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Literature summary extracted from

  • Velho, R.V.; De Pace, R.; Kluender, S.; Sperb-Ludwig, F.; Lourenco, C.M.; Schwartz, I.V.; Braulke, T.; Pohl, S.
    Analyses of disease-related GNPTAB mutations define a novel GlcNAc-1-phosphotransferase interaction domain and an alternative site-1 protease cleavage site (2015), Hum. Mol. Genet., 24, 3497-3505.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

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

Protein Variants

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

Localization

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
-
-

Molecular Weight [Da]

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

Natural Substrates/ Products (Substrates)

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
-
?

Organism

EC Number Organism UniProt Comment Textmining
2.7.8.17 Homo sapiens Q3T906
-
-

Posttranslational Modification

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

Substrates and Products (Substrate)

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
-
?

Subunits

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

Synonyms

EC Number Synonyms Comment Organism
2.7.8.17 GlcNAc-1-phosphotransferase
-
Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.7.8.17 37
-
assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.7.8.17 7.4
-
assay at Homo sapiens

General Information

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