HEXA encodes the alpha subunit of lysosomal beta-hexosaminidase, a glycoside hydrolase family 20 (GH20) enzyme (EC 3.2.1.52). With the beta subunit (HEXB) it forms beta-hexosaminidase A, the alpha-beta heterodimer; the beta-beta homodimer is hexosaminidase B and the alpha-alpha homodimer is hexosaminidase S. The enzyme hydrolyses terminal non-reducing beta-linked N-acetyl-D-hexosamine (beta-GalNAc/GlcNAc, including sulfated hexosamine) residues from a range of glycoconjugates. The alpha-subunit active site is uniquely able, together with the GM2-activator protein (GM2A), to hydrolyse the GM2 ganglioside (removing the terminal GalNAc to give GM3); only hexosaminidase A performs this reaction in vivo. Because the alpha active site accepts negatively charged/sulfated substrates, hexosaminidase A/S also degrade sulfated glycosaminoglycan fragments (dermatan sulfate, keratan sulfate) and other glycoconjugates such as the sulfated glycosphingolipid SM2. The enzyme acts in the lysosome / lysosomal lumen. Loss of HEXA activity causes GM2-gangliosidosis type 1 (Tay-Sachs disease), an autosomal-recessive lysosomal storage disease characterised by neuronal accumulation of GM2 ganglioside.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004563 beta-N-acetylhexosaminidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) propagation of the family-defining beta-N-acetylhexosaminidase activity. This is the exact molecular function of the HEXA alpha subunit and the core catalytic activity of the enzyme. Reason: Correct core molecular function, matching the UniProt catalytic activity (EC 3.2.1.52) and multiple independent experimental annotations. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Hydrolyzes the non-reducing end N-acetyl-D-hexosamine |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA propagation of an extracellular-region location. HEXA is fundamentally a lysosomal enzyme; a fraction is secreted (precursor alpha-beta complexes are secreted), and the enzyme is detected extracellularly, but this is not its core site of action. Reason: Peripheral/secreted localization of a normally lysosomal hydrolase; retain but not as a core location. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Lysosome |
| GO:0005764 lysosome | IBA GO_REF:0000033 | ACCEPT | Summary: IBA propagation of lysosomal localization, the canonical site of action of beta-hexosaminidase A/S. This is a core cellular component. Reason: Correct core localization; matches UniProt subcellular location and the acid-hydrolase biology of the enzyme. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Lysosome |
| GO:0030203 glycosaminoglycan metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA propagation of glycosaminoglycan metabolism. The alpha active site removes terminal (sulfated) hexosamines from GAG fragments such as dermatan sulfate and keratan sulfate, so HEXA participates in lysosomal GAG catabolism. Reason: Well supported core process; the alpha/Hex A active site degrades sulfated GAG fragments (dermatan/keratan sulfate). Supporting Evidence: PMID:11707436 active on water-soluble and amphiphilic glycoconjugates including artificial substrates, sulfated GAG fragments, and the sulfated glycosphingolipid SM2 PMID:6458607 keratan sulfate-derived oligosaccharides with beta-N-acetylhexosaminidase A analogously resulted in the liberation of N-acetylglucosamine-6-sulfate |
| GO:0006689 ganglioside catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA propagation of ganglioside catabolism. The alpha subunit, within Hex A and together with GM2A, is uniquely responsible for GM2 ganglioside degradation. This is a core biological process and the process whose failure causes Tay-Sachs disease. Reason: Core, alpha-specific process; only Hex A (containing alpha) degrades GM2 in vivo. Supporting Evidence: PMID:16698036 Only the alpha-subunit active site can hydrolyze GM2 gangliosides file:human/HEXA/HEXA-uniprot.txt Only the isozyme A is responsible for the |
| GO:0004553 hydrolase activity, hydrolyzing O-glycosyl compounds | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO electronic mapping to the parent O-glycosyl hydrolase activity. This is a correct but more general parent of the specific GO:0004563 beta-N-acetylhexosaminidase activity. Reason: Correct (if general) parent term; consistent with the GH20 glycosidase activity and not misleading. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Belongs to the glycosyl hydrolase 20 family |
