HEXB encodes the beta subunit of lysosomal beta-hexosaminidase, a glycoside hydrolase family 20 (GH20) exo-glycosidase. The beta subunit is shared by two isozymes: hexosaminidase A, an alpha-beta heterodimer of HEXA and HEXB, and hexosaminidase B, a beta-beta homodimer of HEXB alone (a third labile isozyme, hexosaminidase S, is the HEXA alpha-alpha homodimer). The enzyme hydrolyses terminal non-reducing N-acetyl-beta-D-hexosamine (beta-GalNAc/GlcNAc) residues (EC 3.2.1.52) from a range of glycoconjugates, including gangliosides (GM2 and GA2), glycosaminoglycans (dermatan sulfate, keratan sulfate and hyaluronan fragments), neutral oligosaccharides and glycoproteins. Each subunit contributes a distinct active site: the beta-active site (present in both Hex A and Hex B) hydrolyses neutral substrates efficiently, whereas the alpha-active site additionally cleaves sulfated/negatively charged substrates; only Hex A together with the GM2 activator protein degrades GM2 ganglioside at physiologically significant rates. The mature enzyme resides in the lysosome / lysosomal lumen. Loss of the beta subunit disables both Hex A and Hex B and causes Sandhoff disease (GM2 gangliosidosis type 2), an autosomal recessive lysosomal storage disorder marked by neuronal GM2 ganglioside accumulation and progressive neurodegeneration.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004563 beta-N-acetylhexosaminidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function. beta-N-acetylhexosaminidase activity (EC 3.2.1.52) is the defining enzymatic activity of the beta subunit, directly supported by biochemical characterization of Hex B and Hex A and consistent across the GH20 phylogenetic clade. Reason: The IBA at the exact right level of specificity matches multiple experimental annotations (IDA/EXP) on the same term. The catalytic activity is well-established biochemically and by active-site mutagenesis. Supporting Evidence: PMID:11707436 Human lysosomal beta-hexosaminidases remove terminal beta-glycosidically bound N-acetylhexosamine residues from a number of glycoconjugates file:human/HEXB/HEXB-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 placing the enzyme in the extracellular region. HEXB is a lysosomal hydrolase that also traffics through secretory routes; a minor secreted pool exists (secreted precursor complexes, exosomes, neutrophil granule release), but the extracellular region is not where the enzyme predominantly acts. Reason: A genuine minor secreted/extracellular pool is documented (secreted precursor alpha-beta complexes; exosome and neutrophil-granule proteomics), so this is not wrong, but it is peripheral to the core lysosomal catabolic function. Supporting Evidence: PMID:6230359 Precursor alpha beta complexes were secreted, along with some precursor alpha monomers |
| GO:0005764 lysosome | IBA GO_REF:0000033 | ACCEPT | Summary: Core cellular location. The mature enzyme is a lysosomal hydrolase and is active in the lysosome, consistent with experimental subcellular localization and with its role in lysosomal catabolism. Reason: Well-supported by experimental localization (PMID:9694901) and by UniProt subcellular location; the IBA is at the correct level. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt SUBCELLULAR LOCATION: Lysosome |
| GO:0030203 glycosaminoglycan metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Core biological process. Hex A and Hex B degrade glycosaminoglycan fragments by removing terminal beta-hexosamine residues (e.g. from dermatan sulfate and keratan sulfate), and defective HEXB blocks GAG degradation. Reason: Supported by experimental IDA annotations on the same term (PMID:11707436, PMID:25645918) and by biochemical demonstration of GAG-fragment hydrolysis. Supporting Evidence: PMID:11707436 recombinant Hex S was highly PMID:6458607 Incubation of 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: Core biological process. The beta subunit is an essential component of Hex A, the only isozyme that degrades GM2 ganglioside (with the GM2 activator protein); loss of the beta subunit causes GM2 ganglioside storage (Sandhoff disease). Reason: Directly supported by experimental IDA annotations on the same term (PMID:8123671, PMID:8672428) and by the disease mechanism. Supporting Evidence: PMID:8672428 Heterodimeric hexosaminidase A (alpha beta) is the only isozyme that can hydrolyze GM2 ganglioside in vivo, requiring the presence of the GM2 activator protein |
