GALM

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0033499 beta-D-galactose catabolic process via UDP-galactose, Leloir pathway	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) inference that GALM participates in the Leloir pathway of galactose catabolism. This is the core biological process of GALM: it catalyzes the first (mutarotase) step supplying alpha-D-galactose to GALK1. Reason: Consistent with the experimentally established Leloir-pathway role and the PANTHER aldose-1-epimerase family. Represents a core function.
GO:0004034 aldose 1-epimerase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) inference of aldose 1-epimerase activity, the core molecular function of GALM, matching the family-level assignment for PTN000009552. Reason: The defining catalytic activity of GALM, independently supported by direct experimental characterization (PMID:12753898). Core molecular function.
GO:0006006 glucose metabolic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic inference that GALM participates in glucose metabolism, reflecting the family's ability to mutarotate glucose in addition to galactose. Reason: GALM does mutarotate D-glucose in vitro, but with lower affinity/turnover than galactose (KM 54 mM vs 37 mM; kcat 4900 vs 12000 s-1), and the enzyme "exhibits a preference for galactose over glucose" (PMID:12753898). Glucose mutarotation is a genuine but secondary activity, not the core physiological role. Supporting Evidence: PMID:12753898 the protein has aldose 1-epimerase activity and exhibits a preference for galactose over glucose
GO:0004034 aldose 1-epimerase activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated (RHEA/EC 5.1.3.3) assignment of aldose 1-epimerase activity, the core molecular function. Reason: Correctly mapped from EC 5.1.3.3 / RHEA:10264,RHEA:28675 to the specific MF term; matches experimental evidence.
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: Subcellular-location mapping (UniProt SL-0086) placing GALM in the cytoplasm. Reason: Consistent with the UniProt subcellular location (Cytoplasm) and the Reactome cytosol annotation. Broader than cytosol but not incorrect.
GO:0005975 carbohydrate metabolic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro2GO mapping to the high-level carbohydrate metabolic process, from the aldose epimerase domains. Reason: True but a very general grouping term. The specific galactose/hexose processes below are more informative; retained as a non-core parent.
GO:0016853 isomerase activity	IEA GO_REF:0000002	MODIFY	Summary: InterPro2GO mapping to the generic parent term isomerase activity. Reason: Correct but overly general: GALM's activity is specifically aldose 1-epimerase activity (GO:0004034), which is a descendant of isomerase activity and is already annotated with strong experimental support. Replace the generic parent with the specific MF. Proposed replacements: aldose 1-epimerase activity
GO:0019318 hexose metabolic process	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Automated mapping (UniPathway/InterPro) to hexose metabolic process, consistent with GALM acting on the hexoses galactose and glucose. Reason: Accurate parent term encompassing galactose and glucose metabolism, but less specific than the galactose process terms. Retained as a non-core grouping term.
GO:0030246 carbohydrate binding	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: InterPro2GO mapping to carbohydrate binding, derived from the sugar-binding beta-sandwich (GH-type carbohydrate-binding) domain signatures. Reason: GALM binds galactose/glucose only transiently as catalytic substrates in its active site, not as a lectin-type carbohydrate-binding module. GO:0030246 (carbohydrate binding) implies a dedicated binding function distinct from catalysis; this is an over-annotation propagated from the structural fold signature. The catalytic substrate interaction is already captured by the aldose 1-epimerase activity annotation.
GO:0033499 beta-D-galactose catabolic process via UDP-galactose, Leloir pathway	TAS Reactome:R-HSA-70370	ACCEPT	Summary: Reactome-curated (TAS) assignment of GALM to the Leloir pathway of galactose catabolism. Reason: Curator-asserted pathway membership matching the established biology; core biological process.
GO:0006012 galactose metabolic process	IEA GO_REF:0000041	ACCEPT	Summary: UniPathway-based (UPA00214) mapping to galactose metabolic process. Reason: Core biological process of GALM; the anomer interconversion it catalyzes initiates galactose metabolism. Independently supported by IDA (PMID:12753898).
GO:0004034 aldose 1-epimerase activity	EXP PMID:12753898 Identification and characterisation of human aldose 1-epimer...	ACCEPT	Summary: Experimental demonstration that recombinant human GALM has aldose 1-epimerase activity, with confirmed catalytic residues. Reason: Core molecular function, directly demonstrated by enzyme assays on purified recombinant protein plus site-directed mutagenesis of catalytic residues. Supporting Evidence: PMID:12753898 Enzyme assays show that the protein has aldose 1-epimerase activity and exhibits a preference for galactose over glucose. Site-directed mutagenesis confirmed the involvement of three residues involved in catalysis and substrate binding.
GO:0004034 aldose 1-epimerase activity	TAS Reactome:R-HSA-9931926	ACCEPT	Summary: Reactome-curated (TAS) assertion of aldose 1-epimerase activity (in the context of the defective-GALM reaction). Reason: Core molecular function; consistent with all other MF evidence.
GO:0005829 cytosol	TAS Reactome:R-HSA-9931853	ACCEPT	Summary: Reactome-curated (TAS) localization of GALM (the "GALM converts beta-D-GAL to alpha-D-GAL" reaction) to the cytosol. Reason: Consistent with the cytoplasmic Leloir pathway; the most specific and appropriate location term for GALM. Core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-9931926	ACCEPT	Summary: Reactome-curated (TAS) cytosol localization (defective-GALM reaction context). Duplicate of the preceding cytosol annotation from a related Reactome reaction. Reason: Correct core localization; duplicate assertion of cytosol is acceptable.
