# PSMB4
**PSMB4** (proteasome 20S subunit beta 4) is a human protein-coding gene on chromosome band 1q21.3 that encodes the β7 subunit of the 20S core particle of the proteasome, the multicatalytic complex that degrades most intracellular proteins[1](https://www.ncbi.nlm.nih.gov/gtr/genes/5692/) • [2](https://www.uniprot.org/uniprotkb/P28070/). The β7 subunit carries no proteolytic active site of its own, but it is rate-limiting for assembly of the 20S particle and is the last β subunit incorporated during its construction[3](https://aacrjournals.org/cancerres/article/74/11/3114/592625/Comparative-Oncogenomics-Identifies-PSMB4-and) • [4](https://pmc.ncbi.nlm.nih.gov/articles/PMC5675778/). Biallelic loss-of-function mutations in PSMB4 cause proteasome-associated autoinflammatory syndrome 3 (PRAAS3), part of the CANDLE disease spectrum[5](https://panelapp.genomicsengland.co.uk/panels/entities/PSMB4).
| Key fact | Detail |
|---|---|
| Gene location | Chromosome band 1q21.3 (GRCh38: NC_000001.11, 151399573..151401937); 7 exons[1](https://www.ncbi.nlm.nih.gov/gtr/genes/5692/) |
| Protein | Proteasome subunit beta type-4 (β7), 264 amino acids, UniProt P28070[2](https://www.uniprot.org/uniprotkb/P28070/) |
| Role in the proteasome | Non-catalytic structural component of the 20S core; rate-limiting for 20S assembly[2](https://www.uniprot.org/uniprotkb/P28070/) • [3](https://aacrjournals.org/cancerres/article/74/11/3114/592625/Comparative-Oncogenomics-Identifies-PSMB4-and) |
| Assembly position | β7 is always the last β subunit to incorporate; its insertion completes half-mer formation and is coupled to dimerization of two half-proteasomes[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC5675778/) |
| Propeptide | Expressed with a 45-amino-acid N-terminal propeptide that is processed during 20S particle assembly[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC7904567/) |
| Disease | Biallelic (autosomal) PSMB4 mutations cause proteasome-associated autoinflammatory syndrome 3, OMIM 617591, and CANDLE syndrome[5](https://panelapp.genomicsengland.co.uk/panels/entities/PSMB4) |
| Alternative names | HsN3, PROS-26, HSBpros 26, macropain beta chain, proteasome chain 3; yeast ortholog PRE4[2](https://www.uniprot.org/uniprotkb/P28070/) • [7](https://diposit.ub.edu/server/api/core/bitstreams/dfd19a8f-4a0f-48e4-83c1-3c12f8d6bb9f/content) |
## Structure and place in the proteasome
The 20S core particle is a barrel-shaped complex of four stacked heptameric rings: two outer rings of seven α subunits and two inner rings of seven β subunits, 28 subunits in total[1](https://www.ncbi.nlm.nih.gov/gtr/genes/5692/) • [4](https://pmc.ncbi.nlm.nih.gov/articles/PMC5675778/). Only three of the seven eukaryotic β subunits (β1, β2, and β5) retain an intact active site, so each core particle has six proteolytic sites; PSMB4 (β7) is one of the four non-catalytic β subunits and contributes to the structural scaffold[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC5675778/) • [2](https://www.uniprot.org/uniprotkb/P28070/). In the older cross-species nomenclature the subunit is called β7 or N3, with the yeast ortholog PRE4[7](https://diposit.ub.edu/server/api/core/bitstreams/dfd19a8f-4a0f-48e4-83c1-3c12f8d6bb9f/content).
Like several other β subunits, PSMB4 is synthesized as a precursor with an N-terminal propeptide, 45 amino acids long in humans, that is removed autocatalytically as the particle matures[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC7904567/). [Native mass spectrometry](https://www.edgepedia.org/native-mass-spectrometry) of human and yeast 20S proteasomes found that the propeptide-containing β subunits, including PSMB4, display a single mature variant in the finished particle[8](https://pubs.acs.org/doi/10.1021/acscentsci.0c00080).
