id: P13929
gene_symbol: ENO3
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  ENO3 encodes beta-enolase (muscle-specific enolase, MSE), the beta subunit of the
  glycolytic metalloenzyme enolase. It catalyses the penultimate step of glycolysis:
  the Mg2+-dependent, reversible dehydration of 2-phospho-D-glycerate (2-PG) to
  phosphoenolpyruvate (PEP) plus water (EC 4.2.1.11); the reverse hydration reaction
  operates in gluconeogenesis. Mammalian enolase functions as a dimer assembled from
  three tissue-specific subunits - alpha (ENO1, ubiquitous), beta (ENO3, muscle) and
  gamma (ENO2, neuronal) - which form homodimers and heterodimers; in striated muscle
  ENO3 forms alpha/beta heterodimers and beta/beta homodimers. The enzyme acts in the
  cytosol, with an additional sarcomeric pool localized to the Z line and, by
  similarity, the M band. Loss-of-function ENO3 variants cause glycogen storage disease
  type XIII (GSD13, beta-enolase deficiency), a metabolic myopathy of distal glycolysis
  characterized by exercise-induced myalgia, muscle weakness and fatigability, raised
  serum creatine kinase, and focal sarcoplasmic glycogen accumulation.
alternative_products:
- name: '1'
  id: P13929-1
- name: '2'
  id: P13929-2
  sequence_note: VSP_037753
- name: '3'
  id: P13929-3
  sequence_note: VSP_037752
existing_annotations:
- term:
    id: GO:0004634
    label: phosphopyruvate hydratase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Phylogenetically-inferred (IBA) assignment of phosphopyruvate hydratase (enolase,
      EC 4.2.1.11) activity, the defining molecular function of the enolase family and
      the core catalytic function of ENO3. Beta-enolase converts 2-phosphoglycerate to
      phosphoenolpyruvate in glycolysis and the reverse in gluconeogenesis.
    action: ACCEPT
    reason: >-
      This is the core molecular function of ENO3, at the correct level of specificity,
      supported by UniProt, EC/RHEA mapping, ISS from mouse ortholog, and multiple TAS
      Reactome annotations. The IBA is well supported across the enolase orthology group.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: Enolase that catalyzes the conversion of 2-phosphoglycerate
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: Reaction=(2R)-2-phosphoglycerate = phosphoenolpyruvate + H2O
- term:
    id: GO:0006096
    label: glycolytic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Phylogenetically-inferred involvement in glycolysis. Enolase catalyses the ninth
      step of glycolysis (2-PG to PEP), a core biological process for ENO3.
    action: ACCEPT
    reason: >-
      Correct and core. ENO3 is a canonical glycolytic enzyme; the muscle beta-enolase
      supplies the high glycolytic flux of striated muscle. Supported by UniProt PATHWAY.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: "glyceraldehyde 3-phosphate: step 4/5"
- term:
    id: GO:0000015
    label: phosphopyruvate hydratase complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: >-
      Phylogenetically-inferred assignment to the phosphopyruvate hydratase (enolase)
      complex - the catalytically active enolase dimer. ENO3 acts as a beta/beta
      homodimer or an alpha/beta heterodimer with ENO1.
    action: ACCEPT
    reason: >-
      Enolase is obligately dimeric and Mg2+ stabilizes the dimer; the complex term
      accurately captures ENO3's quaternary organization. This is where the informative
      content of the bare protein-binding IPIs (ENO1-ENO3) is properly represented.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: "SUBUNIT: Mammalian enolase is composed of 3 isozyme subunits, alpha,"
- term:
    id: GO:0000015
    label: phosphopyruvate hydratase complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: part_of
  review:
    summary: >-
      InterPro2GO (IPR000941 Enolase) electronic assignment to the enolase dimer complex.
      Duplicates the IBA complex annotation.
    action: ACCEPT
    reason: >-
      Correct InterPro-based mapping; consistent with the IBA part_of annotation and with
      the obligately dimeric nature of enolase.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: "SUBUNIT: Mammalian enolase is composed of 3 isozyme subunits, alpha,"
- term:
    id: GO:0000287
    label: magnesium ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro2GO (IPR000941 Enolase) electronic assignment of magnesium ion binding.
