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Literature summary for 2.7.8.17 extracted from

  • van Meel, E.; Lee, W.S.; Liu, L.; Qian, Y.; Doray, B.; Kornfeld, S.
    Multiple domains of GlcNAc-1-phosphotransferase mediate recognition of lysosomal enzymes (2016), J. Biol. Chem., 291, 8295-8307.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

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

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

Localization Comment Organism GeneOntology No. Textmining
Golgi apparatus
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Homo sapiens 5794
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Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
UDP-N-acetyl-D-glucosamine + lysosomal-enzyme D-mannose Homo sapiens
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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

Organism UniProt Comment Textmining
Homo sapiens Q3T906 AND Q9UJJ9 alpha/beta-, and gamma-subunit encoding genes
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
UDP-N-acetyl-D-glucosamine + lysosomal-enzyme D-mannose
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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

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

Synonyms Comment Organism
GlcNAc-1-phosphotransferase
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Homo sapiens
UDP-GlcNAc:lysosomal enzymeN-acetylglucosamine-1-phosphotransferase
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Homo sapiens

General Information

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