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USP46 belongs to the peptidase C19 family and requires co-activators UAF1/WDR48 and WDR20 for full enzymatic activity. It shares 88% amino acid identity with its paralog USP12 and exhibits tissue-specific expression with high abundance in brain tissues.
Key findings:
Deubiquitinates GluA1/GluA2 subunits, reducing Lys63-linked ubiquitination by 55%
USP46 knockdown decreases surface AMPAR levels by 35% and mEPSC amplitudes by 42% in neurons
Colocalizes with PSD95 at synapses, affecting GABAergic transmission and depressive behaviors in mice
Cancer Pathogenesis
USP46 exhibits tumor-suppressive roles through multiple pathways:
Cancer Type
Mechanism
Clinical Correlation
Lung Cancer
Stabilizes PHLPP1, inhibiting AKT (60% reduction in p-AKT)
Restores chemosensitivity in 65% of resistant cell lines
Clinical and Therapeutic Relevance
Emerging evidence positions USP46 as a potential therapeutic target:
Neurological disorders: USP46 knockout mice show 40% reduced GAD67 levels linked to depression
Cancer therapeutics: USP46 overexpression decreases lung cancer proliferation by 65% in vitro
Diagnostic marker: 2.8-fold lower USP46 expression in chemoresistant ovarian tumors
Product Specs
Introduction
Ubiquitin specific peptidase 46 (USP46) is a member of a large family of cysteine proteases that act as deubiquitinating enzymes. USP46 forms a complex with WD repeat-containing protein 48 (WDR48) to enhance its deubiquitinating activity. This enzyme specifically targets and removes ubiquitin molecules from glutamate decarboxylase 1 (GAD1) and GAD67, thereby regulating their function.
Description
Recombinant human USP46 protein has been produced in E. coli. The protein consists of a single polypeptide chain of 389 amino acids, encompassing residues 1 to 366 of the USP46 sequence, with a molecular weight of 44.8 kDa. A 23-amino acid His-tag is fused to the N-terminus of the protein to facilitate purification using proprietary chromatographic methods.
Physical Appearance
Clear solution that has been sterilized by filtration.
Formulation
The USP46 solution is provided at a concentration of 0.25 mg/ml in a buffer consisting of 20 mM Tris-HCl (pH 8.0), 0.15 M NaCl, 10% glycerol, and 1 mM DTT.
Stability
For short-term storage (2-4 weeks), the solution can be stored at 4°C. For extended storage, it is recommended to store the solution at -20°C. To ensure long-term stability, the addition of a carrier protein such as 0.1% HSA or BSA is advised. Repeated freezing and thawing of the solution should be avoided.
Purity
The purity of the USP46 protein is greater than 90% as assessed by SDS-PAGE analysis.