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Molecular analysis of the GlcNac‐1‐phosphotransferase
Author(s) -
Braulke T.,
Pohl S.,
Storch S.
Publication year - 2008
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-008-0862-5
Subject(s) - human genetics , phosphotransferase , phosphotransferases , chemistry , biochemistry , computational biology , biology , kinase , phosphorylation , gene
Summary Modification of the carbohydrate chains of soluble lysosomal enzymes with mannose 6‐phosphate residues is a prerequisite for their mannose 6‐phosphate receptor‐dependent transport to lysosomes. GlcNac‐1‐phosphotransferase localized in the Golgi apparatus represents a hexameric α 2 β 2 γ 2 subunit complex and plays a key role in the formation of the mannose 6‐phosphate recognition marker. Defects in the GlcNac‐1‐phosphotransferase complex cause two diseases, mucolipidosis type II and III, which are characterized by missorting and cellular loss of lysosomal enzymes, and lysosomal accumulation of storage material. The recent identification of two genes, GNPTAB and GNPTG , encoding the three subunits of GlcNac‐1‐phosphotransferase leads to an improvement of both pre‐ and postnatal diagnosis of affected individuals, and permits the analysis of structural requirements for efficient formation of mannose 6‐phosphate residues on lysosomal enzymes. The α/β subunits precursor matures by proteolytic cleavage and contains the catalytic activity as well as the capability to recognize lysosomal enzymes. The role of the γ‐subunits for activity, stability and oligomerization of the GlcNac‐1‐phosphotransferase subunits is still unclear.