IDUA

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003940 L-iduronidase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of the defining catalytic activity of IDUA, L-iduronidase activity. This is the core molecular function of the gene and is concordant with direct experimental structural/biochemical evidence. Reason: L-iduronidase activity is the well-established core function of IDUA, confirmed by crystal structures and enzyme kinetics of the human enzyme. The IBA call is consistent with the manual experimental annotations. Supporting Evidence: PMID:24036510 IDUA participates in the stepwise degradation of the glycosaminoglycans (GAGs) heparan sulphate and dermatan sulphate, by removing a single α-L-iduronyl residue from the non-reducing ends of these complex polysaccharides. file:human/IDUA/IDUA-uniprot.txt RecName: Full=Alpha-L-iduronidase;
GO:0003940 L-iduronidase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (multi-method IEA) assignment of L-iduronidase activity, mapped in part from EC 3.2.1.76. Correct and identical to the experimentally supported core molecular function. Reason: Redundant with the experimentally supported GO:0003940 annotations; the EC 3.2.1.76 mapping is exactly the enzyme's activity. Supporting Evidence: file:human/IDUA/IDUA-uniprot.txt EC=3.2.1.76;
GO:0004553 hydrolase activity, hydrolyzing O-glycosyl compounds	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro-derived (IPR000514, Glyco_hydro_39) mapping to the general parent term for O-glycosyl hydrolases. Correct but less informative than the specific L-iduronidase activity term. Reason: IDUA is a glycoside hydrolase family 39 member and does hydrolyse O-glycosyl (alpha-L-iduronosidic) linkages, so the term is not wrong, but it is a broad grouping term subsumed by the specific GO:0003940 L-iduronidase activity. Kept as non-core rather than treated as the representative molecular function. Supporting Evidence: file:human/IDUA/IDUA-uniprot.txt Belongs to the glycosyl hydrolase 39 family.
GO:0005764 lysosome	IEA GO_REF:0000044	ACCEPT	Summary: UniProt Subcellular-Location keyword mapping placing IDUA in the lysosome. This is the correct and physiologically relevant compartment for the enzyme. Reason: IDUA is a mannose-6-phosphate-targeted lysosomal hydrolase; lysosomal localization is central to its function and is asserted by UniProt with literature support. Supporting Evidence: file:human/IDUA/IDUA-uniprot.txt SUBCELLULAR LOCATION: Lysosome
GO:0005975 carbohydrate metabolic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro-derived high-level biological-process term. IDUA does participate in carbohydrate metabolism, but this is a very broad grouping term subsumed by the specific glycosaminoglycan catabolic annotations. Reason: Not incorrect, but far too general; the informative processes are heparan sulfate and dermatan sulfate catabolism. Retained as non-core. Supporting Evidence: PMID:24036510 IDUA participates in the stepwise degradation of the glycosaminoglycans (GAGs) heparan sulphate and dermatan sulphate, by removing a single α-L-iduronyl residue from the non-reducing ends of these complex polysaccharides.
GO:0030200 heparan sulfate proteoglycan catabolic process	IEA GO_REF:0000117	ACCEPT	Summary: ARBA electronic assignment of heparan sulfate proteoglycan catabolism, one of the two core degradative pathways in which IDUA acts. Well supported by experimental and structural evidence. Reason: IDUA removes terminal alpha-L-iduronate from heparan sulfate during its stepwise lysosomal degradation; loss of IDUA blocks HS breakdown (HS accumulation in Idua-deficient mice). Supporting Evidence: PMID:24036510 IDUA participates in the stepwise degradation of the glycosaminoglycans (GAGs) heparan sulphate and dermatan sulphate, by removing a single α-L-iduronyl residue from the non-reducing ends of these complex polysaccharides. PMID:21873421 representing the terminal iduronic acid residue capping the non-reducing end of the HS chain, where no further degradation can occur in the absence of Idua.
