id: P51570
gene_symbol: GALK1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  GALK1 is the human galactokinase, a cytosolic ATP-dependent enzyme (EC 2.7.1.6)
  that catalyzes the phosphorylation of alpha-D-galactose to alpha-D-galactose
  1-phosphate, consuming ATP and producing ADP. This is the first committed,
  phosphorylation step of galactose catabolism in the Leloir pathway, which
  ultimately converts dietary galactose into glucose 1-phosphate for entry into
  glycolysis. The enzyme uses an ordered ternary-complex kinetic mechanism in
  which ATP binds first, followed by galactose, and it displays strict specificity
  for the galactose configuration at carbons 4 and 6 of the sugar ring (D-galactose
  and 2-deoxy-D-galactose are substrates, whereas D-glucose, D-fucose, L-arabinose
  and N-acetyl-D-galactosamine are not). GALK1 is a member of the GHMP kinase
  superfamily (GalK subfamily) and functions as a homodimer. Loss-of-function
  variants cause autosomal recessive galactokinase deficiency (galactosemia type II,
  GALAC2), whose principal manifestation is early-onset cataracts resulting from
  accumulation of the galactose-derived polyol galactitol in the lens.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      InterPro2GO pipeline. Correctly transfers galactokinase and ATP-binding terms
      from GHMP-kinase/galactokinase InterPro signatures, but also assigns generic
      parent MF terms (kinase activity, phosphotransferase) that are less informative
      than the specific galactokinase activity term.
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PAN-GO/GO_Central phylogenetic (IBA) annotations. The three IBA calls
      (galactokinase activity, galactose metabolic process, cytosol) match the
      experimentally established function and localization of the human enzyme.
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Combined automated (ARBA/ensembl/RHEA/EC) pipeline. Correctly infers
      galactokinase activity and Leloir-pathway galactose catabolism.
- id: PMID:7542884
  title: Comparison of the enzymatic activities of human galactokinase GALK1 and a
    related human galactokinase protein GK2.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Demonstrates that GALK1 (expressed in COS cells) produces high galactokinase
      activity and is the major galactose-metabolizing enzyme, distinguishing it from
      the related GK2 protein. Basis for the EXP and IDA galactokinase-activity
      annotations.
- id: PMID:12694189
  title: Functional analysis of disease-causing mutations in human galactokinase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Purified recombinant human GALK1 characterized kinetically (ordered ternary
      mechanism, ATP first; KM ~970 uM galactose, ~34 uM ATP) and multiple
      disease-causing variants assayed. Basis for galactokinase-activity and
      ATP-binding IDA annotations and the EC 2.7.1.6 catalytic-activity assertion.
- id: PMID:14596685
  title: Sugar recognition by human galactokinase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Full-text available. Establishes substrate/sugar recognition of the human
      enzyme: D-galactose and 2-deoxy-D-galactose are substrates; D-glucose,
      D-fucose, L-arabinose and N-acetyl-D-galactosamine are not phosphorylated.
      Basis for the galactose-binding IDA annotation.
- id: PMID:15024738
  title: Biochemical characterization of two GALK1 mutations in patients with galactokinase
    deficiency.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Biochemical characterization of the V32M and R239Q GALK1 variants in patients,
      showing drastic reduction of GALK activity, establishing pathogenicity and the
      enzyme's role in galactose metabolism (IMP).
- id: PMID:8908517
  title: Fine structure of the human galactokinase GALK1 gene.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      In vitro translation shows the GALK1 protein is cytosolic and not associated
      with the ER membrane. Basis for the cytoplasm IDA and the NOT|membrane IDA
      (informative negation).
- id: PMID:19056867
  title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      High-throughput urinary exosome proteomics; GALK1 detected as one of many
      co-purifying proteins. Localization is incidental, not a functional site for
      this soluble metabolic enzyme.
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
  reference_review:
    relevance: LOW
    correctness: LOW_QUALITY
    review_notes: >-
      High-throughput NK-cell membrane proteome. The resulting "membrane"
      localization is a proteomic co-purification and is directly contradicted by the
      curated NOT|located_in membrane IDA (PMID:8908517).
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      HuRI high-throughput yeast two-hybrid interactome. Reports a single binary
      interactor (PNRC2, Q9NPJ4). Supports only a bare, uninformative "protein
      binding" annotation with no established functional consequence.
- id: Reactome:R-HSA-5610026
  title: Defective GALK1 does not phosphorylate Gal
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Reactome reaction annotation capturing GALK1 galactokinase activity in the
      cytosol.