| GO:0004553 hydrolase activity, hydrolyzing O-glycosyl compounds | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO parent term for the glycoside-hydrolase activity. Correct but more general than the specific beta-N-acetylhexosaminidase activity that is experimentally established. Reason: The term is accurate but too broad; the specific child term GO:0004563 (beta-N-acetylhexosaminidase activity) is well supported and should be used. Proposed replacements: beta-N-acetylhexosaminidase activity Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt Belongs to the glycosyl hydrolase 20 family |
| GO:0004563 beta-N-acetylhexosaminidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated (ARBA/multi-method, includes EC:3.2.1.52 mapping) assignment of the exact core molecular function, matching the experimental annotations. Reason: Correct core MF term; redundant with the experimental IDA/EXP annotations on GO:0004563. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt Hydrolyzes the non-reducing end N-acetyl-D-hexosamine |
| GO:0005764 lysosome | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell mapping to lysosome, matching the experimental localization. Reason: Correct core location; redundant with the experimental EXP annotation (PMID:9694901). Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt SUBCELLULAR LOCATION: Lysosome |
| GO:0005975 carbohydrate metabolic process | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro2GO high-level carbohydrate metabolism term. Correct but very general relative to the specific ganglioside/GAG catabolic processes. Reason: Not wrong, but uninformatively broad; the specific catabolic BP terms (GO:0006689, GO:0030203) capture the biology. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt Belongs to the glycosyl hydrolase 20 family |
| GO:0008375 acetylglucosaminyltransferase activity | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA-predicted glycosyltransferase activity. HEXB is a GH20 exo-glycosidase (a hydrolase, EC 3.2.1.52), not a glycosyltransferase; the paucimannose generation described for the enzyme is N-glycan trimming (hydrolysis), not sugar transfer. Reason: Transferase activity is inconsistent with the well-established hydrolase mechanism and fold; this is a mis-typing of the glycosidase activity. Per curation policy the paired experimental IDA is retained but flagged rather than removed. Supporting Evidence: PMID:25645918 azurophilic granule-resident Ξ²-hexosaminidase A displayed the capacity to generate paucimannosidic N-glycans by trimming hybrid/complex type N-glycan intermediates |
| GO:0016042 lipid catabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA-predicted lipid catabolism. HEXB does participate in glycosphingolipid (ganglioside) catabolism, so this broad term is consistent, but the specific ganglioside catabolic process term is more informative. Reason: Correct in spirit (ganglioside/glycosphingolipid degradation is lipid catabolism) but too general; GO:0006689 is preferred. Supporting Evidence: PMID:8672428 Heterodimeric hexosaminidase A (alpha beta) is the only isozyme that can hydrolyze GM2 ganglioside in vivo |
| GO:0042582 azurophil granule | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA-predicted azurophil granule localization, corroborated by an experimental IDA (PMID:25645918) showing HEXB in human neutrophil azurophilic granules. Reflects the secreted/granule pool of this lysosomal enzyme. Reason: Genuine localization for the neutrophil granule pool, but peripheral to the core lysosomal catabolic role. Supporting Evidence: PMID:25645918 azurophilic granule-resident Ξ²-hexosaminidase A |
| GO:0043202 lysosomal lumen | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA mapping to lysosomal lumen, the correct compartment for this soluble lysosomal hydrolase, matching numerous Reactome TAS annotations. Reason: Correct core location for a soluble lysosomal enzyme. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt SUBCELLULAR LOCATION: Lysosome |
| GO:0060473 cortical granule | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Cortical-granule localization inferred by orthology from mouse Hexb (UniProtKB:P20060). Documented for oocytes in the zona-block-to-polyspermy role; not directly demonstrated for the human protein. Reason: Supported by orthology to the well-characterized mouse cortical-granule function; a legitimate but non-core, tissue-specific localization. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt Cytoplasmic vesicle, secretory vesicle, Cortical granule |
