PSMD14: Proteasome 26S Subunit, Non-ATPase 14
A key deubiquitinating enzyme of the 26S proteasome involved in protein degradation and cancer
Gene Information Card
| Symbol | PSMD14 |
|---|---|
| Full Name | Proteasome 26S Subunit, Non-ATPase 14 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q24.2 |
| NCBI Gene ID | 10213 ncbi.nlm.nih.gov/gene/10213 |
| Ensembl ID | ENSG00000115233 |
| UniProt ID | O00487 |
| OMIM ID | 607173 |
| HGNC ID | 9560 |
| Aliases | POH1, Rpn11, 26S proteasome non-ATPase regulatory subunit 14 |
Description
PSMD14 (Proteasome 26S Subunit, Non-ATPase 14) encodes a metalloprotease that functions as a deubiquitinating enzyme (DUB) within the 19S regulatory particle of the 26S proteasome. It cleaves ubiquitin chains from substrates prior to their degradation, thereby recycling ubiquitin and regulating proteasomal degradation. PSMD14 is essential for cell cycle progression, DNA repair, and apoptosis. Overexpression is observed in multiple cancers and is associated with poor prognosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | PSMD14 overexpression promotes degradation of tumor suppressors (e.g., p53) and enhances cell proliferation | PMID: 25977332 |
| Lung cancer | PSMD14 upregulation correlates with poor survival; silencing reduces tumor growth in xenografts | PMID: 29262337 |
| Colorectal cancer | PSMD14 deubiquitinates β-catenin, activating Wnt signaling and promoting metastasis | PMID: 30523277 |
| Multiple myeloma | PSMD14 is a target of bortezomib resistance; inhibition restores proteasome stress sensitivity | PMID: 27641692 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Lymph node | 22.1 | High |
| Bone marrow | 19.8 | High |
| Brain | 8.3 | Medium |
| Liver | 6.7 | Medium |
| Heart | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 32.4 | Embryonic kidney; high expression |
| HeLa | 29.1 | Cervical carcinoma; high expression |
| A549 | 25.6 | Lung carcinoma; high expression |
| MCF7 | 22.3 | Breast carcinoma; moderate expression |
| K562 | 18.9 | Leukemia; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.329A>G (p.Asn110Ser) | Missense | 0.01% (gnomAD) | Unknown; likely benign |
| c.1A>G (p.Met1?) | Start loss | <0.01% | Loss of function; rare |
| c.637C>T (p.Arg213Trp) | Missense | 0.02% | Unknown; predicted damaging by SIFT |
Mutation functional classification
Loss of Function (LOF)
Rare start-loss and nonsense mutations are predicted to cause loss of function, impairing proteasomal deubiquitination.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in PSMD14.
Dominant Negative (DN)
No dominant-negative mutations described for PSMD14.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Proteasome degradation (KEGG hsa03050)
• Ubiquitin mediated proteolysis (KEGG hsa04120)
• p53 signaling pathway (KEGG hsa04115)
Protein Summary
PSMD14 (POH1/Rpn11) is a 310-amino-acid metalloprotease that forms part of the 19S regulatory particle of the 26S proteasome. It contains a JAMM (JAB1/MPN/Mov34) motif that coordinates a zinc ion for catalytic deubiquitination. The enzyme removes ubiquitin chains from proteasome substrates, allowing their translocation into the 20S core for degradation. PSMD14 is essential for cell viability and is implicated in cancer progression, DNA damage response, and immune regulation.
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