DPAGT1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003975 UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of the defining GlcNAc-1-P transferase molecular function. This is the correct, well-supported core catalytic activity of DPAGT1/GPT and matches abundant experimental evidence in human and orthologs. Reason: This is the core molecular function of DPAGT1, confirmed enzymatically and structurally in human and by cross-species conservation. The IBA is at the correct level of specificity. Supporting Evidence: PMID:29459785 catalyzes the first and committed step of N-linked glycosylation on the cytosolic face of endoplasmic reticulum (ER) membrane PMID:30388443 It catalyzes the transfer of an N-acetyl-D-glucosamine-1-phosphoryl unit (GlcNAc-1-P) from UDP-N-acetyl glucosamine (UDP-GlcNAc) onto dolichyl phosphate (Dol-P)
GO:0016020 membrane	IBA GO_REF:0000033	MODIFY	Summary: Phylogenetic assignment placing DPAGT1 activity in a membrane. Correct but generic; DPAGT1 is specifically a multi-pass endoplasmic reticulum membrane protein. Reason: The essence (membrane-embedded catalysis) is correct, but 'membrane' is a high-level term. The informative location is the ER membrane (GO:0005789), where the enzyme is a multi-pass integral membrane protein acting on the cytosolic leaflet. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:29459785 catalyzes the first and committed step of N-linked glycosylation on the cytosolic face of endoplasmic reticulum (ER) membrane file:human/DPAGT1/DPAGT1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum
GO:0003975 UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated (ARBA/InterPro/RHEA/EC 2.7.8.15) assignment of the GlcNAc-1-P transferase activity. Consistent with the experimentally validated catalytic activity and correct EC number. Reason: The IEA maps to the correct, specific molecular function (EC 2.7.8.15, RHEA:13289) that matches the experimental characterization of DPAGT1. Supporting Evidence: file:human/DPAGT1/DPAGT1-uniprot.txt transferring GlcNAc-1-P from
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: Subcellular-location mapping to ER membrane. This is the correct and informative localization of DPAGT1, an ER-resident multi-pass membrane enzyme. Reason: ER membrane is the experimentally and structurally supported location of DPAGT1; the enzyme acts on the cytoplasmic leaflet of the ER membrane. Supporting Evidence: file:human/DPAGT1/DPAGT1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum PMID:29459785 hGPT crystallized as a homodimer with one tunicamycin molecule bound to the active site of each protomer near the cytosolic side of the ER membrane
GO:0006488 dolichol-linked oligosaccharide biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO mapping to the LLO biosynthetic process. DPAGT1 catalyzes the first, committed step of dolichol-linked oligosaccharide assembly, so this BP is directly and correctly assigned. Reason: DPAGT1 initiates the dolichol cycle producing GlcNAc-PP-dolichol; this is the correct core biological process. Supporting Evidence: PMID:30388443 The product GlcNAc-PP-Dol is anchored to the ER membrane by its dolichyl moiety
GO:0016020 membrane	IEA GO_REF:0000120	MODIFY	Summary: Automated (ARBA/InterPro) assignment of generic membrane localization. Correct but far less specific than ER membrane, which is available and directly supported. Reason: Correct that DPAGT1 is membrane-integral, but 'membrane' is uninformative; the specific ER membrane term (GO:0005789) is supported and preferred. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: file:human/DPAGT1/DPAGT1-uniprot.txt Multi-pass membrane protein
GO:0016780 phosphotransferase activity, for other substituted phosphate groups	IEA GO_REF:0000002	MODIFY	Summary: InterPro2GO mapping to a broad phosphotransferase class. This is a correct but general parent of the specific DPAGT1 activity (GO:0003975), which is available and experimentally validated. Reason: GO:0016780 is a high-level ancestor of the specific UDP-GlcNAc:dolichyl-P GlcNAc-1-P transferase activity. The specific term GO:0003975 should be used. Proposed replacements: UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase activity Supporting Evidence: PMID:30388443 It catalyzes the transfer of an N-acetyl-D-glucosamine-1-phosphoryl unit (GlcNAc-1-P) from UDP-N-acetyl glucosamine (UDP-GlcNAc) onto dolichyl phosphate (Dol-P)
