PSMD4 (Proteasome 26S Subunit Ubiquitin Receptor, Non-ATPase 4)
A key component of the 26S proteasome involved in ubiquitin-dependent protein degradation, with roles in cancer, neurodegeneration, and immune regulation.
Gene Information Card
| Symbol | PSMD4 |
|---|---|
| Full Name | Proteasome 26S Subunit Ubiquitin Receptor, Non-ATPase 4 |
| Gene Type | protein coding |
| Chromosomal Location | 1q21.3 |
| NCBI Gene ID | 5710 ncbi.nlm.nih.gov/gene/5710 |
| Ensembl ID | ENSG00000100519 |
| UniProt ID | P55036 |
| OMIM ID | 601681 |
| HGNC ID | 9561 |
| Aliases | AF, RPN10, S5A, pUB-R5 |
Description
PSMD4 encodes a non-ATPase subunit of the 19S regulatory particle of the 26S proteasome. It functions as a ubiquitin receptor, recognizing polyubiquitinated proteins and facilitating their degradation. PSMD4 is involved in protein quality control, cell cycle regulation, apoptosis, and immune responses. Alterations in PSMD4 expression have been linked to various cancers and neurodegenerative diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression of PSMD4 enhances proteasome activity, promoting degradation of tumor suppressors and supporting cell proliferation. | COSMIC; PMID: 25691811 |
| Neurodegenerative disorders (e.g., Alzheimer's) | Impaired proteasome function due to PSMD4 dysregulation may lead to accumulation of toxic proteins. | UniProt; PMID: 23376485 |
| Inflammatory diseases | PSMD4 modulates NF-kappaB signaling via degradation of IkB, affecting inflammatory responses. | PMID: 15121844 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 17.4 | Medium |
| Liver | 12.3 | Medium |
| Testis | 20.1 | High |
| Kidney | 15.2 | Medium |
| Heart | 10.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 18.5 | Cervical cancer cell line |
| A549 | 14.2 | Lung carcinoma |
| MCF7 | 16.8 | Breast cancer |
| HEK293 | 15.9 | Embryonic kidney |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.123C>T (p.Asp41Asp) | Synonymous | 0.01% | No known effect |
| c.456G>A (p.Met152Ile) | Missense | 0.02% | Potential impact on protein stability |
| c.789delA (p.Lys263Serfs*12) | Frameshift | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations leading to truncated protein may impair proteasome function, causing accumulation of ubiquitinated substrates.
Gain of Function (GOF)
Missense mutations that increase ubiquitin binding affinity could enhance proteasome activity, potentially promoting oncogenesis.
Dominant Negative (DN)
Mutations that disrupt subunit interaction may interfere with proteasome assembly, acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin binding | • proteasome regulatory particle |
| • lid subcomplex | • protein ubiquitination |
| • proteasome-mediated ubiquitin-dependent protein catabolic process | • negative regulation of apoptotic process |
Pathways
• Proteasome degradation
• Ubiquitin-mediated proteolysis
• Antigen processing and presentation
• Cell cycle regulation
Protein Summary
PSMD4 (also known as RPN10 or S5A) is a 26S proteasome subunit that directly binds polyubiquitin chains via its ubiquitin-interacting motif (UIM). It is essential for substrate recognition and degradation. The protein is localized to the 19S regulatory particle and also exists in free form, where it may regulate other cellular processes. PSMD4 is highly conserved and expressed in all tissues, with elevated levels in testis and brain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PSMD4 Knockout HEK293T Cell Line | EDJ-KQ78075 | Human | 5710 | Details Get a Quote |
| PSMD4 Knockout HAP1 Cell Line | EDJ-KQ78107 | Human | 5710 | Details Get a Quote |
| PSMD4 Knockout HCT 116 Cell Line | EDJ-KQ78138 | Human | 5710 | Details Get a Quote |
