages 13-15, fernandes2024decodingthesecrets pages 1-2)

Substrate specificity and cleavage products (quantitative behavior)

Proteasomal cleavage generates peptide products on the order of ~5–18 amino acids (reviewed in the myeloma-focused pharmacology review) (pelon2024factorsdeterminingthe pages 1-2), with a reported mean peptide length ~6–9 residues in a proteasome biology dissertation (nowak2024experimentalinvestigationson pages 23-27). The proteasome is also described as directly cleaving only ~10–15% of peptide bonds in proteins (with further trimming by cellular peptidases). (nowak2024experimentalinvestigationson pages 23-27)

Maturation and assembly: propeptide removal exposes Thr1

Catalytic Ξ² subunits are synthesized with N-terminal propeptides that are removed by autolysis after correct assembly. The propeptides are described as being autolyzed between a glycine residue and a threonine residue, yielding the mature catalytic subunit with Thr1 at the N-terminus; Ξ²5 propeptides also contribute to proteasome assembly. (habib2022functionaldifferencesbetween pages 3-4)

Pathway context: UPS and antigen presentation

Beyond bulk proteostasis, proteasome proteolysis contributes to MHC class I antigen presentation by generating peptides that can be transported into the ER and loaded onto MHC I. Proteasome subtype composition (standard vs immunoproteasome and intermediates) shifts cleavage preferences, influencing production of peptides with hydrophobic/basic C-termini favored by MHC I. (habib2022functionaldifferencesbetween pages 1-3, habib2022functionaldifferencesbetween pages 13-15)

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

2.1 2024: Structural/computational analysis of Ξ²5 resistance mutations

A 2024 Frontiers in Chemistry study used molecular dynamics and docking to analyze mutations in the Ξ²5 (PSMB5) active-site region relevant to proteasome inhibitor binding. The Ξ²5 CT-L S1 pocket was described as involving residues Ala20, Met45, Ala49, and Cys52, and the study explicitly modeled A49T, A50V, and C52F substitutions. The authors report that Cys52Phe (C52F) β€œcritically impacts protein–ligand binding,” supporting a plausible resistance mechanism through reduced inhibitor affinity. (2024-01; https://doi.org/10.3389/fchem.2023.1322628) (fernandes2024decodingthesecrets pages 1-2)

This work is important because it provides an analytically reproducible workflow to anticipate how active-site mutations in PSMB5 could alter inhibitor engagementβ€”useful for interpreting resistance genotypes and prioritizing next-generation inhibitors. (fernandes2024decodingthesecrets pages 1-2)

2.2 2023–2024: Systems-level view of proteasome inhibitor sensitivity/resistance in myeloma

A 2024 Frontiers in Pharmacology review emphasizes that sensitivity to proteasome inhibitors in multiple myeloma depends on multiple cellular factors, including proteasome composition/subunit expression, proteasome loading, metabolic adaptation, and transcriptional/epigenetic programs, with Ξ²5 being the CT-L catalytic subunit. (2024-03; https://doi.org/10.3389/fphar.2024.1351565) (pelon2024factorsdeterminingthe pages 1-2)

A 2023 Frontiers in Immunology review on clonal evolution in multiple myeloma highlights drug-resistance mechanisms, explicitly including point mutations affecting PSMB5 or other proteasome components. (2023-09; https://doi.org/10.3389/fimmu.2023.1243997) (fernandes2024decodingthesecrets pages 1-2)

2.3 2023: Combination strategies exploiting compensatory proteostasis (autophagy)

In a 2023 PLOS ONE study, clarithromycin was reported to overcome stromal cell-mediated resistance to proteasome inhibitors in myeloma cells by blocking autophagy flux (thereby sustaining pro-apoptotic NOXA), supporting the broader concept that PI resistance can be buffered by alternative protein disposal routes (autophagy) and that co-targeting can restore efficacy. (2023-12; https://doi.org/10.1371/journal.pone.0295273) (fernandes2024decodingthesecrets pages 1-2)

3) Current applications and real-world implementations

3.1 PSMB5 as a validated drug target (Ξ²5/CT-L site)

Clinically successful proteasome inhibitors largely exploit the Ξ²5/CT-L site:
- Bortezomib is described as a reversible inhibitor of the chymotrypsin-like activity that binds the 20S Ξ²5 subunit (PSMB5) and was first FDA-approved in 2003 for multiple myeloma; it is also used in other malignancies. (2023-07; https://doi.org/10.3389/fmed.2023.1209425) (tychhon2023theprognosticvalue pages 1-2)
- Carfilzomib (epoxyketone) is described as an irreversible CT-L inhibitor, and Ixazomib as an approved oral proteasome inhibitor used in myeloma; a recent review provides approval dates of 2012 (carfilzomib) and 2015 (ixazomib). (2026-05; https://doi.org/10.3389/fphar.2026.1806787) (zhao2026targetingtheproteasome pages 5-6)

Mechanistically, inhibitor classes covalently engage the Ξ²-subunit Thr1 nucleophile via distinct chemistries (boronates, epoxyketones, Ξ²-lactones), explaining the centrality of Thr1 and Ξ²5 pocket residues in pharmacology and resistance. (https://doi.org/10.26434/chemrxiv-2025-v5w42) (rahimi2025theevolutionand pages 18-21)

3.2 Disease association and therapeutic maturity (database synthesis)

OpenTargets lists an association between PSMB5 and multiple myeloma, with supporting clinical-stage evidence including approval-stage links and a phase 4 trial identifier among the evidence rows, consistent with the mature clinical use of Ξ²5-directed proteasome inhibitors in myeloma. (OpenTargets Search: multiple myeloma,plasma cell myeloma,cancer-PSMB5)

4) Expert opinions and analysis (authoritative perspectives)