| GO:0004563 beta-N-acetylhexosaminidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (ARBA/InterPro/EC) assignment of the family-defining beta-N-acetylhexosaminidase activity (EC 3.2.1.52), consistent with the experimental catalytic activity. Reason: Correct core molecular function derived from EC 3.2.1.52 and family membership. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Hydrolyzes the non-reducing end N-acetyl-D-hexosamine |
| GO:0005764 lysosome | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic mapping from the UniProt subcellular location (Lysosome) keyword. Correct core localization. Reason: Matches the curated UniProt subcellular location and lysosomal biology. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Lysosome |
| GO:0005975 carbohydrate metabolic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO electronic mapping to a broad carbohydrate-metabolism process. Correct but very general parent of the specific glycoconjugate/GAG/ganglioside catabolic processes. Reason: Broad but not incorrect; a high-level parent of the specific catabolic processes captured elsewhere. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt oligosaccharide moieties from proteins and neutral glycolipids, or from |
| GO:0008375 acetylglucosaminyltransferase activity | IEA GO_REF:0000117 | REMOVE | Summary: Electronic ARBA assignment of a glycosyltransferase (acetylglucosaminyltransferase) activity. This is biologically incorrect - HEXA is a GH20 glycoside hydrolase (EC 3.2.1.52) that removes terminal hexosamines by hydrolysis, not a transferase that adds GlcNAc. The transferase reading likely arises from misinterpreting N-glycan trimming reports as sugar transfer. Reason: Wrong enzyme class for an electronic inference; HEXA is a hydrolase, not a glycosyltransferase. This ARBA mapping contradicts the well-established catalytic activity and family assignment. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Belongs to the glycosyl hydrolase 20 family |
| GO:0016042 lipid catabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: Electronic ARBA mapping to lipid catabolism. This is a reasonable broad parent given the role in glycosphingolipid (ganglioside GM2, SM2) degradation. Reason: Correct high-level parent of glycosphingolipid/ganglioside catabolism; consistent with GM2 and SM2 degradation. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt degradation of GM2 gangliosides in the presence of GM2A |
| GO:0042582 azurophil granule | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Electronic ARBA mapping to azurophil granule, mirroring the experimental IDA (PMID:25645918) that detected azurophilic-granule-resident beta-hexosaminidase A in neutrophils. A real but non-core, cell-type-specific location. Reason: Neutrophil azurophil granules are lysosome-related organelles; a legitimate but specialized, non-core location for this normally lysosomal enzyme. Supporting Evidence: PMID:25645918 azurophilic granule-resident |
| GO:0043202 lysosomal lumen | IEA GO_REF:0000117 | ACCEPT | Summary: Electronic ARBA mapping to lysosomal lumen, the precise compartment where the soluble acid hydrolase acts. Core localization. Reason: Accurate soluble-lumen localization consistent with UniProt and Reactome. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Lysosome |
| GO:1901135 carbohydrate derivative metabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: Electronic ARBA mapping to a very broad carbohydrate-derivative metabolism process. Correct but extremely general. Reason: High-level parent; not incorrect but uninformative relative to the specific catabolic processes. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt oligosaccharide moieties from proteins and neutral glycolipids, or from |
| GO:0005515 protein binding | IPI PMID:16698036 Crystallographic structure of human beta-hexosaminidase A: i... | MARK AS OVER ANNOTATED | Summary: IPI protein-binding annotation from the Hex A crystal structure, capturing the HEXA-HEXB (alpha-beta) interaction. Bare 'protein binding' is uninformative; the biologically meaningful heterodimerization and complex membership are captured separately by GO:0046982 and GO:1905379. Reason: Uninformative generic 'protein binding'; the specific HEXA-HEXB interaction is better represented by the heterodimerization activity and complex-membership annotations. Supporting Evidence: PMID:16698036 Hex A reveals an alphabeta heterodimer, with each subunit having a functional active site |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: IPI protein-binding annotation from a large-scale interactome study (with/from HEXB). Bare 'protein binding' is uninformative for function. Reason: Generic protein-binding from a high-throughput interactome; not an informative molecular function. The relevant HEXA-HEXB interaction is captured by GO:0046982 / GO:1905379. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt is a heterodimer composed of one subunit alpha and |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: IPI protein-binding annotation from a proteome-scale interactome network study (with/from HEXB). Bare 'protein binding' is uninformative. Reason: Generic protein-binding from a high-throughput interactome; superseded for curation purposes by the specific heterodimerization/complex annotations. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt is a heterodimer composed of one subunit alpha and |
