| Aspect | Key points (concise) | Evidence type (review/primary/computational/patient cohort/database) | Key citations (pqac ids) | Publication year(s) and URL(s) when available |
|---|---|---|---|---|
| Identity / complex membership | Human **PSMB5** encodes the constitutive **20S proteasome β5 catalytic subunit** (older alias **LMPX**), one of the three active β subunits in the 20S core and part of the 26S proteasome. | Review; primary; database | (pqac-00000001, pqac-00000003, pqac-00000020, pqac-00000000) | 2022, https://doi.org/10.3390/cells11030421; 2025, https://doi.org/10.1038/s41467-025-56867-x; 2023, https://doi.org/10.3389/fmed.2023.1209425; OpenTargets context: multiple myeloma association (pqac-00000000) |
| Catalytic activity & substrate specificity | β5 provides the **chymotrypsin-like (CT-L)** activity of the proteasome and preferentially cleaves **after hydrophobic residues**; β5 can also display branched/small neutral amino-acid preferences in some analyses. | Review; dissertation/research synthesis | (pqac-00000006, pqac-00000007, pqac-00000008, pqac-00000009) | 2024, https://doi.org/10.5282/edoc.33581; 2022, https://doi.org/10.3390/cells11030421; 2024, https://doi.org/10.3389/fphar.2024.1351565 |
| Catalytic mechanism (Thr1) | Proteolysis uses the **N-terminal Thr1** nucleophile; Thr1 hydroxyl attacks the peptide carbonyl to form an acyl-enzyme intermediate, later hydrolyzed to release products. | Review; computationally framed structural study | (pqac-00000010, pqac-00000015) | 2022, https://doi.org/10.3390/cells11030421; 2024, https://doi.org/10.3389/fchem.2023.1322628 |
| Maturation / propeptide processing | Catalytic β subunits are synthesized with propeptides that are **autolyzed between Gly and Thr**, exposing active **Thr1**; β5 propeptide also contributes to **20S assembly**. | Review | (pqac-00000001, pqac-00000007) | 2022, https://doi.org/10.3390/cells11030421 |
| Localization & proteasome architecture | β5 active sites are buried inside the **central chamber** of the barrel-shaped 20S core (αββα arrangement); 26S proteasome degrades **ubiquitin-tagged cytosolic proteins** and access is controlled by regulatory caps/gates. | Review; dissertation/research synthesis | (pqac-00000006, pqac-00000009, pqac-00000011) | 2024, https://doi.org/10.5282/edoc.33581; 2024, https://doi.org/10.3389/fphar.2024.1351565; figure context from 2022 review: https://doi.org/10.3390/cells11030421 |
| Role in antigen presentation | Proteasome cleavage products feed **MHC class I antigen presentation**; proteasome subtype composition changes cleavage preferences and peptide repertoire, with β5/β5i activity shaping hydrophobic C-termini favored for MHC-I loading. | Review | (pqac-00000005, pqac-00000010) | 2022, https://doi.org/10.3390/cells11030421 |
| Proteasome inhibitor targeting (bortezomib/carfilzomib/ixazomib) & approval years | Approved proteasome inhibitors clinically exploit β5/CT-L activity: **bortezomib** binds/inhibits β5 and was first FDA-approved in **2003**; **carfilzomib** irreversibly targets CT-L/β5 and was approved in **2012**; **ixazomib** is the first oral PI, approved in **2015**. Bortezomib forms covalent interactions via **Thr1**; carfilzomib is an epoxyketone CT-L inhibitor. | Review; clinical/translational review | (pqac-00000020, pqac-00000021, pqac-00000022, pqac-00000013) | 2023, https://doi.org/10.3389/fmed.2023.1209425; 2025, https://doi.org/10.26434/chemrxiv-2025-v5w42; 2026, https://doi.org/10.3389/fphar.2026.1806787 |
| Resistance mutations (A49T/A50V/C52F) & effects | Active-site pocket mutations **A49T, A50V, C52F** in β5/PSMB5 are linked to PI resistance models; 2024 MD/docking analysis predicted **C52F** most strongly disrupts ligand binding. A49T is also shown structurally in β5-bound BTZ models. | Computational structural study; review | (pqac-00000015, pqac-00000017, pqac-00000022, pqac-00000025) | 2024, https://doi.org/10.3389/fchem.2023.1322628; 2026, https://doi.org/10.3389/fphar.2026.1806787 |
| Non-mutational resistance (upregulation, autophagy shift) | PI resistance can also arise through **PSMB5 upregulation/subunit replacement** and compensatory **autophagy**. In MM, post-treatment PSMB5 reduction with increased LC3II supports a shift from proteasomal to autophagic degradation; reviews also cite PSMB5 overexpression as a resistance mechanism. | Patient cohort; review; translational review | (pqac-00000016, pqac-00000018, pqac-00000019, pqac-00000024) | 2025, https://doi.org/10.3390/cimb47010032; 2026, https://doi.org/10.3389/fphar.2026.1806787 |
| Quantitative statistics | Reported proteasome product lengths: **~5–18 aa** or mean **~6–9 aa**; proteasome directly cleaves **~10–15%** of peptide bonds. In a **110-patient** MM cohort, post-PI PSMB5 decreased (**p=0.014**), proteasome activity decreased (**p<0.001**), LC3II increased (**p=0.041**), relapse ROS increased (**p<0.001**), and baseline PSMB5 cutoff 1.06 associated with disease-free survival **12.0 ± 6.7 vs 36 ± 12.1 months (p<0.001)**. | Review; dissertation/research synthesis; patient cohort | (pqac-00000006, pqac-00000009, pqac-00000024) | 2024, https://doi.org/10.5282/edoc.33581; 2024, https://doi.org/10.3389/fphar.2024.1351565; 2025, https://doi.org/10.3390/cimb47010032 |
| Disease associations (OpenTargets multiple myeloma) | OpenTargets lists **PSMB5–multiple myeloma** association with clinical-stage evidence, including **approval-stage** and **phase 4** links; this aligns with real-world therapeutic targeting of the β5 site in myeloma. | Database | (pqac-00000000) | OpenTargets context retrieved in this session (multiple myeloma association for PSMB5) |


*Table: This table condenses the main functional annotation findings for human PSMB5, including core enzymology, proteasome context, therapeutic targeting, resistance mechanisms, and quantitative clinical data. It is useful as a quick-reference evidence map linking each annotation point to specific cited contexts.*