Why Ξ²5 (PSMB5) is the dominant catalytic drug target

Expert reviews emphasize that Ξ²5/CT-L is a primary pharmacologic target because inhibition of this activity strongly suppresses proteasomal degradation capacity. The 2024 Frontiers in Chemistry study underscores the functional importance of Ξ²5 and structurally rationalizes how mutations in and around the S1 pocket could reduce drug binding. (fernandes2024decodingthesecrets pages 1-2)

Resistance is multifactorial: mutations plus adaptive proteostasis

A key modern viewpoint emerging from myeloma-focused literature is that resistance is not purely genetic at PSMB5: it can also arise from altered expression of proteasome subunits, altered proteasome loading, metabolic rewiring, and use of compensatory proteolysis pathways such as autophagyβ€”hence the therapeutic interest in combination strategies. (pelon2024factorsdeterminingthe pages 1-2, fernandes2024decodingthesecrets pages 1-2, plakoula2025prognosticvalueof pages 18-20)

5) Relevant statistics and data (recent studies)

5.1 Patient cohort statistics linking PSMB5 to outcome in PI-treated myeloma

A 2025 study measured PSMB5 protein, proteasome proteolytic activity (PPA), autophagy markers, and ROS in bone marrow mononuclear cells from 110 multiple myeloma patients sampled at baseline, remission, and relapse. Key reported statistics include:
- PSMB5 accumulation decreased after PI treatment (p = 0.014), and PPA decreased (p < 0.001). (2025-01; https://doi.org/10.3390/cimb47010032) (plakoula2025prognosticvalueof pages 1-2)
- LC3II was higher at remission and relapse vs baseline (p = 0.041), consistent with altered autophagy in the treated disease course. (plakoula2025prognosticvalueof pages 1-2)
- ROS in plasma cells was higher at relapse (p < 0.001). (plakoula2025prognosticvalueof pages 1-2)
- A baseline PSMB5 cutoff of 1.06 units stratified disease-free survival: 12.0 Β± 6.7 vs 36 Β± 12.1 months (p < 0.001). (plakoula2025prognosticvalueof pages 1-2)

These data support a clinically meaningful link between PSMB5 levels/proteasome activity and myeloma trajectory under PI therapy, and they align with mechanistic models where diminished proteasome reliance may be compensated by autophagy in resistant disease. (plakoula2025prognosticvalueof pages 1-2)

5.2 Quantitative properties of proteasome proteolysis relevant to Ξ²5

Proteasome-generated peptides are reported as ~5–18 aa (review) (pelon2024factorsdeterminingthe pages 1-2) with an average of ~6–9 residues in another synthesis (nowak2024experimentalinvestigationson pages 23-27). The proteasome is described as directly cleaving only ~10–15% of peptide bonds in substrates (the remainder subsequently trimmed). (nowak2024experimentalinvestigationson pages 23-27)

Evidence map (table)

The following table summarizes the major functional-annotation claims and their supporting sources (including URLs and dates where available in the underlying papers).

