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Name^help_outline N⁴-[α-D-mannosyl-(1→2)-α-D-mannosyl-(glycan)]-L-asparaginyl-[protein] Identifier RHEA-COMP:14507 Reactive part ^help_outline
- Name ^help_outline N⁴-[α-D-mannosyl-(1→2)-α-D-mannosyl-glycan]-L-asparagine residue Identifier CHEBI:140357 Charge 0 Formula C16H26N2O13R SMILES^help_outline [C@H]1([C@H](O[C@@H]([C@H]([C@@H]1O)O)CO)O*NC(C[C@@H](C(*)=O)N*)=O)O[C@@H]2[C@@H]([C@H]([C@H]([C@H](O2)CO)O)O)O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Search links Involved in 1 reaction(s) Find proteins in UniProtKB for this molecule
Name ^help_outline UDP-N-acetyl-α-D-glucosamine Identifier CHEBI:57705 (Beilstein: 4286654) ^help_outline Charge -2 Formula C17H25N3O17P2 InChIKey^help_outline LFTYTUAZOPRMMI-CFRASDGPSA-L SMILES^help_outline CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OP([O-])(=O)OP([O-])(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)n1ccc(=O)[nH]c1=O 2D coordinates Mol file for the small molecule Search links Involved in 88 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name ^help_outline H⁺ Identifier CHEBI:15378 Charge 1 Formula H InChIKey^help_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILES^help_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,431 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name^help_outline N⁴-[6-(N-acetyl-α-D-glucosaminyl-1-phospho)-α-D-mannosyl-(1→2)-α-D-mannosyl-(glycan)]-L-asparaginyl-[protein] Identifier RHEA-COMP:14508 Reactive part ^help_outline
- Name ^help_outline N⁴-[6-(N-acetyl-α-D-glucosaminyl-1-phospho)-α-D-mannosyl-(1→2)-α-D-mannosyl-glycan]-L-asparagine residue Identifier CHEBI:140369 Charge -1 Formula C24H39N3O21PR SMILES^help_outline [C@H]1([C@H](O[C@@H]([C@H]([C@@H]1O)O)CO)O*NC(C[C@@H](C(*)=O)N*)=O)O[C@@H]2[C@@H]([C@H]([C@H]([C@H](O2)COP(O[C@@H]3[C@@H]([C@H]([C@@H]([C@H](O3)CO)O)O)NC(C)=O)([O-])=O)O)O)O 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Search links Involved in 2 reaction(s) Find proteins in UniProtKB for this molecule
Name ^help_outline UMP Identifier CHEBI:57865 (Beilstein: 3570858) ^help_outline Charge -2 Formula C9H11N2O9P InChIKey^help_outline DJJCXFVJDGTHFX-XVFCMESISA-L SMILES^help_outline O[C@@H]1[C@@H](COP([O-])([O-])=O)O[C@H]([C@@H]1O)n1ccc(=O)[nH]c1=O 2D coordinates Mol file for the small molecule Search links Involved in 53 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule

Cross-references

	RHEA:13581	RHEA:13582	RHEA:13583	RHEA:13584
Reaction direction	undefined	left-to-right	right-to-left	bidirectional
UniProtKB ^help_outline	3 proteins
EC numbers ^help_outline	2.7.8.17
Gene Ontology ^help_outline	GO:0003976
KEGG ^help_outline				R04291
MetaCyc ^help_outline		2.7.8.17-RXN

Publications

Subcellular location of two enzymes involved in the synthesis of phosphorylated recognition markers in lysosomal enzymes.

Waheed A., Pohlmann R., Hasilik A., von Figura K.

Phosphorylated recognition markers in lysosomal enzyme appear to be synthesized by transfer of alpha-N-acetylglucosamine 1-phosphate groups to C6 hydroxyl of mannose residues in glycosylated enzyme precursors and a subsequent hydrolysis from the diester groups of the N-acetylglucosamine residues. ... >> More

Phosphorylated recognition markers in lysosomal enzyme appear to be synthesized by transfer of alpha-N-acetylglucosamine 1-phosphate groups to C6 hydroxyl of mannose residues in glycosylated enzyme precursors and a subsequent hydrolysis from the diester groups of the N-acetylglucosamine residues. The transfer and the diesterase activities were studied in subcellular fractions of rat liver. Both activities fractionated like the Golgi marker galactosyltransferase. << Less

J Biol Chem 256:4150-4152(1981) [PubMed] [EuropePMC]
UDP-N-acetylglucosamine:glycoprotein N-acetylglucosamine-1-phosphotransferase. Proposed enzyme for the phosphorylation of the high mannose oligosaccharide units of lysosomal enzymes.

Reitman M.L., Kornfeld S.

