HS3ST2 (Heparan Sulfate-Glucosamine 3-Sulfotransferase 2) is a gene encoding an enzyme critical for the biosynthesis of 3-O-sulfated heparan sulfate (3S-HS), a specialized form of heparan sulfate proteoglycans (HSPGs). Recent research has identified HS3ST2 as a key modulator of tau pathology in Alzheimer's disease and related tauopathies through the TGFβ1-HS3ST2-tau signaling axis (PMID: 41810327).
| Attribute | Value |
|---|---|
| Gene Symbol | HS3ST2 |
| Full Name | Heparan Sulfate-Glucosamine 3-Sulfotransferase 2 |
| Chromosome | 16p13.3 |
| Entrez ID | 9956 |
| UniProt ID | Q9Y5P9 |
| Aliases | 3-OST-2, 3OST2 |
HS3ST2 catalyzes the transfer of sulfate groups to the 3-O position of heparan sulfate chains, producing 3-O-sulfated heparan sulfate (3S-HS). This specific sulfation pattern creates binding sites for various proteins, including:
HS3ST2 plays a central role in the recently characterized TGFβ1-HS3ST2-tau signaling axis:
Elevated HS3ST2 expression in AD brain leads to:
Knockdown of HS3ST2:
This makes HS3ST2 a promising therapeutic target for AD and tauopathies.
| Gene | Relationship |
|---|---|
| TGFB1 | Regulator of HS3ST2 expression |
| MAPT | Target of 3S-HS-modulated pathology |
| SMAD2 | TGFβ signaling intermediate |
| SMAD3 | TGFβ signaling intermediate |