Aspect Key points (concise) Evidence type (review/primary/computational/patient cohort/database) Key citations (pqac ids) Publication year(s) and URL(s) when available
Identity / complex membership Human PSMB5 encodes the constitutive 20S proteasome Ξ²5 catalytic subunit (older alias LMPX), one of the three active Ξ² subunits in the 20S core and part of the 26S proteasome. Review; primary; database (habib2022functionaldifferencesbetween pages 3-4, wang2025thedyt6dystonia pages 1-2, tychhon2023theprognosticvalue pages 1-2, OpenTargets Search: multiple myeloma,plasma cell myeloma,cancer-PSMB5) 2022, https://doi.org/10.3390/cells11030421; 2025, https://doi.org/10.1038/s41467-025-56867-x; 2023, https://doi.org/10.3389/fmed.2023.1209425; OpenTargets context: multiple myeloma association (OpenTargets Search: multiple myeloma,plasma cell myeloma,cancer-PSMB5)
Catalytic activity & substrate specificity Ξ²5 provides the chymotrypsin-like (CT-L) activity of the proteasome and preferentially cleaves after hydrophobic residues; Ξ²5 can also display branched/small neutral amino-acid preferences in some analyses. Review; dissertation/research synthesis (nowak2024experimentalinvestigationson pages 23-27, habib2022functionaldifferencesbetween pages 3-4, habib2022functionaldifferencesbetween pages 4-5, pelon2024factorsdeterminingthe pages 1-2) 2024, https://doi.org/10.5282/edoc.33581; 2022, https://doi.org/10.3390/cells11030421; 2024, https://doi.org/10.3389/fphar.2024.1351565
Catalytic mechanism (Thr1) Proteolysis uses the N-terminal Thr1 nucleophile; Thr1 hydroxyl attacks the peptide carbonyl to form an acyl-enzyme intermediate, later hydrolyzed to release products. Review; computationally framed structural study (habib2022functionaldifferencesbetween pages 13-15, fernandes2024decodingthesecrets pages 1-2) 2022, https://doi.org/10.3390/cells11030421; 2024, https://doi.org/10.3389/fchem.2023.1322628
Maturation / propeptide processing Catalytic Ξ² subunits are synthesized with propeptides that are autolyzed between Gly and Thr, exposing active Thr1; Ξ²5 propeptide also contributes to 20S assembly. Review (habib2022functionaldifferencesbetween pages 3-4) 2022, https://doi.org/10.3390/cells11030421
Localization & proteasome architecture Ξ²5 active sites are buried inside the central chamber of the barrel-shaped 20S core (Ξ±Ξ²Ξ²Ξ± arrangement); 26S proteasome degrades ubiquitin-tagged cytosolic proteins and access is controlled by regulatory caps/gates. Review; dissertation/research synthesis (nowak2024experimentalinvestigationson pages 23-27, pelon2024factorsdeterminingthe pages 1-2, habib2022functionaldifferencesbetween media d4ef57f2) 2024, https://doi.org/10.5282/edoc.33581; 2024, https://doi.org/10.3389/fphar.2024.1351565; figure context from 2022 review: https://doi.org/10.3390/cells11030421
Role in antigen presentation Proteasome cleavage products feed MHC class I antigen presentation; proteasome subtype composition changes cleavage preferences and peptide repertoire, with Ξ²5/Ξ²5i activity shaping hydrophobic C-termini favored for MHC-I loading. Review (habib2022functionaldifferencesbetween pages 1-3, habib2022functionaldifferencesbetween pages 13-15) 2022, https://doi.org/10.3390/cells11030421
Proteasome inhibitor targeting (bortezomib/carfilzomib/ixazomib) & approval years Approved proteasome inhibitors clinically exploit Ξ²5/CT-L activity: bortezomib binds/inhibits Ξ²5 and was first FDA-approved in 2003; carfilzomib irreversibly targets CT-L/Ξ²5 and was approved in 2012; ixazomib is the first oral PI, approved in 2015. Bortezomib forms covalent interactions via Thr1; carfilzomib is an epoxyketone CT-L inhibitor. Review; clinical/translational review (tychhon2023theprognosticvalue pages 1-2, rahimi2025theevolutionand pages 23-25, zhao2026targetingtheproteasome pages 5-6, rahimi2025theevolutionand pages 18-21) 2023, https://doi.org/10.3389/fmed.2023.1209425; 2025, https://doi.org/10.26434/chemrxiv-2025-v5w42; 2026, https://doi.org/10.3389/fphar.2026.1806787
Resistance mutations (A49T/A50V/C52F) & effects Active-site pocket mutations A49T, A50V, C52F in Ξ²5/PSMB5 are linked to PI resistance models; 2024 MD/docking analysis predicted C52F most strongly disrupts ligand binding. A49T is also shown structurally in Ξ²5-bound BTZ models. Computational structural study; review (fernandes2024decodingthesecrets pages 1-2, zhao2026targetingtheproteasome pages 5-6) 2024, https://doi.org/10.3389/fchem.2023.1322628; 2026, https://doi.org/10.3389/fphar.2026.1806787
Non-mutational resistance (upregulation, autophagy shift) PI resistance can also arise through PSMB5 upregulation/subunit replacement and compensatory autophagy. In MM, post-treatment PSMB5 reduction with increased LC3II supports a shift from proteasomal to autophagic degradation; reviews also cite PSMB5 overexpression as a resistance mechanism. Patient cohort; review; translational review (plakoula2025prognosticvalueof pages 18-20, zhao2026targetingtheproteasome pages 3-5, plakoula2025prognosticvalueof pages 1-2) 2025, https://doi.org/10.3390/cimb47010032; 2026, https://doi.org/10.3389/fphar.2026.1806787
Quantitative statistics Reported proteasome product lengths: ~5–18 aa or mean ~6–9 aa; proteasome directly cleaves ~10–15% of peptide bonds. In a 110-patient MM cohort, post-PI PSMB5 decreased (p=0.014), proteasome activity decreased (p<0.001), LC3II increased (p=0.041), relapse ROS increased (p<0.001), and baseline PSMB5 cutoff 1.06 associated with disease-free survival 12.0 Β± 6.7 vs 36 Β± 12.1 months (p<0.001). Review; dissertation/research synthesis; patient cohort (nowak2024experimentalinvestigationson pages 23-27, pelon2024factorsdeterminingthe pages 1-2, plakoula2025prognosticvalueof pages 1-2) 2024, https://doi.org/10.5282/edoc.33581; 2024, https://doi.org/10.3389/fphar.2024.1351565; 2025, https://doi.org/10.3390/cimb47010032
Disease associations (OpenTargets multiple myeloma) OpenTargets lists PSMB5–multiple myeloma association with clinical-stage evidence, including approval-stage and phase 4 links; this aligns with real-world therapeutic targeting of the Ξ²5 site in myeloma. Database (OpenTargets Search: multiple myeloma,plasma cell myeloma,cancer-PSMB5) OpenTargets context retrieved in this session (multiple myeloma association for PSMB5)

Table: This table condenses the main functional annotation findings for human PSMB5, including core enzymology, proteasome context, therapeutic targeting, resistance mechanisms, and quantitative clinical data. It is useful as a quick-reference evidence map linking each annotation point to specific cited contexts.

Summary of primary functional annotation for PSMB5 (human)

PSMB5 encodes the constitutive Ξ²5 catalytic subunit of the 20S proteasome core, providing the chymotrypsin-like proteolytic activity that preferentially cleaves after hydrophobic residues. Catalysis is mediated by an N-terminal Thr1 nucleophile exposed by propeptide autolysis during proteasome assembly. Ξ²5 resides within the interior catalytic chamber of the 20S/26S proteasome, functioning centrally in the UPS and influencing peptide repertoires for antigen presentation. Its pharmacologic importance is underscored by multiple FDA-approved proteasome inhibitors that act primarily via Ξ²5/CT-L inhibition and by resistance mechanisms that include Ξ²5 active-site mutations (A49T/A50V/C52F) and adaptive non-mutational proteostasis rewiring. (nowak2024experimentalinvestigationson pages 23-27, habib2022functionaldifferencesbetween pages 3-4, pelon2024factorsdeterminingthe pages 1-2, habib2022functionaldifferencesbetween pages 13-15, fernandes2024decodingthesecrets pages 1-2, tychhon2023theprognosticvalue pages 1-2, zhao2026targetingtheproteasome pages 5-6)

References

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  2. (wang2025thedyt6dystonia pages 1-2): Yan Wang, Yi Wang, Tomohiro Iriki, Eiichi Hashimoto, Maki Inami, Sota Hashimoto, Ayako Watanabe, Hiroshi Takano, Ryo Motosugi, Shoshiro Hirayama, Hiroki Sugishita, Yukiko Gotoh, Ryoji Yao, Jun Hamazaki, and Shigeo Murata. The dyt6 dystonia causative protein thap1 is responsible for proteasome activity via psmb5 transcriptional regulation. Nature Communications, Feb 2025. URL: https://doi.org/10.1038/s41467-025-56867-x, doi:10.1038/s41467-025-56867-x. This article has 7 citations and is from a highest quality peer-reviewed journal.

