EC Number | Cloned (Comment) | Organism |
---|---|---|
2.7.8.17 | recombinant expression of C-terminally myc-tagged wild-type and mutant enzymes in HEK-293 cells | Homo sapiens |
EC Number | Protein Variants | Comment | Organism |
---|---|---|---|
2.7.8.17 | C505Y | naturally occuring missense mutation identified in Brazilian mucolipidosis MLII/MLIII alpha/beta patients. The mutant shows 7% of wild-type activity | Homo sapiens |
2.7.8.17 | G575R | naturally occuring missense mutation identified in Brazilian mucolipidosis MLII/MLIII alpha/beta patients. The mutant shows 3% of wild-type activity | Homo sapiens |
2.7.8.17 | I403T | naturally occuring missense mutation identified in Brazilian mucolipidosis MLII/MLIII alpha/beta patients, lack of processing of the mutant alpha/beta-subunit precursor I403T | Homo sapiens |
2.7.8.17 | additional information | the frameshift E757KfsX1 and the non-sense R587X mutations result in the retention of enzymatically inactive truncated precursor proteins in the endoplasmic reticulum due to loss of cytosolic endoplasmic reticulum exit motifs consistent with a severe clinical phenotype in homozygosity. Subcellular localization study of wild-type and mutant enzymes, as well as isolated alpha- and beta-subunits, overview | Homo sapiens |
2.7.8.17 | T1223del | naturally occurig heterozygous mutation identified in Brazilian mucolipidosis MLII/MLIII alpha/beta patients. The mutant T1223del is correctly transported and proteolytically cleaved into mature alpha- and beta-subunits exhibiting 85% of GlcNAc-1-phosphotransferase activity of the wild-type enzyme | Homo sapiens |
2.7.8.17 | T644M | naturally occuring heterozygous mutation identified in Brazilian mucolipidosis MLII/MLIII alpha/beta patients. The mutant T644M is correctly transported and proteolytically cleaved into mature alpha- and beta-subunits exhibiting 50% of GlcNAc-1-phosphotransferase activity of the wild-type enzyme | Homo sapiens |
EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|---|
2.7.8.17 | Golgi apparatus | proteolytic S1P-mediated activation of the alpha/beta-subunit precursor of GlcNAc-1-phosphotransferase into mature subunits occurs in the cis-Golgi apparatus | Homo sapiens | 5794 | - |
2.7.8.17 | membrane | the alpha/beta-subunit precursor is a type III membrane protein of 1256 amino acids with two transmembrane domains. Its exit from the endoplasmic reticulum requires a combinatorial sorting motif located in the N- and C-terminal cytoplasmic tails. The luminal alpha-subunit exhibits a conserved modular structure | Homo sapiens | 16020 | - |
2.7.8.17 | additional information | subcellular localization study of wild-type and mutant enzymes, as well as isolated alpha- and beta-subunits, phenotypes, overview. Amino acid residues at positions I346, W357, S399 and I403 in the stealth domain 2 play an important role for the export of the alpha/beta-subunit precursor from the endoplasmic reticulum | Homo sapiens | - |
- |
EC Number | Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|---|
2.7.8.17 | 45000 | - |
- |
Homo sapiens |
2.7.8.17 | 145000 | - |
- |
Homo sapiens |
2.7.8.17 | 190000 | - |
alpha/beta-subunit enzyme precursor | Homo sapiens |
EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|---|
2.7.8.17 | UDP-N-acetyl-D-glucosamine + lysosomal-enzyme D-mannose | Homo sapiens | - |
UMP + lysosomal-enzyme N-acetyl-D-glucosaminyl-phospho-D-mannose | - |
? |
EC Number | Organism | UniProt | Comment | Textmining |
---|---|---|---|---|
2.7.8.17 | Homo sapiens | Q3T906 | - |
- |
EC Number | Posttranslational Modification | Comment | Organism |
---|---|---|---|
2.7.8.17 | glycoprotein | an N-linked oligosaccharide, hydrolysis by peptide-N-glycosidase F (PNGase F) | Homo sapiens |
2.7.8.17 | proteolytic modification | upon arrival in the Golgi apparatus, the newly synthesized alpha/beta subunit precursor is catalytically activated by site-1 protease (S1P). A stretch of amino acids in the N-terminus of the beta-subunit is essential for precise S1P-mediated cleavage and activity of theGlcNAc-1-phosphotransferase. The proteolytic cleavage of the alpha/beta-subunit precursor protein is a prerequisite for the catalytic activity of the GlcNAc-1-phosphotransferase and therefore plays an important role in the biogenesis of lysosomes. Proteolytic S1P-mediated activation of the alpha/beta-subunit precursor of GlcNAc-1-phosphotransferase into mature subunits occurs in the cis-Golgi apparatus | Homo sapiens |
EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|---|
2.7.8.17 | UDP-N-acetyl-D-glucosamine + alpha-methyl D-mannoside | - |
Homo sapiens | UMP + 6-(N-acetyl-D-glucosaminyl-phospho)-alpha-methyl D-mannoside | - |
? | |
2.7.8.17 | UDP-N-acetyl-D-glucosamine + lysosomal-enzyme D-mannose | - |
Homo sapiens | UMP + lysosomal-enzyme N-acetyl-D-glucosaminyl-phospho-D-mannose | - |
? |
EC Number | Subunits | Comment | Organism |
---|---|---|---|
2.7.8.17 | heterodimer | alphabeta, 1 * 145000, alpha-subunit + 1 * 45000, beta-subunit, about, SDS-PAGE | Homo sapiens |
2.7.8.17 | More | domain organization of the full-length wild-type and mutant apha/beta-subunit precursor protein of the GlcNAc-1-phosphotransferase, overview | Homo sapiens |
EC Number | Synonyms | Comment | Organism |
---|---|---|---|
2.7.8.17 | GlcNAc-1-phosphotransferase | - |
Homo sapiens |
EC Number | Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|---|
2.7.8.17 | 37 | - |
assay at | Homo sapiens |
EC Number | pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|---|
2.7.8.17 | 7.4 | - |
assay at | Homo sapiens |
EC Number | General Information | Comment | Organism |
---|---|---|---|
2.7.8.17 | malfunction | mucolipidosis II (MLII) and III alpha/beta are autosomal-recessive diseases of childhood caused by mutations in GNPTAB encoding the alpha/beta-subunit precursor protein of the GlcNAc-1-phosphotransferase complex. Biological significance of eight selected disease-causing GNPTAB mutations found in MLII and MLIII alpha/beta patients in Brazil, overview. The frameshift E757KfsX1 and the non-sense R587X mutations result in a severe clinical phenotype in homozygosity. In addition to the loss of combinatorial cytosolic targeting motifs, luminal missense mutations located in the stealth region 2 of the alpha-subunit impair the transport of the alpha/beta-subunit precursor to the Golgi apparatus | Homo sapiens |
2.7.8.17 | physiological function | the enzyme modifies lysosomal hydrolases with mannose 6-phosphate targeting signals. The proteolytic cleavage of alpha/beta-subunit precursor protein is a prerequisite for the catalytic activity of the GlcNAc-1-phosphotransferase and therefore plays an important role in the biogenesis of lysosomes | Homo sapiens |