GO:0004034 aldose 1-epimerase activity	IDA PMID:30451973 Biallelic GALM pathogenic variants cause a novel type of gal...	ACCEPT	Summary: Direct assay (IDA) of aldose 1-epimerase activity in the study that identified GALM deficiency as a novel galactosemia; patient/variant proteins showed altered activity. Reason: Core molecular function, independently confirmed in the disease-gene study.
GO:0004034 aldose 1-epimerase activity	IMP PMID:30451973 Biallelic GALM pathogenic variants cause a novel type of gal...	ACCEPT	Summary: Mutant-phenotype (IMP) evidence that pathogenic GALM variants reduce aldose 1-epimerase activity, linking loss of this MF to disease. Reason: Loss-of-function variants causing galactosemia type IV support the physiological relevance of this core molecular function.
GO:0033499 beta-D-galactose catabolic process via UDP-galactose, Leloir pathway	IMP PMID:30451973 Biallelic GALM pathogenic variants cause a novel type of gal...	ACCEPT	Summary: Mutant-phenotype (IMP) evidence that GALM loss disrupts the Leloir pathway of galactose catabolism, causing galactose accumulation / galactosemia type IV. Reason: Biallelic GALM variants cause a novel type of galactosemia by impairing the Leloir pathway; core biological process supported by human disease genetics.
GO:0033499 beta-D-galactose catabolic process via UDP-galactose, Leloir pathway	IDA PMID:30451973 Biallelic GALM pathogenic variants cause a novel type of gal...	ACCEPT	Summary: Direct-assay (IDA) evidence supporting GALM's participation in the Leloir galactose catabolic pathway. Reason: Core biological process, directly supported. Duplicate of the IBA/TAS Leloir-pathway annotations with independent experimental backing.
GO:0004034 aldose 1-epimerase activity	IDA PMID:12753898 Identification and characterisation of human aldose 1-epimer...	ACCEPT	Summary: Direct assay (IDA) of aldose 1-epimerase activity on purified recombinant human GALM. Reason: Core molecular function; the foundational biochemical characterization of the enzyme. Supporting Evidence: PMID:12753898 Enzyme assays show that the protein has aldose 1-epimerase activity and exhibits a preference for galactose over glucose.
GO:0005975 carbohydrate metabolic process	IDA PMID:12753898 Identification and characterisation of human aldose 1-epimer...	KEEP AS NON CORE	Summary: Direct-assay evidence placing GALM in carbohydrate metabolism (mutarotation of hexose sugars), a high-level grouping process. Reason: Correct but very general; the specific galactose/glucose metabolic process terms are more informative. Retained as a non-core parent. GALM is described as "a key enzyme of carbohydrate metabolism" (PMID:12753898). Supporting Evidence: PMID:12753898 Aldose 1-epimerase or mutarotase (EC 5.1.3.3) is a key enzyme of carbohydrate metabolism catalysing the interconversion of the alpha- and beta-anomers of hexose sugars such as glucose and galactose.
GO:0042803 protein homodimerization activity	IDA NOT PMID:12753898 Identification and characterisation of human aldose 1-epimer...	ACCEPT	Summary: Negated (NOT) annotation: GALM does not have protein homodimerization activity. Biochemical and structural characterization established that GALM is a monomer. Reason: The NOT annotation correctly records that GALM does not homodimerize. UniProt reports the SUBUNIT as Monomer (from PMID:12753898 and PMID:15026423). Retaining the negation is informative and consistent with the monomeric solution and crystal state.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: High-throughput mass-spectrometry (HDA) detection of GALM among proteins recovered from human urinary exosomes. Reason: Reflects broad proteomic detection in secreted exosomes rather than the enzyme's site of catalytic function, which is the cytosol. Kept as a non-core localization; not part of the core Leloir-pathway function. Supporting Evidence: PMID:19056867 we used LC-MS/MS to profile the proteome of human urinary exosomes. Overall, the analysis identified 1132 proteins unambiguously
GO:0006006 glucose metabolic process	IDA PMID:12753898 Identification and characterisation of human aldose 1-epimer...	KEEP AS NON CORE	Summary: Direct-assay evidence that GALM mutarotates D-glucose, participating in glucose metabolism. Reason: GALM does interconvert glucose anomers, but with lower efficiency than galactose and a demonstrated preference for galactose (PMID:12753898). A real but secondary activity, not the core physiological role. Supporting Evidence: PMID:12753898 catalysing the interconversion of the alpha- and beta-anomers of hexose sugars such as glucose and galactose
GO:0006012 galactose metabolic process	IDA PMID:12753898 Identification and characterisation of human aldose 1-epimer...	ACCEPT	Summary: Direct-assay evidence that GALM participates in galactose metabolism via mutarotation of galactose anomers. Reason: Core biological process; directly demonstrated and consistent with the enzyme's preference for galactose. Foundational to the Leloir pathway. Supporting Evidence: PMID:12753898 catalysing the interconversion of the alpha- and beta-anomers of hexose sugars such as glucose and galactose

Gene Description

Existing Annotations Review

Core Functions

Aldose 1-epimerase (galactose mutarotase) activity: GALM interconverts the beta- and alpha-anomers of D-galactose in the cytosol, catalyzing the first step of the Leloir pathway and supplying the alpha-D-galactose required by galactokinase (GALK1).

References

📚 Additional Documentation

Notes

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