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NAGPA

Domain

The tyrosine-based internalization signal may be essential for its retrieval from the plasma membrane to the TGN.

The C-terminal NPFKD sequence is an attractive candidate for either an endocytosis signal acting at the plasma membrane or a retrieval signal acting at the TGN to return the enzyme to the cis/medial-Golgi.

Function

Catalyzes the second step in the formation of the mannose 6-phosphate targeting signal on lysosomal enzyme oligosaccharides by removing GlcNAc residues from GlcNAc-alpha-P-mannose moieties, which are formed in the first step. Also hydrolyzes UDP-GlcNAc, a sugar donor for Golgi N-acetylglucosaminyltransferases.

Involvement in disease

Defects in NAGPA have been suggested to play a role in susceptibility to persistent stuttering. Stuttering is a common speech disorder characterized by repetitions, prolongations, and interruptions in the flow of speech.

Pathway

Protein modification; protein glycosylation.

Post-translational modifications

The precursor is cleaved and activated in the trans-Golgi network by a furin endopeptidase.

Tissue Specificity

Isoform 2 may be brain-specific.

Cellular localization

Alternative names

N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase, Mannose 6-phosphate-uncovering enzyme, Phosphodiester alpha-GlcNAcase, NAGPA

swissprot:Q9UK23 entrezGene:51172 omim:607985