GO:0030209 dermatan sulfate proteoglycan catabolic process	IEA GO_REF:0000117	ACCEPT	Summary: ARBA electronic assignment of dermatan sulfate proteoglycan catabolism, the second core degradative pathway of IDUA. Duplicated by an experimental IDA annotation below. Reason: IDUA hydrolyses the unsulfated alpha-L-iduronosidic linkages of dermatan sulfate (this is its defining EC 3.2.1.76 reaction); a core biological process. Supporting Evidence: file:human/IDUA/IDUA-uniprot.txt Hydrolysis of unsulfated alpha-L-iduronosidic linkages in PMID:24036510 IDUA participates in the stepwise degradation of the glycosaminoglycans (GAGs) heparan sulphate and dermatan sulphate, by removing a single α-L-iduronyl residue from the non-reducing ends of these complex polysaccharides.
GO:0030211 heparin proteoglycan catabolic process	IEA GO_REF:0000117	ACCEPT	Summary: ARBA electronic assignment of heparin proteoglycan catabolism. Heparin is a highly sulfated relative of heparan sulfate bearing the same alpha-L-iduronosidic linkages, on which IDUA acts. Supported experimentally by the Idua-knockout mouse (below) and retained consistent with that IMP. Reason: Heparin shares the alpha-L-iduronosidic linkages of heparan sulfate, and the Idua-deficient mouse demonstrates that terminal iduronate removal from these chains requires IDUA. Kept consistent with the IMP annotation to the same term. Supporting Evidence: PMID:21873421 representing the terminal iduronic acid residue capping the non-reducing end of the HS chain, where no further degradation can occur in the absence of Idua.
GO:0043202 lysosomal lumen	IEA GO_REF:0000117	ACCEPT	Summary: ARBA electronic assignment of lysosomal lumen localization. This is the precise compartment in which IDUA carries out GAG degradation and is well supported. Reason: IDUA is a soluble lysosomal hydrolase acting in the acidic lumen; the more specific lumen term is preferable to the generic lysosome term and is retained as a core localization. Supporting Evidence: file:human/IDUA/IDUA-uniprot.txt SUBCELLULAR LOCATION: Lysosome
GO:0005102 signaling receptor binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic annotation transferred from the rat ortholog (D3ZE16) via Ensembl Compara. There is no evidence that IDUA, a soluble lysosomal glycosidase, acts as a signaling receptor ligand. Reason: IDUA is a lysosomal hydrolase with no established signaling-ligand role; this is an uninformative binding term propagated electronically from an ortholog and is not supported by the human literature or structural/functional characterization. Supporting Evidence: file:human/IDUA/IDUA-uniprot.txt Lysosomal hydrolase responsible for the degradation of the
GO:0006027 glycosaminoglycan catabolic process	IEA GO_REF:0000107	ACCEPT	Summary: Ensembl-transferred annotation to the parent glycosaminoglycan catabolic process term. This correctly captures IDUA's role in GAG breakdown and is the immediate parent of the HS and DS catabolic annotations. Reason: IDUA is a bona fide GAG-degrading lysosomal exo-glycosidase; the term is correct, if broader than the HS/DS-specific terms. Supporting Evidence: PMID:24036510 IDUA participates in the stepwise degradation of the glycosaminoglycans (GAGs) heparan sulphate and dermatan sulphate, by removing a single α-L-iduronyl residue from the non-reducing ends of these complex polysaccharides.
GO:0030200 heparan sulfate proteoglycan catabolic process	TAS Reactome:R-HSA-2024096	ACCEPT	Summary: Reactome traceable-author annotation placing IDUA in the HS-GAG degradation pathway. Concordant with the experimentally supported role in heparan sulfate catabolism. Reason: Reactome curates IDUA as a step in lysosomal heparan sulfate degradation, consistent with the enzyme's characterized activity. Supporting Evidence: Reactome:R-HSA-1678716 The lysosomal enzyme alpha-L-iduronidase (IDUA) cleaves the terminal L-iduronic acid residue from either heparan sulfate or dermatan sulfate chains of proteoglycans