      Mg2+ is the essential catalytic cofactor of enolase; the structure of P13929 has
      annotated Mg2+-binding residues (Ser-245, Asp-293, Asp-318).
    action: ACCEPT
    reason: >-
      Well supported. Mg2+ is required for catalysis and for stabilizing the enolase
      dimer, and UniProt lists explicit Mg2+ BINDING sites in ENO3. A genuine cofactor
      function; retained as core because catalysis is Mg2+-dependent.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: Note=Mg(2+) is required for catalysis and for stabilizing the dimer
- term:
    id: GO:0004634
    label: phosphopyruvate hydratase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Electronic assignment of phosphopyruvate hydratase activity via combined IEA
      methods (EC 4.2.1.11, RHEA:10164, InterPro, mouse ortholog). Duplicates the core
      enolase molecular function.
    action: ACCEPT
    reason: >-
      Correct EC/RHEA/InterPro mapping to the core catalytic function of ENO3.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: Reaction=(2R)-2-phosphoglycerate = phosphoenolpyruvate + H2O
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Electronic assignment of cytoplasmic localization from the UniProt subcellular
      location vocabulary. Enolase is a soluble cytoplasmic/cytosolic enzyme.
    action: ACCEPT
    reason: >-
      Correct but general; the more specific GO:0005829 cytosol (IDA, HPA) is the
      preferred core location. Kept as an accurate parent-level localization.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm. Note=Localized to the Z line"
- term:
    id: GO:0006094
    label: gluconeogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      ARBA electronic assignment of involvement in gluconeogenesis. Enolase catalyses the
      reversible 2-PG/PEP interconversion; running in the hydration (PEP to 2-PG)
      direction, it participates in the gluconeogenic pathway.
    action: ACCEPT
    reason: >-
      Biologically correct - the enolase reaction is reversible and operates in both
      glycolysis and gluconeogenesis, as stated explicitly in the UniProt FUNCTION line.
      Note that muscle is not a major gluconeogenic tissue, so this is a shared enzymatic
      capability rather than the dominant physiological role of ENO3, but the annotation
      is not wrong.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: to phosphoenolpyruvate in glycolysis and the reverse reaction in
- term:
    id: GO:0006096
    label: glycolytic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      Electronic assignment (InterPro + UniPathway UPA00109) of involvement in glycolysis.
      Duplicates the IBA glycolytic process annotation.
    action: ACCEPT
    reason: >-
      Correct core biological process; consistent with the IBA and Reactome annotations.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: "glyceraldehyde 3-phosphate: step 4/5"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: >-
      IntAct-curated physical interaction (BioPlex AP-MS interactome) of ENO3 with ENO1
      (UniProtKB:P06733), i.e. the alpha/beta enolase heterodimer. Annotated with the
      uninformative generic term protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Bare "protein binding" (GO:0005515) is uninformative and per curation guidelines
      should not be treated as a core function. The biologically meaningful content - the
      ENO1-ENO3 (alpha/beta) association - is properly represented by GO:0000015
      phosphopyruvate hydratase complex. The interaction itself is a real, high-throughput
      AP-MS observation, so it is not removed, only flagged as over-annotation.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: >-
        affinity purification of 10,128 human proteins-half the proteome-in 293T cells
        and includes 118,162 interactions among 14,586 proteins
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: >-
      IntAct-curated physical interaction (OpenCell endogenous-tagging IP-MS) of ENO3 with
      ENO1 (UniProtKB:P06733), again the alpha/beta enolase heterodimer, annotated with the
      generic term protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      As for the BioPlex IPI, bare "protein binding" is uninformative; the ENO1-ENO3
      interaction is captured more specifically by GO:0000015 phosphopyruvate hydratase
      complex. The interaction is a genuine large-scale IP-MS observation, so it is flagged
      as over-annotation rather than removed.
    supported_by:
    - reference_id: PMID:35271311
      supporting_text: >-
        systematically map the localization and interactions of human proteins
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: is_active_in
  review:
    summary: >-
      Ensembl-Compara electronic transfer (from mouse ortholog) of active localization in
      the cytosol - the compartment where glycolysis, and thus the enolase reaction, occurs.