| GO:0030203 glycosaminoglycan metabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl-orthology electronic transfer of glycosaminoglycan metabolic process from mouse Hexa. Consistent with the alpha-subunit role in degrading sulfated GAG fragments. Reason: Correct process, corroborated by experimental evidence for GAG (dermatan/ keratan sulfate) turnover by Hex A. Supporting Evidence: PMID:6458607 keratan sulfate-derived oligosaccharides with beta-N-acetylhexosaminidase A analogously resulted in the liberation of N-acetylglucosamine-6-sulfate |
| GO:0004563 beta-N-acetylhexosaminidase activity | IDA PMID:11707436 Physiological substrates for human lysosomal beta -hexosamin... | ACCEPT | Summary: Direct assay of recombinant hexosaminidase (Hex S, the alpha-alpha homodimer) showing beta-hexosaminidase activity on multiple glycoconjugate substrates including sulfated GAG fragments and SM2. Confirms the alpha-subunit catalytic activity. Reason: Experimental confirmation of the core molecular function of the alpha subunit. Supporting Evidence: PMID:11707436 Human lysosomal beta-hexosaminidases remove terminal beta-glycosidically bound PMID:11707436 N-acetylhexosamine residues from a number of glycoconjugates |
| GO:0036021 endolysosome lumen | IC PMID:11707436 Physiological substrates for human lysosomal beta -hexosamin... | KEEP AS NON CORE | Summary: Curator inference (IC) that the enzyme acts in the endolysosome lumen, consistent with the acidic acid-hydrolase compartment. A more specific sibling of lysosomal lumen; both are legitimate, and the core lumen location is retained via GO:0043202. Reason: Reasonable inferred compartment; endolysosome lumen refines the lumen site of action but the canonical/core term used here is lysosomal lumen. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Lysosome |
| GO:0036021 endolysosome lumen | IC PMID:27498570 Endolysosomes Are the Principal Intracellular Sites of Acid ... | KEEP AS NON CORE | Summary: Curator inference from a study showing endolysosomes are the principal intracellular sites of acid-hydrolase activity, applied to HEXA (an acid hydrolase) via its ganglioside catabolic role. Reasonable but non-core. Reason: The paper establishes endolysosomes as the acid-hydrolase-active compartment; inferring HEXA acts there is sound but the core lumen term used is lysosomal lumen. Supporting Evidence: PMID:27498570 endolysosomes are the principal organelles in which substrates are hydrolyzed |
| GO:0004563 beta-N-acetylhexosaminidase activity | TAS Reactome:R-HSA-9035976 | ACCEPT | Summary: Reactome (TAS) assertion of beta-N-acetylhexosaminidase activity. The source reaction describes a defective HEXA variant in hyaluronan metabolism, but the molecular function assigned (beta-N-acetylhexosaminidase activity) is the correct wild-type activity. Reason: Correct core molecular function; the enzyme cleaves terminal hexosamines from hyaluronan/GAG fragments in the lysosome. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Hydrolyzes the non-reducing end N-acetyl-D-hexosamine |
| GO:0004563 beta-N-acetylhexosaminidase activity | IDA PMID:9694901 A Pro504 --> Ser substitution in the beta-subunit of beta-he... | ACCEPT | Summary: Biochemical characterization of Hex A (alpha-beta) showing GM2-ganglioside hydrolysis by the alpha active site. Direct evidence for beta-hexosaminidase activity of the alpha-containing enzyme. Reason: Experimental confirmation of the core catalytic activity via GM2 hydrolysis assays. Supporting Evidence: PMID:9694901 the active site associated with the hydrolysis of PMID:9694901 GM2 ganglioside, as well as part of the binding site for the |
| GO:0006689 ganglioside catabolic process | IDA PMID:9694901 A Pro504 --> Ser substitution in the beta-subunit of beta-he... | ACCEPT | Summary: Direct evidence that the alpha active site of Hex A hydrolyses GM2 ganglioside; a beta-Pro504Ser mutation selectively impairs this natural-substrate activity, causing chronic Sandhoff disease. Core ganglioside catabolism. Reason: Experimental support for the alpha-specific GM2 catabolic process. Supporting Evidence: PMID:9694901 ganglioside-activator complex, is associated with the alpha-subunit |
