PSMB5 Gene

HGNC Family	Proteasome (prosome, macropain) subunits (PSM)
Name	proteasome (prosome, macropain) subunit, beta type, 5
Description	The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit in the proteasome. This catalytic subunit is not present in the immunoproteasome and is replaced by catalytic subunit 3i (proteasome beta 8 subunit). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPSMB5 encodes the proteasome’s catalytic β5‐subunit and is a key molecular target of proteasome inhibitors such as bortezomib. In multiple hematological malignancies, including multiple myeloma and T-cell lymphoblastic leukemia, several studies have shown that acquired point mutations in PSMB5 (for example, those leading to amino acid substitutions such as A108T and Ala49Thr) and its selective overexpression result in reduced binding affinity to bortezomib. These alterations shield cancer cells from drug‐induced inhibition of chymotrypsin‐like activity and suppress apoptosis. Moreover, siRNA screens have identified PSMB5 as one of the strongest modulators of bortezomib sensitivity, and experimental modulation of its expression in resistant cell lines confirms that reducing PSMB5 levels can restore drug sensitivity. Such findings suggest that structural and quantitative changes in PSMB5 contribute substantially to proteasome inhibitor resistance in these cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in drug resistance, modulation of PSMB5 expression plays important roles in cellular homeostasis and tumor progression outside hematologic malignancies. Overexpression of PSMB5 in lens epithelial cells and in culture‐expanded human bone marrow stromal cells restores proteasome activity, promotes cell growth, and confers cytoprotection against oxidative stress. In solid tumors such as hepatocellular carcinoma, elevated PSMB5 expression is associated with enhanced cell proliferation and migration, likely through modulation of signaling pathways (for example, via STAT3), while in prostate cancer, the loss of regulatory microRNAs targeting PSMB5 correlates with increased invasiveness and bone metastasis. These studies underscore the critical role of PSMB5 not only in maintaining proteasome function under normal conditions but also in driving aggressive tumor behavior."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOther investigations reveal broader biological functions of PSMB5 beyond proteasome inhibitor response. The proteasome, with PSMB5 as a key subunit, is integral to antigen processing and presentation—a process exemplified by interactions between proteasome subunits and transporters, as well as in shaping the immunopeptidome. In ovarian cancer, a role for antigen‐processing pathway components (including PSMB5) has been explored for their prognostic value; similarly, genetic studies have identified variants in PSMB5 that influence hematologic traits in diverse populations. Notably, in a Drosophila model of fragile X–associated tremor/ataxia syndrome, knockdown of PSMB5 alleviated neurodegeneration by suppressing both repeat‐associated non‐ATG translation and RNA–mediated toxicities. Furthermore, studies assessing PSMB gene variation in patient tumors and atherosclerotic plaques shed light on the potential impact of PSMB5 variants in determining treatment outcomes and non–cancer pathologies. Collectively, these findings highlight the multifaceted roles of PSMB5 in immune regulation, disease progression, and even neurodegeneration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shuqing Lü, Jianmin Yang, Xianmin Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "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."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pharmacol Exp Ther (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/jpet.108.138131"}], "href": "https://doi.org/10.1124/jpet.108.138131"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18502982"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18502982"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Shuqing Lü, Zhilong Chen, Jianmin Yang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Molecular basis of bortezomib resistance: proteasome subunit beta5 (PSMB5) gene mutation and overexpression of PSMB5 protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2007-08-104950"}], "href": "https://doi.org/10.1182/blood-2007-08-104950"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18565852"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18565852"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Shuqing Lü, Jianmin Yang, Zhilong Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Different mutants of PSMB5 confer varying bortezomib resistance in T lymphoblastic lymphoma/leukemia cells derived from the Jurkat cell line."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Hematol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.exphem.2009.04.001"}], "href": "https://doi.org/10.1016/j.exphem.2009.04.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19426847"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19426847"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "M Ri, S Iida, T Nakashima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bortezomib-resistant myeloma cell lines: a role for mutated PSMB5 in preventing the accumulation of unfolded proteins and fatal ER stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leukemia (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/leu.2010.137"}], "href": "https://doi.org/10.1038/leu.2010.137"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20555361"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20555361"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yuan Xiao Zhu, Rodger Tiedemann, Chang-Xin Shi, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Bortezomib resistance in a myeloma cell line is associated to PSMβ5 overexpression and polyploidy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leuk Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.leukres.2011.09.011"}], "href": "https://doi.org/10.1016/j.leukres.2011.09.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21978467"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21978467"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "H M Mo, Q Y Wu, D Y Han, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Identification of "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "PSMB5"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " as a genetic modifier of fragile X-associated tremor/ataxia syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2118124119"}], "href": "https://doi.org/10.1073/pnas.2118124119"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35617426"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35617426"}]}]}]}
Synonyms	LMPX, X, MB1
Proteins	PSB5_HUMAN
NCBI Gene ID	5693
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PSMB5 has 9,007 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 124 datasets.

Click the + buttons to view associations for PSMB5 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PSMB5 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by PSMB5 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PSMB5 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of PSMB5 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of PSMB5 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PSMB5 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of PSMB5 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PSMB5 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving PSMB5 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PSMB5 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PSMB5 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of PSMB5 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PSMB5 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of PSMB5 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PSMB5 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PSMB5 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PSMB5 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PSMB5 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of PSMB5 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of PSMB5 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing PSMB5 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PSMB5 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PSMB5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PSMB5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PSMB5 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing PSMB5 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PSMB5 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PSMB5 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing PSMB5 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PSMB5 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PSMB5 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PSMB5 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PSMB5 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DGIdb Drug Targets 2026	interacting drugs for PSMB5 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PSMB5 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PSMB5 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PSMB5 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with PSMB5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PSMB5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for PSMB5 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PSMB5 gene from the ENCODE Histone Modification Site Profiles dataset.