    action: ACCEPT
    reason: >-
      Correct and core; the cytosol is where ENO3 performs its glycolytic function. The
      is_active_in qualifier is appropriate for a soluble metabolic enzyme. Corroborated by
      the HPA IDA cytosol annotation.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm. Note=Localized to the Z line"
- term:
    id: GO:0061621
    label: canonical glycolysis
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      Electronic assignment (ARBA + mouse ortholog) of involvement in canonical glycolysis,
      the ATP-generating glucose-to-pyruvate route. This is a more specific child of
      glycolytic process describing exactly the pathway ENO3 participates in.
    action: ACCEPT
    reason: >-
      Correct and appropriately specific; ENO3 catalyses the penultimate step of canonical
      glycolysis. Consistent with the Reactome TAS canonical glycolysis annotation.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: "glyceraldehyde 3-phosphate: step 4/5"
- term:
    id: GO:0006094
    label: gluconeogenesis
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-70263
  qualifier: involved_in
  review:
    summary: >-
      Reactome traceable-author-statement placing ENO3 (as part of the enolase dimers) in
      the Gluconeogenesis pathway, catalysing the hydration of PEP to 2-PG.
    action: ACCEPT
    reason: >-
      Biologically correct; the reversible enolase reaction operates in gluconeogenesis.
      Consistent with the ARBA IEA gluconeogenesis annotation and with UniProt FUNCTION.
      Shared enzymatic capability rather than the dominant muscle role, but not incorrect.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: to phosphoenolpyruvate in glycolysis and the reverse reaction in
- term:
    id: GO:0061621
    label: canonical glycolysis
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-70171
  qualifier: involved_in
  review:
    summary: >-
      Reactome traceable-author-statement placing ENO3 in the Glycolysis pathway
      (canonical glycolysis).
    action: ACCEPT
    reason: >-
      Correct and core; duplicates the IEA canonical glycolysis annotation with expert
      Reactome pathway curation.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: "glyceraldehyde 3-phosphate: step 4/5"
- term:
    id: GO:0004634
    label: phosphopyruvate hydratase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-70494
  qualifier: enables
  review:
    summary: >-
      Reactome traceable-author-statement for the enolase reaction ("Enolase dimers
      (ENO1,2,3) convert PEP to 2PG"), assigning phosphopyruvate hydratase activity to ENO3.
    action: ACCEPT
    reason: >-
      Expert-curated statement of the core catalytic function of ENO3; duplicates the
      IBA/IEA/ISS enolase MF annotations.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: Reaction=(2R)-2-phosphoglycerate = phosphoenolpyruvate + H2O
- term:
    id: GO:0004634
    label: phosphopyruvate hydratase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-71660
  qualifier: enables
  review:
    summary: >-
      Reactome traceable-author-statement ("Enolase dimers dehydrates 2PG") for the
      phosphopyruvate hydratase activity of ENO3.
    action: ACCEPT
    reason: >-
      Expert-curated statement of the core enolase catalytic function; duplicates the other
      enolase MF annotations.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: Reaction=(2R)-2-phosphoglycerate = phosphoenolpyruvate + H2O
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      Direct assay (Human Protein Atlas immunofluorescence) localizing ENO3 to the cytosol,
      the primary site of the glycolytic enolase reaction.
    action: ACCEPT
    reason: >-
      Experimental, specific, and core. This is the preferred cellular-component annotation
      for ENO3 and is consistent with UniProt (Cytoplasm) and the Ensembl is_active_in
      cytosol annotation.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm. Note=Localized to the Z line"
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      Direct assay (Human Protein Atlas immunofluorescence) reporting a plasma-membrane
      signal for ENO3. Cell-surface enolase pools have been reported for enolases generally,
      but this is not the core cytosolic catalytic localization.
