NEU1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004308 exo-alpha-sialidase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) propagation of the core, experimentally established exo-alpha-sialidase molecular function. Correct and central to NEU1.
GO:0005737 cytoplasm	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: IBA propagation of a broad "cytoplasm" location. NEU1 is a lysosomal and membrane sialidase; the cytosolic mammalian sialidase is the paralog NEU2. Although "cytoplasm" technically subsumes the lysosome, it is uninformative and potentially misleading here relative to the specific lysosomal terms already annotated. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH COMPARTMENT OR COMPLEX MISMATCH
GO:0005764 lysosome	IBA GO_REF:0000033	ACCEPT	Summary: IBA support for the lysosome as the site where NEU1 acts. Well corroborated by direct human evidence (IDA/IMP) and UniProt. Core location.
GO:0016020 membrane	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Generic "membrane" from IBA. NEU1 does associate with the lysosomal and plasma membranes, but this term is uninformatively broad; the specific lysosomal-membrane and plasma-membrane annotations capture it better. Retain as non-core.
GO:0009313 oligosaccharide catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: IBA support for NEU1's role in oligosaccharide catabolism, consistent with its removal of terminal sialic acid from oligosaccharide chains. Core biological process.
GO:0006689 ganglioside catabolic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: NEU1 can desialylate glycolipids/gangliosides (e.g. GM3 to lactosylceramide) within the lysosomal multienzyme complex, so this is not incorrect. However, in vivo ganglioside sialidase activity is predominantly attributed to the paralogs NEU3/NEU4; for NEU1 this is a peripheral rather than the defining catabolic role.
GO:0004308 exo-alpha-sialidase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (ARBA/InterPro/EC) assertion of the core exo-alpha-sialidase activity. Concordant with the experimental evidence.
GO:0005765 lysosomal membrane	IEA GO_REF:0000044	ACCEPT	Summary: Subcellular-location mapping to lysosomal membrane, matching UniProt (Lysosome membrane; peripheral membrane protein, lumenal side) and direct evidence (PMID:27917893). Accept.
GO:0005886 plasma membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Plasma-membrane location from UniProt SubCell mapping; independently supported by direct evidence (PMID:27917893) and cell-surface desialylation biology. Real but secondary to the core lysosomal catabolic role.
GO:0043202 lysosomal lumen	IEA GO_REF:0000044	ACCEPT	Summary: Lysosomal lumen from SubCell mapping, matching UniProt (Lysosome lumen) and the soluble luminal form of NEU1 within the multienzyme complex. Core location.
GO:0005515 protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" IPI from a high-throughput disease-variant interactome (Y2H). Uninformative as a molecular function and it does not capture the biologically meaningful CTSA/GLB1 multienzyme-complex interaction. Over-annotation; retained per policy (never remove an IPI).
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" IPI from the HuRI systematic binary interactome; the ~18 partners are largely unrelated ER/Golgi/membrane proteins with no established NEU1 biology, and the functionally important CTSA/GLB1 interactions are absent. Term is uninformative for molecular function. Over-annotation; retained per policy.
GO:0004308 exo-alpha-sialidase activity	TAS Reactome:R-HSA-4084999	ACCEPT	Summary: Reactome TAS for NEU1 hydrolysing Neu5Ac from glycoconjugates in the lysosomal multienzyme complex. Correct core molecular function.
GO:0004308 exo-alpha-sialidase activity	IMP PMID:25153125 In silico identification of new putative pathogenic variants...	ACCEPT	Summary: Direct functional (IMP) evidence: sialidosis-candidate variants (V217A, D234N) significantly reduce NEU1 sialidase activity, confirming exo-alpha-sialidase activity. Core molecular function. Supporting Evidence: PMID:25153125 remove the terminal sialic acid from oligosaccharide chains
GO:0005764 lysosome	IMP PMID:25153125 In silico identification of new putative pathogenic variants...	ACCEPT	Summary: Direct evidence that NEU1 acts in the lysosome; the study shows correct (or, for mutants, altered) lysosomal localization dependent on PPCA/CTSA. Core location. Supporting Evidence: PMID:25153125 essential for the correct
GO:0005765 lysosomal membrane	IDA PMID:27917893 New Insights into Molecular Organization of Human Neuraminid...	ACCEPT	Summary: Direct (IDA) evidence for NEU1 at the lysosomal membrane. Consistent with UniProt. Accept (note the transmembrane-topology model of this paper was later disputed by the crystal structure, but membrane association of NEU1 is well supported). Supporting Evidence: PMID:27917893 Neuraminidase 1 (NEU1) is a lysosomal sialidase catalyzing the removal of