GO:0030209 dermatan sulfate proteoglycan catabolic process	TAS Reactome:R-HSA-1793186	ACCEPT	Summary: Reactome traceable-author annotation placing IDUA in dermatan sulfate degradation (hydrolysis of the unsulfated alpha-L-iduronosidic link in DS). Concordant with the enzyme's EC 3.2.1.76 reaction. Reason: Curated Reactome pathway step matching IDUA's defining catalytic reaction on dermatan sulfate. Supporting Evidence: Reactome:R-HSA-1793186 The lysosomal enzyme alpha-L-iduronidase (IDUA) hydrolyzes the nonreducing terminal iduronide glycosidic bond in heparan sulfate and dermatan sulfate
GO:0003940 L-iduronidase activity	TAS Reactome:R-HSA-1678716	ACCEPT	Summary: Reactome traceable-author assertion of L-iduronidase activity (cleavage of terminal L-iduronate from HS chains). Core molecular function. Reason: Restates the enzyme's defining catalytic activity within a curated reaction. Supporting Evidence: Reactome:R-HSA-1678716 The lysosomal enzyme alpha-L-iduronidase (IDUA) cleaves the terminal L-iduronic acid residue from either heparan sulfate or dermatan sulfate chains of proteoglycans
GO:0003940 L-iduronidase activity	TAS Reactome:R-HSA-1793186	ACCEPT	Summary: Reactome traceable-author assertion of L-iduronidase activity (hydrolysis of the unsulfated alpha-L-iduronosidic link in DS). Core molecular function. Reason: Restates the enzyme's defining catalytic activity within a curated dermatan sulfate reaction. Supporting Evidence: Reactome:R-HSA-1793186 The lysosomal enzyme alpha-L-iduronidase (IDUA) hydrolyzes the nonreducing terminal iduronide glycosidic bond in heparan sulfate and dermatan sulfate
GO:0003940 L-iduronidase activity	TAS Reactome:R-HSA-2090037	ACCEPT	Summary: Reactome traceable-author assertion of L-iduronidase activity within a heparan sulfate chain hydrolysis reaction. Core molecular function. Reason: Duplicate curated assertion of the enzyme's defining catalytic activity. Supporting Evidence: Reactome:R-HSA-1678716 The lysosomal enzyme alpha-L-iduronidase (IDUA) cleaves the terminal L-iduronic acid residue from either heparan sulfate or dermatan sulfate chains of proteoglycans
GO:0003940 L-iduronidase activity	TAS Reactome:R-HSA-2206299	ACCEPT	Summary: Reactome traceable-author assertion of L-iduronidase activity (associated with a defective-IDUA/disease reaction). Core molecular function. Reason: Duplicate curated assertion of the enzyme's defining catalytic activity in the MPS I disease context. Supporting Evidence: Reactome:R-HSA-1678716 The lysosomal enzyme alpha-L-iduronidase (IDUA) cleaves the terminal L-iduronic acid residue from either heparan sulfate or dermatan sulfate chains of proteoglycans
GO:0003940 L-iduronidase activity	TAS Reactome:R-HSA-9036037	ACCEPT	Summary: Reactome traceable-author assertion of L-iduronidase activity within a heparan-sulfate-chain reaction. Core molecular function. Reason: Duplicate curated assertion of the enzyme's defining catalytic activity. Supporting Evidence: Reactome:R-HSA-1678716 The lysosomal enzyme alpha-L-iduronidase (IDUA) cleaves the terminal L-iduronic acid residue from either heparan sulfate or dermatan sulfate chains of proteoglycans
GO:0003940 L-iduronidase activity	TAS Reactome:R-HSA-9036041	ACCEPT	Summary: Reactome traceable-author assertion of L-iduronidase activity (associated with the defective-IDUA dermatan sulfate reaction). Core molecular function. Reason: Duplicate curated assertion of the enzyme's defining catalytic activity. Supporting Evidence: Reactome:R-HSA-1793186 The lysosomal enzyme alpha-L-iduronidase (IDUA) hydrolyzes the nonreducing terminal iduronide glycosidic bond in heparan sulfate and dermatan sulfate