## Role in assembly
Eukaryotic 20S assembly proceeds by sequential addition of β subunits to a preformed α ring, assisted by chaperones such as Pba1–Pba2 (PAC1–PAC2 in humans) and Ump1 (POMP)[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC5675778/). β7 is always the last subunit to incorporate; its insertion completes half-mer formation, which is closely coupled to dimerization of two half-proteasomes into the preholoproteasome, after which the β propeptides are autoprocessed and the particle becomes active[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC5675778/). During this dimerization the C-terminal region of PSMB4 intercalates between β subunits of the opposing half-proteasome[9](https://link.springer.com/content/pdf/10.1007/s00018-020-03590-z.pdf).
**Rate-limiting subunit.** Although PSMB4 has no intrinsic hydrolytic activity, experiments with siRNA knockdown in [NCI-H1299](https://www.edgepedia.org/nci-h1299) and ES-2 cancer cells showed a time-dependent decrease in both cell number and chymotrypsin-like protease activity over a 72-hour course, with accumulation of polyubiquitinated (K48-linked) proteins and of unprocessed precursor forms of PSMB5, PSMB6, and PSMB7; the paper concludes that PSMB4 is rate-limiting for 20S proteasome assembly[3](https://aacrjournals.org/cancerres/article/74/11/3114/592625/Comparative-Oncogenomics-Identifies-PSMB4-and).
## Genetic mapping and paralogy
[Fluorescence in situ hybridization](https://www.edgepedia.org/fluorescence-in-situ-hybridization) mapped PSMB4 (then called beta7 hs, HSBpros 26) to chromosome band 1q21, completing the mapping of the human proteasome β-subunit loci. PSMB2 and PSMB4 mapped to a region of chromosome 1 proposed to be paralogous to the regions on chromosome 6 (containing the major histocompatibility complex) and chromosome 9 where other β proteasome genes reside; the study concluded that expression of these genes is independently regulated, consistent with a coordinating role for proteasome assembly[10](https://pubmed.ncbi.nlm.nih.gov/9344661/). The refined current location is 1q21.3[1](https://www.ncbi.nlm.nih.gov/gtr/genes/5692/).
## Interacting proteins
Several proteins bind PSMB4 and modulate proteasome function. The presynaptic cytomatrix protein Bassoon was found to interact with PSMB4 through three independent interfaces, identified in a yeast two-hybrid screen with a bait spanning amino acids 1692–3263 of rat Bassoon; one interaction involves a 14-amino-acid region of PSMB4 that likely interferes with half-proteasome dimerization, and Bassoon inhibits proteasome activity through this interaction[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC7904567/). Cereblon (CRBN), the target of thalidomide-derived drugs, was identified as a direct binding partner of PSMB4, the β7 subunit of the 20S core, and inhibits proteasome activity by this binding[11](https://www.ncbi.nlm.nih.gov/gene/5692). Among all β subunits, PSMB4 was pulled down with the Catalytic Core Regulator CBR3 at the highest levels, indicating that it harbors an interaction site for this allosteric regulator within the 20S particle[12](https://pmc.ncbi.nlm.nih.gov/articles/PMC10229617/).
## Disease: PRAAS3 and CANDLE
Biallelic PSMB4 mutations are listed on Genomics England's PanelApp as causing proteasome-associated autoinflammatory syndrome 3 (OMIM 617591) and CANDLE syndrome (autoinflammation, lipodystrophy, and dermatosis syndrome), with biallelic autosomal inheritance and digenic forms noted[5](https://panelapp.genomicsengland.co.uk/panels/entities/PSMB4). In a Journal of Clinical Investigation study of CANDLE/PRAAS patients, a patient with a PSMB4 mutation showed a significant increase in ubiquitin-positive keratinocytes in lesional skin biopsies compared with healthy controls and with psoriasis as an inflammatory control, and the -9G>A mutation in β7 caused decreased protein expression in transfected cells; the study's title finding is that additive loss-of-function proteasome subunit mutations promote type I interferon production[13](https://www.jci.org/articles/view/81260/files/pdf).