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: IntAct IPI annotation from a large-scale neurodegenerative-disease interactome (yeast two-hybrid) screen, recording a single interaction with huntingtin (HTT, UniProtKB:P42858). 'Protein binding' conveys no specific molecular function for DPAGT1. Reason: Per curation guidelines, bare 'protein binding' is uninformative and should be avoided as a function term. The interaction derives from a high-throughput ND-focused interactome screen and does not establish a specific molecular function or a validated biological role for DPAGT1. Retained (not removed) as an IPI-supported interaction record but flagged as over-annotation. Supporting Evidence: PMID:32814053 It facilitates the identification of interacting proteins that significantly influence mutant TDP-43 and HTT toxicity in transgenic flies
GO:0006488 dolichol-linked oligosaccharide biosynthetic process	TAS Reactome:R-HSA-446193	ACCEPT	Summary: Reactome traceable assertion linking DPAGT1 to biosynthesis of the dolichol lipid-linked oligosaccharide (LLO) precursor. Consistent with DPAGT1's role initiating the 14-sugar N-glycan precursor pathway. Reason: Reactome curates DPAGT1 as the first catalytic step of the LLO/N-glycan precursor pathway; this is a correct core biological process assignment. Supporting Evidence: PMID:30388443 The product GlcNAc-PP-Dol is anchored to the ER membrane by its dolichyl moiety and then monosaccharide units are added sequentially to build the N-glycan that is then transferred
GO:0003975 UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase activity	TAS Reactome:R-HSA-446191	ACCEPT	Summary: Reactome TAS for the GlcNAc-1-P transferase reaction (addition of N-acetylglucosamine to dolichyl phosphate). Matches the defining catalytic activity of DPAGT1. Reason: Reactome curates DPAGT1 as the enzyme that adds GlcNAc to dolichyl phosphate in the first step of LLO synthesis, the correct core molecular function. Supporting Evidence: PMID:29459785 This reaction involves the transfer of N-acetylglucosamine-1-phosphate (GlcNAc-1-P) from UDP-N-acetylglucosamine (UDP-GlcNAc) to the carrier lipid dolichyl-phosphate (Dol-P).
GO:0003975 UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase activity	TAS Reactome:R-HSA-4549334	ACCEPT	Summary: Reactome TAS (disease-variant reaction 'Defective DPAGT1 does not transfer GlcNAc to DOLP') again attributing the GlcNAc-1-P transferase activity to DPAGT1. Duplicate of the core catalytic function. Reason: Correct core molecular function; the disease-reaction framing reflects loss of the same activity in CDG1J/CMS13 variants. Supporting Evidence: PMID:29459785 This reaction involves the transfer of N-acetylglucosamine-1-phosphate (GlcNAc-1-P) from UDP-N-acetylglucosamine (UDP-GlcNAc) to the carrier lipid dolichyl-phosphate (Dol-P).
GO:0003975 UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase activity	EXP PMID:30388443 Structures of DPAGT1 Explain Glycosylation Disease Mechanism...	ACCEPT	Summary: Experimental (structural/enzymatic) evidence for GlcNAc-1-P transferase activity: crystal structures of human DPAGT1 with UDP-GlcNAc and tunicamycin, Michaelis-Menten kinetics, and extensive active-site mutagenesis. Reason: Direct experimental characterization of the catalytic activity with defined kinetic parameters and mechanism; strongly supports the core molecular function. Supporting Evidence: PMID:30388443 It catalyzes the transfer of an N-acetyl-D-glucosamine-1-phosphoryl unit (GlcNAc-1-P) from UDP-N-acetyl glucosamine (UDP-GlcNAc) onto dolichyl phosphate (Dol-P)
GO:0003975 UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase activity	EXP PMID:9451016 Cloning and functional expression of the human GlcNAc-1-P tr...	ACCEPT	Summary: Experimental evidence: the human GPT cDNA was cloned by complementation of a conditional-lethal yeast GPT strain, and recombinant enzyme produced GlcNAc- and GlcNAc2-PP-dolichol, stimulated by dolichol phosphate and inhibited by tunicamycin. Reason: Functional expression demonstrating the GlcNAc-1-P transferase activity of human DPAGT1; supports the core molecular function. Supporting Evidence: PMID:9451016 GlcNAc2-PP-Dolichol biosynthesis could be shown with isolated S.cerevisiae PMID:9451016 the enzyme for the committed step of the dolichol cycle