| GO:1901135 carbohydrate derivative metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA high-level carbohydrate-derivative metabolism term; extremely broad relative to the specific catabolic functions. Reason: Uninformatively general; specific catabolic BP terms are preferred. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt Belongs to the glycosyl hydrolase 20 family |
| GO:0005515 protein binding | IPI PMID:16698036 Crystallographic structure of human beta-hexosaminidase A: i... | MARK AS OVER ANNOTATED | Summary: IPI from the Hex A crystal-structure study, with HEXA (P06865) as partner. This captures the genuine, biologically central beta-alpha interaction that forms the Hex A heterodimer, but the term itself (bare protein binding) is uninformative. Reason: The underlying HEXA interaction is real and central (Hex A heterodimer), better represented by the beta-N-acetylhexosaminidase complex annotation (GO:1905379); bare protein binding adds no functional information. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt hexosaminidase A is CC a heterodimer composed of one subunit alpha and one subunit beta |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: High-throughput AP-MS interactome IPI (BioPlex). Uninformative bare protein binding term. Reason: Systematic-screen protein binding without a defined functional partner relationship; provides no informative molecular function. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: High-throughput binary (Y2H) interactome IPI (HuRI). Uninformative bare protein binding term. Reason: Systematic-screen protein binding; not informative for molecular function. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: High-throughput neurodegenerative-disease interactome IPI. Uninformative bare protein binding term. Reason: Systematic-screen protein binding; not informative for molecular function. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: High-throughput AP-MS interactome IPI (BioPlex 3.0), with HEXA (P06865). Recapitulates the HEXA interaction but via a bare protein binding term. Reason: As for PMID:16698036, the HEXA interaction is meaningful but bare protein binding is uninformative and better captured by the complex annotation. |
| GO:0006044 N-acetylglucosamine metabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl orthology projection (rat). Consistent with release of GlcNAc residues during glycoconjugate degradation, but broad and indirect. Reason: Consistent with the enzyme liberating N-acetylglucosamine from substrates, but not a core process descriptor; retained as non-core. Supporting Evidence: PMID:6458607 liberation of N-acetylglucosamine-6-sulfate |
| GO:0007338 single fertilization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Fertilization role projected by orthology from mouse Hexb. In mouse, the cortical-granule enzyme contributes to the zona block to polyspermy; a legitimate but non-core, organism-specific developmental role. Reason: Supported by the well-documented mouse ortholog function; peripheral to the core lysosomal catabolic function of the human enzyme. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt During fertilization CC is responsible, at least in part, for the zona block to polyspermy |
| GO:0008360 regulation of cell shape | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology projection from mouse. A weak, indirect phenotype association with no mechanistic link to the enzyme's glycosidase function. Reason: No molecular basis connects a lysosomal exo-glycosidase to direct regulation of cell shape; likely an over-propagated phenotype-based projection. |
| GO:0015929 hexosaminidase activity | IEA GO_REF:0000107 | MODIFY | Summary: Ensembl orthology projection of hexosaminidase activity. Correct but a parent of the specific beta-N-acetylhexosaminidase activity. Reason: Accurate but too general; the specific child term GO:0004563 is well supported experimentally. Proposed replacements: beta-N-acetylhexosaminidase activity Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt Hydrolyzes the non-reducing end N-acetyl-D-hexosamine |
| GO:0016231 beta-N-acetylglucosaminidase activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl orthology projection. The beta-active site does hydrolyse terminal beta-GlcNAc residues; this is a valid, slightly narrower sibling of the beta-N-acetylhexosaminidase activity (which spans GlcNAc and GalNAc). Reason: Consistent with the enzyme's substrate range (releases N-acetylglucosamine from keratan sulfate and N-glycans); the broader GO:0004563 is the primary core MF, so this narrower term is retained as non-core. Supporting Evidence: PMID:6458607 Incubation of keratan sulfate-derived oligosaccharides with beta-N-acetylhexosaminidase A analogously resulted in the liberation of N-acetylglucosamine-6-sulfate |