## Cancer
A comparative oncogenomics study identified PSMB4, together with SHMT2, as a potential cancer driver gene, and showed that suppressing PSMB4 inhibits proteasomal activity and the processing of the catalytic β-ring subunits[3](https://aacrjournals.org/cancerres/article/74/11/3114/592625/Comparative-Oncogenomics-Identifies-PSMB4-and). Gene record summaries report further associations: PSMB4 overexpression enhances growth and viability of breast cancer cells with poor prognosis, contributes to melanoma development under regulation by miR-148b, promotes proliferation in epithelial ovarian cancer and cervical cancer via a FoxM1-PSMB4 axis, and supports multiple myeloma cell growth through NF-κB-miR-21 signaling[11](https://www.ncbi.nlm.nih.gov/gene/5692). A pan-cancer analysis found that high expression of PSMB4, along with [PSMA1](https://www.edgepedia.org/proteasome-prosome-macropain-subunit-alpha-1) and [PSMD2](https://www.edgepedia.org/psmd2), has been correlated with poor prognosis in breast, lung, and gastric cancer[14](https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-022-10079-4).
## References
1. [PSMB4 proteasome 20S subunit beta 4, NIH Genetic Testing Registry (NCBI)](https://www.ncbi.nlm.nih.gov/gtr/genes/5692/)
2. [PSMB4 (P28070), Proteasome subunit beta type-4, UniProtKB](https://www.uniprot.org/uniprotkb/P28070/)
3. [Comparative Oncogenomics Identifies PSMB4 and SHMT2 as Potential Cancer Driver Genes, Cancer Research (AACR)](https://aacrjournals.org/cancerres/article/74/11/3114/592625/Comparative-Oncogenomics-Identifies-PSMB4-and)
4. [Budenholzer L, Cheng CL, Li Y, Hochstrasser M (2017). Proteasome Structure and Assembly. J Mol Biol (PMC5675778)](https://pmc.ncbi.nlm.nih.gov/articles/PMC5675778/)
5. [PSMB4, PanelApp, Genomics England](https://panelapp.genomicsengland.co.uk/panels/entities/PSMB4)
6. [Bassoon inhibits proteasome activity via interaction with PSMB4, Cell Mol Life Sci (PMC7904567)](https://pmc.ncbi.nlm.nih.gov/articles/PMC7904567/)
7. [Proteasome subunit nomenclature table, Universitat de Barcelona thesis](https://diposit.ub.edu/server/api/core/bitstreams/dfd19a8f-4a0f-48e4-83c1-3c12f8d6bb9f/content)
8. [Comparative Structural Analysis of 20S Proteasome Ortholog Protein Complexes by Native Mass Spectrometry, ACS Central Science](https://pubs.acs.org/doi/10.1021/acscentsci.0c00080)
9. [Bassoon inhibits proteasome activity via interaction with PSMB4 (PDF), Springer](https://link.springer.com/content/pdf/10.1007/s00018-020-03590-z.pdf)
10. [Genetic relationships of the genes encoding the human proteasome beta subunits and the proteasome PA28 complex, Genomics (PMID 9344661)](https://pubmed.ncbi.nlm.nih.gov/9344661/)
11. [PSMB4 proteasome 20S subunit beta 4, Gene record, NCBI](https://www.ncbi.nlm.nih.gov/gene/5692)
12. [Allosteric regulation of the 20S proteasome by the Catalytic Core Regulators (CCRs) family, Nature Communications (PMC10229617)](https://pmc.ncbi.nlm.nih.gov/articles/PMC10229617/)
13. [Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production, Journal of Clinical Investigation](https://www.jci.org/articles/view/81260/files/pdf)
14. [Pan-cancer analysis of genomic and transcriptomic data reveals the prognostic relevance of human proteasome genes, BMC Cancer](https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-022-10079-4)
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*Topic: Encyclopedia › Life and health › Biological foundations › Biochemistry and metabolism › Enzyme classes and activities › Proteolytic and peptidase enzymes › Proteases by catalytic mechanism › Threonine proteases and the proteasome › Proteasome subunits and assembly*
*Initially written Sep 17, 2026 · Reviewed: Oct 21, 2026 · Edited: Oct 15, 2026; Oct 21, 2026 · Last review: Oct 21, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license