GNPTAB encodes the alpha/beta-subunit precursor of UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (EC 2.7.8.17), the alpha2beta2gamma2 Golgi membrane enzyme complex (with GNPTG) that transfers GlcNAc-1-phosphate from UDP-GlcNAc to mannose residues of high-mannose N-glycans on soluble lysosomal acid hydrolases. This is the first step in generating the mannose 6-phosphate (M6P) recognition marker that directs hydrolases to M6P receptors and thence to endosomes and lysosomes. The alpha/beta subunits are catalytic and also recognise a conformational protein determinant on acid hydrolases; the precursor is activated in the Golgi by site-1 protease cleavage and depends on LYSET/TMEM251 for stability and Golgi retention. Biallelic loss of GNPTAB causes mucolipidosis II (I-cell disease) and, with residual activity, mucolipidosis III alpha/beta.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | EXP PMID:16120602 The alpha- and beta-subunits of the human UDP-N-acetylglucos... | ACCEPT | Summary: GNPTAB alpha and beta subunits are Golgi membrane proteins. Reason: Multiple experimental studies localise the alpha/beta precursor and its cleaved subunits to the Golgi, where it is activated and acts on newly synthesised hydrolases. Supporting Evidence: PMID:16200072 expression and localization of GNPTA in the Golgi apparatus, accompanied by the correction of hypersecretion of lysosomal enzymes PMID:25788519 Upon arrival in the Golgi apparatus, the newly synthesized Ξ±/Ξ²-subunit precursor is catalytically activated by site-1 protease (S1P). |
| GO:0000139 Golgi membrane | EXP PMID:16200072 Mucolipidosis II is caused by mutations in GNPTA encoding th... | ACCEPT | Summary: GNPTAB alpha and beta subunits are Golgi membrane proteins. Reason: Multiple experimental studies localise the alpha/beta precursor and its cleaved subunits to the Golgi, where it is activated and acts on newly synthesised hydrolases. Supporting Evidence: PMID:16200072 expression and localization of GNPTA in the Golgi apparatus, accompanied by the correction of hypersecretion of lysosomal enzymes PMID:25788519 Upon arrival in the Golgi apparatus, the newly synthesized Ξ±/Ξ²-subunit precursor is catalytically activated by site-1 protease (S1P). |
| GO:0000139 Golgi membrane | EXP PMID:21719679 A key enzyme in the biogenesis of lysosomes is a protease th... | ACCEPT | Summary: GNPTAB alpha and beta subunits are Golgi membrane proteins. Reason: Multiple experimental studies localise the alpha/beta precursor and its cleaved subunits to the Golgi, where it is activated and acts on newly synthesised hydrolases. Supporting Evidence: PMID:16200072 expression and localization of GNPTA in the Golgi apparatus, accompanied by the correction of hypersecretion of lysosomal enzymes PMID:25788519 Upon arrival in the Golgi apparatus, the newly synthesized Ξ±/Ξ²-subunit precursor is catalytically activated by site-1 protease (S1P). |
| GO:0000139 Golgi membrane | EXP PMID:25788519 Analyses of disease-related GNPTAB mutations define a novel ... | ACCEPT | Summary: GNPTAB alpha and beta subunits are Golgi membrane proteins. Reason: Multiple experimental studies localise the alpha/beta precursor and its cleaved subunits to the Golgi, where it is activated and acts on newly synthesised hydrolases. Supporting Evidence: PMID:16200072 expression and localization of GNPTA in the Golgi apparatus, accompanied by the correction of hypersecretion of lysosomal enzymes PMID:25788519 Upon arrival in the Golgi apparatus, the newly synthesized Ξ±/Ξ²-subunit precursor is catalytically activated by site-1 protease (S1P). |
| GO:0000139 Golgi membrane | EXP PMID:28918368 GNPTAB missense mutations cause loss of GlcNAc-1-phosphotran... | ACCEPT | Summary: GNPTAB alpha and beta subunits are Golgi membrane proteins. Reason: Multiple experimental studies localise the alpha/beta precursor and its cleaved subunits to the Golgi, where it is activated and acts on newly synthesised hydrolases. Supporting Evidence: PMID:16200072 expression and localization of GNPTA in the Golgi apparatus, accompanied by the correction of hypersecretion of lysosomal enzymes PMID:25788519 Upon arrival in the Golgi apparatus, the newly synthesized Ξ±/Ξ²-subunit precursor is catalytically activated by site-1 protease (S1P). |
| GO:0000139 Golgi membrane | IDA PMID:23733939 The DMAP interaction domain of UDP-GlcNAc:lysosomal enzyme N... | ACCEPT | Summary: GNPTAB alpha and beta subunits are Golgi membrane proteins. Reason: Multiple experimental studies localise the alpha/beta precursor and its cleaved subunits to the Golgi, where it is activated and acts on newly synthesised hydrolases. Supporting Evidence: PMID:16200072 expression and localization of GNPTA in the Golgi apparatus, accompanied by the correction of hypersecretion of lysosomal enzymes PMID:25788519 Upon arrival in the Golgi apparatus, the newly synthesized Ξ±/Ξ²-subunit precursor is catalytically activated by site-1 protease (S1P). |
