USP46 Human

Ubiquitin Specific Peptidase 46 Human Recombinant
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Description

Overview of USP46 Human

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 TypeMechanismClinical Correlation
Lung CancerStabilizes PHLPP1, inhibiting AKT (60% reduction in p-AKT) Downregulated in 78% of NSCLC samples
Hepatocellular CarcinomaPromotes MST1-mediated YAP1 degradation (3.2-fold tumor suppression) Low USP46 correlates with poor survival (HR=2.1)
Ovarian CancerModulates Bcl-2/caspase-3 axis, enhancing cisplatin sensitivity 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.
Synonyms
Ubiquitin carboxyl-terminal hydrolase 46, Deubiquitinating enzyme 46, Ubiquitin thioesterase 46, Ubiquitin-specific-processing protease 46, USP46.
Source
Escherichia Coli.
Amino Acid Sequence
MGSSHHHHHH SSGLVPRGSH MGSMTVRNIA SICNMGTNAS ALEKDIGPEQ FPINEHYFGL VNFGNTCYCN SVLQALYFCR PFRENVLAYK AQQKKKENLL TCLADLFHSI ATQKKKVGVI PPKKFISRLR KENDLFDNYM QQDAHEFLNY LLNTIADILQ EEKKQEKQNG KLKNGNMNEP AENNKPELTW VHEIFQGTLT NETRCLNCET VSSKDEDFLD LSVDVEQNTS ITHCLRDFSN TETLCSEQKY YCETCCSKQE AQKRMRVKKL PMILALHLKR FKYMEQLHRY TKLSYRVVFP LELRLFNTSS DAVNLDRMYD LVAVVVHCGS GPNRGHYITI VKSHGFWLLF DDDIVEKIDA QAIEEFYGLT SDISKNSESG YILFYQSRE.

Product Science Overview

References

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