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.

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 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
Displaying Records 1 To 4 Of 4 Records
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