    action: KEEP_AS_NON_CORE
    reason: >-
      Enolase is a well-known moonlighting cell-surface protein in several isozymes, so a
      plasma-membrane pool is plausible and the experimental HPA signal is retained; however
      it does not represent the core glycolytic function of ENO3 and is marked non-core.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm. Note=Localized to the Z line"
- term:
    id: GO:0004634
    label: phosphopyruvate hydratase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: >-
      Sequence-similarity-based transfer (from the rat/mouse ortholog UniProtKB:P15429) of
      phosphopyruvate hydratase activity to ENO3. Duplicates the core enolase MF.
    action: ACCEPT
    reason: >-
      Correct ortholog-based transfer of the core catalytic function; the human ENO3 EC
      4.2.1.11 assignment itself is ISS-inferred from P15429 in UniProt.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: Reaction=(2R)-2-phosphoglycerate = phosphoenolpyruvate + H2O
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:19433310
  qualifier: located_in
  review:
    summary: >-
      CAFA-sourced direct-assay annotation to the generic term membrane, from a study of
      cathepsin X cleavage of enolase. The cited paper concerns alpha- and gamma-enolase
      neuronal biology, not muscle beta-enolase.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      "Membrane" (GO:0016020) is a very general cellular-component term and does not
      represent the core cytosolic localization of ENO3. The supporting paper studies
      alpha/gamma-enolase (neurotrophic, cell-surface enolase), so its relevance to muscle
      beta-enolase is peripheral. Flagged as over-annotation rather than removed, since a
      moonlighting cell-surface/membrane enolase pool is documented for the family.
    supported_by:
    - reference_id: PMID:19433310
      supporting_text: >-
        we identify isozymes alpha- and gamma-enolases as targets for cathepsin X
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  qualifier: located_in
  review:
    summary: >-
      High-throughput proteomic detection of ENO3 in exosomes isolated from expressed
      prostatic secretions in urine. A bulk secretome/exosome proteomics survey.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Glycolytic enzymes, including enolases, are ubiquitously detected in exosome/secretome
      proteomes, and such detections rarely reflect a dedicated biological function. This is
      not a core localization for muscle beta-enolase and is flagged as over-annotation. Kept
      (not removed) as it is a valid mass-spectrometry observation.
    supported_by:
    - reference_id: PMID:23533145
      supporting_text: >-
        exosome preparations were characterized by a shotgun proteomics procedure
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: HDA
  original_reference_id: PMID:22664934
  qualifier: located_in
  review:
    summary: >-
      High-throughput proteomic detection of ENO3 in tear fluid (a comparative breast-cancer
      tear-proteome study). A bulk body-fluid proteomics survey.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Detection of an abundant cytosolic glycolytic enzyme in a body fluid does not establish
      a dedicated extracellular function; such findings are common contaminant/secretome
      observations. Not a core localization for ENO3, so flagged as over-annotation while
      retaining the experimental record.
    supported_by:
    - reference_id: PMID:22664934
      supporting_text: >-
        semi-quantitative comparison of tear protein levels in cancer (CA) and control
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-70494
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable-author-statement localizing the ENO3-containing enolase reaction to
      the cytosol.
    action: ACCEPT
    reason: >-
      Correct and core; the enolase reaction occurs in the cytosol. Duplicates the HPA IDA
      cytosol annotation with expert pathway curation.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm. Note=Localized to the Z line"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-71660
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable-author-statement localizing the ENO3 enolase reaction to the cytosol.
    action: ACCEPT
    reason: >-
      Correct and core; consistent with the other cytosol/cytoplasm annotations.
    supported_by:
    - reference_id: file:human/ENO3/ENO3-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm. Note=Localized to the Z line"
- term:
    id: GO:0004634
    label: phosphopyruvate hydratase activity
  evidence_type: TAS
  original_reference_id: PMID:8513787
  qualifier: enables
  review:
    summary: >-
      Traceable-author-statement (PINC) assigning phosphopyruvate hydratase activity to ENO3.
