id: Q68CP4
gene_symbol: HGSNAT
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  HGSNAT (heparan-alpha-glucosaminide N-acetyltransferase; TMEM76; EC 2.3.1.78) is a
  polytopic lysosomal membrane transacetylase that carries out an essential step of
  heparan sulfate degradation. It transfers an acetyl group from cytosolic acetyl-CoA
  onto the free amino group of the terminal non-reducing alpha-glucosamine residue of
  intralysosomal heparan sulfate (and heparin), converting it to
  N-acetyl-alpha-glucosamine so that the downstream lysosomal exoglycosidase NAGLU
  (alpha-N-acetylglucosaminidase) can remove it and degradation can proceed. Unlike the
  other three enzymes of the heparan sulfate degradation pathway, which are soluble
  luminal hydrolases/sulfatases, HGSNAT is the only membrane-bound member and the only
  transferase, spanning the lysosomal membrane with 11 transmembrane helices; its
  active-site nucleophile (His297) is positioned to access cytoplasmic acetyl-CoA and
  transfer the acetyl group across the membrane to the luminal glucosamine substrate. The
  enzyme is synthesised as an inactive precursor that is trafficked to lysosomes via
  adaptor-protein/dileucine- and tyrosine-based signals, proteolytically cleaved into an
  N-terminal alpha-chain and C-terminal beta-chain, and assembled into active
  homo-oligomers. Loss-of-function mutations cause mucopolysaccharidosis type IIIC
  (Sanfilippo syndrome C), an autosomal recessive lysosomal storage disorder with severe
  progressive neurodegeneration; certain HGSNAT variants also cause non-syndromic
  retinitis pigmentosa (RP73).
alternative_products:
- name: '1'
  id: Q68CP4-1
- name: '2'
  id: Q68CP4-2
  sequence_note: VSP_040504
existing_annotations:
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetic (IBA) assignment that HGSNAT acts in the lysosomal membrane. This is
      the correct core subcellular location: HGSNAT is a multi-pass lysosomal membrane
      protein whose enzymatic action occurs at that membrane. Directly supported by
      experimental evidence in this gene (colocalization with LAMP-2; lysosomal-membrane
      proteomics) and consistent with the UniProt subcellular-location annotation.
    action: ACCEPT
    reason: >-
      Correct core location, supported experimentally in human HGSNAT and by the
      phylogenetic model.
    supported_by:
    - reference_id: file:human/HGSNAT/HGSNAT-uniprot.txt
      supporting_text: Lysosome membrane
    - reference_id: PMID:19823584
      supporting_text: almost completely co-localized with the lysosomal markers LysoTracker Red or LAMP-2
- term:
    id: GO:0015019
    label: heparan-alpha-glucosaminide N-acetyltransferase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Phylogenetic (IBA) assignment of the exact-match molecular function:
      acetyl-CoA:alpha-glucosaminide N-acetyltransferase activity (EC 2.3.1.78;
      RHEA:15125). This is the core catalytic activity of HGSNAT and is confirmed
      experimentally by direct N-acetyltransferase assays of the recombinant human enzyme.
    action: ACCEPT
    reason: >-
      Exact-match term for the demonstrated core catalytic activity; well supported by
      experimental data and the phylogenetic model.
    supported_by:
    - reference_id: file:human/HGSNAT/HGSNAT-uniprot.txt
      supporting_text: Lysosomal acetyltransferase that acetylates the non-reducing
    - reference_id: PMID:20650889
      supporting_text: catalyzes the transmembrane acetylation of heparan sulfate in lysosomes required
- term:
    id: GO:0030200
    label: heparan sulfate proteoglycan catabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Phylogenetic (IBA) assignment placing HGSNAT in heparan sulfate proteoglycan
      catabolism. This is the core biological process: HGSNAT's N-acetylation step is an
      obligatory intermediate in stepwise lysosomal degradation of heparan sulfate, and
      its deficiency blocks the pathway and causes lysosomal HS storage (MPS IIIC).
    action: ACCEPT
    reason: >-
      Correct core catabolic pathway; the enzyme's step is required for heparan sulfate
      degradation and its loss causes HS accumulation.
