Iduronate Sulfatase Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Iduronate sulfatase (IDS) is a lysosomal sulfatase encoded by the IDS gene. It catalyzes the removal of sulfate groups from iduronic acid residues in glycosaminoglycans (heparan sulfate and dermatan sulfate). Deficiency causes Mucopolysaccharidosis type II (Hunter syndrome), an X-linked lysosomal storage disorder.
| Property |
Value |
| Protein Name |
Iduronate sulfatase |
| Gene |
IDS |
| UniProt ID |
P22304 |
| Molecular Weight |
56 kDa (precursor) |
| Subcellular Localization |
Lysosome |
| Protein Family |
Sulfatase family |
Iduronate sulfatase:
- Type I transmembrane protein: Contains signal peptide and transmembrane domain
- Propeptide: Cleaved in the Golgi
- Formylglycine (FGly): Critical post-translational modification at active site
- N-glycosylation: Important for stability and lysosomal targeting
The enzyme removes sulfate groups from:
- Heparan sulfate: Component of brain extracellular matrix
- Dermatan sulfate: Found in connective tissue and brain
This desulfation is essential for complete lysosomal degradation of GAGs.
Accumulation of partially degraded GAGs causes:
- Lysosomal storage: Swollen, dysfunctional lysosomes
- Neuronal dysfunction: Impaired cellular processes
- White matter disease: Demyelination
- Cognitive decline: Progressive intellectual disability
- Behavioral problems: Autism-like behaviors, aggression
- Lysosomal dysfunction
- Impaired autophagy
- Oxidative stress
- Neuroinflammation
- Synaptic dysfunction
- Enzyme replacement therapy (Idursulfase/Elaprase): FDA-approved, does not cross BBB
- Idursulfase beta (idursulfase-beta): Improved CNS penetration
- Gene therapy: AAV9-IDS in clinical trials
- Substrate reduction therapy: Under development
- Intrathecal enzyme therapy: For CNS disease
- GAG levels: Elevated heparan sulfate in urine
- Iduronate sulfatase activity: Absent or reduced in patient cells
- CSF heparan sulfate: Elevated in patients with CNS involvement
[1] Scarcy M, et al. (2005). Iduronate-2-sulfatase gene mutations in patients with Hunter syndrome. Human Mutation.
[2] Muenzer J, et al. (2009). Idursulfase for the treatment of Hunter syndrome. Genetics in Medicine.
The study of Iduronate Sulfatase Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- [1] Platt FM, et al. "Lysosomal storage disorders." Nat Rev Dis Primers. 2024;10(1):50. PMID:38693102
- [2] Walkley SU, et al. "Lysosomal storage diseases: Pathways and therapeutic strategies." Nat Rev Neurol. 2023;19(12):715-734. PMID:37993567
- [3] Parenti G, et al. "Lysosomal storage diseases: From pathophysiology to therapy." Adv Pharmacol. 2023;97:1-30. PMID:37633281
- [4] Sun A. "Lysosomal storage disease overview." J Biochem. 2022;171(3):287-305. PMID:35040912
- [5] Wang RY, et al. "Enzyme replacement therapy for mucopolysaccharidoses." Mol Genet Metab. 2021;133(2):105-121. PMID:33865689
- Martin R, Beck M, Eng C, et al. Recognition and diagnosis of mucopolysaccharidosis type II (Hunter syndrome). Pediatrics. 2008;121(2):e377-e386. PMID:18245410
- Scarpa M, Almassy Z, Beck M, et al. Hunter Syndrome: a European consensus document on mucopolysaccharidosis type II. Eur J Med Genet. 2011;54(3):230-235. PMID:21215957
- Muenzer J, Gucsavas-Calikoglu M. Exploring the heterogeneity of MPS II. J Inherit Metab Dis. 2007;30(4):511-519. PMID:17598256
- Wraith JE, Scarpa M, Beck M, et al. Mucopolysaccharidosis type II: a clinical review. J Inherit Metab Dis. 2008;31(2):197-207. PMID:18297388
- Burton BK, Giugliani R. Diagnosing hunter syndrome in clinical practice. Mol Genet Metab. 2012;107(1-2):5-9. PMID:22938858