PSMA3 Gene

The PSMA3 gene (PSMA3 stands for proteasome 20S subunit alpha 3) is a protein-coding gene located on chromosome 14q23.1. Two alternative transcripts encoding different isoforms have been identified.

Proteasome subunit alpha7 is a component of the 20S core proteasome complex, which is involved in the proteolytic degradation of most intracellular proteins. This complex plays an important role within the cell by associating with various regulatory particles. Proteasome subunit alpha7, together with two 19S regulatory particles, forms the 26S proteasome and is thus involved in the ATP-dependent degradation of ubiquitinated proteins.

The 26S proteasome plays a key role in maintaining protein homeostasis by removing misfolded or damaged proteins that may impair cellular functions and degrading proteins whose functions are no longer required.

In conjunction with PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required for several processes, including spermatogenesis (20S-PA200 complex) or the formation of a subset of MHC class I-presenting antigenic peptides (20S-PA28 complex).

Binds to the C-terminus of CDKN1A, thereby mediating its degradation. Negatively regulates membrane trafficking of cell surface thromboxane A2 receptor (TBXA2R) isoform 2.

Diseases associated with PSMA3 include:

• cystic fibrosis (cystic fibrosis)
• nodular episcleritis.
• An autosomal recessive mutation in PSMA3 leads to panniculitis, lipodystrophy and autoimmune hemolytic anemia via increased IFN synthesis (mechanism is yet unknown).

The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure consists of 4 rings with 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed in high concentration in eukaryotic cells and cleave peptides in an ATP/ubiquitin-dependent process by a non-lysosomal pathway. A major function of a modified proteasome, the immunoproteasome, is to process class I MHC peptides. This gene encodes a member of the peptidase T1A family, i.e., a 20S core alpha subunit.

1. Abeliovich D et al (1992) Screening for five mutations detects 97% of cystic fibrosis (CF) chromosomes and predicts a carrier frequency of 1:29 in the Jewish Ashkenazi population. Am J Hum Genet 51: 951-956.
2. Allan JL et al (1981) Familial occurrence of meconium ileus. Europ J Pediat 135: 291-292.
3. Azad AK et al (2009) Mutations in the amiloride-sensitive epithelial sodium channel in patients with cystic fibrosis-like disease. Hum. Mutat 30: 1093-1103.
4. Barreto C et al (1991) A fertile male with cystic fibrosis: molecular genetic analysis. J Med Genet 28: 420-421.
5. Brehm A et al (2015) Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production. J Clin Invest 125:4196-211.
6. Cao X et al (2021) Targeting lncRNA PSMA3-AS1, a Prognostic Marker, Suppresses Malignant Progression of Oral Squamous Cell Carcinoma. Dis Markers: 3138046.
7. Yadav S et al (2015) Tubercular nodular episcleritis: A Case Report. J Clin Diagn Res 9:ND01-2.
8. Zhou LL et al (2020) Long non-coding RNA PSMA3-AS1 enhances cell proliferation, migration and invasion by regulating miR-302a-3p/RAB22A in glioma. Biosci Rep 40:BSR20191571.