    supported_by:
    - reference_id: PMID:19823584
      supporting_text: acetylation of the terminal glucosamine residues of heparan sulfate prior to
    - reference_id: PMID:20650889
      supporting_text: for its further catabolism
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Electronic (UniProt SubCell mapping SL-0157) annotation of lysosomal membrane
      location, derived from the curated UniProt subcellular-location statement. Correct
      and redundant with the experimentally supported location.
    action: ACCEPT
    reason: >-
      Consistent with curated UniProt location and experimental evidence for lysosomal
      membrane localization.
    supported_by:
    - reference_id: file:human/HGSNAT/HGSNAT-uniprot.txt
      supporting_text: Lysosome membrane
- term:
    id: GO:0015019
    label: heparan-alpha-glucosaminide N-acetyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Electronic assignment of the exact-match N-acetyltransferase activity based on
      EC 2.3.1.78 / RHEA:15125 and ortholog evidence. Correct and redundant with the
      experimentally and phylogenetically supported MF annotation.
    action: ACCEPT
    reason: >-
      Exact-match MF term mapped from EC/RHEA; correct core catalytic activity.
    supported_by:
    - reference_id: file:human/HGSNAT/HGSNAT-uniprot.txt
      supporting_text: Lysosomal acetyltransferase that acetylates the non-reducing
- term:
    id: GO:0030200
    label: heparan sulfate proteoglycan catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Electronic transfer (Ensembl Compara) of the heparan sulfate proteoglycan catabolic
      process annotation from the experimentally characterized mouse ortholog. Correct
      core biological process.
    action: ACCEPT
    reason: >-
      Correct core catabolic pathway, transferred from an experimentally characterized
      ortholog; consistent with human experimental data.
    supported_by:
    - reference_id: PMID:20650889
      supporting_text: for its further catabolism
- term:
    id: GO:0015019
    label: heparan-alpha-glucosaminide N-acetyltransferase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2263492
  qualifier: enables
  review:
    summary: >-
      Reactome traceable-author annotation of the exact-match N-acetyltransferase
      activity, from a reaction representing HGSNAT acetylation of the heparan chain (the
      "defective" reaction node modelling loss of this activity in MPS IIIC). Supports the
      core catalytic function.
    action: ACCEPT
    reason: >-
      Exact-match core catalytic activity, curated by Reactome; consistent with all other
      evidence.
    supported_by:
    - reference_id: file:human/HGSNAT/HGSNAT-uniprot.txt
      supporting_text: Lysosomal acetyltransferase that acetylates the non-reducing
- term:
    id: GO:0015019
    label: heparan-alpha-glucosaminide N-acetyltransferase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9036056
  qualifier: enables
  review:
    summary: >-
      Reactome traceable-author annotation of the exact-match N-acetyltransferase
      activity (second Reactome reaction node). Redundant with the other MF annotations
      and supports the core catalytic function.
    action: ACCEPT
    reason: >-
      Exact-match core catalytic activity, curated by Reactome.
    supported_by:
    - reference_id: file:human/HGSNAT/HGSNAT-uniprot.txt
      supporting_text: Lysosomal acetyltransferase that acetylates the non-reducing
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2263492
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable-author annotation of lysosomal membrane location. Correct core
      location, redundant with the experimentally supported CC annotations.
    action: ACCEPT
    reason: >-
      Correct core location, curated by Reactome; consistent with experimental data.
    supported_by:
    - reference_id: file:human/HGSNAT/HGSNAT-uniprot.txt
      supporting_text: Lysosome membrane
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9036056
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable-author annotation of lysosomal membrane location (second reaction
      node). Correct core location, redundant with other CC annotations.
    action: ACCEPT
    reason: >-
      Correct core location, curated by Reactome.
    supported_by:
    - reference_id: file:human/HGSNAT/HGSNAT-uniprot.txt
      supporting_text: Lysosome membrane
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6798747
  qualifier: located_in
  review:
    summary: >-
      Reactome annotation of plasma membrane location, from the "Exocytosis of tertiary
      granule membrane proteins" reaction in the neutrophil degranulation pathway. This
      reflects mobilization of granule-membrane HGSNAT to the cell surface during
      degranulation rather than the enzyme's core lysosomal site of action. Not wrong in
      that specific context, but peripheral to HGSNAT's core catalytic role.