| GO:0000139 Golgi membrane | IDA PMID:24375680 Mucolipidosis II-related mutations inhibit the exit from the... | ACCEPT | Summary: GNPTAB alpha and beta subunits are Golgi membrane proteins. Reason: Multiple experimental studies localise the alpha/beta precursor and its cleaved subunits to the Golgi, where it is activated and acts on newly synthesised hydrolases. Supporting Evidence: PMID:16200072 expression and localization of GNPTA in the Golgi apparatus, accompanied by the correction of hypersecretion of lysosomal enzymes PMID:25788519 Upon arrival in the Golgi apparatus, the newly synthesized Ξ±/Ξ²-subunit precursor is catalytically activated by site-1 protease (S1P). |
| GO:0000139 Golgi membrane | IEA GO_REF:0000120 | ACCEPT | Summary: GNPTAB alpha and beta subunits are Golgi membrane proteins. Reason: Multiple experimental studies localise the alpha/beta precursor and its cleaved subunits to the Golgi, where it is activated and acts on newly synthesised hydrolases. Supporting Evidence: PMID:16200072 expression and localization of GNPTA in the Golgi apparatus, accompanied by the correction of hypersecretion of lysosomal enzymes PMID:25788519 Upon arrival in the Golgi apparatus, the newly synthesized Ξ±/Ξ²-subunit precursor is catalytically activated by site-1 protease (S1P). |
| GO:0003976 UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: GlcNAc-1-phosphotransferase activity is the core catalytic function of GNPTAB. Reason: Recombinant alpha/beta subunits carry the catalytic activity (EC 2.7.8.17); disease mutations in catalytic and recognition domains abolish phosphorylation of acid hydrolases. Supporting Evidence: PMID:19955174 the alpha/beta subunits recognize the protein determinant of acid hydrolases in addition to mediating the catalytic function of the transferase PMID:16120602 results in a 3.6- or 17-fold increase in GlcNAc-phosphotransferase activity in cell lysates, suggesting that the precursor cDNA contains the catalytic domain PMID:25505245 We show that the Stealth domain harbors the catalytic site |
| GO:0003976 UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase activity | IDA PMID:19955174 Functions of the alpha, beta, and gamma subunits of UDP-GlcN... | ACCEPT | Summary: GlcNAc-1-phosphotransferase activity is the core catalytic function of GNPTAB. Reason: Recombinant alpha/beta subunits carry the catalytic activity (EC 2.7.8.17); disease mutations in catalytic and recognition domains abolish phosphorylation of acid hydrolases. Supporting Evidence: PMID:19955174 the alpha/beta subunits recognize the protein determinant of acid hydrolases in addition to mediating the catalytic function of the transferase PMID:16120602 results in a 3.6- or 17-fold increase in GlcNAc-phosphotransferase activity in cell lysates, suggesting that the precursor cDNA contains the catalytic domain PMID:25505245 We show that the Stealth domain harbors the catalytic site |
| GO:0003976 UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase activity | IDA PMID:23733939 The DMAP interaction domain of UDP-GlcNAc:lysosomal enzyme N... | ACCEPT | Summary: GlcNAc-1-phosphotransferase activity is the core catalytic function of GNPTAB. Reason: Recombinant alpha/beta subunits carry the catalytic activity (EC 2.7.8.17); disease mutations in catalytic and recognition domains abolish phosphorylation of acid hydrolases. Supporting Evidence: PMID:19955174 the alpha/beta subunits recognize the protein determinant of acid hydrolases in addition to mediating the catalytic function of the transferase PMID:16120602 results in a 3.6- or 17-fold increase in GlcNAc-phosphotransferase activity in cell lysates, suggesting that the precursor cDNA contains the catalytic domain PMID:25505245 We show that the Stealth domain harbors the catalytic site |
| GO:0003976 UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase activity | IDA PMID:25788519 Analyses of disease-related GNPTAB mutations define a novel ... | ACCEPT | Summary: GlcNAc-1-phosphotransferase activity is the core catalytic function of GNPTAB. Reason: Recombinant alpha/beta subunits carry the catalytic activity (EC 2.7.8.17); disease mutations in catalytic and recognition domains abolish phosphorylation of acid hydrolases. Supporting Evidence: PMID:19955174 the alpha/beta subunits recognize the protein determinant of acid hydrolases in addition to mediating the catalytic function of the transferase PMID:16120602 results in a 3.6- or 17-fold increase in GlcNAc-phosphotransferase activity in cell lysates, suggesting that the precursor cDNA contains the catalytic domain PMID:25505245 We show that the Stealth domain harbors the catalytic site |
