Falcon (Edison Scientific) deep research report on rat Aga (P30919, aspartylglucosaminidase)
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Aga is the lysosomal amidase aspartylglucosaminidase (EC 3.5.1.26) that catabolizes N-linked glycoproteins.
"Aspartylglucosaminidase (AGA) is a lysosomal amidase (**EC 3.5.1.26**) required for catabolism of **N-linked glycoproteins**"
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Aga cleaves the Asn-GlcNAc amide bond in glycoasparagine degradation intermediates.
"it cleaves the **amide bond between N-acetylglucosamine (GlcNAc) in the glycan and the asparagine (Asn) side chain** (i.e., the Asn–GlcNAc linkage) in glycoasparagine degradation intermediates."
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Aga is a soluble lysosomal hydrolase, not a cytoplasmic protein.
"AGA is a **soluble lysosomal hydrolase**."
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Aga is trafficked to lysosomes via the mannose-6-phosphate pathway and secreted enzyme can be recaptured by M6P receptor-mediated endocytosis.
"trafficked to lysosomes through the **mannose-6-phosphate (M6P) pathway**, and secreted AGA can be **recaptured by M6P receptor–mediated endocytosis**"
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Aga acts at a terminal step of the lysosomal N-linked glycoprotein degradation pathway.
"AGA functions in the **lysosomal N-linked glycoprotein degradation pathway**, acting at a terminal step in which glycoasparagine intermediates are converted into products that can be fully catabolized."
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Active Aga assembles by self-association of identical alpha/beta heterodimers into an alpha2beta2 tetramer.
"Mature AGA assembles as an active **αβ heterodimer** or more commonly an **α2β2 / (αβ)2 tetramer**, depending on species and preparation."
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Aga is synthesized as a precursor that undergoes autocatalytic cleavage between Asp205 and Thr206, exposing the catalytic N-terminal Thr206 nucleophile (Ntn-hydrolase).
"Precursor molecules dimerize and undergo **autocatalytic cleavage** between **Asp205-Thr206**, generating **α** and **β** subunits; cleavage exposes the catalytic **N-terminal Thr206** nucleophile required for activity."
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Rat liver Aga was purified as a ~49 kDa heterodimer with ~24 kDa alpha and ~20 kDa beta subunits, confirming the alpha/beta processing architecture.
"Rat liver glycosylasparaginase has been purified and characterized as an approximately **49 kDa heterodimer** with subunits around **24 kDa (α)** and **20 kDa (β)**, providing direct rat evidence of the expected α/β processing architecture."
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Aga deficiency causes the lysosomal storage disorder aspartylglucosaminuria (AGU) with accumulation of uncleaved glycoasparagines.
"AGA deficiency causes **aspartylglucosaminuria (AGU)**, a lysosomal storage disorder characterized by accumulation of **uncleaved glycoasparagines/aspartylglucosamine** in tissues and body fluids."