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[Biochemistry](https://durgical.com/en/biochemistry/) · Enzyme

# Iduronate 2-sulfatase (I2S)

Iduronate 2-sulfatase strips the sulfate off iduronic acid in dermatan and heparan sulfate. Its loss causes Hunter syndrome (MPS II).

Updated 2026-11-01

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## Key facts

- It removes the 2-sulfate from α-L-iduronic acid at the end of dermatan sulfate and heparan sulfate; only then can α-L-iduronidase cut the sugar off.
- IDS gene on Xq28: MPS II (Hunter) is the only X-linked mucopolysaccharidosis, so it affects almost only boys.
- Like every sulfatase it needs a formylglycine in its active site, made from a cysteine by the formylglycine-generating enzyme (SUMF1); without SUMF1 all sulfatases fail (multiple sulfatase deficiency).
- One Ca²⁺ ion sits next to the formylglycine; the 3D model centres the active site on that calcium (PDB 5FQL, human enzyme).

**Also called**
I2S, IDS

**EC number**
[3.1.6.13](https://www.enzyme-database.org/query.php?ec=3.1.6.13)

**Genes**
IDS

**Structure (PDB)**
[5FQL](https://www.rcsb.org/structure/5FQL)

## Regulation

- Works at the acid pH of the lysosome.
- Made as a larger precursor and cut by proteolysis into its mature, active chains.
- Reaches the lysosome tagged with mannose 6-phosphate; secreted enzyme can be taken up by neighbouring cells (cross-correction).

## Inhibitors and toxins

- No inhibitor is used in medicine; the clinically relevant molecule is the recombinant enzyme given as replacement therapy.

## Clinical notes

- Hunter syndrome: coarse features, hepatosplenomegaly, stiff joints, valve disease and airway obstruction, with clear corneas (unlike Hurler).
- Diagnosis: raised urine dermatan and heparan sulfate, low I2S activity with another sulfatase normal (to exclude multiple sulfatase deficiency), and IDS gene testing.
- Intravenous enzyme replacement improves organs, breathing and movement but does not cross the blood–brain barrier.

## Related conditions

- [Hunter syndrome (mucopolysaccharidosis type II)](https://durgical.com/en/conditions/hunter-syndrome/)
- [Hurler syndrome (mucopolysaccharidosis type I)](https://durgical.com/en/conditions/hurler-syndrome/)

## Related

- [α-L-Iduronidase](https://durgical.com/en/biochemistry/enzymes/l-iduronidase/)
- [Glycosaminoglycans (mucopolysaccharides)](https://durgical.com/en/biochemistry/topics/glycosaminoglycans/)
- [Lysosomal storage diseases](https://durgical.com/en/biochemistry/topics/lysosomal-storage-diseases/)
- [Mannose 6-phosphate tagging (sending enzymes to the lysosome)](https://durgical.com/en/biochemistry/topics/mannose-6-phosphate-tagging/)
- [Arylsulfatase A (ARSA)](https://durgical.com/en/biochemistry/enzymes/arylsulfatase-a/)

## Test yourself

Think of the answer, then tap the question to see it.

## Which enzyme acts right after iduronate 2-sulfatase on dermatan sulfate?

α-L-Iduronidase, which removes the now unsulfated iduronic acid; it is the enzyme missing in Hurler syndrome.

## Why does Hunter syndrome affect almost only males?

The IDS gene is on the X chromosome, so a boy with one altered copy has no working enzyme, while carrier girls keep a normal copy.

## Which modified residue must every human sulfatase carry in its active site?

A formylglycine made from a cysteine by SUMF1; if SUMF1 fails, all sulfatases fail together (multiple sulfatase deficiency).

## How do Hunter and Hurler syndromes differ at the eye?

The corneas stay clear in Hunter syndrome and become cloudy in Hurler syndrome.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [IDS: Iduronate 2-sulfatase (human)](https://www.uniprot.org/uniprotkb/P22304/entry) (UniProt, 2026); [IDS gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/ids/) (MedlinePlus, US National Library of Medicine, 2026); [RCSB PDB - 5FQL: Insights into Hunter syndrome from the structure of iduronate-2- sulfatase](https://www.rcsb.org/structure/5FQL) (RCSB Protein Data Bank, 2026); [MPS II - Hunter syndrome (HS-GAG degradation)](https://reactome.org/PathwayBrowser/#/R-HSA-2206296) (Reactome, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/biochemistry/enzymes/iduronate-2-sulfatase/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/iduronate-2-sulfatase/