Reaction participants Show >> << Hide
-
Namehelp_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 SMILEShelp_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
- Name help_outline UDP-N-acetyl-α-D-glucosamine Identifier CHEBI:57705 (Beilstein: 4286654) help_outline Charge -2 Formula C17H25N3O17P2 InChIKeyhelp_outline LFTYTUAZOPRMMI-CFRASDGPSA-L SMILEShelp_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 InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_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
-
Namehelp_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 SMILEShelp_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
- Name help_outline UMP Identifier CHEBI:57865 (Beilstein: 3570858) help_outline Charge -2 Formula C9H11N2O9P InChIKeyhelp_outline DJJCXFVJDGTHFX-XVFCMESISA-L SMILEShelp_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 help_outline | undefined | left-to-right | right-to-left | bidirectional |
UniProtKB help_outline |
|
|||
EC numbers help_outline | ||||
Gene Ontology help_outline | ||||
KEGG help_outline | ||||
MetaCyc help_outline |
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
-
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
-
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
-
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.
-
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