PSME4: Proteasome Activator Subunit 4
A key regulator of proteasome function and cellular protein degradation
Gene Information Card
| Symbol | PSME4 |
|---|---|
| Full Name | proteasome activator subunit 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 2p16.2 |
| NCBI Gene ID | 23198 ncbi.nlm.nih.gov/gene/23198 |
| Ensembl ID | ENSG00000168876 |
| UniProt ID | Q14997 |
| OMIM ID | 607628 |
| HGNC ID | 9553 |
| Aliases | PA200, KIAA0077, MGC131986 |
Description
PSME4 encodes the proteasome activator subunit 4 (PA200), a nuclear protein that binds to the 20S proteasome core and activates its peptidase activity. PA200 plays a critical role in ubiquitin-independent protein degradation, particularly during spermatogenesis, DNA repair, and cellular stress responses. It is involved in the degradation of acetylated histones and oxidized proteins.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | PSME4 overexpression may promote tumor growth by enhancing proteasome-mediated degradation of tumor suppressors | COSMIC, literature |
| Male infertility | PSME4 knockout in mice leads to defective spermatogenesis and reduced fertility | OMIM, literature |
| Neurodegenerative disorders | Altered PSME4 expression may affect clearance of aggregated proteins | NCBI Gene, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 38.5 | High |
| Brain | 12.3 | Medium |
| Lung | 8.7 | Medium |
| Liver | 6.2 | Low |
| Kidney | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | Embryonic kidney cells |
| HeLa | 12.8 | Cervical cancer cells |
| K562 | 9.4 | Leukemia cells |
| A549 | 7.1 | Lung cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Trp) | Missense | <0.01% | Unknown functional impact |
| c.2567_2568del (p.Leu856fs) | Frameshift | <0.01% | Likely loss of function |
| c.3456G>A (p.Glu1152Lys) | Missense | <0.01% | Reported in COSMIC |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations predicted to truncate PA200, impairing proteasome activation.
Gain of Function (GOF)
Missense mutations in regulatory domains may enhance proteasome activity, potentially contributing to cancer.
Dominant Negative (DN)
Not well characterized; some missense variants may interfere with wild-type PA200 function.
View complete mutation data：
Gene Ontology (GO)
| • proteasome activator activity | • protein binding |
| • proteasome-mediated ubiquitin-independent protein catabolic process | • DNA repair |
| • spermatogenesis | • nucleus |
Pathways
• Proteasome degradation (ubiquitin-independent)
• DNA double-strand break repair via homologous recombination
• Cellular response to oxidative stress
Protein Summary
PSME4 encodes PA200, a 200 kDa nuclear protein that activates the 20S proteasome in an ATP- and ubiquitin-independent manner. PA200 forms a dome-shaped complex that opens the proteasome gate, facilitating degradation of unstructured and oxidized proteins. It is highly expressed in testis and plays essential roles in chromatin remodeling, DNA repair, and male fertility.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PSME4 Knockout HEK293 Cell Line | EDJ-KQ7214 | Human | 23198 | Details Get a Quote |
| PSME4 Knockout A-549 Cell Line | EDJ-KQ33493 | Human | 23198 | Details Get a Quote |
| PSME4 Knockout HCT 116 Cell Line | EDJ-KQ33494 | Human | 23198 | Details Get a Quote |
| PSME4 Knockout HeLa Cell Line | EDJ-KQ33495 | Human | 23198 | Details Get a Quote |