| GO:0030203 glycosaminoglycan metabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl orthology projection of GAG metabolism, matching the experimental IDA annotations on the same term. Reason: Correct core BP; redundant with experimental annotations (PMID:11707436, PMID:25645918). Supporting Evidence: PMID:11707436 sulfated GAG fragments, and the sulfated glycosphingolipid SM2 |
| GO:0030246 carbohydrate binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology projection of carbohydrate binding. The enzyme necessarily binds carbohydrate substrates in its active site, but as an independent MF this is redundant with the catalytic activity. Reason: Substrate binding is subsumed by the catalytic activity annotation; a standalone carbohydrate binding MF adds little. |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl orthology projection of identical protein binding. Reflects the beta-beta homodimer (Hex B), a genuine self-association. Reason: The beta-beta homodimerization is real (Hex B) and supported experimentally (PMID:6230359); better captured by the complex annotation, so retained as non-core. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt hexosaminidase B is a homodimer of two beta subunits |
| GO:0043615 astrocyte cell migration | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology projection from mouse. A phenotype-level association (Hexb loss affects CNS/glial biology) with no direct mechanistic tie to the enzyme's molecular function. Reason: Indirect, phenotype-derived process not representing a direct molecular role of the human enzyme. |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology projection. Generic complex-binding term with no defined partner complex. Reason: Uninformative generic binding term; the meaningful complex membership is the hexosaminidase complex (GO:1905379). |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology projection. No mechanism links a lysosomal exo-glycosidase to direct positive regulation of RNA polymerase II transcription. Reason: Biologically implausible as a direct molecular role for HEXB; over-propagated projection. |
| GO:0004563 beta-N-acetylhexosaminidase activity | TAS Reactome:R-HSA-9035982 | ACCEPT | Summary: Reactome TAS for the core catalytic activity (in the context of defective HEXB failing to cleave terminal GalNAc from hyaluronan fragments). Reason: Correct core MF term, consistent with experimental evidence. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt Hydrolyzes the non-reducing end N-acetyl-D-hexosamine |
| GO:0030203 glycosaminoglycan metabolic process | IDA PMID:11707436 Physiological substrates for human lysosomal beta -hexosamin... | ACCEPT | Summary: ComplexPortal IDA. Hex isozymes were shown to act on sulfated GAG fragments (dermatan sulfate) and neutral N-glycan fragments, establishing a direct role in glycosaminoglycan metabolism. Reason: Direct experimental evidence for GAG-fragment hydrolysis by the enzyme. Supporting Evidence: PMID:11707436 sulfated GAG fragments, and the sulfated glycosphingolipid SM2 |
| GO:0030203 glycosaminoglycan metabolic process | IDA PMID:25645918 Human neutrophils secrete bioactive paucimannosidic proteins... | ACCEPT | Summary: ComplexPortal IDA linking HEXB activity to processing of glycan substrates (N-glycan trimming in neutrophils). Supports involvement in glycan/glycosaminoglycan metabolism. Reason: Direct experimental demonstration of the enzyme acting on glycan substrates. Supporting Evidence: PMID:25645918 azurophilic granule-resident Ξ²-hexosaminidase A displayed the capacity to generate paucimannosidic N-glycans by trimming hybrid/complex type N-glycan intermediates |
| GO:0043202 lysosomal lumen | NAS PMID:6458607 Liberation of N-acetylglucosamine-6-sulfate by human beta-N-... | ACCEPT | Summary: ComplexPortal NAS for lysosomal lumen localization of the soluble lysosomal hydrolase. Reason: Correct core compartment; consistent with experimental lysosomal localization and the enzyme's biology. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt SUBCELLULAR LOCATION: Lysosome |