    action: KEEP_AS_NON_CORE
    reason: >-
      Neutrophil-degranulation exocytosis context; a secondary, cell-type-restricted
      localization, not the core lysosomal membrane location where catalysis occurs.
    supported_by:
    - reference_id: Reactome:R-HSA-6798747
      supporting_text: Exocytosis of tertiary granule membrane proteins
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6799350
  qualifier: located_in
  review:
    summary: >-
      Reactome annotation of plasma membrane location from the "Exocytosis of specific
      granule membrane proteins" neutrophil-degranulation reaction. As above, reflects
      degranulation-associated surface exposure rather than the core lysosomal site of
      action.
    action: KEEP_AS_NON_CORE
    reason: >-
      Neutrophil-degranulation exocytosis context; peripheral to the core lysosomal
      function.
    supported_by:
    - reference_id: Reactome:R-HSA-6799350
      supporting_text: Exocytosis of specific granule membrane proteins
- term:
    id: GO:0035579
    label: specific granule membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6799350
  qualifier: located_in
  review:
    summary: >-
      Reactome annotation placing HGSNAT in the neutrophil specific granule membrane
      (neutrophil degranulation pathway). A real cell-type-specific granule localization
      but peripheral to the core lysosomal catabolic function of the enzyme.
    action: KEEP_AS_NON_CORE
    reason: >-
      Cell-type-restricted neutrophil granule localization; not the core lysosomal site of
      action.
    supported_by:
    - reference_id: Reactome:R-HSA-6799350
      supporting_text: Exocytosis of specific granule membrane proteins
- term:
    id: GO:0070821
    label: tertiary granule membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6798747
  qualifier: located_in
  review:
    summary: >-
      Reactome annotation placing HGSNAT in the neutrophil tertiary granule membrane
      (neutrophil degranulation pathway). A real cell-type-specific granule localization
      but peripheral to the core lysosomal catabolic function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Cell-type-restricted neutrophil granule localization; not the core lysosomal site of
      action.
    supported_by:
    - reference_id: Reactome:R-HSA-6798747
      supporting_text: Exocytosis of tertiary granule membrane proteins
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: HDA
  original_reference_id: PMID:17897319
  qualifier: located_in
  review:
    summary: >-
      High-throughput direct assay (lysosomal-membrane proteomics of purified placental
      lysosomes) identifying HGSNAT among proteins residing in the lysosomal membrane.
      Independent experimental support for the core lysosomal membrane location.
    action: ACCEPT
    reason: >-
      Experimental proteomic support for the core lysosomal membrane location.
    supported_by:
    - reference_id: PMID:17897319
      supporting_text: proteins, known to reside at least partially in the lysosomal membrane
    - reference_id: PMID:17897319
      supporting_text: In membranes purified from placental lysosomes
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1678660
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable-author annotation of lysosomal membrane location (from the
      "HGSNAT oligomer acetylates Heparan sulfate chain" reaction). Correct core location.
    action: ACCEPT
    reason: >-
      Correct core location, curated by Reactome.
    supported_by:
    - reference_id: file:human/HGSNAT/HGSNAT-uniprot.txt
      supporting_text: Lysosome membrane
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2090085
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable-author annotation of lysosomal membrane location (from the
      "HGSNAT oligomer acetylates Heparan chain" reaction). Correct core location.
    action: ACCEPT
    reason: >-
      Correct core location, curated by Reactome.
    supported_by:
    - reference_id: file:human/HGSNAT/HGSNAT-uniprot.txt
      supporting_text: Lysosome membrane
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: IDA
  original_reference_id: PMID:19823584
  qualifier: located_in
  review:
    summary: >-
      Direct assay: confocal immunofluorescence of recombinant HGSNAT in human fibroblasts
      showed near-complete colocalization with the lysosomal markers LysoTracker Red and
      LAMP-2. Strong experimental support for the core lysosomal membrane location.
    action: ACCEPT
    reason: >-
      Direct experimental colocalization with lysosomal markers; core location.