| GO:0004563 beta-N-acetylhexosaminidase activity | EXP PMID:11707436 Physiological substrates for human lysosomal beta -hexosamin... | ACCEPT | Summary: Experimental (EXP) determination of the catalytic activity of the alpha subunit enzyme on physiological substrates. Duplicate evidence for the core MF. Reason: Direct experimental confirmation of beta-N-acetylhexosaminidase activity. Supporting Evidence: PMID:11707436 Human lysosomal beta-hexosaminidases remove terminal beta-glycosidically bound |
| GO:0030203 glycosaminoglycan metabolic process | IDA PMID:25645918 Human neutrophils secrete bioactive paucimannosidic proteins... | ACCEPT | Summary: ComplexPortal IDA linking Hex A to glycosaminoglycan/glycan metabolism. Consistent with the alpha-subunit role in removing terminal hexosamines from GAG and glycan substrates. Reason: Correct core process; corroborated by direct GAG-degradation evidence (dermatan/keratan sulfate). Supporting Evidence: PMID:11707436 substrates, sulfated GAG fragments, and the sulfated glycosphingolipid SM2 |
| GO:0043202 lysosomal lumen | NAS PMID:6458607 Liberation of N-acetylglucosamine-6-sulfate by human beta-N-... | ACCEPT | Summary: Non-traceable-author-statement localization to lysosomal lumen (the site where Hex A degrades sulfated keratan-sulfate oligosaccharides). Core lumen localization. Reason: Correct soluble-lumen localization of the acid hydrolase. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Lysosome |
| GO:1905379 beta-N-acetylhexosaminidase complex | IPI PMID:16698036 Crystallographic structure of human beta-hexosaminidase A: i... | ACCEPT | Summary: HEXA is a subunit of the beta-N-acetylhexosaminidase complex (Hex A alpha-beta heterodimer), established by the crystal structure. Core complex membership. Reason: Correct, structurally defined complex membership central to enzyme function. Supporting Evidence: PMID:16698036 Hex A reveals an alphabeta heterodimer, with each subunit having a functional active site |
| GO:0030203 glycosaminoglycan metabolic process | IDA PMID:11707436 Physiological substrates for human lysosomal beta -hexosamin... | ACCEPT | Summary: ComplexPortal IDA (from the Hex S physiological-substrate study) linking the alpha-subunit enzyme to glycosaminoglycan metabolism via degradation of sulfated GAG fragments and dermatan sulfate. Reason: Directly supported core process; the enzyme degrades sulfated GAG fragments and dermatan-sulfate-derived glycans. Supporting Evidence: PMID:11707436 the anionic glycans were identified as products of incomplete dermatan |
| GO:1905379 beta-N-acetylhexosaminidase complex | IDA PMID:11707436 Physiological substrates for human lysosomal beta -hexosamin... | ACCEPT | Summary: ComplexPortal IDA placing the alpha subunit in the beta-N-acetylhexosaminidase complex, consistent with the alpha-alpha (Hex S) and alpha-beta (Hex A) dimers characterized in this study. Core complex membership. Reason: Correct complex membership; the functional enzyme is an obligate dimer of hexosaminidase subunits. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt isozyme S (hexosaminidase S) is a homodimer of two alpha subunits |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-1605595 | ACCEPT | Summary: Reactome (TAS) localization to lysosomal lumen for the GM2A:GM2 to GM2A:GM3 reaction catalyzed by Hex A. Core lumen localization. Reason: Accurate soluble-lumen localization for the GM2-degradation reaction. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Lysosome |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-1605632 | ACCEPT | Summary: Reactome (TAS) localization to lysosomal lumen for a glycosphingolipid (Gb4Cer) degradation reaction. Core lumen localization. Reason: Accurate soluble-lumen localization consistent with lysosomal acid-hydrolase biology. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Lysosome |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-1638053 | ACCEPT | Summary: Reactome (TAS) localization to lysosomal lumen for HEXA cleaving terminal GlcNAc from keratan sulfate. Core lumen localization. Reason: Accurate soluble-lumen localization for keratan-sulfate degradation. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Lysosome |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-2105001 | ACCEPT | Summary: Reactome (TAS) localization to lysosomal lumen for HEXA cleaving terminal GalNAc from dermatan sulfate. Core lumen localization. Reason: Accurate soluble-lumen localization for dermatan-sulfate degradation. