GO:0015016 heparan sulfate N-sulfotransferase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0015016 describes the enzymatic activity that transfers sulfate from 3'-phosphoadenylyl sulfate (PAPS) to the N-position of glucosamine residues in heparan sulfate, a critical modification for heparan sulfate function.
• This activity is carried out by the N-deacetylase/N-sulfotransferase (NDST) family of enzymes, which in humans includes NDST1, NDST2, NDST3, and NDST4.
• The N-sulfotransferase catalytic domain resides in the carboxyl half of the NDST holoenzyme, while the N-deacetylase domain is located in the amino-terminal region.
• N-sulfation creates binding sites for growth factors, morphogens, and antithrombin, thereby regulating development, angiogenesis, and coagulation.
• Dysregulated heparan sulfate N-sulfation is implicated in cancer progression, viral infections, and developmental disorders.
• CRISPR-based knockout, point mutation, and knock-in models are powerful tools to dissect the specific roles of NDST isozymes and their catalytic domains.
Description
Heparan sulfate (HS) is a linear polysaccharide attached to core proteins, forming heparan sulfate proteoglycans (HSPGs) that modulate a myriad of biological processes, including cell signaling, development, and host-pathogen interactions. The functional diversity of HS largely depends on its sulfation pattern, which is established by a series of enzymatic modifications in the Golgi apparatus. Among these, N-sulfation of glucosamine residues is a pivotal step that creates the necessary substrate for subsequent O-sulfation and epimerization, thereby determining the overall sulfation density and domain structure of HS. The enzyme activity responsible for this step is heparan sulfate N-sulfotransferase, encoded by the NDST genes. This activity is essential for the generation of high-affinity binding sites for numerous proteins, such as fibroblast growth factors (FGFs), Wnt, and antithrombin. Consequently, understanding the molecular mechanism, regulation, and pathophysiological roles of heparan sulfate N-sulfotransferase activity is of great interest to researchers in developmental biology, cancer, and infectious diseases. This article provides a comprehensive overview of GO:0015016, integrating authoritative QuickGO data with insights from published literature.
heparan sulfate N-sulfotransferase activity At A Glance
| GO ID | GO:0015016 |
|---|---|
| GO term | heparan sulfate N-sulfotransferase activity |
| Ontology | molecular_function |
| Synonym | heparin N-sulfotransferase activity; N-HSST activity; glucosaminyl N-deacetylase/N-sulfotransferase activity; heparan sulfate N-deacetylase/N-sulfotransferase activity |
| Major function | Catalyzes the transfer of sulfate from PAPS to the N-position of glucosamine in heparan sulfate, a critical modification for HS bioactivity. |
| Reaction | 3'-phosphoadenylyl sulfate + alpha-D-glucosaminyl-[heparan sulfate](n) = adenosine 3',5'-bisphosphate + 2 H+ + N-sulfo-alpha-D-glucosaminyl-[heparan sulfate](n) |
| Enzyme family | N-deacetylase/N-sulfotransferase (NDST) family; bifunctional enzymes with N-deacetylase and N-sulfotransferase domains. |
| Cellular location | Golgi apparatus membrane; type II transmembrane proteins. |
| Substrates | PAPS (sulfate donor); heparan sulfate with N-acetylglucosamine or N-unsubstituted glucosamine residues. |
What Is GO:0015016?
Heparan sulfate N-sulfotransferase activity (GO:0015016) is defined as the catalysis of the reaction: 3'-phosphoadenylyl sulfate (PAPS) + alpha-D-glucosaminyl-[heparan sulfate](n) = adenosine 3',5'-bisphosphate + 2 H+ + N-sulfo-alpha-D-glucosaminyl-[heparan sulfate](n). In simpler terms, this enzymatic activity transfers a sulfate group from the universal sulfate donor PAPS to the nitrogen atom of glucosamine residues within heparan sulfate chains, converting N-acetylglucosamine or N-unsubstituted glucosamine to N-sulfoglucosamine. This modification is a key step in heparan sulfate biosynthesis and is catalyzed by the N-sulfotransferase domain of bifunctional N-deacetylase/N-sulfotransferase (NDST) enzymes.
Why Is heparan sulfate N-sulfotransferase activity Important in Cell Biology?
Heparan sulfate N-sulfotransferase activity is a master regulator of heparan sulfate fine structure and function. By generating N-sulfated glucosamine residues, it creates the necessary code for subsequent O-sulfation and epimerization, which together determine the binding affinity of HS for a wide array of signaling molecules and extracellular matrix proteins. This activity is indispensable for embryonic development, as NDST1 knockout mice exhibit severe defects and die shortly after birth. In adult tissues, it modulates angiogenesis, inflammation, and coagulation, and its dysregulation is linked to cancer, viral infections, and neurological disorders. Therefore, precise understanding of this enzymatic activity is crucial for both basic biology and therapeutic development.
