SGSH

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005764 lysosome	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred lysosomal localisation, consistent with SGSH's site of action in heparan sulfate degradation and with direct experimental localisation. Reason: SGSH is a lysosomal sulfatase; lysosomal localisation is directly demonstrated experimentally (PMID:15146460) and stated by UniProt, so the IBA is well supported and represents a core aspect of the gene product. Supporting Evidence: file:human/SGSH/SGSH-uniprot.txt SUBCELLULAR LOCATION: Lysosome
GO:0016250 N-sulfoglucosamine sulfohydrolase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred N-sulfoglucosamine sulfohydrolase activity, the defining molecular function of SGSH (EC 3.10.1.1). Reason: This is the exact molecular function of SGSH, independently supported by direct enzyme assays and structural work. The IBA correctly captures the core catalytic activity. Supporting Evidence: PMID:24816101 SGSH belongs to the sulfatase family
GO:0030200 heparan sulfate proteoglycan catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred involvement in heparan sulfate catabolism, the specific pathway to which SGSH's N-sulfatase activity contributes. Reason: SGSH removes N-sulfate from terminal N-sulfoglucosamine residues during exolytic breakdown of the heparan sulfate chain; loss of activity causes lysosomal HS accumulation (MPS IIIA). This HS-specific catabolic term is the most informative biological process. Supporting Evidence: PMID:24816101 catalyses the cleavage of N-linked sulfate groups from the GAGs heparan sulfate and heparin PMID:7493035 lysosomal degradation of heparan sulphate
GO:0006027 glycosaminoglycan catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred involvement in glycosaminoglycan catabolism (the parent process of heparan sulfate degradation). Reason: Correct but more general than the heparan-sulfate-specific term GO:0030200; both are biologically accurate. Retained as a valid grouping annotation for the GAG catabolic role. Supporting Evidence: PMID:24816101 catalyses the cleavage of N-linked sulfate groups from the GAGs heparan sulfate and heparin
GO:0005764 lysosome	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation to lysosome from the UniProt subcellular-location mapping (SL-0158), consistent with experimental data. Reason: The SubCell-derived IEA agrees with the curated UniProt location and the IDA evidence; correct and non-redundant electronic support for lysosomal localisation. Supporting Evidence: file:human/SGSH/SGSH-uniprot.txt SUBCELLULAR LOCATION: Lysosome
GO:0016250 N-sulfoglucosamine sulfohydrolase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation of the N-sulfoglucosamine sulfohydrolase activity via the EC 3.10.1.1 / RHEA:17881 reaction mapping. Reason: The EC/RHEA mapping correctly assigns SGSH's characterized catalytic reaction (N-sulfo-D-glucosamine + H2O = D-glucosamine + sulfate); accurate electronic support that matches the experimental molecular function. Supporting Evidence: file:human/SGSH/SGSH-uniprot.txt N-sulfo-D-glucosamine + H2O = D-glucosamine + sulfate
GO:0005515 protein binding	IPI PMID:15962010 Sulphatase activities are regulated by the interaction of su...	MARK AS OVER ANNOTATED	Summary: Bare protein-binding IPI capturing the physical association of SGSH with the sulphatase-modifying factor machinery (SUMF1, UniProtKB:Q8NBK3). Reason: "protein binding" is uninformative and is not retained as a core function. The underlying SGSH-SUMF1 interaction is biologically real and meaningful (SUMF1/FGE generates the catalytic formylglycine required for SGSH activity), but a specific molecular function or biological process term would be needed to convey it; the bare term is over-annotation. Supporting Evidence: PMID:15962010 SUMF2 was able to stably associate with IDS and with SGSH alone or in a complex with SUMF1
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Bare protein-binding IPI from a high-throughput AP-MS interactome (BioPlex), interactor SUMF1 (UniProtKB:Q8NBK3). Reason: Uninformative molecular function term derived from a proteome-scale interaction screen. Consistent with the SGSH-SUMF1 relationship but conveys no specific function; not a core annotation. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: Bare protein-binding IPI from a multimodal cell-map interactome resource, interactor SUMF1 (UniProtKB:Q8NBK3). Reason: Uninformative "protein binding" term from a large-scale mapping study; not retained as a core function for the same reasons as the other protein-binding IPIs. Supporting Evidence: PMID:40205054 Multimodal cell maps as a foundation for structural and functional genomics.
GO:0016250 N-sulfoglucosamine sulfohydrolase activity	EXP PMID:24816101 Structure of sulfamidase provides insight into the molecular...	ACCEPT	Summary: Experimentally supported N-sulfoglucosamine sulfohydrolase activity from the SGSH crystal structure and accompanying enzymatic characterization. Reason: The structural/biochemical study confirms SGSH as an N-sulfatase that cleaves N-linked sulfate from heparan sulfate/heparin via a catalytic formylglycine; this is the core molecular function. Supporting Evidence: PMID:24816101 catalyses the cleavage of N-linked sulfate groups from the GAGs heparan sulfate and heparin PMID:24816101 The leading cysteine is post-translationally converted to a formylglycine (FGly) residue, which is crucial for the catalytic process