| GO:0003976 UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: GlcNAc-1-phosphotransferase activity is the core catalytic function of GNPTAB. Reason: Recombinant alpha/beta subunits carry the catalytic activity (EC 2.7.8.17); disease mutations in catalytic and recognition domains abolish phosphorylation of acid hydrolases. Supporting Evidence: PMID:19955174 the alpha/beta subunits recognize the protein determinant of acid hydrolases in addition to mediating the catalytic function of the transferase PMID:16120602 results in a 3.6- or 17-fold increase in GlcNAc-phosphotransferase activity in cell lysates, suggesting that the precursor cDNA contains the catalytic domain PMID:25505245 We show that the Stealth domain harbors the catalytic site |
| GO:0003976 UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase activity | IMP PMID:25505245 Analysis of mucolipidosis II/III GNPTAB missense mutations i... | ACCEPT | Summary: GlcNAc-1-phosphotransferase activity is the core catalytic function of GNPTAB. Reason: Recombinant alpha/beta subunits carry the catalytic activity (EC 2.7.8.17); disease mutations in catalytic and recognition domains abolish phosphorylation of acid hydrolases. Supporting Evidence: PMID:19955174 the alpha/beta subunits recognize the protein determinant of acid hydrolases in addition to mediating the catalytic function of the transferase PMID:16120602 results in a 3.6- or 17-fold increase in GlcNAc-phosphotransferase activity in cell lysates, suggesting that the precursor cDNA contains the catalytic domain PMID:25505245 We show that the Stealth domain harbors the catalytic site |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Calcium ion binding is inferred from an EF-hand-like InterPro signature only. Reason: The signature support is stronger than an EF-hand domain call alone - UniProt annotates per-residue Ca(2+) BINDING features, in the EF-hand domain at 1005..1040 and in the LNR repeats - but every one is ECO:0000255, inferred from a sequence model rather than measured, so calcium binding by GNPTAB and its functional relevance still have not been demonstrated experimentally. Non-core on the strength of the evidence, not on doubt about the signature. Supporting Evidence: file:human/GNPTAB/GNPTAB-uniprot.txt /note="EF-hand" file:human/GNPTAB/GNPTAB-uniprot.txt /ligand="Ca(2+)" |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: High-throughput interactome hit without functional support. Reason: Binary Y2H/AP-MS interaction from a proteome-scale screen; the partner has no known role in M6P tagging and several are nuclear or cytosolic, inconsistent with the luminal/Golgi topology of GNPTAB. 'protein binding' is in any case uninformative. Removal does not assert the interaction is false. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: High-throughput interactome hit without functional support. Reason: Binary Y2H/AP-MS interaction from a proteome-scale screen; the partner has no known role in M6P tagging and several are nuclear or cytosolic, inconsistent with the luminal/Golgi topology of GNPTAB. 'protein binding' is in any case uninformative. Removal does not assert the interaction is false. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: High-throughput interactome hit without functional support. Reason: Binary Y2H/AP-MS interaction from a proteome-scale screen; the partner has no known role in M6P tagging and several are nuclear or cytosolic, inconsistent with the luminal/Golgi topology of GNPTAB. 'protein binding' is in any case uninformative. Removal does not assert the interaction is false. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: High-throughput interactome hit without functional support. Reason: Binary Y2H/AP-MS interaction from a proteome-scale screen; the partner has no known role in M6P tagging and several are nuclear or cytosolic, inconsistent with the luminal/Golgi topology of GNPTAB. 'protein binding' is in any case uninformative. Removal does not assert the interaction is false. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: High-throughput interactome hit without functional support. Reason: Binary Y2H/AP-MS interaction from a proteome-scale screen; the partner has no known role in M6P tagging and several are nuclear or cytosolic, inconsistent with the luminal/Golgi topology of GNPTAB. 'protein binding' is in any case uninformative. Removal does not assert the interaction is false. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network |