    supported_by:
    - reference_id: PMID:19823584
      supporting_text: almost completely co-localized with the lysosomal markers LysoTracker Red or LAMP-2
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: IDA
  original_reference_id: PMID:20650889
  qualifier: located_in
  review:
    summary: >-
      Direct assay from the biogenesis/trafficking study: HGSNAT is a lysosomal membrane
      enzyme trafficked to and residing in lysosomes. Independent experimental support for
      the core location.
    action: ACCEPT
    reason: >-
      Experimental support for the core lysosomal membrane location.
    supported_by:
    - reference_id: PMID:20650889
      supporting_text: transported to the lysosomes via an adaptor protein-mediated pathway
- term:
    id: GO:0007041
    label: lysosomal transport
  evidence_type: IDA
  original_reference_id: PMID:20650889
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to "lysosomal transport" derived from the biogenesis study, which
      characterized the adaptor-protein/tyrosine- and dileucine-signal-mediated trafficking
      of the HGSNAT precursor to lysosomes. That work describes how HGSNAT itself is
      delivered to the lysosome, not a role for HGSNAT in transporting cargo (the sense of
      GO:0007041, transport of substances into/within the lysosome). HGSNAT is an
      acetyltransferase, not a transporter, so this is an over-interpretation of the
      trafficking/targeting observation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The supporting paper documents targeting/biogenesis of HGSNAT to the lysosome, not
      HGSNAT-mediated lysosomal cargo transport; annotating the enzyme to "lysosomal
      transport" over-extends the trafficking observation. Not removed (it is an
      experimental annotation whose full text was read by the curator), but flagged as an
      over-annotation relative to HGSNAT's actual transferase function.
    supported_by:
    - reference_id: PMID:20650889
      supporting_text: transported to the lysosomes via an adaptor protein-mediated pathway
- term:
    id: GO:0016746
    label: acyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:19823584
  qualifier: enables
  review:
    summary: >-
      Direct assay of N-acetyltransferase activity of recombinant HGSNAT (activity of
      wild-type vs. MPS IIIC mutants was measured). The annotation captures this as the
      general parent term "acyltransferase activity", but the specific, exact-match child
      term GO:0015019 (heparan-alpha-glucosaminide N-acetyltransferase activity) is
      warranted because the assay measured precisely this activity.
    action: MODIFY
    reason: >-
      Correct in essence but too general; the measured activity is specifically
      heparan-alpha-glucosaminide N-acetyltransferase activity. Replace with the
      exact-match MF term.
    proposed_replacement_terms:
    - id: GO:0015019
      label: heparan-alpha-glucosaminide N-acetyltransferase activity
    supported_by:
    - reference_id: PMID:19823584
      supporting_text: assayed for N-acetyltransferase activity
    - reference_id: file:human/HGSNAT/HGSNAT-uniprot.txt
      supporting_text: Lysosomal acetyltransferase that acetylates the non-reducing
- term:
    id: GO:0051259
    label: protein complex oligomerization
  evidence_type: IDA
  original_reference_id: PMID:20650889
  qualifier: involved_in
  review:
    summary: >-
      Direct experimental demonstration that HGSNAT assembles into ~440-kDa homo-oligomers
      and that homo-oligomerization is required for enzymatic activity. This is a genuine,
      experimentally supported property, but it describes a biogenesis/assembly step rather
      than HGSNAT's core molecular function (acetyltransferase) or its core catabolic
      pathway role.
    action: KEEP_AS_NON_CORE
    reason: >-
      Real and experimentally supported (homo-oligomerization needed for activity), but an
      assembly/biogenesis process peripheral to the core MF/BP; retain as non-core.
    supported_by:
    - reference_id: PMID:20650889
      supporting_text: assembled into active ∼440-kDa oligomers
    - reference_id: file:human/HGSNAT/HGSNAT-uniprot.txt
      supporting_text: Homooligomerization is necessary for enzyme
- term:
    id: GO:0016746
    label: acyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:20650889
  qualifier: enables
  review:
    summary: >-
      Direct assay of N-acetyltransferase activity in the biogenesis study (N-acetyltransferase
      activity was measured to track functional maturation of HGSNAT). As with the other
      acyltransferase IDA, the general parent term should be refined to the exact-match
      child GO:0015019, which precisely describes the activity assayed.