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-2263444	ACCEPT	Summary: Reactome-asserted lysosomal lumen localisation for the mature SGSH enzyme. Reason: SGSH is a soluble lysosomal enzyme acting in the lysosomal lumen; the more specific lumen term is consistent with experimental lysosomal localisation and the site of HS degradation. Supporting Evidence: file:human/SGSH/SGSH-uniprot.txt SUBCELLULAR LOCATION: Lysosome
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-9036050	ACCEPT	Summary: Reactome-asserted lysosomal lumen localisation (duplicate assertion from a distinct Reactome reaction). Reason: Consistent with experimental lysosomal localisation and SGSH's luminal site of action; duplicate lumen annotations are acceptable. Supporting Evidence: file:human/SGSH/SGSH-uniprot.txt SUBCELLULAR LOCATION: Lysosome
GO:0005764 lysosome	IDA PMID:15146460 Transport, enzymatic activity, and stability of mutant sulfa...	ACCEPT	Summary: Direct experimental demonstration of lysosomal localisation of SGSH (immunofluorescence / cellular expression studies). Reason: Primary experimental evidence for lysosomal localisation of the mature enzyme; this is a core cellular-component annotation for SGSH. Supporting Evidence: PMID:15146460 autosomal recessive lysosomal file:human/SGSH/SGSH-uniprot.txt SUBCELLULAR LOCATION: Lysosome
GO:0006027 glycosaminoglycan catabolic process	IDA PMID:15146460 Transport, enzymatic activity, and stability of mutant sulfa...	ACCEPT	Summary: Direct experimental evidence that SGSH participates in glycosaminoglycan (heparan sulfate) catabolism; loss of activity causes lysosomal HS accumulation. Reason: SGSH's N-sulfatase step is required for heparan sulfate breakdown; mutant expression studies tie loss of activity to the MPS IIIA HS-storage phenotype, supporting the GAG catabolic role. Supporting Evidence: PMID:15146460 storage disease caused by mutations in the N-sulfoglucosamine sulfohydrolase
GO:0006027 glycosaminoglycan catabolic process	IDA PMID:7493035 Cloning of the sulphamidase gene and identification of mutat...	ACCEPT	Summary: Direct experimental evidence (original cloning/characterization) placing SGSH in the lysosomal degradation of heparan sulphate, a glycosaminoglycan. Reason: The founding study identifies sulphamidase (EC 3.10.1.1) as an enzyme of lysosomal heparan sulphate degradation whose deficiency causes Sanfilippo A; supports the GAG catabolic annotation. Supporting Evidence: PMID:7493035 lysosomal degradation of heparan sulphate
GO:0016250 N-sulfoglucosamine sulfohydrolase activity	IDA PMID:15146460 Transport, enzymatic activity, and stability of mutant sulfa...	ACCEPT	Summary: Direct assay of N-sulfoglucosamine sulfohydrolase (sulfamidase) activity of recombinant wild-type and mutant SGSH. Reason: Enzyme-activity measurements on expressed SGSH confirm the N-sulfoglucosamine sulfohydrolase molecular function; this is the core catalytic activity. Supporting Evidence: PMID:15146460 enzymatically inactive with the exception of c.318C>A (p.Ser106Arg), which
GO:0016250 N-sulfoglucosamine sulfohydrolase activity	IDA PMID:7493035 Cloning of the sulphamidase gene and identification of mutat...	ACCEPT	Summary: Direct experimental identification of sulphamidase (EC 3.10.1.1) enzymatic activity from the cloned SGSH cDNA. Reason: The original characterization established SGSH/sulphamidase enzymatic activity (EC 3.10.1.1); direct support for the core N-sulfoglucosamine sulfohydrolase molecular function. Supporting Evidence: PMID:7493035 sulphamidase (EC 3.10.1.1)
GO:0030200 heparan sulfate proteoglycan catabolic process	IMP PMID:15146460 Transport, enzymatic activity, and stability of mutant sulfa...	ACCEPT	Summary: Mutation-based (IMP) evidence that SGSH function is required for heparan sulfate catabolism; pathogenic SGSH variants abolish activity and cause HS accumulation in MPS IIIA. Reason: Loss-of-function SGSH mutants are enzymatically inactive and lead to lysosomal heparan sulfate storage, directly implicating SGSH in the heparan sulfate catabolic process. This HS-specific term is the most informative BP for SGSH. Supporting Evidence: PMID:15146460 all the mutants were PMID:15146460 storage disease caused by mutations in the N-sulfoglucosamine sulfohydrolase
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	MARK AS OVER ANNOTATED	Summary: SGSH detected by high-throughput proteomics in exosomes from urinary prostatic secretions. Reason: Detection in an exosome proteome reflects secretion/vesicular trafficking of a soluble lysosomal enzyme rather than its functional compartment. SGSH acts in the lysosomal lumen; the exosome location is not a core annotation and is treated as over-annotation. Supporting Evidence: PMID:23533145 exosomes isolated from expressed prostatic
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-1678708	ACCEPT	Summary: Reactome-asserted lysosomal lumen localisation (from the HS-GAG degradation pathway). Reason: Consistent with SGSH being a soluble luminal lysosomal enzyme acting in heparan sulfate degradation; agrees with the experimental lysosomal localisation. Supporting Evidence: file:human/SGSH/SGSH-uniprot.txt SUBCELLULAR LOCATION: Lysosome
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-2090043	ACCEPT	Summary: Reactome-asserted lysosomal lumen localisation (duplicate assertion from a distinct Reactome reaction). Reason: Duplicate luminal localisation consistent with experimental lysosomal localisation and SGSH's site of action. Supporting Evidence: file:human/SGSH/SGSH-uniprot.txt SUBCELLULAR LOCATION: Lysosome

Gene Description

Existing Annotations Review

Core Functions

References

📚 Additional Documentation

Notes

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