| GO:1905379 beta-N-acetylhexosaminidase complex | IPI PMID:16698036 Crystallographic structure of human beta-hexosaminidase A: i... | ACCEPT | Summary: Core complex membership. The beta subunit is part of the beta-N-acetylhexosaminidase complex (Hex A alpha-beta heterodimer and Hex B beta-beta homodimer). This is the informative representation of the HEXA interaction and the homodimer. Reason: Directly supported by the Hex A crystal structure and by the biochemistry of subunit association; captures the biologically central complexes. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt hexosaminidase A is CC a heterodimer composed of one subunit alpha and one subunit beta PMID:16698036 essential for the degradation of GM2 gangliosides in the central and peripheral nervous system |
| GO:0004563 beta-N-acetylhexosaminidase activity | EXP PMID:11329289 Characterization of the Glu and Asp residues in the active s... | ACCEPT | Summary: Experimental characterization of the Hex B (beta-beta) active site, identifying beta-Glu355 as the general acid/base catalytic residue and Asp354/Asp241 as catalytically important. Direct evidence for the beta subunit's catalytic activity. Reason: Active-site mutagenesis and kinetics directly establish the beta-N-acetylhexosaminidase catalytic activity of the beta subunit. Supporting Evidence: PMID:11329289 the general acid/base catalytic residue (Glu 314 in chitobiase and Ξ² Glu 355 in human Ξ² -hexosaminidase) |
| GO:0004563 beta-N-acetylhexosaminidase activity | EXP PMID:11707436 Physiological substrates for human lysosomal beta -hexosamin... | ACCEPT | Summary: Experimental catalytic activity of the beta-active site on neutral and sulfated glycoconjugate substrates (soluble/amphiphilic substrates, sulfated GAG fragments, SM2). Reason: Direct biochemical demonstration of the core catalytic activity. Supporting Evidence: PMID:11707436 Human lysosomal beta-hexosaminidases remove terminal beta-glycosidically bound N-acetylhexosamine residues from a number of glycoconjugates |
| GO:0004563 beta-N-acetylhexosaminidase activity | EXP PMID:9694901 A Pro504 --> Ser substitution in the beta-subunit of beta-he... | ACCEPT | Summary: Experimental characterization of Hex A catalytic activity via a beta-subunit variant (Pro504Ser) affecting GM2 hydrolysis, confirming the beta subunit's contribution to enzymatic activity. Reason: Direct experimental evidence for the catalytic activity of the Hex A complex containing the beta subunit. Supporting Evidence: PMID:9694901 The GM2 gangliosidoses are caused by mutations in the genes encoding the alpha- (Tay-Sachs) or beta- (Sandhoff) subunits of heterodimeric beta-hexosaminidase A |
| GO:0005764 lysosome | EXP PMID:9694901 A Pro504 --> Ser substitution in the beta-subunit of beta-he... | ACCEPT | Summary: Experimental subcellular localization to the lysosome (the study analysed transport and processing of the Hex A heterodimer bearing the beta subunit). Reason: Direct experimental evidence for lysosomal localization; core compartment. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt SUBCELLULAR LOCATION: Lysosome |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-1605595 | ACCEPT | Summary: Reactome TAS for lysosomal lumen localization (GM2 degradation reaction context). Reason: Correct core compartment for the soluble lysosomal enzyme. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt SUBCELLULAR LOCATION: Lysosome |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-1605632 | ACCEPT | Summary: Reactome TAS for lysosomal lumen localization (glycosphingolipid degradation context). Reason: Correct core compartment; redundant with other lysosomal lumen annotations. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt SUBCELLULAR LOCATION: Lysosome |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-1638053 | ACCEPT | Summary: Reactome TAS for lysosomal lumen localization (keratan sulfate degradation context). Reason: Correct core compartment; redundant with other lysosomal lumen annotations. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt SUBCELLULAR LOCATION: Lysosome |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-2105001 | ACCEPT | Summary: Reactome TAS for lysosomal lumen localization (dermatan sulfate degradation context). Reason: Correct core compartment; redundant with other lysosomal lumen annotations. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt SUBCELLULAR LOCATION: Lysosome |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-2162225 | ACCEPT | Summary: Reactome TAS for lysosomal lumen localization (hyaluronan fragment degradation context). Reason: Correct core compartment; redundant with other lysosomal lumen annotations. