PSMD4 Gene

HGNC Family	Proteasome (prosome, macropain) subunits (PSM)
Name	proteasome (prosome, macropain) 26S subunit, non-ATPase, 4
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. This gene encodes one of the non-ATPase subunits of the 19S regulator lid. Pseudogenes have been identified on chromosomes 10 and 21. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPSMD4, also known as the proteasome subunit S5a, plays a critical role in the regulated degradation of proteins by binding polyubiquitinated substrates and escorting them to the 26S proteasome. Its structure contains two distinct ubiquitin‐interacting motifs (UIMs) that recognize ubiquitin chains through an array of alternating hydrophobic residues, enabling efficient substrate recruitment into the proteolytic complex."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDetailed structural studies have demonstrated that these dual UIMs can engage ubiquitin moieties from diubiquitin chains simultaneously in a subunit‐selective fashion—for instance, favoring the proximal subunit in K48–linked chains—and coordinate with other proteasome receptors such as Rpn13 to ensure proper substrate processing."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAlterations in PSMD4 expression have clinical implications as well; in multiple myeloma, for example, higher PSMD4 levels and increased copy number of its chromosomal locus (1q21) correlate with adverse patient outcomes. This finding suggests that PSMD4 not only functions in substrate recognition but may also influence sensitivity to proteasome inhibitors, contributing to therapeutic resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, PSMD4 interacts with ubiquitin‐like domains found in shuttle proteins—such as hHR23a—thereby facilitating the delivery of ubiquitinated proteins to the proteasome while preventing the formation of aberrant or “forked” ubiquitin chain structures. These interactions underscore a broader role for PSMD4 in maintaining protein homeostasis by modulating both the recognition and specificity of ubiquitin signals."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "P Young, Q Deveraux, R E Beal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of two polyubiquitin binding sites in the 26 S protease subunit 5a."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (1998)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.273.10.5461"}], "href": "https://doi.org/10.1074/jbc.273.10.5461"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "9488668"}], "href": "https://pubmed.ncbi.nlm.nih.gov/9488668"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Qinghua Wang, Patrick Young, Kylie J Walters "}, {"type": "b", "children": [{"type": "t", "text": "Structure of S5a bound to monoubiquitin provides a model for polyubiquitin recognition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2005.03.007"}], "href": "https://doi.org/10.1016/j.jmb.2005.03.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15826667"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15826667"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Naixia Zhang, Qinghua Wang, Aaron Ehlinger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure of the s5a:k48-linked diubiquitin complex and its interactions with rpn13."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2009.06.010"}], "href": "https://doi.org/10.1016/j.molcel.2009.06.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19683493"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19683493"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "John D Shaughnessy, Pingping Qu, Saad Usmani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pharmacogenomics of bortezomib test-dosing identifies hyperexpression of proteasome genes, especially PSMD4, as novel high-risk feature in myeloma treated with Total Therapy 3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2010-12-328252"}], "href": "https://doi.org/10.1182/blood-2010-12-328252"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21628408"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21628408"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kylie J Walters, Maurits F Kleijnen, Amanda M Goh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural studies of the interaction between ubiquitin family proteins and proteasome subunit S5a."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi011892y"}], "href": "https://doi.org/10.1021/bi011892y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11827521"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11827521"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kylie J Walters, Patrycja J Lech, Amanda M Goh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1634989100"}], "href": "https://doi.org/10.1073/pnas.1634989100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14557549"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14557549"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hyoung Tae Kim, Kwang Pyo Kim, Tomoaki Uchiki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "S5a promotes protein degradation by blocking synthesis of nondegradable forked ubiquitin chains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2009.115"}], "href": "https://doi.org/10.1038/emboj.2009.115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19387488"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19387488"}]}]}]}
Synonyms	S5A, AF, PUB-R5, RPN10, MCB1
Proteins	PSMD4_HUMAN
NCBI Gene ID	5710
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PSMD4 has 8,016 functional associations with biological entities spanning 8 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) extracted from 120 datasets.

Click the + buttons to view associations for PSMD4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PSMD4 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 PSMD4 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 PSMD4 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 PSMD4 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 PSMD4 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 PSMD4 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 PSMD4 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 PSMD4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving PSMD4 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PSMD4 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 PSMD4 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 PSMD4 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 PSMD4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PSMD4 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 PSMD4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PSMD4 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PSMD4 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 PSMD4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PSMD4 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 PSMD4 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 PSMD4 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 PSMD4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PSMD4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PSMD4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PSMD4 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 PSMD4 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 PSMD4 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 PSMD4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing PSMD4 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PSMD4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PSMD4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PSMD4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PSMD4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PSMD4 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PSMD4 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 PSMD4 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 PSMD4 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 PSMD4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PSMD4 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 PSMD4 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 PSMD4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.