GALK1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006012 galactose metabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) annotation placing GALK1 in galactose metabolism. Correct but general; the enzyme specifically performs the phosphorylation step of galactose catabolism (Leloir pathway). 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. Supporting Evidence: PMID:12694189 Galactokinase (EC 2.7.1.6) catalyzes the first committed step in the catabolism of galactose.
GO:0004335 galactokinase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assertion of galactokinase activity, the core, defining molecular function of GALK1. 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. Supporting Evidence: PMID:7542884 only the GALK1 cDNA produced high levels of galactokinase activity. This result would suggest that GALK1 is the major enzyme for galactose metabolism
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assertion that GALK1 is active in the cytosol, consistent with experimental evidence that the human protein is cytosolic. 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. Supporting Evidence: PMID:8908517 In vitro translation experiments of the GALK1 cDNA indicate that the protein is cytosolic and not associated with the endoplasmic reticulum membrane.
GO:0004335 galactokinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated (ARBA/RHEA/EC) inference of galactokinase activity, redundant with and corroborating the experimental and phylogenetic annotations. 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.
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based inference of ATP binding, consistent with the GHMP-kinase ATP binding motif and directly demonstrated ATP binding/kinetics. 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. Supporting Evidence: PMID:12694189 the most likely kinetic mechanism of the enzyme was an ordered ternary complex one in which ATP is the first substrate to bind
GO:0005737 cytoplasm	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based cytoplasm localization, consistent with the experimentally determined cytosolic localization of GALK1. Reason: GALK1 is a cytosolic protein; the cytoplasm assignment is correct though less specific than cytosol. Consistent with the IDA cytoplasm annotation. Supporting Evidence: PMID:8908517 the protein is cytosolic and not associated with the endoplasmic reticulum membrane
GO:0006012 galactose metabolic process	IEA GO_REF:0000120	ACCEPT	Summary: Automated inference of involvement in galactose metabolic process, redundant with the IBA and IMP annotations. Reason: Correct: GALK1 performs the phosphorylation step of galactose catabolism. General but valid.
GO:0016301 kinase activity	IEA GO_REF:0000002	MODIFY	Summary: Generic parent molecular-function term (kinase activity) inferred from InterPro. Too general given the specific galactokinase activity is known. 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 replacements: galactokinase activity
GO:0016773 phosphotransferase activity, alcohol group as acceptor	IEA GO_REF:0000002	MODIFY	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. Reason: Although mechanistically accurate (galactose C1-OH is the acceptor), this is a broad parent of galactokinase activity. Replace with the specific term. Proposed replacements: galactokinase activity
GO:0046835 carbohydrate phosphorylation	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Generic biological-process term (carbohydrate phosphorylation) inferred from InterPro. Accurate but subsumed by the more specific galactose catabolic process. 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.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from a single high-throughput yeast two-hybrid interaction (HuRI) with PNRC2 (Q9NPJ4). Uninformative regarding molecular function. 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). Supporting Evidence: PMID:32296183 we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI'.
GO:0033499 beta-D-galactose catabolic process via UDP-galactose, Leloir pathway	IEA GO_REF:0000120	ACCEPT	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".) 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. Supporting Evidence: PMID:14596685 Galactokinase catalyses the first committed step of galactose catabolism in which the sugar is phosphorylated at the expense of MgATP.
GO:0033499 beta-D-galactose catabolic process via UDP-galactose, Leloir pathway	TAS Reactome:R-HSA-70370	ACCEPT	Summary: Reactome (TAS) assertion of Leloir-pathway galactose catabolism, corroborating the IEA annotation of the same term. Reason: Reactome curates GALK1 as the galactokinase step of galactose catabolism; this is the correct specific process. Supporting Evidence: PMID:14596685 Galactose is metabolised via the Leloir pathway [1] in order to produce glucose-6-phosphate that can enter glycolysis.
GO:0004335 galactokinase activity	EXP PMID:7542884 Comparison of the enzymatic activities of human galactokinas...	ACCEPT	Summary: Experimental (EXP) galactokinase activity from expression of GALK1 cDNA in COS cells producing high galactokinase activity. Directly supports the core function. Reason: Direct experimental demonstration that GALK1 confers galactokinase activity and is the major galactose-metabolizing enzyme. Core function. Supporting Evidence: PMID:7542884 only the GALK1 cDNA produced high levels of galactokinase activity. This result would suggest that GALK1 is the major enzyme for galactose metabolism
