id: Q9H3H5
gene_symbol: DPAGT1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: DPAGT1 (GlcNAc-1-P transferase, GPT; EC 2.7.8.15) is a polytopic (10-transmembrane)
  endoplasmic reticulum membrane enzyme that catalyzes the first and committed step of
  dolichol-linked oligosaccharide (LLO) assembly for protein N-linked glycosylation. On
  the cytoplasmic face of the ER membrane it transfers N-acetylglucosamine-1-phosphate
  (GlcNAc-1-P) from cytosolic UDP-GlcNAc onto the carrier lipid dolichyl phosphate (Dol-P),
  yielding GlcNAc-PP-dolichol (Dol-PP-GlcNAc), the membrane-anchored precursor onto which
  further sugars are added to build the 14-sugar N-glycan that is subsequently transferred
  to nascent proteins by oligosaccharyltransferase. The enzyme requires Mg2+, functions as
  a homodimer, and is a member of the polyprenyl-phosphate N-acetylhexosamine-1-phosphate
  transferase (PNPT) / glycosyltransferase family 4. It is the eukaryotic target of the
  nucleoside antibiotic tunicamycin, which acts as a competitive inhibitor mimicking
  UDP-GlcNAc. Loss-of-function variants cause DPAGT1-congenital disorder of glycosylation
  type Ij (CDG1J) and a limb-girdle form of congenital myasthenic syndrome (CMS13, with
  tubular aggregates); DPAGT1 overexpression contributes to aberrant N-glycosylation in
  oral cancer.
alternative_products:
- name: '1'
  id: Q9H3H5-1
- name: '2'
  id: Q9H3H5-2
  sequence_note: VSP_001803
- name: '3'
  id: Q9H3H5-3
  sequence_note: VSP_008886
existing_annotations:
- term:
    id: GO:0003975
    label: UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase
      activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:29459785
      supporting_text: "catalyzes the first and committed step of N-linked glycosylation\
        \ on the cytosolic face of endoplasmic reticulum (ER) membrane"
    - reference_id: PMID:30388443
      supporting_text: "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)"
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic assignment placing DPAGT1 activity in a membrane. Correct but
      generic; DPAGT1 is specifically a multi-pass endoplasmic reticulum membrane protein.
    action: MODIFY
    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."
    proposed_replacement_terms:
    - id: GO:0005789
      label: endoplasmic reticulum membrane
    propagation_review:
      root_cause: TERM_SCOPING_PROBLEM
      failure_modes:
      - GRANULARITY_MISMATCH
    supported_by:
    - reference_id: PMID:29459785
      supporting_text: "catalyzes the first and committed step of N-linked glycosylation\
        \ on the cytosolic face of endoplasmic reticulum (ER) membrane"
    - reference_id: file:human/DPAGT1/DPAGT1-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Endoplasmic reticulum"
- term:
    id: GO:0003975
    label: UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase
      activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: "The IEA maps to the correct, specific molecular function (EC 2.7.8.15,\
      \ RHEA:13289) that matches the experimental characterization of DPAGT1."
    supported_by:
    - reference_id: file:human/DPAGT1/DPAGT1-uniprot.txt
      supporting_text: "transferring GlcNAc-1-P from"
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Subcellular-location mapping to ER membrane. This is the correct and
      informative localization of DPAGT1, an ER-resident multi-pass membrane enzyme.
    action: ACCEPT
    reason: "ER membrane is the experimentally and structurally supported location of\
      \ DPAGT1; the enzyme acts on the cytoplasmic leaflet of the ER membrane."
    supported_by:
    - reference_id: file:human/DPAGT1/DPAGT1-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Endoplasmic reticulum"
    - reference_id: PMID:29459785
      supporting_text: "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"
- term:
    id: GO:0006488
    label: dolichol-linked oligosaccharide biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: "DPAGT1 initiates the dolichol cycle producing GlcNAc-PP-dolichol; this is\
      \ the correct core biological process."
    supported_by:
    - reference_id: PMID:30388443
      supporting_text: "The product GlcNAc-PP-Dol is anchored to the ER membrane by its\
        \ dolichyl moiety"
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Automated (ARBA/InterPro) assignment of generic membrane localization.