    action: MODIFY
    reason: >-
      Correct but too general; the assayed activity is specifically
      heparan-alpha-glucosaminide N-acetyltransferase activity. Replace with the
      exact-match MF term.
    proposed_replacement_terms:
    - id: GO:0015019
      label: heparan-alpha-glucosaminide N-acetyltransferase activity
    supported_by:
    - reference_id: PMID:20650889
      supporting_text: of the acetyl group to the terminal glucosamine on heparan sulfate
    - reference_id: file:human/HGSNAT/HGSNAT-uniprot.txt
      supporting_text: Lysosomal acetyltransferase that acetylates the non-reducing
core_functions:
- description: >-
    Lysosomal-membrane acetyl-CoA:alpha-glucosaminide N-acetyltransferase: transfers an
    acetyl group from cytosolic acetyl-CoA onto the free amino group of the terminal
    non-reducing alpha-glucosamine residue of intralysosomal heparan sulfate, producing
    N-acetyl-alpha-glucosamine. This transmembrane acetylation is an obligatory step in
    the stepwise lysosomal catabolism of heparan sulfate: it converts the terminal
    residue into a substrate for the exoglycosidase NAGLU so degradation can continue. The
    enzyme is a polytopic (11-TM) lysosomal membrane protein and is the only membrane-bound,
    transferase member of the heparan sulfate degradation pathway.
  molecular_function:
    id: GO:0015019
    label: heparan-alpha-glucosaminide N-acetyltransferase activity
  directly_involved_in:
  - id: GO:0030200
    label: heparan sulfate proteoglycan catabolic process
  locations:
  - id: GO:0005765
    label: lysosomal membrane
  supported_by:
  - reference_id: file:human/HGSNAT/HGSNAT-uniprot.txt
    supporting_text: Lysosomal acetyltransferase that acetylates the non-reducing
  - reference_id: PMID:20650889
    supporting_text: catalyzes the transmembrane acetylation of heparan sulfate in lysosomes required
  - reference_id: PMID:19823584
    supporting_text: acetylation of the terminal glucosamine residues of heparan sulfate prior to
proposed_new_terms: []
suggested_questions:
- question: >-
    What is the precise mechanism by which the active-site nucleophile accesses cytosolic
    acetyl-CoA and transfers the acetyl group across the lysosomal membrane to the luminal
    glucosamine substrate (ping-pong vs. direct transfer), and how do the recent cryo-EM
    structures explain this transmembrane catalysis?
- question: >-
    How does the requirement for intralysosomal proteolytic cleavage and homo-oligomer
    assembly relate to catalytic activation, and could these steps be therapeutic targets?
suggested_experiments:
- description: >-
    Structure-guided mutagenesis of candidate acetyl-CoA-binding and catalytic residues in
    the cytosolic loops, combined with transmembrane-acetylation assays, to define the
    acetyl-transfer path across the membrane.
- description: >-
    Pharmacological-chaperone (e.g. glucosamine-analog) screens on a panel of misfolding
    MPS IIIC missense mutants to identify variants amenable to enzyme-enhancement therapy.
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PAN-GO/IBA pipeline reference; the phylogenetic model correctly assigns the
      exact-match MF (GO:0015019), the core BP (GO:0030200), and the lysosomal membrane
      location, all corroborated by human experimental data.
- 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: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: SubCell (SL-0157) mapping to lysosomal membrane; consistent with curated location.
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Ensembl Compara transfer of the HS catabolic-process annotation from the mouse ortholog.
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: EC/RHEA-based electronic mapping to the exact-match MF term.
- id: PMID:17897319
  title: Integral and associated lysosomal membrane proteins.
  findings:
  - statement: >-
      Lysosomal-membrane proteomics of purified placental lysosomes identified HGSNAT among
      proteins residing at least partially in the lysosomal membrane.
    reference_section_type: ABSTRACT
    supporting_text: proteins, known to reside at least partially in the lysosomal membrane
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Abstract-only in cache; supports the HDA lysosomal-membrane annotation. HGSNAT is
      among the enriched lysosomal membrane proteins in this placental-lysosome proteome.