GO:0003940 L-iduronidase activity	EXP PMID:23959878 Human α-L-iduronidase uses its own N-glycan as a substrate-b...	ACCEPT	Summary: Experimental (EXP) assignment of L-iduronidase activity from a structural/kinetic study of human IDUA that determined the crystal structure with iduronate bound and characterized catalysis, including the role of the Asn372 N-glycan. Reason: Direct experimental determination of the enzyme's catalytic activity in humans; this is the strongest evidence for the core molecular function. Supporting Evidence: PMID:23959878 human α-l-iduronidase (hIDUA), of which a dysfunction causes accumulation of dermatan/heparan sulfate leading to mucopolysaccharidosis type I, uses its own N-glycan as a substrate binding and catalytic module.
GO:0030211 heparin proteoglycan catabolic process	IMP PMID:21873421 Mucopolysaccharidosis type I, unique structure of accumulate...	ACCEPT	Summary: IMP annotation from a murine Idua-knockout study showing accumulation of heparan sulfate with a terminal iduronate-capped disaccharide, demonstrating that Idua is required for degradation of iduronate-containing heparan sulfate/heparin chains. Reason: Loss of Idua in mice blocks removal of terminal iduronate from HS/heparin, causing pathological accumulation; strong genetic evidence for IDUA's role in catabolism of iduronate-bearing HS/heparin. Retained (heparin is closely related to HS, and the phenotype is directly demonstrated). Supporting Evidence: PMID:21873421 representing the terminal iduronic acid residue capping the non-reducing end of the HS chain, where no further degradation can occur in the absence of Idua.
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	KEEP AS NON CORE	Summary: High-throughput mass-spectrometry detection of IDUA among ~900 proteins in exosomes isolated from expressed prostatic secretions in urine. This reflects presence of the secretory/lysosomal protein in extracellular vesicles rather than a distinct functional site. Reason: A proteomics survey placed IDUA in urinary exosomes; lysosomal/secretory hydrolases are commonly recovered in extracellular vesicles. This is a valid detection but not the enzyme's primary functional location, so it is retained as non-core. Supporting Evidence: PMID:23533145 In pooled EPS-urine exosome samples, ~900 proteins were detected.
GO:0003940 L-iduronidase activity	IDA PMID:24036510 Insights into mucopolysaccharidosis I from the structure and...	ACCEPT	Summary: Direct assay (IDA) of L-iduronidase activity from the human IDUA crystal-structure and enzymology study that captured Michaelis and glycosyl-enzyme intermediate complexes with iduronate analogs and defined the retaining double-displacement mechanism. Reason: Definitive experimental characterization of the enzyme's catalytic activity and mechanism; the primary evidence for the core molecular function. Supporting Evidence: PMID:24036510 IDUA is an α-retaining glycoside hydrolase with strict substrate specificity for L-IdoA
GO:0030209 dermatan sulfate proteoglycan catabolic process	IDA PMID:24036510 Insights into mucopolysaccharidosis I from the structure and...	ACCEPT	Summary: IDA annotation of dermatan sulfate proteoglycan catabolism from the structural and enzymological study showing IDUA removes alpha-L-iduronate from the non-reducing ends of dermatan sulfate (and heparan sulfate). Reason: Experimentally grounded in IDUA's demonstrated action on dermatan sulfate; a core biological process. Supporting Evidence: PMID:24036510 IDUA participates in the stepwise degradation of the glycosaminoglycans (GAGs) heparan sulphate and dermatan sulphate, by removing a single α-L-iduronyl residue from the non-reducing ends of these complex polysaccharides.
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-2206299	ACCEPT	Summary: Reactome traceable-author localization of IDUA to the lysosomal lumen (disease reaction context). Correct core compartment. Reason: Consistent with IDUA being a soluble lysosomal-lumen hydrolase. Supporting Evidence: Reactome:R-HSA-1678716 The lysosomal enzyme alpha-L-iduronidase (IDUA)
