| Topic | Key findings (1-2 sentences) | Quantitative/statistical details | Source (author year journal) | Publication date (month year) | URL | Evidence context id(s) |
|---|---|---|---|---|---|---|
| Identity / complex role | PSMA1 (UniProt P25786) is the human proteasome 20S subunit alpha 1, a **non-catalytic α-ring subunit** of the 20S core particle; the catalytic protease active sites reside in β subunits, not PSMA1. In the 20S/26S architecture, PSMA1 is one of PSMA1-7 forming the outer α rings that regulate access to the proteolytic chamber. | 20S core is arranged as α1-7 β1-7 β1-7 α1-7; the PSM family comprises 49 genes including 19 20S α/β ring subunits. | Larsson et al. 2022 *BMC Cancer* | Sep 2022 | https://doi.org/10.1186/s12885-022-10079-4 | (pqac-00000003) |
| Gate / structure | PSMA1 belongs to the α ring that forms the gated pore of the 20S core; α-subunit N termini create the gate controlling substrate entry, whereas proteolysis is executed by β catalytic subunits. Activator docking and gate opening occur through interactions at α-ring pockets, linking PSMA1 structurally to proteasome regulation rather than catalysis. | α-ring surface binds regulators such as PA700/19S, PA28, and PA200; gate opening is mediated by C-terminal HbYX motifs from regulators inserting between adjacent α subunits. | Xiong et al. 2024 *Frontiers in Molecular Neuroscience*; Steinberger et al. 2023 *Biomolecules* | Jan 2024; Jun 2023 | https://doi.org/10.3389/fnmol.2023.1330853; https://doi.org/10.3390/biom13060992 | (pqac-00000001, pqac-00000014) |
| Assembly / biogenesis | Human 20S biogenesis begins with formation of a complete α ring assisted by PAC1/2 and PAC3/4, followed by ordered β-subunit addition, half-core formation, half-core fusion, and β-propeptide cleavage. These structural studies are directly relevant to PSMA1 because it is one of the α-ring building blocks assembled before catalytic maturation of β sites. | ~3,000 core particles/min are produced in proliferating HeLa cells; total CP copy number is ~4 × 10^6. Five immature intermediates were resolved by cryo-EM at 2.67-2.95 Å; mature CP superimposed with r.m.s.d. 0.703 Å. | Adolf et al. 2024 *Nature Structural & Molecular Biology* | Apr 2024 | https://doi.org/10.1038/s41594-024-01268-9 | (pqac-00000002, pqac-00000022, pqac-00000025) |
| Localization | Proteasomes are present in both cytoplasm and nucleus, and stress can drive formation of nuclear proteasome granules containing 26S complexes. When 26S integrity is perturbed, free 20S-containing complexes remain predominantly nuclear while liberated 19S material accumulates in the cytoplasm, supporting compartment-specific behavior of PSMA1-containing cores. | Under osmotic/salt stress, nuclear 26S granules appear within minutes and peak at ~4-12 min. PSMD1 knockdown causes marked loss of intact 26S and increase in 20S signal; PSMD1-depleted cells die after 4-5 days of doxycycline treatment. | Steinberger et al. 2023 *Biomolecules* | Jun 2023 | https://doi.org/10.3390/biom13060992 | (pqac-00000013, pqac-00000014, pqac-00000015, pqac-00000016) |
| Free 20S substrates / pathway context | PSMA1-containing free 20S particles represent a major proteasome pool and can degrade proteins independently of ubiquitin/26S. Identified substrates are enriched for intrinsically disordered RNA- and DNA-binding proteins, especially nuclear and stress-granule proteins, highlighting a pathway context in stress responses and non-canonical proteostasis. | Approximately half of cellular proteasomes are free 20S; PiP-MS identified 280 candidate 20S substrates from 2,180 cleavage-informative peptides. About 20% of proteins in the proteomic analysis had at least three peptides indicative of 20S cleavage. | Pepelnjak et al. 2024 *Molecular Systems Biology* | Jan 2024 | https://doi.org/10.1038/s44320-024-00015-y | (pqac-00000018, pqac-00000019, pqac-00000020, pqac-00000021) |
| Disease / cancer association | Across TCGA pan-cancer data, PSMA1 expression is frequently elevated in tumors and is associated with worse prognosis in many cancer types, suggesting biomarker value rather than direct catalytic druggability. This aligns with proteasome dependence in cancer, although approved proteasome inhibitors primarily target catalytic β subunits (especially PSMB5), not PSMA1. | ~11,000 TCGA samples across 33 cancer types were analyzed; PSMA1 and PSMD11 were linked to unfavorable OS and PFI in ≥30% of cancer types. | Larsson et al. 2022 *BMC Cancer* | Sep 2022 | https://doi.org/10.1186/s12885-022-10079-4 | (pqac-00000003) |
| Disease / cancer association | In lung squamous cell carcinoma (LUSC), PSMA1 is overexpressed in tumors and behaves as a poor prognostic factor; functional perturbation shows PSMA1 promotes proliferation and suppresses apoptosis in vitro. The study supports PSMA1 as a candidate prognostic biomarker, while noting mechanism remains unresolved. | TCGA comparison used normal n = 52 vs primary tumor n = 503. Survival: OS HR = 1.33 (95% CI 1.05-1.69), log-rank P = 0.017; first progression HR = 1.6 (95% CI 0.93-2.74), P = 0.087. Clinical cohort: 30 patients split into 15 low vs 15 high PSMA1; high expression associated with TNM stage (P = 0.02) and pathological grading (P = 0.046). | Liu et al. 2023 *Disease Markers* | Feb 2023 | https://doi.org/10.1155/2023/5386635 | (pqac-00000009, pqac-00000010, pqac-00000011) |
| AD bioinformatics | In Alzheimer disease transcriptomic analyses, PSMA1 was analyzed as part of the α-ring module (PSMA1-7) together with the ATPase subunit PSMC6. The study suggests coordinated downregulation of α-ring genes and PSMC6 tracks AD progression, but these are computational associations requiring biological validation. | PCA/SVM analyses used GSE1297 and GSE5281; no PSMA1-specific effect size or AUC was provided in the extracted evidence. The authors report decreased total proteasome numbers with progression but inferred compensatory coordination/activity in remaining complexes. | Xiong et al. 2024 *Frontiers in Molecular Neuroscience* | Jan 2024 | https://doi.org/10.3389/fnmol.2023.1330853 | (pqac-00000001, pqac-00000004) |
| Clinical / evidence-platform associations | Open Targets lists PSMA1 disease associations largely reflecting the broader therapeutic relevance of proteasome inhibition in oncology and related disorders; these associations should be interpreted as pathway-level/target-family evidence, not proof that PSMA1 itself is the direct pharmacologic target. | Reported disease associations include neoplasm (score 0.6318), multiple myeloma (0.5999), mantle cell lymphoma (0.5023), HIV infection (0.4771), and amyloidosis (0.3992); evidence rows include approval/Phase 4 records. | Open Targets Platform | Accessed in current session | https://platform.opentargets.org/target/ENSG00000129084 | (pqac-00000000) |


*Table: This table summarizes key evidence for human PSMA1/P25786 across structural biology, localization, free-20S proteostasis, and disease-association studies. It is useful for distinguishing PSMA1’s structural non-catalytic role in the proteasome from the catalytic functions of proteasomal beta subunits and for highlighting recent 2023-2024 findings.*