• Essential for embryonic development; NDST1 deficiency leads to neonatal lethality and multiple organ defects.
• Regulates growth factor signaling (e.g., FGF, Wnt, Hedgehog) by creating specific sulfation patterns in heparan sulfate.
• Controls blood coagulation through the generation of antithrombin-binding heparan sulfate.
• Modulates cancer progression; loss of antithrombin-binding HS suppresses pancreatic tumorigenesis.
• Influences viral entry and pathogenesis, including varicella-zoster virus and herpes simplex virus.
• Plays a role in inflammation and immune cell recruitment by mediating chemokine presentation.
• Dysregulation is associated with developmental syndromes and neurological disorders.
• Target for engineering heparan sulfate mimetics and anticoagulant drugs.
• Provides a model for studying Golgi-resident enzyme kinetics and substrate specificity.
• Enables production of bioengineered heparosan with defined sulfation for biomedical applications.
What Happens During heparan sulfate N-sulfotransferase activity?
Substrate Recognition and Binding
In simple terms: The enzyme grabs the heparan sulfate chain and the sulfate donor molecule.
The N-sulfotransferase domain of NDST enzymes recognizes specific sequences within the heparan sulfate chain, preferentially binding to regions rich in N-acetylglucosamine (GlcNAc) or N-unsubstituted glucosamine (GlcNH2) residues. The sulfate donor, 3'-phosphoadenylyl sulfate (PAPS), binds to a conserved PAPS-binding motif in the catalytic domain. Structural and biochemical studies indicate that the enzyme undergoes conformational changes upon substrate binding to position the glucosamine residue for sulfate transfer.
Catalytic Transfer of Sulfate
In simple terms: The enzyme moves a sulfate group from PAPS onto the nitrogen of glucosamine.
The catalytic mechanism involves the nucleophilic attack of the glucosamine nitrogen on the sulfur atom of PAPS, resulting in the transfer of the sulfate group and the release of adenosine 3',5'-bisphosphate (PAP). This reaction is dependent on the presence of a conserved histidine residue in the active site, which acts as a general base to deprotonate the glucosamine nitrogen. The N-sulfotransferase activity is strictly dependent on the prior action of the N-deacetylase domain, which removes acetyl groups from GlcNAc residues to generate the N-unsubstituted glucosamine substrate.
Domain Cooperation in Bifunctional NDST Enzymes
In simple terms: The enzyme has two working parts: one removes acetyl groups, the other adds sulfate.
NDST enzymes are bifunctional, with an N-terminal N-deacetylase domain and a C-terminal N-sulfotransferase domain. The N-deacetylase domain first removes acetyl groups from a subset of GlcNAc residues, creating N-unsubstituted glucosamine (GlcNH2) sites. The N-sulfotransferase domain then sulfates these sites. This sequential action is processive, allowing the formation of extended N-sulfated domains. The two domains are functionally coupled, and the deacetylase activity is required for efficient N-sulfation in vivo.
Formation of N-Sulfated Domains and Downstream Modifications
In simple terms: The sulfation creates patches that allow further modifications and protein binding.
N-sulfation generates N-sulfoglucosamine (GlcNS) residues, which serve as substrates for subsequent C5-epimerization of glucuronic acid to iduronic acid and O-sulfation at various positions. These modifications cluster into highly sulfated domains (NS domains) separated by less sulfated regions, creating a mosaic structure that dictates the binding specificity of HS for proteins such as antithrombin, FGFs, and chemokines. The extent and pattern of N-sulfation are critical for these interactions, and alterations in NDST activity can lead to profound changes in HS function.
Key Genes Involved in GO:0015016 heparan sulfate N-sulfotransferase activity
The following genes encode proteins that either possess heparan sulfate N-sulfotransferase activity or are directly involved in its regulation and downstream effects.