  3. (tychhon2023theprognosticvalue pages 1-2): Boranai Tychhon, Jesse C. Allen, Mayra A. Gonzalez, Idaly M. Olivas, Jonathan P. Solecki, Mehrshad Keivan, Vanessa V. Velazquez, Emily B. McCall, Desiree N. Tapia, Andres J. Rubio, Connor Jordan, David Elliott, and Anna M. Eiring. The prognostic value of 19s atpase proteasome subunits in acute myeloid leukemia and other forms of cancer. Frontiers in Medicine, Jul 2023. URL: https://doi.org/10.3389/fmed.2023.1209425, doi:10.3389/fmed.2023.1209425. This article has 9 citations.

  4. (nowak2024experimentalinvestigationson pages 23-27): Johannes Nowak. Experimental investigations on the role of the immunoproteasome in lung fibrogenesis. Dissertation, Jan 2024. URL: https://doi.org/10.5282/edoc.33581, doi:10.5282/edoc.33581. This article has 0 citations.

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  6. (habib2022functionaldifferencesbetween media d4ef57f2): Joanna Abi Habib, Julie Lesenfants, Nathalie Vigneron, and Benoit J. Van den Eynde. Functional differences between proteasome subtypes. Cells, 11:421, Jan 2022. URL: https://doi.org/10.3390/cells11030421, doi:10.3390/cells11030421. This article has 104 citations.

  7. (habib2022functionaldifferencesbetween media dbc3a546): Joanna Abi Habib, Julie Lesenfants, Nathalie Vigneron, and Benoit J. Van den Eynde. Functional differences between proteasome subtypes. Cells, 11:421, Jan 2022. URL: https://doi.org/10.3390/cells11030421, doi:10.3390/cells11030421. This article has 104 citations.

  8. (habib2022functionaldifferencesbetween pages 13-15): Joanna Abi Habib, Julie Lesenfants, Nathalie Vigneron, and Benoit J. Van den Eynde. Functional differences between proteasome subtypes. Cells, 11:421, Jan 2022. URL: https://doi.org/10.3390/cells11030421, doi:10.3390/cells11030421. This article has 104 citations.

  9. (fernandes2024decodingthesecrets pages 1-2): Pedro M. P. Fernandes, Romina A. Guedes, Bruno L. Victor, Jorge A. R. Salvador, and Rita C. Guedes. Decoding the secrets: how conformational and structural regulators inhibit the human 20s proteasome. Frontiers in Chemistry, Jan 2024. URL: https://doi.org/10.3389/fchem.2023.1322628, doi:10.3389/fchem.2023.1322628. This article has 4 citations.

  10. (habib2022functionaldifferencesbetween pages 1-3): Joanna Abi Habib, Julie Lesenfants, Nathalie Vigneron, and Benoit J. Van den Eynde. Functional differences between proteasome subtypes. Cells, 11:421, Jan 2022. URL: https://doi.org/10.3390/cells11030421, doi:10.3390/cells11030421. This article has 104 citations.

  11. (zhao2026targetingtheproteasome pages 5-6): Xiu‐Li Zhao, Shanshan Liu, Xinrui Zeng, Yu-Rou Liao, Mao Zhang, Qiang Wang, Dan Zhang, Qifeng Chen, Miao Xian, and Yong Qin. Targeting the proteasome in cancer therapy: development and future opportunities in natural products. Frontiers in Pharmacology, May 2026. URL: https://doi.org/10.3389/fphar.2026.1806787, doi:10.3389/fphar.2026.1806787. This article has 0 citations.

  12. (rahimi2025theevolutionand pages 18-21): Najmeh Rahimi. The evolution and diversification of proteasome inhibitors in cancer and beyond. ChemRxiv, Jun 2025. URL: https://doi.org/10.26434/chemrxiv-2025-v5w42, doi:10.26434/chemrxiv-2025-v5w42. This article has 2 citations.

  13. (OpenTargets Search: multiple myeloma,plasma cell myeloma,cancer-PSMB5): Open Targets Query (multiple myeloma,plasma cell myeloma,cancer-PSMB5, 2 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

  14. (plakoula2025prognosticvalueof pages 18-20): Eva Plakoula, Georgios Kalampounias, Spyridon Alexis, Evgenia Verigou, Alexandra Kourakli, Kalliopi Zafeiropoulou, and Argiris Symeonidis. Prognostic value of psmb5 and correlations with lc3ii and reactive oxygen species levels in the bone marrow mononuclear cells of bortezomib-resistant multiple myeloma patients. Current Issues in Molecular Biology, 47:32, Jan 2025. URL: https://doi.org/10.3390/cimb47010032, doi:10.3390/cimb47010032. This article has 3 citations.

  15. (plakoula2025prognosticvalueof pages 1-2): Eva Plakoula, Georgios Kalampounias, Spyridon Alexis, Evgenia Verigou, Alexandra Kourakli, Kalliopi Zafeiropoulou, and Argiris Symeonidis. Prognostic value of psmb5 and correlations with lc3ii and reactive oxygen species levels in the bone marrow mononuclear cells of bortezomib-resistant multiple myeloma patients. Current Issues in Molecular Biology, 47:32, Jan 2025. URL: https://doi.org/10.3390/cimb47010032, doi:10.3390/cimb47010032. This article has 3 citations.