- id: Reactome:R-HSA-70355
  title: GALK1 phosphorylates Gal to Gal1P
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Reactome reaction: GALK1 phosphorylates galactose to galactose 1-phosphate in
      the cytosol. Directly captures the core Leloir-pathway step.
- id: Reactome:R-HSA-70370
  title: Galactose catabolism
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Reactome "Galactose catabolism" pathway; basis for the Leloir-pathway galactose
      catabolic process TAS annotation.
existing_annotations:
- term:
    id: GO:0006012
    label: galactose metabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Phylogenetic (IBA) annotation placing GALK1 in galactose metabolism. Correct
      but general; the enzyme specifically performs the phosphorylation step of
      galactose catabolism (Leloir pathway).
    action: ACCEPT
    reason: >-
      GALK1 catalyzes the ATP-dependent phosphorylation of galactose, the first
      committed step of galactose catabolism, so it is validly involved in galactose
      metabolic process. Retained; the more specific catabolic term (GO:0019388) is
      captured in core_functions.
    supported_by:
    - reference_id: PMID:12694189
      supporting_text: >-
        Galactokinase (EC 2.7.1.6) catalyzes the first committed step in the
        catabolism of galactose.
- term:
    id: GO:0004335
    label: galactokinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Phylogenetic (IBA) assertion of galactokinase activity, the core, defining
      molecular function of GALK1.
    action: ACCEPT
    reason: >-
      Galactokinase activity is the experimentally established, defining function of
      GALK1 (EC 2.7.1.6) and is well supported across the phylogeny. This is a core
      function.
    supported_by:
    - reference_id: PMID:7542884
      supporting_text: >-
        only the GALK1 cDNA produced high levels of galactokinase activity. This
        result would suggest that GALK1 is the major enzyme for galactose metabolism
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetic (IBA) assertion that GALK1 is active in the cytosol, consistent
      with experimental evidence that the human protein is cytosolic.
    action: ACCEPT
    reason: >-
      GALK1 is a soluble cytosolic enzyme; in vitro translation showed the protein is
      cytosolic and not membrane-associated, and Reactome places its activity in the
      cytosol. This is the correct site of action.
    supported_by:
    - reference_id: PMID:8908517
      supporting_text: >-
        In vitro translation experiments of the GALK1 cDNA indicate that the protein
        is cytosolic and not associated with the endoplasmic reticulum membrane.
- term:
    id: GO:0004335
    label: galactokinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Automated (ARBA/RHEA/EC) inference of galactokinase activity, redundant with and
      corroborating the experimental and phylogenetic annotations.
    action: ACCEPT
    reason: >-
      Correctly transfers the EC 2.7.1.6 / RHEA:13553 galactokinase activity based on
      the galactokinase InterPro signature and orthology; matches the experimentally
      demonstrated function.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro-based inference of ATP binding, consistent with the GHMP-kinase ATP
      binding motif and directly demonstrated ATP binding/kinetics.
    action: ACCEPT
    reason: >-
      GALK1 is an ATP-dependent kinase; ATP is a bona fide substrate that binds first
      in the ordered ternary mechanism, and ATP-binding residues are mapped in the
      structure. Corroborated by the IDA annotation from PMID:12694189.
    supported_by:
    - reference_id: PMID:12694189
      supporting_text: >-
        the most likely kinetic mechanism of the enzyme was an ordered ternary complex
        one in which ATP is the first substrate to bind
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: located_in
  review:
    summary: >-
      InterPro-based cytoplasm localization, consistent with the experimentally
      determined cytosolic localization of GALK1.
    action: ACCEPT
    reason: >-
      GALK1 is a cytosolic protein; the cytoplasm assignment is correct though less
      specific than cytosol. Consistent with the IDA cytoplasm annotation.
    supported_by:
    - reference_id: PMID:8908517
      supporting_text: >-
        the protein is cytosolic and not associated with the endoplasmic reticulum
        membrane
- term:
    id: GO:0006012
    label: galactose metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      Automated inference of involvement in galactose metabolic process, redundant
      with the IBA and IMP annotations.
    action: ACCEPT
    reason: >-
      Correct: GALK1 performs the phosphorylation step of galactose catabolism.
      General but valid.
- term:
    id: GO:0016301
    label: kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Generic parent molecular-function term (kinase activity) inferred from InterPro.