| Gene | Major Role | Research Relevance |
|---|---|---|
| NDST1 | Major NDST isozyme; carries out N-deacetylation and N-sulfation of HS in most tissues. | Knockout causes neonatal lethality and multiple developmental defects; key for studying HS function in development and disease. |
| NDST2 | NDST isozyme highly expressed in mast cells; contributes to heparin biosynthesis. | Important for understanding mast cell biology and allergic responses; knockout viable but with mast cell defects. |
| NDST3 | NDST isozyme predominantly expressed in brain; involved in neural development. | Associated with neurological disorders; potential target for brain-specific HS functions. |
| NDST4 | NDST isozyme expressed in specific tissues; role less characterized. | Emerging interest in cancer and tissue-specific HS sulfation. |
| EXT1 | Glycosyltransferase involved in HS chain polymerization. | Mutations cause hereditary multiple exostoses; essential for HS biosynthesis. |
| EXT2 | Glycosyltransferase involved in HS chain polymerization. | Mutations cause hereditary multiple exostoses; essential for HS biosynthesis. |
| HS3ST1 | 3-O-sulfotransferase that acts on N-sulfated HS to create antithrombin-binding sites. | Critical for anticoagulant activity; requires prior N-sulfation. |
| HS3ST3A1 | 3-O-sulfotransferase acting on N-sulfated HS. | Modulates HS-protein interactions; potential role in cancer. |
| HS6ST1 | 6-O-sulfotransferase acting on N-sulfated HS. | Regulates growth factor signaling; mutations linked to developmental disorders. |
| SULF1 | Extracellular sulfatase that removes 6-O-sulfate from HS. | Modulates HS function in cancer and development. |
| SULF2 | Extracellular sulfatase that removes 6-O-sulfate from HS. | Implicated in tumor progression and metastasis. |
| PAPSS1 | PAPS synthase 1; synthesizes the sulfate donor PAPS. | Provides substrate for all sulfotransferases; knockout affects global sulfation. |
| PAPSS2 | PAPS synthase 2; synthesizes PAPS. | Mutations cause skeletal dysplasia; affects sulfation of HS and other molecules. |
| GPC1 | Glypican-1; a heparan sulfate proteoglycan. | Regulates growth factor signaling; involved in cancer. |
| SDC1 | Syndecan-1; a heparan sulfate proteoglycan. | Mediates cell-matrix interactions; role in inflammation and cancer. |
| FGF2 | Fibroblast growth factor 2; binds N-sulfated HS to signal. | Requires N-sulfation for high-affinity binding; key for angiogenesis. |
| ATIII | Antithrombin III; binds a specific N-sulfated HS sequence. | Anticoagulant activity depends on N-sulfation; therapeutic target. |
| VZV gB | Varicella-zoster virus glycoprotein B; binds HS for entry. | N-sulfation enhances viral fusion; relevant for antiviral strategies. |
How Is heparan sulfate N-sulfotransferase activity Regulated?
The activity of heparan sulfate N-sulfotransferase is primarily regulated at the level of gene expression of the NDST isozymes, which exhibit tissue-specific and developmental stage-specific patterns. For example, NDST1 is widely expressed, while NDST2 is prominent in mast cells, and NDST3 is enriched in the brain. At the protein level, the bifunctional NDST enzymes are regulated by the availability of the substrate PAPS, which is synthesized by PAPS synthases (PAPSS1 and PAPSS2). Additionally, the N-deacetylase activity of NDST1 modulates the extent of N-sulfation by generating N-unsubstituted glucosamine sites, and this activity can be influenced by the local HS structure and interacting proteins. Post-translational modifications and Golgi retention signals also contribute to the regulation of NDST localization and activity. Furthermore, the expression of NDSTs can be altered in pathological conditions such as cancer, where changes in N-sulfation affect tumor cell signaling and metastasis.
heparan sulfate N-sulfotransferase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| NDST1 | Developmental defects, cancer | Knockout mouse, conditional KO, point mutation of catalytic residues |
| NDST2 | Mast cell disorders, allergy | Knockout mouse, mast cell-specific KO |
| NDST3 | Neurological disorders | Brain-specific KO, overexpression in neurons |
| NDST4 | Cancer, tissue-specific functions | Knockout and overexpression in cancer cell lines |
| HS3ST1 | Coagulation disorders, cancer | Knockout, point mutation to abolish 3-O-sulfation |
Cancer
Alterations in heparan sulfate N-sulfation are frequently observed in cancer. Loss of antithrombin-binding heparan sulfate, which requires N-sulfation, suppresses pancreatic tumorigenesis, indicating a tumor-suppressive role for specific N-sulfated HS structures. Conversely, increased NDST expression and N-sulfation can promote tumor growth by enhancing growth factor signaling, such as FGF2-mediated angiogenesis. Therefore, targeting NDST activity or downstream sulfation patterns is a potential therapeutic strategy.
Developmental Disorders
NDST1 deficiency in mice leads to neonatal lethality with defects in multiple organs, including the lungs, kidneys, and skeleton, underscoring the essential role of N-sulfation in development. In humans, mutations in genes involved in HS biosynthesis, including NDST1, have been linked to developmental syndromes, although direct NDST1 mutations are rare. The precise regulation of N-sulfation is critical for morphogen gradients and tissue patterning.