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-9036037	ACCEPT	Summary: Reactome traceable-author localization of IDUA to the lysosomal lumen (heparan sulfate reaction context). Correct core compartment. Reason: Consistent with IDUA being a soluble lysosomal-lumen hydrolase. Supporting Evidence: Reactome:R-HSA-1678716 The lysosomal enzyme alpha-L-iduronidase (IDUA)
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-9036041	ACCEPT	Summary: Reactome traceable-author localization of IDUA to the lysosomal lumen (dermatan sulfate reaction context). Correct core compartment. Reason: Consistent with IDUA being a soluble lysosomal-lumen hydrolase. Supporting Evidence: Reactome:R-HSA-1793186 The lysosomal enzyme alpha-L-iduronidase (IDUA)
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-1678716	ACCEPT	Summary: Reactome traceable-author localization of IDUA to the lysosomal lumen (HS chain cleavage reaction). Correct core compartment. Reason: Consistent with IDUA being a soluble lysosomal-lumen hydrolase. Supporting Evidence: Reactome:R-HSA-1678716 The lysosomal enzyme alpha-L-iduronidase (IDUA)
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-1793186	ACCEPT	Summary: Reactome traceable-author localization of IDUA to the lysosomal lumen (DS link hydrolysis reaction). Correct core compartment. Reason: Consistent with IDUA being a soluble lysosomal-lumen hydrolase. Supporting Evidence: Reactome:R-HSA-1793186 The lysosomal enzyme alpha-L-iduronidase (IDUA)
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-2090037	ACCEPT	Summary: Reactome traceable-author localization of IDUA to the lysosomal lumen (heparan sulfate chain reaction). Correct core compartment. Reason: Consistent with IDUA being a soluble lysosomal-lumen hydrolase. Supporting Evidence: Reactome:R-HSA-1678716 The lysosomal enzyme alpha-L-iduronidase (IDUA)
GO:0003940 L-iduronidase activity	TAS PMID:2470345 Immunopurification and characterization of human alpha-L-idu...	ACCEPT	Summary: Traceable-author annotation of L-iduronidase activity from the immunopurification and biochemical characterization of the human liver enzyme, which measured its activity toward heparan sulfate- and dermatan sulfate-derived substrates. Reason: An early experimental characterization establishing the enzyme's catalytic activity on GAG-derived substrates; core molecular function. Supporting Evidence: PMID:2470345 activities towards disaccharide substrates derived from two glycosaminoglycan sources, heparan sulphate and dermatan sulphate.
GO:0005984 disaccharide metabolic process	TAS PMID:2470345 Immunopurification and characterization of human alpha-L-idu...	MARK AS OVER ANNOTATED	Summary: Traceable-author annotation of disaccharide metabolic process, derived from an in vitro assay in which the two enzyme forms were tested against GAG-derived disaccharide substrates. IDUA's physiological substrates are polymeric heparan sulfate and dermatan sulfate, not free disaccharides. Reason: The disaccharide substrates were an experimental convenience for measuring activity; the in vivo role is exolytic removal of terminal iduronate from GAG polymers, captured by the glycosaminoglycan/HS/DS catabolic terms. This general metabolic-process term overstates a biological role in disaccharide metabolism. Supporting Evidence: PMID:2470345 activities towards disaccharide substrates derived from two glycosaminoglycan sources, heparan sulphate and dermatan sulphate. PMID:24036510 by removing a single α-L-iduronyl residue from the non-reducing ends of these complex polysaccharides.

Gene Description

Existing Annotations Review

Core Functions

Hydrolysis of terminal, non-reducing alpha-L-iduronic acid residues from the glycosaminoglycans heparan sulfate and dermatan sulfate in the lysosomal lumen, a required exolytic step of lysosomal glycosaminoglycan catabolism.

References

📚 Additional Documentation

Notes

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