GO:0005886 plasma membrane	IDA PMID:27917893 New Insights into Molecular Organization of Human Neuraminid...	KEEP AS NON CORE	Summary: Direct evidence for a plasma-membrane pool of NEU1 that desialylates cell-surface receptors. Biologically real but non-core relative to the lysosomal catabolic function. Supporting Evidence: PMID:27917893 At the plasma membrane, NEU1 has been shown to be required for signal transduction and elastogenesis through the elastin receptor complex
GO:0004308 exo-alpha-sialidase activity	IDA PMID:37205763 Structure of the immunoregulatory sialidase NEU1.	ACCEPT	Summary: Direct (IDA) enzymatic evidence: purified human NEU1 hydrolyses the sialidase substrate 4MU-NANA (CTSA-dependent, ~150-fold activation), and active-site mutants abolish activity. Definitive core molecular function. Supporting Evidence: PMID:37205763 NEU1 removes terminal sialic acid residues from glycans on lysosomal degradation products and on cell surface proteins
GO:0030054 cell junction	IDA GO_REF:0000052	MARK AS OVER ANNOTATED	Summary: Single HPA immunofluorescence localization to cell junction. Not corroborated by other data as a functional NEU1 site and inconsistent with the well-established lysosomal/plasma-membrane biology. Likely over-annotation from a single imaging screen.
GO:0005576 extracellular region	TAS Reactome:R-HSA-6798749	KEEP AS NON CORE	Summary: Reactome TAS reflecting release of NEU1 from neutrophil specific granules on degranulation (exocytosis of specific granule lumen proteins). A genuine but peripheral, cell-type-specific localization, not the core catabolic site.
GO:0035580 specific granule lumen	TAS Reactome:R-HSA-6798749	KEEP AS NON CORE	Summary: Reactome TAS placing NEU1 in the neutrophil specific-granule lumen (as degranulation cargo). Real but peripheral to the core lysosomal function.
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-4341669	ACCEPT	Summary: Reactome TAS for the luminal lysosomal localization (in the context of the "defective NEU1" sialidosis reaction). Consistent with the core luminal location.
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	MARK AS OVER ANNOTATED	Summary: High-throughput proteomic detection of NEU1 in prostatic-secretion exosomes. Typical HDA over-detection of an abundant lysosomal/secreted protein; not evidence of a functional exosomal site.
GO:0004308 exo-alpha-sialidase activity	IDA PMID:8985184 Characterization of human lysosomal neuraminidase defines th...	ACCEPT	Summary: Original direct characterization: transient expression of NEU1 restored neuraminidase (exo-alpha-sialidase) activity in deficient fibroblasts in a PPCA-dependent manner. Foundational evidence for the core molecular function. Supporting Evidence: PMID:8985184 restored neuraminidase activity in a
GO:0005764 lysosome	IDA PMID:8985184 Characterization of human lysosomal neuraminidase defines th...	ACCEPT	Summary: Direct evidence that expressed NEU1 is compartmentalized in lysosomes. Core location. Supporting Evidence: PMID:8985184 the enzyme is compartmentalized in lysosomes
GO:0009313 oligosaccharide catabolic process	IMP PMID:8985184 Characterization of human lysosomal neuraminidase defines th...	ACCEPT	Summary: Direct (IMP) evidence tying NEU1 to sialidase-dependent catabolism of sialoglycoconjugates; inactivating sialidosis mutations abolish activity. Supports the core catabolic biological process. Supporting Evidence: PMID:8985184 occurs in complex with beta-galactosidase and
GO:0070062 extracellular exosome	HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid...	MARK AS OVER ANNOTATED	Summary: High-throughput proteomic detection of NEU1 in parotid-gland exosomes. As with the other exosome HDA annotation, this reflects proteomic over-detection rather than a functional site.
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-1605724	ACCEPT	Summary: Reactome TAS for the luminal lysosomal localization in the context of NEU1/NEU4 hydrolysis of ganglioside GM3. Consistent with the core luminal location.
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-4084999	ACCEPT	Summary: Reactome TAS placing NEU1 in the lysosomal lumen where it hydrolyses Neu5Ac from glycoconjugates in the multienzyme complex. Core location (duplicates the other lysosomal-lumen annotations).
GO:0006516 glycoprotein catabolic process	IDA PMID:37205763 Structure of the immunoregulatory sialidase NEU1.	NEW	Summary: Proposed new annotation. NEU1 desialylates glycoproteins and glycopeptides, performing the committed step of their lysosomal catabolism; this more precisely captures the substrate class than the generic oligosaccharide term. Not currently in GOA. Supporting Evidence: PMID:37205763 NEU1 removes terminal sialic acid residues from glycans on lysosomal degradation products and on cell surface proteins
GO:0019262 N-acetylneuraminate catabolic process	IDA PMID:37205763 Structure of the immunoregulatory sialidase NEU1.	NEW	Summary: Proposed new annotation. Release of N-acetylneuraminate (sialic acid) from sialoconjugates by NEU1 is the committed, rate-limiting step initiating its catabolism. Not currently in GOA. Supporting Evidence: PMID:37205763 NEU1 removes terminal sialic acid residues from glycans on lysosomal degradation products and on cell surface proteins

Gene Description

Existing Annotations Review

Core Functions

References

📚 Additional Documentation

Notes

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