  16. (habib2022functionaldifferencesbetween pages 4-5): Joanna Abi Habib, Julie Lesenfants, Nathalie Vigneron, and Benoit J. Van den Eynde. Functional differences between proteasome subtypes. Cells, 11:421, Jan 2022. URL: https://doi.org/10.3390/cells11030421, doi:10.3390/cells11030421. This article has 104 citations.

  17. (rahimi2025theevolutionand pages 23-25): Najmeh Rahimi. The evolution and diversification of proteasome inhibitors in cancer and beyond. ChemRxiv, Jun 2025. URL: https://doi.org/10.26434/chemrxiv-2025-v5w42, doi:10.26434/chemrxiv-2025-v5w42. This article has 2 citations.

  18. (zhao2026targetingtheproteasome pages 3-5): Xiu‐Li Zhao, Shanshan Liu, Xinrui Zeng, Yu-Rou Liao, Mao Zhang, Qiang Wang, Dan Zhang, Qifeng Chen, Miao Xian, and Yong Qin. Targeting the proteasome in cancer therapy: development and future opportunities in natural products. Frontiers in Pharmacology, May 2026. URL: https://doi.org/10.3389/fphar.2026.1806787, doi:10.3389/fphar.2026.1806787. This article has 0 citations.

Artifacts

Citations

  1. pelon2024factorsdeterminingthe pages 1-2
  2. nowak2024experimentalinvestigationson pages 23-27
  3. habib2022functionaldifferencesbetween pages 3-4
  4. fernandes2024decodingthesecrets pages 1-2
  5. tychhon2023theprognosticvalue pages 1-2
  6. zhao2026targetingtheproteasome pages 5-6
  7. rahimi2025theevolutionand pages 18-21
  8. plakoula2025prognosticvalueof pages 1-2
  9. habib2022functionaldifferencesbetween pages 13-15
  10. habib2022functionaldifferencesbetween pages 1-3
  11. plakoula2025prognosticvalueof pages 18-20
  12. habib2022functionaldifferencesbetween pages 4-5
  13. rahimi2025theevolutionand pages 23-25
  14. zhao2026targetingtheproteasome pages 3-5
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  16. https://doi.org/10.3389/fphar.2024.1351565
  17. https://doi.org/10.3389/fimmu.2023.1243997
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πŸ“š Additional Documentation

Notes

(PSMB5-notes.md)

PSMB5 notes

PSMB5 encodes proteasome subunit beta type-5, the constitutive beta5 catalytic
subunit of the 20S proteasome core. Unlike PSMA1, PSMB5 should receive direct
enzyme-function attribution because it carries the mature beta5 active site.

Evidence summary:

  • The eukaryotic 26S proteasome contains a 20S core particle of 28 subunits capped
    by 19S regulatory particles PMID:23495936.
  • The beta1, beta2, and beta5 subunits carry the core proteolytic active sites
    PMID:23495936.
  • PSMB5's UniProt feature table identifies residues 1-59 as a removed propeptide and
    Thr60 as the nucleophilic active site [genes/human/PSMB5/PSMB5-uniprot.txt
    "ACT_SITE 60"].
  • Human 20S proteasome activity assays support multicatalytic protease activity
    PMID:27176742.
  • Structural and inhibitor studies support beta5 chymotrypsin-like activity and
    inhibitor-pocket interpretation [PMID:18565852 "marked changes in chymotrypsin-like
    proteasome activity"; PMID:25599644 "selectivity for chymotrypsin-like sites"].
  • AKIRIN2-mediated nuclear import supports nuclear localization/active-location
    annotations for assembled proteasomes PMID:34711951.

Curation decisions:

  • Accept threonine-type endopeptidase activity as the core molecular function.
  • Modify broader peptidase/endopeptidase/proteolysis annotations to the more specific
    threonine-type endopeptidase or proteasomal protein catabolic process terms.
  • Accept specific 20S beta/core complex membership annotations.
  • Keep cytosol, cytoplasm, nucleus, nucleoplasm, and other localization annotations as
    non-core context.
  • Keep proteasome assembly as non-core context: PSMB5 maturation and incorporation are
    real, but the mature gene product's main role is beta5 proteolysis.
  • Mark generic protein binding and pathway-level exports such as DNA repair, apoptosis,
    spermatogenesis, and immune response as over-annotated for the individual PSMB5
    subunit.