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Lysosome |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-2162225 | ACCEPT | Summary: Reactome (TAS) localization to lysosomal lumen for HEXA cleaving terminal GlcNAc from small hyaluronan fragments. Core lumen localization. Reason: Accurate soluble-lumen localization for hyaluronan-fragment degradation. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Lysosome |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-9840833 | ACCEPT | Summary: Reactome (TAS) localization to lysosomal lumen for the GM2A:GA2 to GM2A:LacCer reaction. Core lumen localization. Reason: Accurate soluble-lumen localization consistent with glycosphingolipid catabolism. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Lysosome |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-9840884 | ACCEPT | Summary: Reactome (TAS) localization to lysosomal lumen for the bHEXA,bHEXS hydrolysis of GM2A:SM2. Core lumen localization. Reason: Accurate soluble-lumen localization for SM2 (sulfated glycosphingolipid) degradation. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Addition of GM2A stimulates the hydrolysis of |
| GO:0005576 extracellular region | IDA PMID:33966596 CREG1 promotes lysosomal biogenesis and function. | KEEP AS NON CORE | Summary: IDA extracellular-region localization from a CREG1 lysosomal-biogenesis study in which HEXA is used as a lysosomal/secreted hydrolase marker. A fraction of the enzyme is secreted, but this is a non-core location for a lysosomal enzyme. Reason: Secreted fraction of a normally lysosomal hydrolase; retain but non-core. Supporting Evidence: PMID:33966596 CREG1 is an endosomal-lysosomal protein |
| GO:0004563 beta-N-acetylhexosaminidase activity | IDA PMID:8123671 Classification of disorders of GM2 ganglioside hydrolysis us... | ACCEPT | Summary: Direct assay of GM2-ganglioside hydrolysis (3H-GM2 substrate) distinguishing normal from Tay-Sachs/Sandhoff fibroblasts, evidencing the beta-hexosaminidase activity of the alpha-containing enzyme. Reason: Experimental confirmation of the core catalytic activity. Supporting Evidence: PMID:8123671 Rates of GM2 ganglioside hydrolysis by fibroblasts from normal controls and |
| GO:0004563 beta-N-acetylhexosaminidase activity | IDA PMID:8672428 Direct determination of the substrate specificity of the alp... | ACCEPT | Summary: Direct determination of the alpha-active-site substrate specificity in heterodimeric Hex A, confirming beta-hexosaminidase activity of the alpha subunit. Reason: Experimental confirmation of the core molecular function and its substrate-specificity in the heterodimer. Supporting Evidence: PMID:8672428 Heterodimeric hexosaminidase A (alpha beta) is the only isozyme |
| GO:0006689 ganglioside catabolic process | IDA PMID:8123671 Classification of disorders of GM2 ganglioside hydrolysis us... | ACCEPT | Summary: Direct GM2-hydrolysis assays in fibroblasts showing loss of GM2 degradation in Tay-Sachs (HEXA-deficient) cells, evidencing the alpha-subunit role in ganglioside catabolism. Reason: Experimental support for the alpha-specific GM2 ganglioside catabolic process. Supporting Evidence: PMID:8123671 cell extracts from patients with Tay-Sachs |
| GO:0006689 ganglioside catabolic process | IDA PMID:8672428 Direct determination of the substrate specificity of the alp... | ACCEPT | Summary: Direct characterization showing the Hex A alpha-active site hydrolyses GM2 ganglioside in vivo with the GM2 activator protein. Core ganglioside catabolism. Reason: Experimental support for the alpha-specific GM2 catabolic process. Supporting Evidence: PMID:8672428 that can hydrolyze GM2 ganglioside in vivo, requiring the presence of the GM2 |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-9035976 | ACCEPT | Summary: Reactome (TAS) localization to lysosomal lumen (from the defective-HEXA hyaluronan reaction). Core lumen localization; the location is correct irrespective of the defective-variant framing of the source reaction. Reason: Accurate soluble-lumen localization of the enzyme. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Lysosome |