      Too general given the specific galactokinase activity is known.
    action: MODIFY
    reason: >-
      Kinase activity is a broad parent of the specific, experimentally established
      galactokinase activity (GO:0004335, EC 2.7.1.6). Replace with the specific term
      to avoid uninformative over-generalization.
    proposed_replacement_terms:
    - id: GO:0004335
      label: galactokinase activity
- term:
    id: GO:0016773
    label: phosphotransferase activity, alcohol group as acceptor
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Generic phosphotransferase parent term inferred from InterPro. The acceptor in
      the GALK1 reaction is the C1 hydroxyl of galactose, but the specific
      galactokinase term is more informative.
    action: MODIFY
    reason: >-
      Although mechanistically accurate (galactose C1-OH is the acceptor), this is a
      broad parent of galactokinase activity. Replace with the specific term.
    proposed_replacement_terms:
    - id: GO:0004335
      label: galactokinase activity
- term:
    id: GO:0046835
    label: carbohydrate phosphorylation
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      Generic biological-process term (carbohydrate phosphorylation) inferred from
      InterPro. Accurate but subsumed by the more specific galactose catabolic
      process.
    action: KEEP_AS_NON_CORE
    reason: >-
      GALK1 does phosphorylate a carbohydrate (galactose), so this term is not wrong,
      but it is a generic process that is captured more specifically by galactose
      catabolic/metabolic process. Retained as non-core rather than removed.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: >-
      Bare "protein binding" from a single high-throughput yeast two-hybrid
      interaction (HuRI) with PNRC2 (Q9NPJ4). Uninformative regarding molecular
      function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Per curation guidelines, bare "protein binding" is uninformative and should be
      avoided. The evidence is a single high-throughput binary Y2H interactome hit
      with no established functional consequence for this soluble cytosolic metabolic
      enzyme, and no adapter/scaffold role is known. It is retained but flagged as an
      over-annotation (not removed, as it is an experimental IPI).
    supported_by:
    - reference_id: PMID:32296183
      supporting_text: >-
        we present a human 'all-by-all' reference interactome map of human binary
        protein interactions, or 'HuRI'.
- term:
    id: GO:0033499
    label: beta-D-galactose catabolic process via UDP-galactose, Leloir pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      Automated inference placing GALK1 in the Leloir-pathway galactose catabolic
      process. This is the correct, specific biological process for the enzyme.
      (Ontology current primary label is "galactose catabolic process via
      UDP-galactose, Leloir pathway".)
    action: ACCEPT
    reason: >-
      GALK1 phosphorylates galactose to galactose 1-phosphate, a Leloir-pathway step
      that feeds galactose into UDP-galactose/glucose-1-phosphate metabolism. This is
      the most specific and accurate BP annotation.
    supported_by:
    - reference_id: PMID:14596685
      supporting_text: >-
        Galactokinase catalyses the first committed step of galactose catabolism in
        which the sugar is phosphorylated at the expense of MgATP.
- term:
    id: GO:0033499
    label: beta-D-galactose catabolic process via UDP-galactose, Leloir pathway
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-70370
  qualifier: involved_in
  review:
    summary: >-
      Reactome (TAS) assertion of Leloir-pathway galactose catabolism, corroborating
      the IEA annotation of the same term.
    action: ACCEPT
    reason: >-
      Reactome curates GALK1 as the galactokinase step of galactose catabolism; this
      is the correct specific process.
    supported_by:
    - reference_id: PMID:14596685
      supporting_text: >-
        Galactose is metabolised via the Leloir pathway [1] in order to produce
        glucose-6-phosphate that can enter glycolysis.
- term:
    id: GO:0004335
    label: galactokinase activity
  evidence_type: EXP
  original_reference_id: PMID:7542884
  qualifier: enables
  review:
    summary: >-
      Experimental (EXP) galactokinase activity from expression of GALK1 cDNA in COS
      cells producing high galactokinase activity. Directly supports the core
      function.
    action: ACCEPT
    reason: >-
      Direct experimental demonstration that GALK1 confers galactokinase activity and
      is the major galactose-metabolizing enzyme. Core function.
    supported_by:
    - reference_id: PMID:7542884
      supporting_text: >-
        only the GALK1 cDNA produced high levels of galactokinase activity. This
        result would suggest that GALK1 is the major enzyme for galactose metabolism
- term:
    id: GO:0004335
    label: galactokinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5610026
  qualifier: enables
  review:
    summary: >-
      Reactome (TAS) assertion of galactokinase activity, corroborating the
      experimental annotations.
    action: ACCEPT
    reason: >-
      Reactome curates GALK1 galactokinase activity (with defective-GALK1 disease
      variants); consistent with the defining function.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5610026
  qualifier: located_in
  review:
    summary: >-
      Reactome (TAS) cytosol localization, matching the experimentally determined
      cytosolic localization.
    action: ACCEPT
    reason: >-
      GALK1 is a soluble cytosolic enzyme; cytosol is the correct compartment.
    supported_by:
    - reference_id: PMID:8908517
      supporting_text: >-
        the protein is cytosolic and not associated with the endoplasmic reticulum
        membrane
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: >-
      High-throughput NK-cell membrane proteome (HDA) placing GALK1 at the membrane.