πŸ“„ View Raw YAML

 
id: P28074
gene_symbol: PSMB5
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: PSMB5 encodes proteasome subunit beta type-5, the constitutive beta5
  catalytic subunit of the human 20S proteasome core. After removal of its N-terminal
  propeptide, the mature chain begins with Thr60, the nucleophilic active-site residue
  that supports chymotrypsin-like threonine endopeptidase activity. PSMB5 therefore
  carries catalytic protease function as a member of the 20S/26S proteasome, in contrast
  to non-catalytic structural subunits such as PSMA1.
alternative_products:
- name: '1'
  id: P28074-1
- name: '2'
  id: P28074-2
  sequence_note: VSP_041263
- name: '3'
  id: P28074-3
  sequence_note: VSP_045686
existing_annotations:
- 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.
  qualifier: involved_in
- 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
      PSMB5.
    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:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: cytosol is a core cellular context for the assembled proteasome containing
      PSMB5.
    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:0004175
    label: endopeptidase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: endopeptidase activity is directionally related to the proteasome role
      but is less specific than the supported proteasome term.
    action: MODIFY
    reason: Replace the broad annotation with threonine-type endopeptidase activity,
      which better captures the gene product role supported by proteasome literature
      and existing specific GOA annotations.
    proposed_replacement_terms:
    - id: GO:0004298
      label: threonine-type endopeptidase activity
    supported_by:
    - reference_id: file:human/PSMB5/PSMB5-deep-research-falcon.md
      supporting_text: >-
        Within the 20S Ξ² rings, Ξ²1, Ξ²2, and Ξ²5 are the three catalytically
        active Ξ²-subunits. Ξ²5 (PSMB5) is assigned the CT-L activity, which
        preferentially cleaves peptide bonds after hydrophobic residues.
      reference_section_type: RESULTS
  qualifier: enables
- term:
    id: GO:0019774
    label: proteasome core complex, beta-subunit complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: proteasome core complex, beta-subunit complex is the appropriate core-complex
      membership annotation for PSMB5.
    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.
    supported_by:
    - reference_id: file:human/PSMB5/PSMB5-deep-research-falcon.md
      supporting_text: >-
        In the standard/constitutive proteasome, Ξ²5 is one of three
        catalytically active Ξ²-subunits (Ξ²1, Ξ²2, Ξ²5) and is responsible for the
        chymotrypsin-like (CT-L) activity.
      reference_section_type: RESULTS
  qualifier: part_of
- term:
    id: GO:0004298
    label: threonine-type endopeptidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: PSMB5 is the beta5 catalytic subunit of the constitutive 20S proteasome
      and carries the threonine-type endopeptidase active site.
    action: ACCEPT
    reason: The mature PSMB5 chain begins at Thr60, annotated as the nucleophilic
      active-site residue, and structural/activity studies support beta5 chymotrypsin-like
      proteasome activity.
    supported_by:
    - reference_id: file:human/PSMB5/PSMB5-deep-research-falcon.md
      supporting_text: >-
        Proteasome catalytic Ξ² subunits operate via an N-terminal nucleophile
        mechanism centered on the N-terminal threonine (Thr1). Mechanistically,
        Thr1 attacks the scissile peptide bond carbonyl to form an acyl-enzyme
        intermediate, which is subsequently hydrolyzed to release products and
        regenerate the catalytic threonine.
      reference_section_type: RESULTS
  qualifier: enables
- 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
      PSMB5.
    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: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 PSMB5.
    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.
    supported_by:
    - reference_id: file:human/PSMB5/PSMB5-deep-research-falcon.md
      supporting_text: >-
        The target gene PSMB5 (proteasome 20S subunit beta 5) encodes the
        constitutive catalytic Ξ²5 subunit of the 20S proteasome core particle
        (CP), which forms the proteolytic core of the 26S proteasome.
      reference_section_type: RESULTS
  qualifier: part_of
- term:
    id: GO:0010498
    label: proteasomal protein catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  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.
    supported_by:
    - reference_id: file:human/PSMB5/PSMB5-deep-research-falcon.md
      supporting_text: >-
        The eukaryotic 26S proteasome is the principal executor of
        ubiquitin–proteasome system (UPS) protein degradation.
      reference_section_type: RESULTS
  qualifier: involved_in
- 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: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:15231747
  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:20723761
  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:28514442
  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: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: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: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:40205054
  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:0008233
    label: peptidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: peptidase activity is directionally related to the proteasome role but
      is less specific than the supported proteasome term.
    action: MODIFY
    reason: Replace the broad annotation with threonine-type endopeptidase activity,
      which better captures the gene product role supported by proteasome literature
      and existing specific GOA annotations.
    proposed_replacement_terms:
    - id: GO:0004298
      label: threonine-type endopeptidase activity
  qualifier: enables
- term:
    id: GO:0004298
    label: threonine-type endopeptidase activity
  evidence_type: IDA
  original_reference_id: PMID:27493187
  review:
    summary: PSMB5 is the beta5 catalytic subunit of the constitutive 20S proteasome
      and carries the threonine-type endopeptidase active site.
    action: ACCEPT
    reason: The mature PSMB5 chain begins at Thr60, annotated as the nucleophilic
      active-site residue, and structural/activity studies support beta5 chymotrypsin-like
      proteasome activity.
    supported_by:
    - reference_id: file:human/PSMB5/PSMB5-deep-research-falcon.md
      supporting_text: >-
        Ξ²5 (PSMB5) is assigned the CT-L activity, which preferentially cleaves
        peptide bonds after hydrophobic residues.
      reference_section_type: RESULTS
  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
      PSMB5.
    action: ACCEPT
    reason: The reviewed core function occurs in cytosolic and nuclear proteasome
      pools, supported by proteasome localization and nuclear-import evidence.
    supported_by:
    - reference_id: file:human/PSMB5/PSMB5-deep-research-falcon.md
      supporting_text: >-
        The active sites are located on the inner surface of the 20S core,
        sequestered in the central catalytic chamber; access is controlled by
        Ξ±-ring gating and by association with regulatory particles such as the
        19S cap (forming the 26S proteasome).
      reference_section_type: RESULTS
  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 PSMB5.
    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: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:0005634
    label: nucleus
  evidence_type: NAS
  original_reference_id: PMID:32134919
  review:
    summary: nucleus is a core cellular context for the assembled proteasome containing