- id: PMID:19823584
  title: Protein misfolding as an underlying molecular defect in mucopolysaccharidosis
    III type C.
  findings:
  - statement: >-
      HGSNAT is a lysosomal membrane enzyme (EC 2.3.1.78) that catalyses transmembrane
      acetylation of the terminal glucosamine residues of heparan sulfate prior to their
      hydrolysis by alpha-N-acetylglucosaminidase; its deficiency causes MPS IIIC.
    reference_section_type: ABSTRACT
    supporting_text: acetylation of the terminal glucosamine residues of heparan sulfate prior to
  - statement: >-
      Recombinant wild-type HGSNAT colocalizes with the lysosomal markers LysoTracker and
      LAMP-2, whereas most MPS IIIC missense mutants misfold and are retained in the ER.
    reference_section_type: RESULTS
    supporting_text: almost completely co-localized with the lysosomal markers LysoTracker Red or LAMP-2
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Full text available; directly supports the N-acetyltransferase activity, the HS
      catabolic role, and the lysosomal membrane localization of human HGSNAT.
- id: PMID:20650889
  title: Analysis of the biogenesis of heparan sulfate acetyl-CoA:alpha-glucosaminide
    N-acetyltransferase provides insights into the mechanism underlying its complete
    deficiency in mucopolysaccharidosis IIIC.
  findings:
  - statement: >-
      HGSNAT catalyzes the transmembrane acetylation of heparan sulfate in lysosomes,
      required for its further catabolism.
    reference_section_type: ABSTRACT
    supporting_text: catalyzes the transmembrane acetylation of heparan sulfate in lysosomes required
  - statement: >-
      The precursor is trafficked to lysosomes via an adaptor-protein-mediated pathway,
      cleaved into alpha and beta chains, and assembled into active ~440-kDa homo-oligomers.
    reference_section_type: ABSTRACT
    supporting_text: assembled into active ∼440-kDa oligomers
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Abstract-only in cache but the abstract supports the transmembrane N-acetyltransferase
      activity, the HS catabolic role, oligomerization requirement, and AP-mediated lysosomal
      targeting used in the reviews above.
- id: Reactome:R-HSA-1678660
  title: HGSNAT oligomer acetylates Heparan sulfate chain(3)
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Reactome reaction node modelling HGSNAT acetylation of heparan sulfate; supports MF/CC.
- id: Reactome:R-HSA-2090085
  title: HGSNAT oligomer acetylates Heparan chain(1)
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Reactome reaction node modelling HGSNAT acetylation of heparan chain; supports MF/CC.
- id: Reactome:R-HSA-2263492
  title: Defective HGSNAT does not acetylate Heparan chain(1)
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Reactome disease reaction node (loss of HGSNAT acetylation in MPS IIIC); supports MF/CC.
- id: Reactome:R-HSA-6798747
  title: Exocytosis of tertiary granule membrane proteins
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Neutrophil-degranulation reaction; source of the plasma-membrane and tertiary-granule
      membrane annotations, which are non-core cell-type-specific localizations.
- id: Reactome:R-HSA-6799350
  title: Exocytosis of specific granule membrane proteins
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Neutrophil-degranulation reaction; source of the plasma-membrane and specific-granule
      membrane annotations, which are non-core cell-type-specific localizations.
- id: Reactome:R-HSA-9036056
  title: Defective HGSNAT does not acetylate Heparan sulfate chain(3)
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Reactome disease reaction node (loss of HGSNAT acetylation in MPS IIIC); supports MF/CC.
- id: file:human/HGSNAT/HGSNAT-uniprot.txt
  title: UniProtKB Q68CP4 (HGNAT_HUMAN) curated entry
  findings:
  - statement: >-
      UniProt describes HGSNAT as a lysosomal acetyltransferase that acetylates the terminal
      alpha-glucosamine of intralysosomal heparin/heparan sulfate, converting it into a
      substrate for luminal alpha-N-acetylglucosaminidase; it is a multi-pass lysosome
      membrane protein and a homo-oligomer whose oligomerization is required for activity.
    supporting_text: Lysosomal acetyltransferase that acetylates the non-reducing
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Primary curated UniProt record for HGSNAT; source of function, catalytic activity, location, and subunit statements.