      Correct but far less specific than ER membrane, which is available and directly
      supported.
    action: MODIFY
    reason: "Correct that DPAGT1 is membrane-integral, but 'membrane' is uninformative;\
      \ the specific ER membrane term (GO:0005789) is supported and preferred."
    proposed_replacement_terms:
    - id: GO:0005789
      label: endoplasmic reticulum membrane
    supported_by:
    - reference_id: file:human/DPAGT1/DPAGT1-uniprot.txt
      supporting_text: "Multi-pass membrane protein"
- term:
    id: GO:0016780
    label: phosphotransferase activity, for other substituted phosphate groups
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    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.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0003975
      label: UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase
        activity
    supported_by:
    - reference_id: PMID:30388443
      supporting_text: "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)"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    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."
    action: MARK_AS_OVER_ANNOTATED
    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."
    supported_by:
    - reference_id: PMID:32814053
      supporting_text: "It facilitates the identification \nof interacting proteins that\
        \ significantly influence mutant TDP-43 and HTT \ntoxicity in transgenic flies"
- term:
    id: GO:0006488
    label: dolichol-linked oligosaccharide biosynthetic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-446193
  qualifier: involved_in
  review:
    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."
    action: ACCEPT
    reason: "Reactome curates DPAGT1 as the first catalytic step of the LLO/N-glycan\
      \ precursor pathway; this is a correct core biological process assignment."
    supported_by:
    - reference_id: PMID:30388443
      supporting_text: "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"
- term:
    id: GO:0003975
    label: UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase
      activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-446191
  qualifier: enables
  review:
    summary: "Reactome TAS for the GlcNAc-1-P transferase reaction (addition of\
      \ N-acetylglucosamine to dolichyl phosphate). Matches the defining catalytic\
      \ activity of DPAGT1."
    action: ACCEPT
    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."
    supported_by:
    - reference_id: PMID:29459785
      supporting_text: "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)."
- term:
    id: GO:0003975
    label: UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase
      activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4549334
  qualifier: enables
  review:
    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."
    action: ACCEPT
    reason: "Correct core molecular function; the disease-reaction framing reflects loss\
      \ of the same activity in CDG1J/CMS13 variants."
    supported_by:
    - reference_id: PMID:29459785
      supporting_text: "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)."
- term:
    id: GO:0003975
    label: UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase
      activity
  evidence_type: EXP
  original_reference_id: PMID:30388443
  qualifier: enables
  review:
    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."
    action: ACCEPT
    reason: "Direct experimental characterization of the catalytic activity with defined\
      \ kinetic parameters and mechanism; strongly supports the core molecular function."
    supported_by:
    - reference_id: PMID:30388443
      supporting_text: "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)"
- term:
    id: GO:0003975
    label: UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase
      activity
  evidence_type: EXP
  original_reference_id: PMID:9451016
  qualifier: enables
  review:
    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."
    action: ACCEPT
    reason: "Functional expression demonstrating the GlcNAc-1-P transferase activity of\
      \ human DPAGT1; supports the core molecular function."
    supported_by:
    - reference_id: PMID:9451016
      supporting_text: "GlcNAc2-PP-Dolichol biosynthesis could be shown with isolated\
        \ S.cerevisiae"
    - reference_id: PMID:9451016
      supporting_text: "the enzyme for the committed step of the dolichol cycle"
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: "Sequence-similarity transfer of ER membrane localization (from ortholog\
      \ UniProtKB:P23338). Consistent with the experimentally/structurally supported\
      \ ER membrane residence of DPAGT1."
    action: ACCEPT
    reason: "ER membrane is the correct, informative localization, corroborated by human\
      \ structural data and UniProt subcellular-location annotation."
    supported_by:
    - reference_id: file:human/DPAGT1/DPAGT1-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Endoplasmic reticulum"
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    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."
    action: KEEP_AS_NON_CORE
    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."
    supported_by:
    - reference_id: file:human/DPAGT1/DPAGT1-uniprot.txt
      supporting_text: "SUBUNIT: Homodimer."