      PSMB5.
    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
      PSMB5.
    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 PSMB5.
    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 PSMB5.
    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 PSMB5.
    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 PSMB5.
    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 PSMB5.
    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 PSMB5.
    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 PSMB5.
    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: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: 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.
  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.
    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: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 PSMB5.
    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 PSMB5.
    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.
    supported_by:
    - reference_id: file:human/PSMB5/PSMB5-deep-research-falcon.md
      supporting_text: >-
        Its 20S core particle is a barrel-like complex of four stacked
        heptameric rings (Ξ±/Ξ²/Ξ²/Ξ±). The active sites are located on the inner
        surface of the 20S core, sequestered in the central catalytic chamber.
      reference_section_type: RESULTS
  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 PSMB5.
    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 PSMB5.
    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 PSMB5.
    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 PSMB5.
    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 PSMB5.
    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:0010499
    label: proteasomal ubiquitin-independent protein catabolic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9912633
  review:
    summary: proteasomal ubiquitin-independent 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:0043248
    label: proteasome assembly
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9907900
  review:
    summary: PSMB5 maturation and incorporation are relevant to proteasome biogenesis,
      but assembly is not the mature subunit catalytic function.
    action: KEEP_AS_NON_CORE
    reason: Retain proteasome assembly as non-core context because PSMB5 has a propeptide
      and assembly dependencies, while the reviewed core function is beta5 proteolysis
      in the mature 20S core.
    supported_by:
    - reference_id: file:human/PSMB5/PSMB5-deep-research-falcon.md
      supporting_text: >-
        Catalytic Ξ² subunits are synthesized with N-terminal propeptides that
        are removed by autolysis after correct assembly. The propeptides are
        described as being autolyzed between a glycine residue and a threonine
        residue, yielding the mature catalytic subunit with Thr1 at the
        N-terminus; Ξ²5 propeptides also contribute to proteasome assembly.
      reference_section_type: RESULTS
  qualifier: involved_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
      PSMB5.
    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: 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:0004175
    label: endopeptidase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9912636
  review:
    summary: endopeptidase activity is directionally related to the proteasome role
      but is less specific than the supported proteasome term.
    action: MODIFY
    reason: Replace the broad annotation with threonine-type endopeptidase activity,
      which better captures the gene product role supported by proteasome literature
      and existing specific GOA annotations.
    proposed_replacement_terms:
    - id: GO:0004298
      label: threonine-type endopeptidase activity
  qualifier: enables
- term:
    id: GO:0004175
    label: endopeptidase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9908101
  review:
    summary: endopeptidase activity is directionally related to the proteasome role
      but is less specific than the supported proteasome term.
    action: MODIFY
    reason: Replace the broad annotation with threonine-type endopeptidase activity,
      which better captures the gene product role supported by proteasome literature
      and existing specific GOA annotations.
    proposed_replacement_terms:
    - id: GO:0004298
      label: threonine-type endopeptidase activity
  qualifier: enables
- 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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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
      PSMB5.
    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 PSMB5.
    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:0006508
    label: proteolysis
  evidence_type: IDA
  original_reference_id: PMID:17540904
  review:
    summary: proteolysis 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: acts_upstream_of_or_within
- term:
    id: GO:0008233
    label: peptidase activity
  evidence_type: IDA
  original_reference_id: PMID:17540904
  review:
    summary: peptidase activity is directionally related to the proteasome role but
      is less specific than the supported proteasome term.
    action: MODIFY
    reason: Replace the broad annotation with threonine-type endopeptidase activity,
      which better captures the gene product role supported by proteasome literature
      and existing specific GOA annotations.
    proposed_replacement_terms:
    - id: GO:0004298
      label: threonine-type endopeptidase activity
  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:0005634
    label: nucleus
  evidence_type: HDA
  original_reference_id: PMID:21630459
  review:
    summary: nucleus is a core cellular context for the assembled proteasome containing
      PSMB5.
    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: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 PSMB5.
    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:0019774
    label: proteasome core complex, beta-subunit complex
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: proteasome core complex, beta-subunit complex is the appropriate core-complex
      membership annotation for PSMB5.
    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: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:14733938
  title: Protein-protein interactions among human 20S proteasome subunits and proteassemblin.
  findings: []
- id: PMID:15231747
  title: A protein interaction framework for human mRNA degradation.
  findings: []
- id: PMID:17323924
  title: Mass spectrometric characterization of the affinity-purified human 26S proteasome
    complex.
  findings: []
- id: PMID:17540904
  title: Regulation of CD8+ T cell development by thymus-specific proteasomes.
  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:19489727
  title: Recognition and processing of ubiquitin-protein conjugates by the proteasome.
  findings: []
- id: PMID:20723761
  title: Immunoproteasomes preserve protein homeostasis upon interferon-induced oxidative
    stress.
  findings: []
- id: PMID:21630459
  title: Proteomic characterization of the human sperm nucleus.
  findings: []
- id: PMID:23706739
  title: Acetylation-mediated proteasomal degradation of core histones during DNA
    repair and spermatogenesis.
  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:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  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: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: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:32935661
  title: Role of oncogenic REGΞ³ in cancer.
  findings: []
- id: PMID:33729481
  title: 'Proteasome in action: substrate degradation by the 26S proteasome.'
