PSME1 Gene

HGNC Family	Proteasome (prosome, macropain) subunits (PSM)
Name	proteasome (prosome, macropain) activator subunit 1 (PA28 alpha)
Description	The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core 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. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase 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. The immunoproteasome contains an alternate regulator, referred to as the 11S regulator or PA28, that replaces the 19S regulator. Three subunits (alpha, beta and gamma) of the 11S regulator have been identified. This gene encodes the alpha subunit of the 11S regulator, one of the two 11S subunits that is induced by gamma-interferon. Three alpha and three beta subunits combine to form a heterohexameric ring. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPSME1, also known as PA28α, is a key regulatory subunit of the 11S proteasome activator complex that binds to the outer surfaces of the 20S proteasome. By enhancing the proteolytic activities of the 20S core, PSME1 plays an essential role in processing intracellular proteins into antigenic peptides. This peptide generation is critical for loading major histocompatibility complex (MHC) class I molecules, thereby ensuring efficient immune surveillance against viruses and tumor cells. Moreover, inducible expression of this activator appears to have implications in autoimmunity, as fluctuations in its levels can influence the repertoire of peptides presented to T cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of tumor biology, altered expression of PSME1 has emerged as a promising biomarker and a potential therapeutic target. Studies in ovarian carcinoma have identified a PA28-derived C-terminal fragment that discriminates between benign and malignant epithelial cells, while down‐regulation in hepatitis B–associated hepatocellular carcinoma underscores its early involvement in tumorigenesis. Enhanced expression of PSME1 is similarly observed in prostate cancer, where it is accessible for targeting via antibody‐mediated delivery, and in multiple myeloma where its upregulation promotes cell growth and influences sensitivity to proteasome inhibitors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its classical immunological functions, PSME1 modulates cellular proteostasis under various stress conditions. Adaptation to proteasome inhibitors, such as bortezomib, involves increased expression and association of PSME1 with the proteasome, permitting residual proteolytic activity and contributing to drug resistance. Furthermore, rhythmic, circadian-driven fluctuations in PA28 expression fine tune proteasome function in response to oxidative stress, and structural analyses reveal that binding of PA28 regulators triggers allosteric changes within the 20S catalytic core. Such dynamic regulation underscores PSME1’s central role in balancing protein turnover and maintaining cellular homeostasis in both normal and diseased states."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alice Sijts, Yuancheng Sun, Katarina Janek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of the proteasome activator PA28 in MHC class I antigen processing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Immunol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0161-5890(02)00099-8"}], "href": "https://doi.org/10.1016/s0161-5890(02"}, {"type": "t", "text": "00099-8) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12200048"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12200048"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Masakazu Matsushita, Yoshinari Takasaki, Ken Takeuchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autoimmune response to proteasome activator 28alpha in patients with connective tissue diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Rheumatol (2004)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14760793"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14760793"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Wieke Freudenburg, Madhav Gautam, Pradipta Chakraborty, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reduction in ATP levels triggers immunoproteasome activation by the 11S (PA28) regulator during early antiviral response mediated by IFNβ in mouse pancreatic β-cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0052408"}], "href": "https://doi.org/10.1371/journal.pone.0052408"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23383295"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23383295"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Martin Keller, Frédéric Ebstein, Elke Bürger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The proteasome immunosubunits, PA28 and ER-aminopeptidase 1 protect melanoma cells from efficient MART-126-35 -specific T-cell recognition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/eji.201445243"}], "href": "https://doi.org/10.1002/eji.201445243"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26399368"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26399368"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Daohai Zhang, Seng Gee Lim, Evelyn S C Koay "}, {"type": "b", "children": [{"type": "t", "text": "Proteomic identification of down-regulation of oncoprotein DJ-1 and proteasome activator subunit 1 in hepatitis B virus-infected well-differentiated hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2007)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17671684"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17671684"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Remi Lemaire, Sonia Ait Menguellet, Jonathan Stauber, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Specific MALDI imaging and profiling for biomarker hunting and validation: fragment of the 11S proteasome activator complex, Reg alpha fragment, is a new potential ovary cancer biomarker."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Proteome Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/pr0702722"}], "href": "https://doi.org/10.1021/pr0702722"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17939699"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17939699"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Rémi Longuespée, Charlotte Boyon, Céline Castellier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The C-terminal fragment of the immunoproteasome PA28S (Reg alpha) as an early diagnosis and tumor-relapse biomarker: evidence from mass spectrometry profiling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histochem Cell Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00418-012-0953-0"}], "href": "https://doi.org/10.1007/s00418-012-0953-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22532226"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22532226"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "David Sánchez-Martín, Jorge Martínez-Torrecuadrada, Tambet Teesalu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteasome activator complex PA28 identified as an accessible target in prostate cancer by in vivo selection of human antibodies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1300013110"}], "href": "https://doi.org/10.1073/pnas.1300013110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23918357"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23918357"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yanyan Gu, Benjamin G Barwick, Mala Shanmugam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of PA28α induces proteasome remodeling and results in resistance to proteasome inhibitors in multiple myeloma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood Cancer J (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41408-020-00393-0"}], "href": "https://doi.org/10.1038/s41408-020-00393-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33318477"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33318477"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "T Rückrich, M Kraus, J Gogel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the ubiquitin-proteasome system in bortezomib-adapted cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leukemia (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/leu.2009.8"}], "href": "https://doi.org/10.1038/leu.2009.8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19225532"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19225532"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Xiaodong Feng, Yuchen Jiang, Liang Xie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of proteasomal activator PA28α serves as a prognostic factor in oral squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-016-0309-z"}], "href": "https://doi.org/10.1186/s13046-016-0309-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26892607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26892607"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Audrey Desvergne, Nicolas Ugarte, Sabrina Radjei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circadian modulation of proteasome activity and accumulation of oxidized protein in human embryonic kidney HEK 293 cells and primary dermal fibroblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Free Radic Biol Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.freeradbiomed.2016.02.037"}], "href": "https://doi.org/10.1016/j.freeradbiomed.2016.02.037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26944190"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26944190"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Jean Lesne, Marie Locard-Paulet, Julien Parra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Conformational maps of human 20S proteasomes reveal PA28- and immuno-dependent inter-ring crosstalks."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-020-19934-z"}], "href": "https://doi.org/10.1038/s41467-020-19934-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33262340"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33262340"}]}]}]}
Synonyms	HEL-S-129m, PA28A, PA28ALPHA, REGALPHA, IFI5111
Proteins	PSME1_HUMAN
NCBI Gene ID	5720
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PSME1 has 7,703 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 122 datasets.

Click the + buttons to view associations for PSME1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PSME1 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 PSME1 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 PSME1 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 PSME1 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 PSME1 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 PSME1 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 PSME1 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 PSME1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PSME1 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 PSME1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PSME1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of PSME1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PSME1 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 PSME1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PSME1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PSME1 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 PSME1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PSME1 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 PSME1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing PSME1 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 PSME1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PSME1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PSME1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PSME1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PSME1 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 PSME1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing PSME1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PSME1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PSME1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PSME1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PSME1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PSME1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PSME1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PSME1 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 PSME1 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 PSME1 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 PSME1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PSME1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PSME1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PSME1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PSME1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.