    - reference_id: PMID:29459785
      supporting_text: "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"
- term:
    id: GO:0003975
    label: UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase
      activity
  evidence_type: IDA
  original_reference_id: PMID:29459785
  qualifier: enables
  review:
    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."
    action: ACCEPT
    reason: "Direct experimental demonstration of the catalytic activity; core molecular\
      \ function."
    supported_by:
    - reference_id: PMID:29459785
      supporting_text: "catalyzes the first and committed step of N-linked glycosylation\
        \ on the cytosolic face of endoplasmic reticulum (ER) membrane"
- term:
    id: GO:0006488
    label: dolichol-linked oligosaccharide biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:29459785
  qualifier: involved_in
  review:
    summary: "Direct evidence that DPAGT1 acts in dolichol-linked oligosaccharide\
      \ biosynthesis, catalyzing the first committed step of LLO assembly on the\
      \ cytosolic ER face."
    action: ACCEPT
    reason: "DPAGT1 initiates the LLO/dolichol-cycle pathway; correct core biological\
      \ process."
    supported_by:
    - reference_id: PMID:29459785
      supporting_text: "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)."
- term:
    id: GO:0003976
    label: UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase
      activity
  evidence_type: IDA
  original_reference_id: PMID:6289658
  qualifier: enables
  review:
    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)."
    action: MARK_AS_OVER_ANNOTATED
    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."
    supported_by:
    - reference_id: PMID:6289658
      supporting_text: "a deficiency \nof the enzyme UDP-N-acetylglucosamine:lysosomal enzyme \nN-acetylglucosamine-1-phosphotransferase"
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4549334
  qualifier: located_in
  review:
    summary: "Reactome TAS localizing DPAGT1 to the ER membrane (disease-variant\
      \ reaction context). Consistent with the experimentally supported ER membrane\
      \ residence."
    action: ACCEPT
    reason: "Correct, informative ER membrane localization curated by Reactome."
    supported_by:
    - reference_id: file:human/DPAGT1/DPAGT1-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Endoplasmic reticulum"
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-446191
  qualifier: located_in
  review:
    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."
    action: ACCEPT
    reason: "Correct core cellular component; the enzyme and its product are ER-membrane\
      \ associated."
    supported_by:
    - reference_id: PMID:30388443
      supporting_text: "The product GlcNAc-PP-Dol is anchored to the ER membrane by its\
        \ dolichyl moiety"
- term:
    id: GO:0006487
    label: protein N-linked glycosylation
  evidence_type: IMP
  original_reference_id: PMID:19549906
  qualifier: involved_in
  review:
    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."
    action: ACCEPT
    reason: "DPAGT1 is upstream of and required for protein N-linked glycosylation;\
      \ perturbing DPAGT1 alters cellular N-glycosylation. Correct core biological\
      \ process."
    supported_by:
    - reference_id: PMID:19549906
      supporting_text: "initiates the synthesis of the lipid-linked oligosaccharide\
        \ (LLO) precursor for protein N-glycosylation in the endoplasmic reticulum"
    - reference_id: PMID:19549906
      supporting_text: "elevated expression of DPAGT1, the gene that initiates protein\
        \ N-glycosylation"
- term:
    id: GO:0003975
    label: UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase
      activity
  evidence_type: IMP
  original_reference_id: PMID:12872255
  qualifier: enables
  review:
    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."