      Contradicted by the curated NOT|located_in membrane IDA.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This "membrane" localization comes from a large-scale membrane-proteome
      dataset and represents co-purification rather than genuine membrane
      association; GALK1 is a soluble cytosolic enzyme. It is directly contradicted by
      the experimental NOT|located_in membrane annotation (PMID:8908517), so it is an
      over-annotation.
    supported_by:
    - reference_id: PMID:8908517
      supporting_text: >-
        the protein is cytosolic and not associated with the endoplasmic reticulum
        membrane
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19056867
  qualifier: located_in
  review:
    summary: >-
      High-throughput urinary exosome proteomics (HDA) detecting GALK1. Incidental
      co-purification, not a functional localization.
    action: KEEP_AS_NON_CORE
    reason: >-
      GALK1 was detected among many proteins in a large-scale urinary exosome
      proteomic survey. Many abundant cytosolic proteins are recovered in exosome
      preparations; this does not reflect the site of catalytic function. Retained as
      non-core rather than removed, as it is a valid detection record.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-70355
  qualifier: located_in
  review:
    summary: >-
      Reactome (TAS) cytosol localization from the "GALK1 phosphorylates Gal to Gal1P"
      reaction, matching experimental cytosolic localization.
    action: ACCEPT
    reason: >-
      Correct compartment for the soluble cytosolic galactokinase; corroborates the
      IBA and other TAS cytosol annotations.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:8908517
  qualifier: located_in
  negated: true
  review:
    summary: >-
      Curated NOT|located_in membrane (IDA), based on in vitro translation showing the
      GALK1 protein is cytosolic and not associated with the ER membrane. An
      informative negation.
    action: ACCEPT
    reason: >-
      Experimentally supported negative annotation that correctly excludes membrane
      localization and reinforces the cytosolic assignment. It also flags the
      high-throughput membrane HDA as spurious. Keep the negation.
    supported_by:
    - reference_id: PMID:8908517
      supporting_text: >-
        In vitro translation experiments of the GALK1 cDNA indicate that the protein
        is cytosolic and not associated with the endoplasmic reticulum membrane.
- term:
    id: GO:0006012
    label: galactose metabolic process
  evidence_type: IMP
  original_reference_id: PMID:15024738
  qualifier: involved_in
  review:
    summary: >-
      Involvement in galactose metabolism inferred from patient GALK1 mutations (V32M,
      R239Q) that drastically reduce galactokinase activity (IMP).
    action: ACCEPT
    reason: >-
      Loss-of-function GALK1 variants in patients cause deficient galactose metabolism
      (galactokinase deficiency), directly implicating the gene in galactose metabolic
      process. Core biological process.
    supported_by:
    - reference_id: PMID:15024738
      supporting_text: >-
        these mutations led to a drastic modification in GALK activity when individual
        mutant cDNAs were expressed in an E. coli system
- term:
    id: GO:0004335
    label: galactokinase activity
  evidence_type: IDA
  original_reference_id: PMID:12694189
  qualifier: enables
  review:
    summary: >-
      Direct assay (IDA) of galactokinase activity using purified recombinant human
      GALK1, with full kinetic characterization.
    action: ACCEPT
    reason: >-
      Purified, active recombinant human GALK1 was kinetically characterized as a
      galactokinase (EC 2.7.1.6); this is the strongest direct evidence for the core
      molecular function.
    supported_by:
    - reference_id: PMID:12694189
      supporting_text: >-
        Human galactokinase (GALK1) was expressed in and purified from Escherichia
        coli. The recombinant enzyme was both soluble and active.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IDA
  original_reference_id: PMID:12694189
  qualifier: enables
  review:
    summary: >-
      Direct evidence (IDA) for ATP binding: kinetic analysis shows an ordered
      ternary-complex mechanism in which ATP binds first, with a measured KM for ATP.
    action: ACCEPT
    reason: >-
      ATP is a bona fide substrate/cofactor of GALK1; product-inhibition and kinetic
      studies establish ATP binding, and the ATP KM (~34 uM) is reported. Core to the
      kinase mechanism.