| GO:0005515 protein binding | IPI PMID:26385638 Subunit interactions of the disease-related hexameric GlcNAc... | MODIFY | Summary: GNPTAB binds the gamma subunit GNPTG as part of the hexameric GlcNAc-1-phosphotransferase. Reason: The interaction is real and functionally important, but is better captured as membership of the GlcNAc-1-phosphotransferase complex than as generic protein binding. Proposed replacements: UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase complex Supporting Evidence: PMID:26385638 we identified the binding regions of Ξ³-subunits in a previously uncharacterized domain of Ξ±-subunits comprising residues 535-698, named GNPTG binding (GB) domain |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: AP-MS co-purification with the Golgi glycosyltransferase B3GALT2 in BioPlex, without functional follow-up. Reason: Co-residence in the Golgi plausibly explains co-purification; there is no evidence of a functional interaction, and 'protein binding' is uninformative. Removal does not assert the interaction is false. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: GNPTAB binds the gamma subunit GNPTG as part of the hexameric GlcNAc-1-phosphotransferase. Reason: The interaction is real and functionally important, but is better captured as membership of the GlcNAc-1-phosphotransferase complex than as generic protein binding. Proposed replacements: UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase complex Supporting Evidence: PMID:26385638 we identified the binding regions of Ξ³-subunits in a previously uncharacterized domain of Ξ±-subunits comprising residues 535-698, named GNPTG binding (GB) domain |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: AP-MS co-purification with the Golgi glycosyltransferase B3GALT2 in BioPlex, without functional follow-up. Reason: Co-residence in the Golgi plausibly explains co-purification; there is no evidence of a functional interaction, and 'protein binding' is uninformative. Removal does not assert the interaction is false. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome |
| GO:0005515 protein binding | IPI PMID:36074821 The human disease gene LYSET is essential for lysosomal enzy... | REMOVE | Summary: GNPTAB binds the Golgi membrane protein LYSET, which stabilises it and retains it in the Golgi. Reason: A functionally validated interaction (LYSET loss destabilises and mislocalises GNPTAB), but the activity belongs to LYSET as a regulator; for GNPTAB the generic 'protein binding' term adds no functional information. The interaction itself is real and is captured on the LYSET review; removal does not assert it is false. Supporting Evidence: PMID:36074821 LYSET deficiency resulted in global loss of M6P tagging and mislocalization of GlcNAc-1-phosphotransferase from the Golgi complex to lysosomes. |
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | ACCEPT | Summary: GNPTAB localises to the Golgi apparatus. Reason: Consistent with its Golgi membrane localisation; Golgi membrane is the more specific term. Supporting Evidence: PMID:16200072 expression and localization of GNPTA in the Golgi apparatus, accompanied by the correction of hypersecretion of lysosomal enzymes PMID:25788519 Upon arrival in the Golgi apparatus, the newly synthesized Ξ±/Ξ²-subunit precursor is catalytically activated by site-1 protease (S1P). |
| GO:0005794 Golgi apparatus | IDA GO_REF:0000052 | ACCEPT | Summary: GNPTAB localises to the Golgi apparatus. Reason: Consistent with its Golgi membrane localisation; Golgi membrane is the more specific term. Supporting Evidence: PMID:16200072 expression and localization of GNPTA in the Golgi apparatus, accompanied by the correction of hypersecretion of lysosomal enzymes PMID:25788519 Upon arrival in the Golgi apparatus, the newly synthesized Ξ±/Ξ²-subunit precursor is catalytically activated by site-1 protease (S1P). |
| GO:0005794 Golgi apparatus | IDA PMID:21719679 A key enzyme in the biogenesis of lysosomes is a protease th... | ACCEPT | Summary: GNPTAB localises to the Golgi apparatus. Reason: Consistent with its Golgi membrane localisation; Golgi membrane is the more specific term. Supporting Evidence: PMID:16200072 expression and localization of GNPTA in the Golgi apparatus, accompanied by the correction of hypersecretion of lysosomal enzymes PMID:25788519 Upon arrival in the Golgi apparatus, the newly synthesized Ξ±/Ξ²-subunit precursor is catalytically activated by site-1 protease (S1P). |