      The cited paper characterizes the human muscle-specific (beta) enolase gene and
      identifies it as the beta isoform of the glycolytic enzyme enolase.
    action: ACCEPT
    reason: >-
      Core catalytic function; the paper explicitly identifies ENO3 as the beta/muscle-specific
      isoform of the glycolytic enzyme enolase. Duplicates the other enolase MF annotations.
    supported_by:
    - reference_id: PMID:8513787
      supporting_text: >-
        the human gene for the beta or muscle-specific isoform of the glycolytic enzyme enolase
core_functions:
- description: >-
    Catalyses the penultimate step of glycolysis, the Mg2+-dependent reversible dehydration
    of 2-phospho-D-glycerate to phosphoenolpyruvate plus water (EC 4.2.1.11), as the
    muscle-specific beta subunit of the enolase dimer; the reverse reaction contributes to
    gluconeogenesis.
  molecular_function:
    id: GO:0004634
    label: phosphopyruvate hydratase activity
  directly_involved_in:
  - id: GO:0006096
    label: glycolytic process
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/ENO3/ENO3-uniprot.txt
    supporting_text: Enolase that catalyzes the conversion of 2-phosphoglycerate
  - reference_id: file:human/ENO3/ENO3-uniprot.txt
    supporting_text: Reaction=(2R)-2-phosphoglycerate = phosphoenolpyruvate + H2O
- description: >-
    The same enolase catalytic activity operating in the hydration (PEP to 2-PG) direction
    contributes to gluconeogenesis.
  molecular_function:
    id: GO:0004634
    label: phosphopyruvate hydratase activity
  directly_involved_in:
  - id: GO:0006094
    label: gluconeogenesis
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/ENO3/ENO3-uniprot.txt
    supporting_text: to phosphoenolpyruvate in glycolysis and the reverse reaction in
- description: >-
    Binds magnesium ion, the essential catalytic cofactor required for the enolase reaction
    and for stabilizing the enolase dimer.
  molecular_function:
    id: GO:0000287
    label: magnesium ion binding
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/ENO3/ENO3-uniprot.txt
    supporting_text: Note=Mg(2+) is required for catalysis and for stabilizing the dimer
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:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:human/ENO3/ENO3-uniprot.txt
  title: UniProtKB entry P13929 (ENOB_HUMAN), Beta-enolase
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Canonical UniProt record for human ENO3/beta-enolase; primary source for the catalytic
      reaction, Mg2+ cofactor, glycolysis/gluconeogenesis pathway, cytoplasmic/Z-line
      localization, isozyme/dimer composition, and GSD13 disease association.
- id: PMID:19433310
  title: Cathepsin X cleaves the C-terminal dipeptide of alpha- and gamma-enolase
    and impairs survival and neuritogenesis of neuronal cells.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; study concerns alpha- and gamma-enolase (neuronal), not muscle
      beta-enolase. Underpins the CAFA membrane IDA annotation, which is peripheral to ENO3.
- id: PMID:22664934
  title: Comparison of tear protein levels in breast cancer patients and healthy controls
    using a de novo proteomic approach.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified body-fluid (tear) proteomics survey; ENO3 detection reflects abundance
      in a body fluid rather than a dedicated extracellular function.
- id: PMID:23533145
  title: In-depth proteomic analyses of exosomes isolated from expressed prostatic
    secretions in urine.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified exosome proteomics survey; supports the extracellular exosome HDA
      annotation but does not indicate a core ENO3 function.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified BioPlex AP-MS interactome; documents the ENO1-ENO3 (alpha/beta)
      interaction, captured more informatively by the phosphopyruvate hydratase complex term.
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified OpenCell IP-MS/imaging resource; documents the ENO1-ENO3 interaction,
      better represented by the enolase complex term than by bare protein binding.
- id: PMID:8513787
  title: Structural features of the human gene for muscle-specific enolase. Differential
    splicing in the 5'-untranslated sequence generates two forms of mRNA.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; characterizes the human ENO3 (beta/muscle-specific) enolase gene and
      identifies it as the beta isoform of the glycolytic enzyme enolase, supporting the
      TAS phosphopyruvate hydratase activity annotation.
- id: Reactome:R-HSA-70171
  title: Glycolysis
  findings: []
- id: Reactome:R-HSA-70263
  title: Gluconeogenesis
  findings: []
- id: Reactome:R-HSA-70494
  title: Enolase dimers (ENO1,2,3) convert PEP to 2PG
  findings: []
- id: Reactome:R-HSA-71660
  title: Enolase dimers dehydrates 2PG
  findings: []