| GO:0006024 glycosaminoglycan biosynthetic process | IDA PMID:25645918 Human neutrophils secrete bioactive paucimannosidic proteins... | MARK AS OVER ANNOTATED | Summary: IDA to a glycosaminoglycan BIOSYNTHETIC process from the neutrophil azurophil-granule paper. This mis-assigns the process direction - HEXA is a hydrolase that trims/degrades N-glycans (generating paucimannosidic structures), it does not synthesize glycosaminoglycans. The underlying activity is catabolic N-glycan trimming. Reason: Wrong process direction (biosynthetic vs catabolic) for an experimental annotation; the actual activity is hydrolytic N-glycan trimming, captured by GO:0004563 and the catabolic GAG/glycan processes. Retained (not removed) per policy for experimental annotations, but flagged as over-/mis-annotated. Supporting Evidence: PMID:25645918 by trimming hybrid/complex type N-glycan intermediates with relative broad |
| GO:0008375 acetylglucosaminyltransferase activity | IDA PMID:25645918 Human neutrophils secrete bioactive paucimannosidic proteins... | MARK AS OVER ANNOTATED | Summary: IDA to acetylglucosaminyltransferase (glycosyltransferase) activity from the neutrophil azurophil-granule paper. This mis-classifies the enzyme - the paper shows Hex A generating paucimannosidic N-glycans by TRIMMING (hydrolysing) hybrid/ complex N-glycan intermediates, i.e. a hydrolase acting in the catabolic direction, not a transferase adding GlcNAc. Reason: Wrong enzyme class for the assigned MF; HEXA is a GH20 hydrolase, not a glycosyltransferase. The observed activity is hydrolytic N-glycan trimming (GO:0004563). Retained (not removed) per policy for experimental annotations, but flagged as mis-/over-annotated. Supporting Evidence: PMID:25645918 displayed the capacity to generate paucimannosidic N-glycans PMID:25645918 by trimming hybrid/complex type N-glycan intermediates with relative broad |
| GO:0042582 azurophil granule | IDA PMID:25645918 Human neutrophils secrete bioactive paucimannosidic proteins... | KEEP AS NON CORE | Summary: IDA localization to neutrophil azurophil granules, with immunocytochemical co-localization of beta-hexosaminidase A with the azurophilic marker MPO. A real but cell-type-specific, non-core location (azurophil granules are lysosome-related organelles). Reason: Legitimate specialized localization in neutrophils; not the core (canonical lysosomal) site of action. Supporting Evidence: PMID:25645918 and the azurophilic marker MPO in human |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: High-throughput proteomic detection of HEXA in urinary prostatic-secretion exosomes. A mass-spectrometry co-purification, indicative of secreted/exosomal presence rather than a core functional location. Reason: Proteomic detection in exosomes; a non-core, incidental extracellular location for a lysosomal enzyme. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt oligosaccharide moieties from proteins and neutral glycolipids, or from |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: High-throughput detection in an NK-cell membrane-proteome study. HEXA is a soluble lumenal enzyme; its appearance in a membrane fraction reflects association with membranes/organelle co-purification, not integral membrane residence. Reason: Non-specific 'membrane' from a high-throughput membrane-proteome dataset; HEXA is a soluble lysosomal enzyme, so integral-membrane localization is not supported. Supporting Evidence: file:human/HEXA/HEXA-uniprot.txt Lysosome |
| GO:0046982 protein heterodimerization activity | IDA PMID:6230359 Association of alpha- and beta-subunits during the biosynthe... | ACCEPT | Summary: Direct biosynthetic study showing the alpha chain associates with the beta chain to form the mature alpha-beta heterodimer, an association required for catalytic activity and lysosomal transport. Informative molecular function underlying Hex A assembly. Reason: Specific, informative heterodimerization activity (alpha-beta assembly), directly supported and biologically central. Supporting Evidence: PMID:6230359 association with beta-chains is necessary not only for acquisition of catalytic PMID:6230359 activity but also for transport of alpha-chains to lysosomes |
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Download this section (compressed HTML)Q: Beyond GM2 ganglioside, dermatan sulfate and keratan sulfate, which glycoconjugate substrates in vivo depend specifically on the HEXA alpha active site (as opposed to the beta active site of HEXB)?
Q: To what extent do secreted/exosomal and neutrophil azurophil-granule pools of hexosaminidase A have physiological (non-lysosomal) roles?
Experiment: Substrate-resolved lysosomal glycomics in HEXA-null versus HEXB-null cells to define the alpha-subunit-specific substrate repertoire in vivo.
Experiment: Structure-guided mutagenesis of the alpha-specific loop and Arg424 to dissect GM2A-dependent GM2 recognition versus general hexosaminidase activity.
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