The recognition marker for the targeting of lysosomal enzymes contains mannose 6-phosphate. The recent discovery of phosphate in diester linkage between N-acetylglucosamine (GlcNAc) and mannose in newly synthesized beta-glucuronidase led to the proposal that the phosphate might be acquired via N-a ... >> More

The recognition marker for the targeting of lysosomal enzymes contains mannose 6-phosphate. The recent discovery of phosphate in diester linkage between N-acetylglucosamine (GlcNAc) and mannose in newly synthesized beta-glucuronidase led to the proposal that the phosphate might be acquired via N-acetylglucosamine-phosphate transfer from UDP-GlcNAc (Tabas, I., and Kornfeld, S. (1980) J. Biol. Chem. 255, 6633-6639). We describe the synthesis of [beta-32P]UDP-[3H]GlcNAc and the use of this compound to demonstrate a UDP-GlcNAc:glycoprotein N-acetylglucosamine-1-phosphotransferase. The basis of the enzyme assay is the incorporation of 32P and 3H into glycopeptides with a high affinity for Concanavalin A-Sepharose. This membrane-associated transferase is neither inhibited by tunicamycin nor stimulated by dolichol-phosphate, indicating that the reaction does not proceed via a dolichylpyrophosphoryl-N-acetylglucosamine intermediate. Characterization of the enzyme reaction products (derived from either endogenous or exogenous acceptors) demonstrated that alpha-linked N-acetylglucosamine 1-phosphate is transferred en bloc to the 6-hydroxyl of mannose in high mannose oligosaccharides of glycoproteins. We propose that the function of this enzyme is to donate N-acetylglucosamine 1-phosphate to mannose residues of newly synthesized lysosomal enzymes. << Less

J Biol Chem 256:4275-4281(1981) [PubMed] [EuropePMC]
Functions of the alpha, beta, and gamma subunits of UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase.

Qian Y., Lee I., Lee W.S., Qian M., Kudo M., Canfield W.M., Lobel P., Kornfeld S.

UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase is an alpha(2)beta(2)gamma(2) hexamer that mediates the first step in the synthesis of the mannose 6-phosphate recognition marker on lysosomal acid hydrolases. Using a multifaceted approach, including analysis of acid hydrolase p ... >> More

UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase is an alpha(2)beta(2)gamma(2) hexamer that mediates the first step in the synthesis of the mannose 6-phosphate recognition marker on lysosomal acid hydrolases. Using a multifaceted approach, including analysis of acid hydrolase phosphorylation in mice and fibroblasts lacking the gamma subunit along with kinetic studies of recombinant alpha(2)beta(2)gamma(2) and alpha(2)beta(2) forms of the transferase, we have explored the function of the alpha/beta and gamma subunits. The findings demonstrate that the alpha/beta subunits recognize the protein determinant of acid hydrolases in addition to mediating the catalytic function of the transferase. In mouse brain, the alpha/beta subunits phosphorylate about one-third of the acid hydrolases at close to wild-type levels but require the gamma subunit for optimal phosphorylation of the rest of the acid hydrolases. In addition to enhancing the activity of the alpha/beta subunits toward a subset of the acid hydrolases, the gamma subunit facilitates the addition of the second GlcNAc-P to high mannose oligosaccharides of these substrates. We postulate that the mannose 6-phosphate receptor homology domain of the gamma subunit binds and presents the high mannose glycans of the acceptor to the alpha/beta catalytic site in a favorable manner. << Less

J. Biol. Chem. 285:3360-3370(2010) [PubMed] [EuropePMC]
UDP-N-acetylglucosamine:lysosomal enzyme precursor N-acetylglucosamine-1-phosphotransferase. Partial purification and characterization of the rat liver Golgi enzyme.

Waheed A., Hasilik A., von Figura K.

J Biol Chem 257:12322-12331(1982) [PubMed] [EuropePMC]
Lysosomal enzyme targeting. N-Acetylglucosaminylphosphotransferase selectively phosphorylates native lysosomal enzymes.

Reitman M.L., Kornfeld S.

Lysosomal enzymes contain 6-phosphomannosyl moieties which mediate their translocation to lysosomes. This recognition marker is synthesized by the sequential action of UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase and alpha-N-acetylglucosaminyl phosphodiesterase ... >> More

Lysosomal enzymes contain 6-phosphomannosyl moieties which mediate their translocation to lysosomes. This recognition marker is synthesized by the sequential action of UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase and alpha-N-acetylglucosaminyl phosphodiesterase. A new assay for the N-acetylglucosaminylphosphotransferase, using alpha-methylmannoside as acceptor, is presented. Using this assay, we partially purified the transferase and examined its substrate specificity. The transferase exhibited a very high affinity toward lysosomal enzymes (apparent Km values of less than 20 microM) and was greater than 100-fold more efficient (Vmax/Km) when using lysosomal enzymes as acceptors as compared to nonlysosomal glycoproteins that contain high mannose oligosaccharide units. Heat denaturation of the lysosomal enzymes resulted in the loss of acceptor activity. The model compounds alpha-methylmannoside and Man5--8GlcNAc were poor acceptors. We propose that this enzyme catalyzes the initial, determining step by which synthesized acid hydrolases are distinguished from other newly synthesized glycoproteins and thus are eventually targeted to lysosomes. << Less

J Biol Chem 256:11977-11980(1981) [PubMed] [EuropePMC]

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Cross-references

Publications

Subcellular location of two enzymes involved in the synthesis of phosphorylated recognition markers in lysosomal enzymes.

UDP-N-acetylglucosamine:glycoprotein N-acetylglucosamine-1-phosphotransferase. Proposed enzyme for the phosphorylation of the high mannose oligosaccharide units of lysosomal enzymes.

Functions of the alpha, beta, and gamma subunits of UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase.

UDP-N-acetylglucosamine:lysosomal enzyme precursor N-acetylglucosamine-1-phosphotransferase. Partial purification and characterization of the rat liver Golgi enzyme.

Lysosomal enzyme targeting. N-Acetylglucosaminylphosphotransferase selectively phosphorylates native lysosomal enzymes.