Viral Infections
Many viruses, including varicella-zoster virus (VZV) and herpes simplex virus, utilize heparan sulfate as an attachment receptor. N-sulfation of HS enhances viral entry and fusogenic activity, as shown for VZV glycoprotein B. Consequently, modulating N-sulfation could be a strategy to inhibit viral infection.
Coagulation Disorders
Heparan sulfate N-sulfation is required for the generation of the antithrombin-binding pentasaccharide sequence, which is essential for the anticoagulant activity of heparin and endogenous HS. Defects in N-sulfation can lead to altered coagulation, and heparin, a highly N-sulfated analog, is widely used as an anticoagulant drug.
From heparan sulfate N-sulfotransferase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| What is the role of NDST1 N-sulfotransferase activity in embryonic development? | NDST1 knockout mouse, conditional KO, or point mutation of the N-sulfotransferase domain |
| How does N-sulfation affect FGF2 signaling? | NDST1 KO cell lines (e.g., CHO cells) reconstituted with wild-type or mutant NDST1 |
| Does NDST2 contribute to heparin biosynthesis in mast cells? | NDST2 knockout mouse, mast cell-specific KO, or overexpression |
| What is the impact of N-sulfation on viral entry? | NDST1 KO cells infected with VZV or HSV, with or without reconstitution |
| Can engineered NDST variants produce tailored heparan sulfate? | Overexpression of NDST mutants in HEK293 or CHO cells, followed by HS structural analysis |
| What are the downstream effects of altered N-sulfation in cancer? | Cancer cell lines with NDST1/2 knockout or overexpression, xenograft models |
How to Study the heparan sulfate N-sulfotransferase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Radioactive PAPS transfer assay | N-sulfotransferase enzymatic activity | Kinetic characterization of wild-type and mutant NDST enzymes |
| HPLC disaccharide analysis | Composition and extent of HS sulfation | Comparing HS from wild-type and NDST-knockout cells |
| CRISPR-Cas9 knockout | Loss-of-function phenotypes | Studying the role of NDST isozymes in development and disease |
| Site-directed mutagenesis | Domain-specific functions | Separating N-deacetylase and N-sulfotransferase activities |
| Surface plasmon resonance | Binding affinity of HS to proteins | Assessing the effect of N-sulfation on growth factor binding |
| Western blotting | Activation of signaling pathways | Measuring FGF2-induced ERK phosphorylation in NDST mutants |
| Mass spectrometry | Fine structure of HS oligosaccharides | Detailed structural analysis of N-sulfated domains |
| Viral infection assays | Viral entry and fusion | Testing the role of N-sulfation in viral pathogenesis |
Enzymatic Activity Assays
The N-sulfotransferase activity can be measured in vitro using radiolabeled PAPS (35S-PAPS) and a heparan sulfate acceptor substrate, followed by separation of products by chromatography. Alternatively, a coupled assay with N-deacetylase can be used to monitor the release of acetate. These assays are essential for characterizing enzyme kinetics and mutant variants.
Heparan Sulfate Structural Analysis
The extent and pattern of N-sulfation in cellular HS can be determined by digesting HS with specific lyases (heparinase I, II, III) and analyzing the resulting disaccharides by HPLC or mass spectrometry. This method reveals the proportion of N-sulfated disaccharides and the domain structure.
CRISPR-Cas9 Genome Editing
CRISPR-Cas9 is used to generate NDST knockout cell lines and animal models to study loss-of-function phenotypes. Point mutations can be introduced to specifically inactivate the N-sulfotransferase domain while preserving N-deacetylase activity, allowing dissection of domain-specific functions.
Protein Interaction and Signaling Studies
The functional consequences of N-sulfation can be assessed by measuring binding of growth factors (e.g., FGF2) to HS using surface plasmon resonance or co-immunoprecipitation. Downstream signaling (e.g., ERK phosphorylation) is monitored by Western blotting. These methods link N-sulfation to cellular responses.
How CRISPR Can Be Used to Study GO:0015016 heparan sulfate N-sulfotransferase activity
Knockout
CRISPR-Cas9 knockout of NDST genes (e.g., NDST1, NDST2) in cell lines or mice abolishes N-sulfotransferase activity, leading to undersulfated heparan sulfate and loss of protein binding. These models are invaluable for studying the physiological roles of N-sulfation in development, cancer, and infection. For example, NDST1 knockout mice exhibit neonatal lethality and multiple organ defects.
