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Literature summary extracted from

  • van Meel, E.; Qian, Y.; Kornfeld, S.A.
    Mislocalization of phosphotransferase as a cause of mucolipidosis III alphabeta (2014), Proc. Natl. Acad. Sci. USA, 111, 3532-3537.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.8.17 gene GNPTAB, the alphabeta precursors of wild-type, and mutant K4Q or S15Y enzymes with a C-terminal V5-tag are expressed in HEK-293 cells Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.7.8.17 K4Q naturally occurring mutation in the N-terminal cytoplasmic tail of the alpha-subunit leading to a mislocated enzyme, mistargeting of the mutant enzymes to lysosomes, where they are degraded, or to the cell surface and release into the medium, the mutant enzymes shows 32% of wild-type activity. The mutant K4Q alphabeta phosphotransferase contains increased complex-type N-linked glycans. Half-life of the mutant is decreased compared to the wild-type enzyme Homo sapiens
2.7.8.17 S15Y naturally occurring mutation in the N-terminal cytoplasmic tail of the alpha-subunit leading to a mislocated enzyme, mistargeting of the mutant enzymes to lysosomes, where they are degraded, or to the cell surface and release into the medium, but the mutant enzyme shows 41% of wild-type activity. Half-life of the mutant is decreased compared to the wild-type enzyme Homo sapiens
2.7.8.17 S399F a naturally occurring mucolipidosis III, MLIII, alphabeta mutant, the mutant enzyme remains in the endoplasmic reticulum and is not translocated to the Golgi due to reduced proteolytic cleavage of the precursor Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.7.8.17 Golgi apparatus single residues in the cytoplasmic tail of a Golgi-resident protein are important for localization to this compartment Homo sapiens 5794
-
2.7.8.17 additional information the mature Golgi-localized phosphotransferase and a small portion of the alphabeta precursor reach the medial/trans cisternae, where they then undergo retrograde transport to maintain their concentration in the cis-Golgi Homo sapiens
-
-

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
2.7.8.17 41000
-
-
 Homo sapiens
2.7.8.17 45000
-
-
 Homo sapiens
2.7.8.17 190000
-
-
 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 the wild-type inactive alphabeta precursor protein contains a very low amount of complex-type glycans, all of the N-linked glycans are of the high mannose-type, which is consistent with its endoplasmic reticulum localization. The mutant K4Q alphabeta phosphotransferase contains increased complex-type N-linked glycans 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 ? x * 190000, inactive mutant alphabeta precursor, SDS-PAGE, x * 45000, K4Q mutant beta subunit, SDS-PAGE, x * 41000, S15Y mutant beta subunit, SDS-PAGE Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
2.7.8.17 GNPTAB
-
 Homo sapiens
2.7.8.17 UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-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 loss of function results in impaired lysosomal targeting of these acid hydrolases and decreased lysosomal degradation. Two mucolipidosis III patient missense mutations, Lys4Gln and Ser15Tyr, in the N-terminal cytoplasmic tail of the alpha-subunit of phosphotransferase impair retention of the catalytically active enzyme in the Golgi complex. This results in mistargeting of the mutant enzymes to lysosomes, where they are degraded, or to the cell surface and release into the medium. The mislocalization of the active enzymes is the basis for mucolipidosis III alphabeta in a subset of patients Homo sapiens
2.7.8.17 physiological function the Golgi-localized enzyme mediates the first step in the synthesis of the mannose 6-phosphate recognition marker on lysosomal acid hydrolases Homo sapiens