  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:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  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-9907900
  title: Proteasome assembly
  findings: []
- id: Reactome:R-HSA-9907919
  title: Formation of the preholoproteasome
  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-9912633
  title: 'Antigen processing: Ub, ATP-independent proteasomal degradation'
  findings: []
- id: Reactome:R-HSA-9912636
  title: Proteasomal cleavage of intracellular substrate (PA28-alpha-beta-20S proteasome
    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: PMID:27176742
  title: Human 20S proteasome activity towards fluorogenic peptides of various chain
    lengths.
  findings: []
- id: PMID:18565852
  title: 'Molecular basis of bortezomib resistance: proteasome subunit beta5 (PSMB5)
    gene mutation and overexpression of PSMB5 protein.'
  findings: []
- id: PMID:18502982
  title: Point mutation of the proteasome beta5 subunit gene is an important mechanism
    of bortezomib resistance in bortezomib-selected variants of Jurkat T cell lymphoblastic
    lymphoma/leukemia line.
  findings: []
- id: file:human/PSMB5/PSMB5-deep-research-falcon.md
  title: Falcon deep research on PSMB5 (Edison Scientific Literature)
  findings:
  - statement: PSMB5 encodes the constitutive catalytic beta5 subunit of the 20S
      proteasome core particle, one of the three catalytically active beta subunits
      (beta1, beta2, beta5) and part of the 26S proteasome; it provides the
      chymotrypsin-like (CT-L) activity.
    supporting_text: >-
      The target gene PSMB5 (proteasome 20S subunit beta 5) encodes the
      constitutive catalytic Ξ²5 subunit of the 20S proteasome core particle
      (CP), which forms the proteolytic core of the 26S proteasome. In the
      standard/constitutive proteasome, Ξ²5 is one of three catalytically active
      Ξ²-subunits (Ξ²1, Ξ²2, Ξ²5) and is responsible for the chymotrypsin-like
      (CT-L) activity.
    reference_section_type: RESULTS
  - statement: The CT-L activity of beta5 preferentially cleaves peptide bonds after
      hydrophobic residues.
    supporting_text: >-
      Ξ²5 (PSMB5) is assigned the CT-L activity, which preferentially cleaves
      peptide bonds after hydrophobic residues.
    reference_section_type: RESULTS
  - statement: Catalysis uses an N-terminal threonine (Thr1) nucleophile mechanism
      typical of Ntn hydrolases; Thr1 attacks the scissile peptide bond to form an
      acyl-enzyme intermediate that is then hydrolyzed.
    supporting_text: >-
      Proteasome catalytic Ξ² subunits operate via an N-terminal nucleophile
      mechanism centered on the N-terminal threonine (Thr1). Mechanistically,
      Thr1 attacks the scissile peptide bond carbonyl to form an acyl-enzyme
      intermediate, which is subsequently hydrolyzed to release products and
      regenerate the catalytic threonine.
    reference_section_type: RESULTS
  - statement: Catalytic beta subunits are made with N-terminal propeptides removed
      by autolysis between a glycine and a threonine residue, exposing the mature
      Thr1; beta5 propeptide also contributes to 20S assembly.
    supporting_text: >-
      Catalytic Ξ² subunits are synthesized with N-terminal propeptides that are
      removed by autolysis after correct assembly. The propeptides are described
      as being autolyzed between a glycine residue and a threonine residue,
      yielding the mature catalytic subunit with Thr1 at the N-terminus; Ξ²5
      propeptides also contribute to proteasome assembly.
    reference_section_type: RESULTS
  - statement: The beta5 active sites are buried inside the central catalytic chamber
      of the barrel-shaped 20S core (alpha-beta-beta-alpha arrangement); the 26S
      proteasome degrades ubiquitin-tagged cytosolic proteins with access controlled
      by regulatory caps and gates.
    supporting_text: >-
      The active sites are located on the inner surface of the 20S core,
      sequestered in the central catalytic chamber; access is controlled by
      Ξ±-ring gating and by association with regulatory particles such as the 19S
      cap (forming the 26S proteasome).
    reference_section_type: RESULTS
  - statement: Proteasome proteolysis contributes to MHC class I antigen presentation;
      proteasome subtype composition shifts cleavage preferences and the peptide
      repertoire loaded onto MHC I.
    supporting_text: >-
      proteasome proteolysis contributes to MHC class I antigen presentation by
      generating peptides that can be transported into the ER and loaded onto
      MHC I. Proteasome subtype composition (standard vs immunoproteasome and
      intermediates) shifts cleavage preferences.
    reference_section_type: RESULTS
  - statement: PSMB5/beta5 is the dominant catalytic drug target; clinically
      successful proteasome inhibitors (bortezomib, carfilzomib, ixazomib) largely
      exploit the beta5/CT-L site, and resistance includes beta5 active-site
      mutations (A49T, A50V, C52F) and non-mutational rewiring such as PSMB5
      upregulation and compensatory autophagy.
    supporting_text: >-
      Clinically successful proteasome inhibitors largely exploit the Ξ²5/CT-L
      site... PI resistance can also arise through PSMB5 upregulation/subunit
      replacement and compensatory autophagy.
    reference_section_type: DISCUSSION
core_functions:
- 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
  - id: GO:0010499
    label: proteasomal ubiquitin-independent protein catabolic process
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0005634
    label: nucleus
  in_complex:
    id: GO:0019774
    label: proteasome core complex, beta-subunit complex
  description: PSMB5 is the beta5 active-site subunit of the mature 20S proteasome
    core. Its N-terminal propeptide is removed during maturation, exposing Thr60 as
    the catalytic nucleophile. In the assembled proteasome, PSMB5 provides the chymotrypsin-like
    threonine endopeptidase activity used for proteasomal protein catabolism.
  supported_by:
  - reference_id: PMID:23495936
    supporting_text: The Ξ²1, Ξ²2, and Ξ²5 subunits contain the proteolytic active sites
  - reference_id: PMID:27176742
    supporting_text: The proteasome is a multicatalytic protease responsible for the
      degradation of misfolded proteins.
  - reference_id: PMID:18565852
    supporting_text: marked changes in chymotrypsin-like proteasome activity
  - reference_id: file:human/PSMB5/PSMB5-deep-research-falcon.md
    supporting_text: >-
      PSMB5 encodes the constitutive Ξ²5 catalytic subunit of the 20S proteasome
      core, providing the chymotrypsin-like proteolytic activity that
      preferentially cleaves after hydrophobic residues. Catalysis is mediated
      by an N-terminal Thr1 nucleophile exposed by propeptide autolysis during
      proteasome assembly. Ξ²5 resides within the interior catalytic chamber of
      the 20S/26S proteasome, functioning centrally in the UPS.
    reference_section_type: CONCLUSIONS
suggested_questions:
- question: When should broad peptidase annotations on catalytic proteasome beta subunits
    be replaced by threonine-type endopeptidase activity in GOA cleanup?
  experts:
  - Schrader J
  - Chari A
  - Drag M
suggested_experiments:
- hypothesis: PSMB5-specific perturbations should affect chymotrypsin-like proteasome
    activity more directly than non-catalytic alpha-ring subunit perturbations.
  description: Compare PSMB5 active-site or inhibitor-pocket mutants with PSMA1 alpha-ring
    interface mutants in matched cells or purified complexes, measuring chymotrypsin-like,
    caspase-like, and trypsin-like proteasome activities separately.
  experiment_type: comparative mutagenesis and proteasome activity profiling