| GO:0005794 Golgi apparatus | IDA PMID:25505245 Analysis of mucolipidosis II/III GNPTAB missense mutations i... | ACCEPT | Summary: GNPTAB localises to the Golgi apparatus. Reason: Consistent with its Golgi membrane localisation; Golgi membrane is the more specific term. Supporting Evidence: PMID:16200072 expression and localization of GNPTA in the Golgi apparatus, accompanied by the correction of hypersecretion of lysosomal enzymes PMID:25788519 Upon arrival in the Golgi apparatus, the newly synthesized Ξ±/Ξ²-subunit precursor is catalytically activated by site-1 protease (S1P). |
| GO:0005794 Golgi apparatus | IDA PMID:25788519 Analyses of disease-related GNPTAB mutations define a novel ... | ACCEPT | Summary: GNPTAB localises to the Golgi apparatus. Reason: Consistent with its Golgi membrane localisation; Golgi membrane is the more specific term. Supporting Evidence: PMID:16200072 expression and localization of GNPTA in the Golgi apparatus, accompanied by the correction of hypersecretion of lysosomal enzymes PMID:25788519 Upon arrival in the Golgi apparatus, the newly synthesized Ξ±/Ξ²-subunit precursor is catalytically activated by site-1 protease (S1P). |
| GO:0006487 protein N-linked glycosylation | IBA GO_REF:0000033 | MODIFY | Summary: GNPTAB modifies existing N-glycans rather than performing N-linked glycosylation. Reason: The more accurate process is the M6P-generating N-glycan processing step. Proposed replacements: N-glycan processing to lysosome Supporting Evidence: PMID:19955174 mediates the first step in the synthesis of the mannose 6-phosphate recognition marker on lysosomal acid hydrolases |
| GO:0007040 lysosome organization | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Lysosome organization/biogenesis depends on M6P-mediated hydrolase delivery. Reason: Loss of GNPTAB (or of its activating protease S1P) disrupts lysosome biogenesis, but this is a downstream consequence of the core N-glycan processing role. Supporting Evidence: PMID:21719679 S1P-deficient cells failed to activate the Ξ±/Ξ²-subunit precursor and exhibited a mucolipidosis II-like phenotype. |
| GO:0007040 lysosome organization | IMP PMID:21719679 A key enzyme in the biogenesis of lysosomes is a protease th... | KEEP AS NON CORE | Summary: Lysosome organization/biogenesis depends on M6P-mediated hydrolase delivery. Reason: Loss of GNPTAB (or of its activating protease S1P) disrupts lysosome biogenesis, but this is a downstream consequence of the core N-glycan processing role. Supporting Evidence: PMID:21719679 S1P-deficient cells failed to activate the Ξ±/Ξ²-subunit precursor and exhibited a mucolipidosis II-like phenotype. |
| GO:0015031 protein transport | IEA GO_REF:0000117 | MODIFY | Summary: Protein transport is too general; GNPTAB acts in the M6P tagging step of lysosomal enzyme targeting. Reason: GNPTAB does not itself transport proteins; it generates the targeting signal. Proposed replacements: N-glycan processing to lysosome Supporting Evidence: PMID:25505245 UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase tags newly synthesized lysosomal enzymes with mannose 6-phosphate recognition markers, which are required for their targeting to the endolysosomal system. |
| GO:0016256 N-glycan processing to lysosome | IBA GO_REF:0000033 | ACCEPT | Summary: GNPTAB catalyses the first step of N-glycan processing that generates the M6P lysosomal targeting signal. Reason: This process is exactly what GlcNAc-1-phosphotransferase does; GNPTAB-null cells hypersecrete hydrolases and wild-type cDNA corrects the defect. Supporting Evidence: PMID:19955174 mediates the first step in the synthesis of the mannose 6-phosphate recognition marker on lysosomal acid hydrolases PMID:19938078 the biochemical phenotypes of MLII and MLIII fibroblasts can be corrected by transfection with wild-type cDNA expression constructs encoding the alpha/beta- and gamma-subunits of GlcNAc-1-phosphotransferase PMID:25505245 UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase tags newly synthesized lysosomal enzymes with mannose 6-phosphate recognition markers, which are required for their targeting to the endolysosomal system. |