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt SUBCELLULAR LOCATION: Lysosome |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-9638075 | ACCEPT | Summary: Reactome TAS for lysosomal lumen localization (HEXB cleaving terminal GalNAc from dermatan sulfate). Reason: Correct core compartment; redundant with other lysosomal lumen annotations. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt SUBCELLULAR LOCATION: Lysosome |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-9638076 | ACCEPT | Summary: Reactome TAS for lysosomal lumen localization (HEXB cleaving terminal GlcNAc from hyaluronan fragments). Reason: Correct core compartment; redundant with other lysosomal lumen annotations. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt SUBCELLULAR LOCATION: Lysosome |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-9638078 | ACCEPT | Summary: Reactome TAS for lysosomal lumen localization (HEXB cleaving terminal GlcNAc from keratan sulfate). Reason: Correct core compartment; redundant with other lysosomal lumen annotations. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt SUBCELLULAR LOCATION: Lysosome |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-9840833 | ACCEPT | Summary: Reactome TAS for lysosomal lumen localization (Hex A/Hex B hydrolysing GM2A:GA2 to GM2A:LacCer). Reason: Correct core compartment; redundant with other lysosomal lumen annotations. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt SUBCELLULAR LOCATION: Lysosome |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-9840884 | ACCEPT | Summary: Reactome TAS for lysosomal lumen localization (Hex A/Hex S hydrolysing GM2A:SM2). Reason: Correct core compartment; redundant with other lysosomal lumen annotations. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt SUBCELLULAR LOCATION: Lysosome |
| GO:0007338 single fertilization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS fertilization role transferred from mouse Hexb (zona block to polyspermy). Non-core, organism-specific developmental function. Reason: Supported by the mouse ortholog's characterized cortical-granule role; peripheral to the core lysosomal catabolic function. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt During fertilization CC is responsible, at least in part, for the zona block to polyspermy |
| GO:0060473 cortical granule | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS cortical-granule localization transferred from mouse Hexb. Non-core, oocyte-specific localization. Reason: Supported by orthology to the mouse cortical-granule enzyme; a legitimate but non-core localization. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt Cytoplasmic vesicle, secretory vesicle, Cortical granule |
| GO:0004563 beta-N-acetylhexosaminidase activity | IDA PMID:8123671 Classification of disorders of GM2 ganglioside hydrolysis us... | ACCEPT | Summary: Direct experimental assay of GM2 ganglioside hydrolysis distinguishing normal, Tay-Sachs and Sandhoff cells, demonstrating the enzyme's catalytic activity. Reason: Direct experimental evidence for the core catalytic activity. Supporting Evidence: PMID:8123671 cell extracts from Sandhoff disease patients hydrolyzed GM2 at about 10% of normal rates |
| GO:0004563 beta-N-acetylhexosaminidase activity | IDA PMID:8672428 Direct determination of the substrate specificity of the alp... | ACCEPT | Summary: Direct experimental determination of the substrate specificity of the alpha- and beta-active sites in Hex A, using a Hex A with an inactivated beta subunit; establishes the catalytic activity of the beta-active site. Reason: Direct experimental evidence for the beta subunit's catalytic activity within Hex A. Supporting Evidence: PMID:8672428 the alpha and beta subunits in hexosaminidase A participate equally in the hydrolysis of neutral substrates |
| GO:0006689 ganglioside catabolic process | IDA PMID:8123671 Classification of disorders of GM2 ganglioside hydrolysis us... | ACCEPT | Summary: Direct experimental evidence that the enzyme degrades GM2 ganglioside, with Sandhoff (HEXB-deficient) cells failing to hydrolyse GM2. Reason: Direct evidence for the core ganglioside catabolic process; consistent with the disease mechanism. Supporting Evidence: PMID:8123671 cell extracts from Sandhoff disease patients hydrolyzed GM2 at about 10% of normal rates |
| GO:0006689 ganglioside catabolic process | IDA PMID:8672428 Direct determination of the substrate specificity of the alp... | ACCEPT | Summary: Direct experimental evidence tied to GM2 ganglioside hydrolysis by Hex A, which contains the beta subunit. Reason: Direct evidence for the core ganglioside catabolic process. Supporting Evidence: PMID:8672428 Heterodimeric hexosaminidase A (alpha beta) is the only isozyme that can hydrolyze GM2 ganglioside in vivo |
