PSMD10: Proteasome 26S Subunit, Non-ATPase 10
A multifunctional proteasome regulatory subunit implicated in oncogenesis and cell cycle control
Gene Information Card
| Symbol | PSMD10 |
|---|---|
| Full Name | Proteasome 26S Subunit, Non-ATPase 10 |
| Gene Type | Protein coding |
| Chromosomal Location | Xq22.3 |
| NCBI Gene ID | 5716 ncbi.nlm.nih.gov/gene/5716 |
| Ensembl ID | ENSG00000101843 |
| UniProt ID | O75832 |
| OMIM ID | 300869 |
| HGNC ID | 9558 |
| Aliases | Gankyrin, p28, p28(GANK) |
Description
PSMD10 encodes a non-ATPase subunit of the 19S regulatory particle of the 26S proteasome. The protein, also known as Gankyrin or p28, is a key component in the ubiquitin-proteasome system, facilitating substrate recognition and deubiquitination. Beyond proteasomal function, PSMD10 acts as an oncoprotein by binding to the retinoblastoma protein (RB1) and promoting its degradation, thereby driving cell cycle progression. It is overexpressed in multiple cancers, including hepatocellular carcinoma, colorectal cancer, and breast cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | PSMD10 overexpression promotes RB1 degradation and enhances cyclin D1/CDK4 activity, accelerating G1/S transition. | PMID: 15694340; NCBI Gene |
| Colorectal cancer | Elevated PSMD10 levels correlate with poor prognosis; drives proliferation via NF-κB and Wnt/β-catenin pathways. | PMID: 23238567; COSMIC |
| Breast cancer | PSMD10 amplification and overexpression linked to tamoxifen resistance and increased metastasis. | PMID: 25636841; ClinVar |
| Cervical cancer | PSMD10 upregulation contributes to HPV-independent tumor growth by stabilizing MDM2 and inhibiting p53. | PMID: 27323850; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Testis | 8.3 | Medium |
| Lymph node | 6.1 | Low |
| Bone marrow | 4.7 | Low |
| Brain | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line |
| HeLa | 10.8 | Cervical adenocarcinoma cell line |
| MCF7 | 9.4 | Breast cancer cell line |
| A549 | 7.6 | Lung carcinoma cell line |
| K562 | 5.3 | Chronic myelogenous leukemia cell line |
Data source:Human Protein Atlas(proteinatlas.org)
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Likely loss of start codon; predicted loss of function |
| c.287C>T (p.Pro96Leu) | Missense | 0.2% | Unknown significance; reported in COSMIC |
| c.512G>A (p.Arg171Gln) | Missense | 0.1% | Reported in hepatocellular carcinoma; functional impact unclear |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported; PSMD10 is essential for proteasome assembly and cell viability.
Gain of Function (GOF)
Overexpression and amplification are the primary gain-of-function mechanisms in cancer; specific activating mutations are not documented.
Dominant Negative (DN)
No dominant-negative mutations described in the literature.
View complete mutation data:
Gene Ontology (GO)
Pathways
• Ubiquitin-mediated proteolysis (KEGG: hsa04120)
• Proteasome (KEGG: hsa03050)
• Cell cycle - G1/S transition (Reactome: R-HSA-69206)
• p53 signaling pathway (KEGG: hsa04115)
Protein Summary
PSMD10 encodes Gankyrin, a 226-amino acid protein (25.6 kDa) containing six ankyrin repeats. It is a component of the 19S regulatory particle base subcomplex, where it interacts with PSMD2 and PSMC6. Gankyrin binds directly to the retinoblastoma protein (RB1) via its ankyrin repeats, promoting RB1 ubiquitination and degradation. It also interacts with MDM2, enhancing p53 degradation. Overexpression of PSMD10 is oncogenic and correlates with poor prognosis in multiple cancers. The protein is predominantly cytoplasmic but can shuttle to the nucleus.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PSMD10 Knockout HEK293 Cell Line | EDJ-KQ3091 | Human | 5716 | Details Get a Quote |
| PSMD10 Knockout HCT 116 Cell Line | EDJ-KQ23024 | Human | 5716 | Details Get a Quote |
| PSMD10 Knockout A-549 Cell Line | EDJ-KQ24400 | Human | 5716 | Details Get a Quote |
| PSMD10 Knockout HeLa Cell Line | EDJ-KQ24402 | Human | 5716 | Details Get a Quote |
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