| GO:0016256 N-glycan processing to lysosome | IMP PMID:19938078 Molecular analysis of cell lines from patients with mucolipi... | ACCEPT | Summary: GNPTAB catalyses the first step of N-glycan processing that generates the M6P lysosomal targeting signal. Reason: This process is exactly what GlcNAc-1-phosphotransferase does; GNPTAB-null cells hypersecrete hydrolases and wild-type cDNA corrects the defect. Supporting Evidence: PMID:19955174 mediates the first step in the synthesis of the mannose 6-phosphate recognition marker on lysosomal acid hydrolases PMID:19938078 the biochemical phenotypes of MLII and MLIII fibroblasts can be corrected by transfection with wild-type cDNA expression constructs encoding the alpha/beta- and gamma-subunits of GlcNAc-1-phosphotransferase PMID:25505245 UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase tags newly synthesized lysosomal enzymes with mannose 6-phosphate recognition markers, which are required for their targeting to the endolysosomal system. |
| GO:0016256 N-glycan processing to lysosome | IMP PMID:25505245 Analysis of mucolipidosis II/III GNPTAB missense mutations i... | ACCEPT | Summary: GNPTAB catalyses the first step of N-glycan processing that generates the M6P lysosomal targeting signal. Reason: This process is exactly what GlcNAc-1-phosphotransferase does; GNPTAB-null cells hypersecrete hydrolases and wild-type cDNA corrects the defect. Supporting Evidence: PMID:19955174 mediates the first step in the synthesis of the mannose 6-phosphate recognition marker on lysosomal acid hydrolases PMID:19938078 the biochemical phenotypes of MLII and MLIII fibroblasts can be corrected by transfection with wild-type cDNA expression constructs encoding the alpha/beta- and gamma-subunits of GlcNAc-1-phosphotransferase PMID:25505245 UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase tags newly synthesized lysosomal enzymes with mannose 6-phosphate recognition markers, which are required for their targeting to the endolysosomal system. |
| GO:0016772 transferase activity, transferring phosphorus-containing groups | IEA GO_REF:0000002 | MODIFY | Summary: Generic phosphorus-group transferase activity; the specific activity is known. Reason: Replace with the specific EC 2.7.8.17 GlcNAc-1-phosphotransferase activity term. Proposed replacements: UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase activity Supporting Evidence: PMID:19955174 the alpha/beta subunits recognize the protein determinant of acid hydrolases in addition to mediating the catalytic function of the transferase |
| GO:0046835 carbohydrate phosphorylation | IDA PMID:19955174 Functions of the alpha, beta, and gamma subunits of UDP-GlcN... | KEEP AS NON CORE | Summary: GNPTAB transfers GlcNAc-1-phosphate to mannose residues, a form of carbohydrate phosphorylation. Reason: Accurate but general; the specific process is N-glycan processing to lysosome. Supporting Evidence: PMID:19955174 the alpha/beta subunits recognize the protein determinant of acid hydrolases in addition to mediating the catalytic function of the transferase PMID:23733939 the DMAP interaction domain of the Ξ± subunit functions in the selective recognition of acid hydrolase substrates |
| GO:0046835 carbohydrate phosphorylation | IDA PMID:23733939 The DMAP interaction domain of UDP-GlcNAc:lysosomal enzyme N... | KEEP AS NON CORE | Summary: GNPTAB transfers GlcNAc-1-phosphate to mannose residues, a form of carbohydrate phosphorylation. Reason: Accurate but general; the specific process is N-glycan processing to lysosome. Supporting Evidence: PMID:19955174 the alpha/beta subunits recognize the protein determinant of acid hydrolases in addition to mediating the catalytic function of the transferase PMID:23733939 the DMAP interaction domain of the Ξ± subunit functions in the selective recognition of acid hydrolase substrates |
| GO:0046835 carbohydrate phosphorylation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: GNPTAB transfers GlcNAc-1-phosphate to mannose residues, a form of carbohydrate phosphorylation. Reason: Accurate but general; the specific process is N-glycan processing to lysosome. Supporting Evidence: PMID:19955174 the alpha/beta subunits recognize the protein determinant of acid hydrolases in addition to mediating the catalytic function of the transferase PMID:23733939 the DMAP interaction domain of the Ξ± subunit functions in the selective recognition of acid hydrolase substrates |
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Download this section (compressed HTML)Q: Is LYSET a stoichiometric subunit of the GlcNAc-1-phosphotransferase complex or a transient chaperone/retention factor?
Suggested experts: lysosomal enzyme trafficking biochemists
Experiment: Cryo-EM of endogenous GlcNAc-1-phosphotransferase purified from human Golgi membranes, with and without LYSET.
Hypothesis: LYSET binds the hydrophilic transmembrane segment of the GNPTAB beta subunit and is part of the active Golgi complex.
Type: structural biology
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