    supported_by:
    - reference_id: PMID:12694189
      supporting_text: >-
        the most likely kinetic mechanism of the enzyme was an ordered ternary complex
        one in which ATP is the first substrate to bind
- term:
    id: GO:0005534
    label: galactose binding
  evidence_type: IDA
  original_reference_id: PMID:14596685
  qualifier: enables
  review:
    summary: >-
      Direct evidence (IDA) for galactose binding from a sugar-recognition study of
      the human enzyme, including mutagenesis of sugar-binding-site residues.
    action: ACCEPT
    reason: >-
      Galactose is the physiological substrate and its binding to the human enzyme is
      directly demonstrated; the enzyme is highly specific for the galactose
      configuration at carbons 4 and 6. This is an informative, substrate-specific MF.
    supported_by:
    - reference_id: PMID:14596685
      supporting_text: >-
        D-galactose and 2-deoxy-D-galactose are substrates for the enzyme, but
        N-acetyl-D-galactosamine, L-arabinose, D-fucose and D-glucose are all not
        phosphorylated.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:8908517
  qualifier: located_in
  review:
    summary: >-
      Direct evidence (IDA) that GALK1 is cytoplasmic, from in vitro translation
      showing the protein is cytosolic and not ER-membrane-associated.
    action: ACCEPT
    reason: >-
      Experimentally supported cytoplasmic localization; consistent with the cytosol
      annotations, though cytosol (GO:0005829) is the more precise compartment.
    supported_by:
    - reference_id: PMID:8908517
      supporting_text: >-
        In vitro translation experiments of the GALK1 cDNA indicate that the protein
        is cytosolic and not associated with the endoplasmic reticulum membrane.
- term:
    id: GO:0004335
    label: galactokinase activity
  evidence_type: IDA
  original_reference_id: PMID:7542884
  qualifier: enables
  review:
    summary: >-
      Direct assay (IDA) of galactokinase activity from expression of the GALK1 cDNA,
      demonstrating high galactokinase activity attributable to GALK1.
    action: ACCEPT
    reason: >-
      Direct experimental confirmation of the core galactokinase function; redundant
      with but corroborating the other galactokinase-activity annotations.
    supported_by:
    - reference_id: PMID:7542884
      supporting_text: >-
        only the GALK1 cDNA produced high levels of galactokinase activity. This
        result would suggest that GALK1 is the major enzyme for galactose metabolism
- term:
    id: GO:0019388
    label: galactose catabolic process
  evidence_type: IDA
  original_reference_id: PMID:14596685
  qualifier: involved_in
  review:
    summary: >-
      Proposed more specific biological process: GALK1 catalyzes the first committed
      step of galactose catabolism (galactose -> galactose 1-phosphate). Existing
      annotations use the broader galactose metabolic process (GO:0006012); this
      catabolic child term is more precise and directly supported.
    action: NEW
    reason: >-
      The catalytic reaction commits galactose to catabolism (Leloir pathway), so
      galactose catabolic process (GO:0019388), a child of GO:0006012, is the most
      accurate process term. Added as NEW because only the broader metabolic-process
      term is present in existing GOA annotations. Also consistent with the specific
      Leloir-pathway term (GO:0033499) already annotated.
    supported_by:
    - reference_id: PMID:14596685
      supporting_text: >-
        Galactokinase catalyses the first committed step of galactose catabolism in
        which the sugar is phosphorylated at the expense of MgATP.
    - reference_id: PMID:12694189
      supporting_text: >-
        Galactokinase (EC 2.7.1.6) catalyzes the first committed step in the catabolism
        of galactose.
core_functions:
- description: >-
    GALK1 is the cytosolic galactokinase that catalyzes the ATP-dependent
    phosphorylation of alpha-D-galactose to alpha-D-galactose 1-phosphate (EC 2.7.1.6),
    the first committed step of galactose catabolism in the Leloir pathway.
  molecular_function:
    id: GO:0004335
    label: galactokinase activity
  directly_involved_in:
  - id: GO:0019388
    label: galactose catabolic process
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:12694189
    supporting_text: >-
      Galactokinase (EC 2.7.1.6) catalyzes the first committed step in the catabolism
      of galactose. The sugar is phosphorylated at position 1 at the expense of ATP.
  - reference_id: PMID:7542884
    supporting_text: >-
      only the GALK1 cDNA produced high levels of galactokinase activity. This result
      would suggest that GALK1 is the major enzyme for galactose metabolism
  - reference_id: PMID:8908517
    supporting_text: >-
      In vitro translation experiments of the GALK1 cDNA indicate that the protein is
      cytosolic and not associated with the endoplasmic reticulum membrane.