GO:0005789 endoplasmic reticulum membrane	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity transfer of ER membrane localization (from ortholog UniProtKB:P23338). Consistent with the experimentally/structurally supported ER membrane residence of DPAGT1. Reason: ER membrane is the correct, informative localization, corroborated by human structural data and UniProt subcellular-location annotation. Supporting Evidence: file:human/DPAGT1/DPAGT1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum
GO:0042802 identical protein binding	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity transfer of identical (self) protein binding. DPAGT1 is a homodimer, so self-association is real, but this describes a quaternary/ structural property rather than the catalytic core function. Reason: Homodimerization is experimentally supported (crystallized as a homodimer; UniProt SUBUNIT: Homodimer), so 'identical protein binding' is valid. It is retained as a non-core structural feature rather than the defining function. Supporting Evidence: file:human/DPAGT1/DPAGT1-uniprot.txt SUBUNIT: Homodimer. PMID:29459785 hGPT crystallized as a homodimer with one tunicamycin molecule bound to the active site of each protomer near the cytosolic side of the ER membrane
GO:0003975 UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase activity	IDA PMID:29459785 GlcNAc-1-P-transferase-tunicamycin complex structure reveals...	ACCEPT	Summary: Direct assay evidence: crystal structure of human GPT with tunicamycin plus functional/enzymatic analyses defining the GlcNAc-1-P transferase reaction and its inhibition. Reason: Direct experimental demonstration of the catalytic activity; core molecular function. Supporting Evidence: PMID:29459785 catalyzes the first and committed step of N-linked glycosylation on the cytosolic face of endoplasmic reticulum (ER) membrane
GO:0006488 dolichol-linked oligosaccharide biosynthetic process	IDA PMID:29459785 GlcNAc-1-P-transferase-tunicamycin complex structure reveals...	ACCEPT	Summary: Direct evidence that DPAGT1 acts in dolichol-linked oligosaccharide biosynthesis, catalyzing the first committed step of LLO assembly on the cytosolic ER face. Reason: DPAGT1 initiates the LLO/dolichol-cycle pathway; correct core biological process. Supporting Evidence: PMID:29459785 This reaction involves the transfer of N-acetylglucosamine-1-phosphate (GlcNAc-1-P) from UDP-N-acetylglucosamine (UDP-GlcNAc) to the carrier lipid dolichyl-phosphate (Dol-P).
GO:0003976 UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase activity	IDA PMID:6289658 Demonstration of the heterozygous state for I-cell disease a...	MARK AS OVER ANNOTATED	Summary: Annotation to the UDP-GlcNAc:LYSOSOMAL-ENZYME GlcNAc-1-phosphotransferase activity, citing Varki et al. 1982 on I-cell disease (mucolipidosis II) and pseudo-Hurler polydystrophy heterozygote enzyme assays. That activity belongs to the distinct lysosomal-enzyme-targeting phosphotransferase (encoded by GNPTAB/GNPTG), not to DPAGT1. DPAGT1 transfers GlcNAc-1-P to the lipid dolichyl phosphate, not to lysosomal enzymes (mannose-6-phosphate marker formation). Reason: This molecular function (GO:0003976) is a different enzyme's activity; the cited paper is entirely about I-cell disease / pseudo-Hurler polydystrophy (mucolipidosis II/III), which are caused by GNPTAB/GNPTG deficiency, not DPAGT1. The annotation conflates two similarly named but mechanistically distinct GlcNAc-1-phosphotransferases (lipid-acceptor DPAGT1 vs protein/lysosomal-enzyme acceptor GNPTAB). Per policy this experimental annotation is flagged as an over-annotation of a function that is not DPAGT1's rather than removed. Supporting Evidence: PMID:6289658 a deficiency of the enzyme UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-4549334	ACCEPT	Summary: Reactome TAS localizing DPAGT1 to the ER membrane (disease-variant reaction context). Consistent with the experimentally supported ER membrane residence. Reason: Correct, informative ER membrane localization curated by Reactome. Supporting Evidence: file:human/DPAGT1/DPAGT1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-446191	ACCEPT	Summary: Reactome TAS localizing DPAGT1 to the ER membrane in the LLO-synthesis reaction. The dolichyl phosphate anchor ties the reaction to the ER membrane. Reason: Correct core cellular component; the enzyme and its product are ER-membrane associated. Supporting Evidence: PMID:30388443 The product GlcNAc-PP-Dol is anchored to the ER membrane by its dolichyl moiety
