Cloned (Comment) | Organism |
---|---|
plasmids encoding WT and K732N alpha/beta cDNA with C-terminal V5/His tags are generated and transfected into HEK-293 cells and monitoring of the proteolytic cleavage of the alpha/beta precursor by the appearance of the mature V5-tagged beta-subunit. Recombinant expression of wild-type and mutant GST-DMAP domain | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
K732N | naturally occurring mutation in the DMAP interaction domain of the alpha-subunit identified in a patient with mucolipidosis II, the mutant exhibits full activity toward the simple sugar alpha-methyl D-mannoside but impaired phosphorylation activity toward acid hydrolases. The K732N mutation does not impair the transport of the alpha/beta precursor from the endoplasmic reticulum to the Golgi, nor the proteolytic cleavage that generates the alpha and beta subunits. Recombinant expression of the K732N mutant in a zebrafish model of mucolipidosis II fails to correct the phenotypic abnormalities | 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 | substrates are lysosomal acid hydrolases | UMP + lysosomal-enzyme N-acetyl-D-glucosaminyl-phospho-D-mannose | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q3T906 AND Q9UJJ9 | alpha/beta-, and gamma-subunit encoding genes | - |
Posttranslational Modification | Comment | Organism |
---|---|---|
proteolytic modification | proteolytic cleavage of the alpha/beta enzyme precursor | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
UDP-N-acetyl-D-glucosamine + alpha-methyl-D-mannoside | - |
Homo sapiens | UMP + 6-(N-acetyl-D-glucosaminyl-phospho)-alpha-methyl D-mannoside | - |
? | |
UDP-N-acetyl-D-glucosamine + lysosomal-enzyme D-mannose | substrates are lysosomal acid hydrolases | Homo sapiens | UMP + lysosomal-enzyme N-acetyl-D-glucosaminyl-phospho-D-mannose | - |
? | |
UDP-N-acetyl-D-glucosamine + lysosomal-enzyme D-mannose | the specificity of the reaction is determined by the ability of the alpha/beta subunits to recognize a conformation-dependent protein determinant present on the acid hydrolases, the DNA methyltransferase-associated protein (DMAP) interaction domain of the alpha subunit functions in this recognition process. Recombinant GST-DMAP domain pulls down several acid hydrolases, but not nonlysosomal glycoproteins | Homo sapiens | UMP + lysosomal-enzyme N-acetyl-D-glucosaminyl-phospho-D-mannose | - |
? |
Subunits | Comment | Organism |
---|---|---|
heterohexamer | alpha2beta2gamma2 | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
GlcNAc-1-phosphotransferase | - |
Homo sapiens |
UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | recombinant GlcNAc-1-phosphotransferase containing a missense mutation in the DMAP interaction domain (Lys732Asn) identified in a patient with mucolipidosis II exhibits full activity toward the simple sugar alpha-methyl D-mannoside but impaired phosphorylation activity toward acid hydrolases, recombinant expression of the K732N mutant in a zebrafish model of mucolipidosis II fails to correct the phenotypic abnormalities | Homo sapiens |
physiological function | UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase mediates the initial step in the formation of the mannose 6-phosphate recognition signal on lysosomal acid hydrolases. The DMAP interaction domain of the alpha subunit functions in the selective recognition of acid hydrolase substrates | Homo sapiens |