    action: ACCEPT
    reason: "Loss-of-activity in disease variants demonstrates that DPAGT1 encodes the\
      \ GlcNAc-1-P transferase; supports the core molecular function."
    supported_by:
    - reference_id: PMID:12872255
      supporting_text: "N-acetyl-glucosamine-1 phosphate transferase (GPT) activity\
        \ encoded by DPAGT1"
    - reference_id: PMID:12872255
      supporting_text: "the GPT activity is reduced to approximately 10% of normal levels"
- term:
    id: GO:0003975
    label: UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase
      activity
  evidence_type: IDA
  original_reference_id: PMID:8179616
  qualifier: enables
  review:
    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."
    action: ACCEPT
    reason: "Direct enzymatic measurement of the GlcNAc-1-P transferase activity in human\
      \ fibroblasts; supports the core molecular function."
    supported_by:
    - reference_id: PMID:8179616
      supporting_text: "activity in CDG syndrome fibroblasts were similar to those in\
        \ normal"
- term:
    id: GO:0016020
    label: membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: "Sequence-similarity transfer of generic membrane localization. Correct\
      \ but subsumed by the more informative ER membrane term."
    action: MODIFY
    reason: "DPAGT1 is membrane-integral, but the specific ER membrane term (GO:0005789)\
      \ is supported and preferable to generic 'membrane'."
    proposed_replacement_terms:
    - id: GO:0005789
      label: endoplasmic reticulum membrane
    supported_by:
    - reference_id: file:human/DPAGT1/DPAGT1-uniprot.txt
      supporting_text: "Multi-pass membrane protein"
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:8179616
  qualifier: located_in
  review:
    summary: "Direct assay associated DPAGT1/GPT activity with a membrane (microsomal)\
      \ fraction. Correct but generic; ER membrane is the informative location."
    action: MODIFY
    reason: "Membrane association is experimentally consistent, but the specific ER\
      \ membrane term (GO:0005789) is supported and preferable."
    proposed_replacement_terms:
    - id: GO:0005789
      label: endoplasmic reticulum membrane
    supported_by:
    - reference_id: file:human/DPAGT1/DPAGT1-uniprot.txt
      supporting_text: "Multi-pass membrane protein"
- term:
    id: GO:0043231
    label: intracellular membrane-bounded organelle
  evidence_type: IDA
  original_reference_id: PMID:12872255
  qualifier: located_in
  review:
    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)."
    action: KEEP_AS_NON_CORE
    reason: "Correct but high-level. The informative core localization is ER membrane\
      \ (GO:0005789), already annotated. Retained as a non-core, less specific location."
    supported_by:
    - reference_id: file:human/DPAGT1/DPAGT1-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Endoplasmic reticulum"
core_functions:
- description: "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."
  molecular_function:
    id: GO:0003975
    label: UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase
      activity
  directly_involved_in:
  - id: GO:0006488
    label: dolichol-linked oligosaccharide biosynthetic process
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: PMID:29459785
    supporting_text: "catalyzes the first and committed step of N-linked glycosylation\
      \ on the cytosolic face of endoplasmic reticulum (ER) membrane"
  - reference_id: PMID:30388443
    supporting_text: "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)"
- description: "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."
  molecular_function:
    id: GO:0003975
    label: UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase
      activity
  directly_involved_in:
  - id: GO:0006487
    label: protein N-linked glycosylation
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: PMID:19549906
    supporting_text: "initiates the synthesis of the lipid-linked oligosaccharide (LLO)\
      \ precursor for protein N-glycosylation in the endoplasmic reticulum"
  - reference_id: PMID:12872255
    supporting_text: "N-acetyl-glucosamine-1 phosphate transferase (GPT) activity\
      \ encoded by DPAGT1"
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:human/DPAGT1/DPAGT1-uniprot.txt
  title: UniProtKB entry Q9H3H5 (GPT_HUMAN) DPAGT1
  findings: []
- id: PMID:12872255
  title: Deficiency of UDP-GlcNAc:Dolichol Phosphate N-Acetylglucosamine-1 Phosphate
    Transferase (DPAGT1) causes a novel congenital disorder of Glycosylation Type
    Ij.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "PubMed-verified. Establishes DPAGT1/GPT deficiency as the cause of\
      \ CDG-Ij, with patient GPT activity ~10% of normal and the Y170C variant; directly\
      \ ties the GlcNAc-1-P transferase activity to DPAGT1."
