Cloned (Comment) | Organism |
---|---|
genes GNPTABG encode the alpha2beta2gamma2 enzyme, generation of generate alpha/beta and gamma bicistronic constructs, recombinant expression of HA-tagged wild-type and GNPTAB-/- and GNPTG-/- mutant enzymes in HeLa cells, recombinant expression of domain deletion mutants in HEK-293 cells | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | construction of GNPTAB-/- and GNPTG-/- mutant enzymes, all three alleles of GNPTAB are disrupted with one allele having a 17-bp deletion, c.216_232del, whereas the other two alleles have a 1-bp deletion c.221delC. The gamma-subunit-deficient DELTAN1-DMAP mutant has catalytic activity but is unable to phosphorylate lysosomal enzymes. Deletion of Notch 2 strongly inhibits phosphorylation of all the glycosidases, whereas deletion of Notch 1 is less detrimental, with levels of phosphorylation ranging from 100% down to 60% of wild-type activity. The effect of deleting the DMAP interaction domain is also variable, ranging from a 10% decrease in phosphorylation relative to wild-type to a 64% decrease in alpha-Man phosphorylation. Deletion of the S2 domain, which results in the loss of binding of the gamma-subunit, strongly inhibits phosphorylation of all the glycosidases | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
Golgi apparatus | - |
Homo sapiens | 5794 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
UDP-N-acetyl-D-glucosamine + lysosomal-enzyme D-mannose | Homo sapiens | - |
UMP + lysosomal-enzyme N-acetyl-D-glucosaminyl-phospho-D-mannose | localization of tagged protein products in the Golgi of wild-type and mutant enzymes expressing HeLa cells, overview | ? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q3T906 AND Q9UJJ9 | alpha/beta-, and gamma-subunit encoding genes | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
UDP-N-acetyl-D-glucosamine + lysosomal-enzyme D-mannose | - |
Homo sapiens | UMP + lysosomal-enzyme N-acetyl-D-glucosaminyl-phospho-D-mannose | - |
? | |
UDP-N-acetyl-D-glucosamine + lysosomal-enzyme D-mannose | - |
Homo sapiens | UMP + lysosomal-enzyme N-acetyl-D-glucosaminyl-phospho-D-mannose | localization of tagged protein products in the Golgi of wild-type and mutant enzymes expressing HeLa cells, overview | ? |
Subunits | Comment | Organism |
---|---|---|
hexamer | alpha2beta2gamma2 | Homo sapiens |
More | the gamma-subunit contains two recognizable domains as follows: a Man-6-P receptor homology (MRH) domain and a DMAP interaction domain. The MRH domain contains residues critical for mannose binding, but it lacks those needed for phosphate binding. The gamma-subunit binds to the spacer region (residues 535-694) of the alpha-subunit. The two Notch repeat modules and the DNA methyltransferase-associated protein interaction domain of the alpha-subunit are key components of the substrate recognition process | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
GlcNAc-1-phosphotransferase | - |
Homo sapiens |
UDP-GlcNAc:lysosomal enzymeN-acetylglucosamine-1-phosphotransferase | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
physiological function | the enzyme mediates the initial step in the addition of the mannose 6-phosphate targeting signal on newly synthesized lysosomal enzymes, which serves to direct the lysosomal enzymes to lysosomes. GlcNAc-1-phosphotransferase is able to distinguish the about 60 lysosomal enzymes from the numerous nonlysosomal glycoproteins with identical Asn-linked glycans, that lack a common structural motif. The two Notch repeat modules and the DNA methyltransferase-associated protein interaction domain of the alpha-subunit are key components of this recognition process. Different combinations of these domains are involved in binding to individual lysosomal enzymes. In the majority of instances the mannose 6-phosphate receptor homology domain of the gamma-subunit is required for optimal phosphorylation, the gamma-binding site is located on the alpha-subunit, the gamma-subunit binds to amino acids 535-694 of the alpha-subunit | Homo sapiens |