GO:0006487 protein N-linked glycosylation	IMP PMID:19549906 Overexpression of DPAGT1 leads to aberrant N-glycosylation o...	ACCEPT	Summary: Mutant-phenotype (siRNA knockdown/overexpression) evidence that DPAGT1 controls the extent of protein N-glycosylation: it initiates LLO synthesis and regulates E-cadherin N-glycosylation in oral cancer cells. Reason: DPAGT1 is upstream of and required for protein N-linked glycosylation; perturbing DPAGT1 alters cellular N-glycosylation. Correct core biological process. Supporting Evidence: PMID:19549906 initiates the synthesis of the lipid-linked oligosaccharide (LLO) precursor for protein N-glycosylation in the endoplasmic reticulum PMID:19549906 elevated expression of DPAGT1, the gene that initiates protein N-glycosylation
GO:0003975 UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase activity	IMP PMID:12872255 Deficiency of UDP-GlcNAc:Dolichol Phosphate N-Acetylglucosam...	ACCEPT	Summary: Mutant-phenotype evidence: patient with CDG-Ij has GPT (DPAGT1) activity reduced to ~10% of normal; the Y170C variant produces near-inactive enzyme, directly tying the GlcNAc-1-P transferase activity to DPAGT1. Reason: Loss-of-activity in disease variants demonstrates that DPAGT1 encodes the GlcNAc-1-P transferase; supports the core molecular function. Supporting Evidence: PMID:12872255 N-acetyl-glucosamine-1 phosphate transferase (GPT) activity encoded by DPAGT1 PMID:12872255 the GPT activity is reduced to approximately 10% of normal levels
GO:0003975 UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase activity	IDA PMID:8179616 Major defect of carbohydrate-deficient-glycoprotein syndrome...	ACCEPT	Summary: Biochemical assay of GlcNAc-1-P transferase activity (and dolichyl phosphate content) in CDG-syndrome versus normal fibroblasts. Directly assays the DPAGT1/GPT enzymatic activity in human cells. Reason: Direct enzymatic measurement of the GlcNAc-1-P transferase activity in human fibroblasts; supports the core molecular function. Supporting Evidence: PMID:8179616 activity in CDG syndrome fibroblasts were similar to those in normal
GO:0016020 membrane	ISS GO_REF:0000024	MODIFY	Summary: Sequence-similarity transfer of generic membrane localization. Correct but subsumed by the more informative ER membrane term. Reason: DPAGT1 is membrane-integral, but the specific ER membrane term (GO:0005789) is supported and preferable to generic 'membrane'. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: file:human/DPAGT1/DPAGT1-uniprot.txt Multi-pass membrane protein
GO:0016020 membrane	IDA PMID:8179616 Major defect of carbohydrate-deficient-glycoprotein syndrome...	MODIFY	Summary: Direct assay associated DPAGT1/GPT activity with a membrane (microsomal) fraction. Correct but generic; ER membrane is the informative location. Reason: Membrane association is experimentally consistent, but the specific ER membrane term (GO:0005789) is supported and preferable. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: file:human/DPAGT1/DPAGT1-uniprot.txt Multi-pass membrane protein
GO:0043231 intracellular membrane-bounded organelle	IDA PMID:12872255 Deficiency of UDP-GlcNAc:Dolichol Phosphate N-Acetylglucosam...	KEEP AS NON CORE	Summary: Direct evidence places DPAGT1 in an intracellular membrane-bounded organelle (microsomal/ER fraction from patient fibroblasts). This is a very general CC term; the specific organelle is the ER (ER membrane). Reason: Correct but high-level. The informative core localization is ER membrane (GO:0005789), already annotated. Retained as a non-core, less specific location. Supporting Evidence: file:human/DPAGT1/DPAGT1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum

Gene Description

Existing Annotations Review

Core Functions

UDP-GlcNAc:dolichyl-phosphate GlcNAc-1-phosphotransferase (GPT) activity: transfers GlcNAc-1-phosphate from UDP-GlcNAc onto dolichyl phosphate to form GlcNAc-PP-dolichol, the first and committed step of dolichol-linked oligosaccharide (LLO) assembly, on the cytoplasmic face of the ER membrane.

Initiation of protein N-linked glycosylation: by producing the membrane-anchored GlcNAc-PP-dolichol precursor, DPAGT1 provides the substrate for subsequent LLO extension and thereby controls the extent of protein N-glycosylation.

References

📚 Additional Documentation

Notes

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