| GO:0042802 identical protein binding | IDA PMID:6230359 Association of alpha- and beta-subunits during the biosynthe... | KEEP AS NON CORE | Summary: Direct evidence relating to beta-subunit association during Hex biosynthesis; reflects the beta-beta homodimerization forming Hex B. Reason: The homodimerization is genuine (Hex B), but is better captured by the complex annotation (GO:1905379); retained as non-core. Supporting Evidence: PMID:6230359 association with beta-chains is necessary not only for acquisition of catalytic activity but also for transport of alpha-chains to lysosomes |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798751 | KEEP AS NON CORE | Summary: Reactome TAS for extracellular localization via exocytosis of azurophil granule lumen proteins (neutrophil degranulation). Reflects the secreted granule pool. Reason: Genuine secreted/granule-release pool, but peripheral to the core lysosomal catabolic function. Supporting Evidence: PMID:25645918 azurophilic granule-resident Ξ²-hexosaminidase A |
| GO:0035578 azurophil granule lumen | TAS Reactome:R-HSA-6798751 | KEEP AS NON CORE | Summary: Reactome TAS for azurophil granule lumen localization, corroborated by neutrophil proteomics (PMID:25645918). Non-core granule pool. Reason: Real neutrophil-granule localization but peripheral to the core lysosomal role. Supporting Evidence: PMID:25645918 azurophilic granule-resident Ξ²-hexosaminidase A |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-9035982 | ACCEPT | Summary: Reactome TAS for lysosomal lumen localization (defective HEXB hyaluronan reaction context). Reason: Correct core compartment; redundant with other lysosomal lumen annotations. Supporting Evidence: file:human/HEXB/HEXB-uniprot.txt SUBCELLULAR LOCATION: Lysosome |
| GO:0008375 acetylglucosaminyltransferase activity | IDA PMID:25645918 Human neutrophils secrete bioactive paucimannosidic proteins... | MARK AS OVER ANNOTATED | Summary: IDA from the neutrophil paucimannosidic-protein study. The described activity is N-glycan trimming (hydrolysis) generating paucimannose, i.e. glycosidase (hydrolase) activity, not a glycosyltransferase reaction. The transferase term mis-types the enzyme's exo-glycosidase mechanism. Reason: HEXB is a GH20 hydrolase (EC 3.2.1.52); transferase activity contradicts the established mechanism/fold. Per policy the experimental annotation is flagged as over-annotation rather than removed; the correct MF is GO:0004563. Supporting Evidence: PMID:25645918 azurophilic granule-resident Ξ²-hexosaminidase A displayed the capacity to generate paucimannosidic N-glycans by trimming hybrid/complex type N-glycan intermediates |
| GO:0042582 azurophil granule | IDA PMID:25645918 Human neutrophils secrete bioactive paucimannosidic proteins... | KEEP AS NON CORE | Summary: Direct experimental localization of HEXB to human neutrophil azurophilic granules. Genuine non-core granule pool of the enzyme. Reason: Real, experimentally demonstrated granule localization, but peripheral to the core lysosomal catabolic function. Supporting Evidence: PMID:25645918 azurophilic granule-resident Ξ²-hexosaminidase A |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | MARK AS OVER ANNOTATED | Summary: High-throughput exosome proteomics (prostatic secretions). Reflects the secreted/exosomal pool of the lysosomal enzyme. Reason: Bulk-proteomics detection in exosomes is a common finding for lysosomal enzymes; not informative about core function. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: High-throughput NK-cell membrane proteomics. HEXB is a soluble lumenal hydrolase; detection in a membrane-enriched fraction likely reflects membrane-associated vesicle/granule co-purification rather than an intrinsic membrane location. Reason: Uninformative and potentially misleading generic membrane localization from a bulk proteomics dataset. |
| GO:0004563 beta-N-acetylhexosaminidase activity | TAS PMID:8663217 Identification of domains in human beta-hexosaminidase that ... | ACCEPT | Summary: TAS for the core catalytic activity from the domain/substrate-specificity study, which mapped the beta- and alpha-subunit active-site determinants. Reason: Correct core MF, supported by the study's characterization of subunit active sites. Supporting Evidence: PMID:8663217 The site on the beta-subunit primarily degrades neutral substrates, whereas the alpha-subunit site is, in addition, active against sulfated substrates |
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)