GO:0004335 galactokinase activity	TAS Reactome:R-HSA-5610026	ACCEPT	Summary: Reactome (TAS) assertion of galactokinase activity, corroborating the experimental annotations. Reason: Reactome curates GALK1 galactokinase activity (with defective-GALK1 disease variants); consistent with the defining function.
GO:0005829 cytosol	TAS Reactome:R-HSA-5610026	ACCEPT	Summary: Reactome (TAS) cytosol localization, matching the experimentally determined cytosolic localization. Reason: GALK1 is a soluble cytosolic enzyme; cytosol is the correct compartment. Supporting Evidence: PMID:8908517 the protein is cytosolic and not associated with the endoplasmic reticulum membrane
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	MARK AS OVER ANNOTATED	Summary: High-throughput NK-cell membrane proteome (HDA) placing GALK1 at the membrane. Contradicted by the curated NOT\|located_in membrane IDA. 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. Supporting Evidence: PMID:8908517 the protein is cytosolic and not associated with the endoplasmic reticulum membrane
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: High-throughput urinary exosome proteomics (HDA) detecting GALK1. Incidental co-purification, not a functional localization. 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-70355	ACCEPT	Summary: Reactome (TAS) cytosol localization from the "GALK1 phosphorylates Gal to Gal1P" reaction, matching experimental cytosolic localization. Reason: Correct compartment for the soluble cytosolic galactokinase; corroborates the IBA and other TAS cytosol annotations.
GO:0016020 membrane	IDA NOT PMID:8908517 Fine structure of the human galactokinase GALK1 gene.	ACCEPT	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. 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. Supporting Evidence: PMID:8908517 In vitro translation experiments of the GALK1 cDNA indicate that the protein is cytosolic and not associated with the endoplasmic reticulum membrane.
GO:0006012 galactose metabolic process	IMP PMID:15024738 Biochemical characterization of two GALK1 mutations in patie...	ACCEPT	Summary: Involvement in galactose metabolism inferred from patient GALK1 mutations (V32M, R239Q) that drastically reduce galactokinase activity (IMP). 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. Supporting Evidence: PMID:15024738 these mutations led to a drastic modification in GALK activity when individual mutant cDNAs were expressed in an E. coli system
GO:0004335 galactokinase activity	IDA PMID:12694189 Functional analysis of disease-causing mutations in human ga...	ACCEPT	Summary: Direct assay (IDA) of galactokinase activity using purified recombinant human GALK1, with full kinetic characterization. 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. Supporting Evidence: PMID:12694189 Human galactokinase (GALK1) was expressed in and purified from Escherichia coli. The recombinant enzyme was both soluble and active.
GO:0005524 ATP binding	IDA PMID:12694189 Functional analysis of disease-causing mutations in human ga...	ACCEPT	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. 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. Supporting Evidence: PMID:12694189 the most likely kinetic mechanism of the enzyme was an ordered ternary complex one in which ATP is the first substrate to bind
GO:0005534 galactose binding	IDA PMID:14596685 Sugar recognition by human galactokinase.	ACCEPT	Summary: Direct evidence (IDA) for galactose binding from a sugar-recognition study of the human enzyme, including mutagenesis of sugar-binding-site residues. 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. Supporting Evidence: PMID:14596685 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.
GO:0005737 cytoplasm	IDA PMID:8908517 Fine structure of the human galactokinase GALK1 gene.	ACCEPT	Summary: Direct evidence (IDA) that GALK1 is cytoplasmic, from in vitro translation showing the protein is cytosolic and not ER-membrane-associated. Reason: Experimentally supported cytoplasmic localization; consistent with the cytosol annotations, though cytosol (GO:0005829) is the more precise compartment. Supporting Evidence: PMID:8908517 In vitro translation experiments of the GALK1 cDNA indicate that the protein is cytosolic and not associated with the endoplasmic reticulum membrane.
GO:0004335 galactokinase activity	IDA PMID:7542884 Comparison of the enzymatic activities of human galactokinas...	ACCEPT	Summary: Direct assay (IDA) of galactokinase activity from expression of the GALK1 cDNA, demonstrating high galactokinase activity attributable to GALK1. Reason: Direct experimental confirmation of the core galactokinase function; redundant with but corroborating the other galactokinase-activity annotations. Supporting Evidence: PMID:7542884 only the GALK1 cDNA produced high levels of galactokinase activity. This result would suggest that GALK1 is the major enzyme for galactose metabolism
GO:0019388 galactose catabolic process	IDA PMID:14596685 Sugar recognition by human galactokinase.	NEW	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. 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. Supporting Evidence: PMID:14596685 Galactokinase catalyses the first committed step of galactose catabolism in which the sugar is phosphorylated at the expense of MgATP. PMID:12694189 Galactokinase (EC 2.7.1.6) catalyzes the first committed step in the catabolism of galactose.

Gene Description

Existing Annotations Review

Core Functions

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.

References

📚 Additional Documentation

Notes

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