- id: PMID:19549906
  title: Overexpression of DPAGT1 leads to aberrant N-glycosylation of E-cadherin
    and cellular discohesion in oral cancer.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "PubMed-verified. Shows DPAGT1 initiates LLO synthesis and controls\
      \ E-cadherin N-glycosylation; supports the protein N-linked glycosylation BP\
      \ annotation."
- id: PMID:29459785
  title: GlcNAc-1-P-transferase-tunicamycin complex structure reveals basis for inhibition
    of N-glycosylation.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "PubMed-verified structural/functional study of human GPT (DPAGT1);\
      \ defines the first committed step of N-glycosylation and the tunicamycin\
      \ inhibition mechanism; homodimer, ER membrane, cytosolic-face catalysis."
- id: PMID:30388443
  title: Structures of DPAGT1 Explain Glycosylation Disease Mechanisms and Advance
    TB Antibiotic Design.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "PubMed-verified. Human DPAGT1 structures with UDP-GlcNAc and\
      \ tunicamycin, kinetics, Mg2+ cofactor, disease-variant characterization\
      \ (CDG1J, CMS13); directly supports the catalytic MF and disease mechanism."
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: "PubMed-verified large-scale ND interactome (Y2H) study. Basis for a\
      \ single DPAGT1-HTT interaction supporting only a bare 'protein binding' IPI; no\
      \ specific molecular function for DPAGT1."
- id: PMID:6289658
  title: Demonstration of the heterozygous state for I-cell disease and pseudo-Hurler
    polydystrophy by assay of N-acetylglucosaminylphosphotransferase in white blood
    cells and fibroblasts.
  findings: []
  reference_review:
    relevance: LOW
    correctness: MISCITED
    review_notes: "PubMed-verified, but the paper is about the DISTINCT lysosomal-enzyme\
      \ GlcNAc-1-phosphotransferase (GNPTAB/GNPTG; I-cell disease / mucolipidosis II-III),\
      \ not DPAGT1. It does not support a DPAGT1 function; used to support the\
      \ GO:0003976 annotation that has been flagged as over-annotation (wrong enzyme)."
- id: PMID:8179616
  title: Major defect of carbohydrate-deficient-glycoprotein syndrome is not found
    in the synthesis of dolichyl phosphate or N-acetylglucosaminyl-pyrophosphoryl-dolichol.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: "PubMed-verified. Assays GlcNAc-1-P transferase (GPT) activity and\
      \ dolichyl phosphate in CDG fibroblasts; supports the enzymatic activity and\
      \ membrane association of the enzyme."
- id: PMID:9451016
  title: Cloning and functional expression of the human GlcNAc-1-P transferase, the
    enzyme for the committed step of the dolichol cycle, by heterologous complementation
    in Saccharomyces cerevisiae.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "PubMed-verified. Cloned human DPAGT1/GPT by yeast complementation;\
      \ recombinant enzyme made GlcNAc(2)-PP-dolichol, dolichol-P-stimulated and\
      \ tunicamycin-inhibited; supports the core catalytic function."
- id: Reactome:R-HSA-446191
  title: Addition of N-acetyl-D-glucosamine to Dolichyl phosphate
  findings: []
- id: Reactome:R-HSA-446193
  title: Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide,
    LLO) and transfer to a nascent protein
  findings: []
- id: Reactome:R-HSA-4549334
  title: Defective DPAGT1 does not transfer GlcNAc to DOLP
  findings: []