Point Mutation
Point mutations can be introduced into the N-sulfotransferase domain to selectively inactivate its catalytic activity without affecting the N-deacetylase domain. This allows researchers to dissect the specific contribution of N-sulfation versus N-deacetylation in HS function. For instance, mutation of the conserved histidine in the active site abolishes sulfate transfer.
Knock-in
Knock-in of epitope-tagged NDST (e.g., FLAG or HA) enables endogenous protein detection, localization, and interaction studies without overexpression artifacts. This is useful for tracking NDST trafficking in the Golgi and for proteomic analysis of associated proteins.
Overexpression
Overexpression of wild-type or mutant NDST in cells (e.g., HEK293, CHO) increases N-sulfation capacity and can be used to produce heparan sulfate with defined sulfation patterns for structural and functional studies. Overexpression models also help identify downstream effects of enhanced N-sulfation on cell signaling and behavior.
How EDITGENE Supports heparan sulfate N-sulfotransferase activity Research
Researchers studying heparan sulfate N-sulfotransferase activity-related genes often need to determine whether a candidate gene is causally involved in heparan sulfate biosynthesis, protein binding, or disease phenotypes. EDITGENE provides a comprehensive suite of CRISPR-based services to generate precisely engineered cell models, enabling rigorous functional interrogation of NDST genes and their domains.
Contact EDITGENE today to design your custom CRISPR model for heparan sulfate N-sulfotransferase activity research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NDST1 Knockout HEK293 Cell Line | EDJ-KQ4951 | Human | 3340 | Details Get a Quote |
| NDST2 Knockout HEK293 Cell Line | EDJ-KQ6262 | Human | 8509 | Details Get a Quote |
| NDST3 Knockout HEK293 Cell Line | EDJ-KQ6555 | Human | 9348 | Details Get a Quote |
| NDST2 Knockout A-549 Cell Line | EDJ-KQ30145 | Human | 8509 | Details Get a Quote |
| NDST2 Knockout HeLa Cell Line | EDJ-KQ30147 | Human | 8509 | Details Get a Quote |
| NDST1 Knockout HeLa Cell Line | EDJ-KQ26602 | Human | 3340 | Details Get a Quote |
| NDST1 Knockout A-549 Cell Line | EDJ-KQ27817 | Human | 3340 | Details Get a Quote |
| NDST1 Knockout HCT 116 Cell Line | EDJ-KQ27818 | Human | 3340 | Details Get a Quote |
| NDST2 Knockout HCT 116 Cell Line | EDJ-KQ28836 | Human | 8509 | Details Get a Quote |
| NDST4 Knockout HEK293 Cell Line | EDJ-KQ51621 | Human | 64579 | Details Get a Quote |
| NDST3 Knockout HeLa Cell Line | EDJ-KQ55133 | Human | 9348 | Details Get a Quote |
| NDST4 Knockout HeLa Cell Line | EDJ-KQ57063 | Human | 64579 | Details Get a Quote |
| NDST3 Knockout A-549 Cell Line | EDJ-KQ63611 | Human | 9348 | Details Get a Quote |
| NDST4 Knockout A-549 Cell Line | EDJ-KQ65576 | Human | 64579 | Details Get a Quote |
| NDST3 Knockout HCT 116 Cell Line | EDJ-KQ72078 | Human | 9348 | Details Get a Quote |
Displaying Records 1 To 15 Of 16 Records
Frequently Asked Questions About heparan sulfate N-sulfotransferase activity
What is heparan sulfate N-sulfotransferase activity?
It is the enzymatic activity (GO:0015016) that transfers a sulfate group from PAPS to the N-position of glucosamine residues in heparan sulfate, a critical modification for HS function.
What genes encode heparan sulfate N-sulfotransferase activity?
The NDST family genes (NDST1, NDST2, NDST3, NDST4) encode bifunctional enzymes with N-deacetylase and N-sulfotransferase activities.
What is the reaction catalyzed by heparan sulfate N-sulfotransferase?
The enzyme catalyzes: 3'-phosphoadenylyl sulfate + alpha-D-glucosaminyl-[heparan sulfate](n) = adenosine 3',5'-bisphosphate + 2 H+ + N-sulfo-alpha-D-glucosaminyl-[heparan sulfate](n).
Where does heparan sulfate N-sulfation occur in the cell?
It occurs in the Golgi apparatus, where NDST enzymes are anchored as type II transmembrane proteins.
What is the role of N-sulfation in heparan sulfate function?
N-sulfation creates binding sites for growth factors, antithrombin, and viruses, and is required for subsequent O-sulfation and epimerization, thus determining HS biological activity.
Which diseases are associated with altered heparan sulfate N-sulfation?
Cancer, developmental disorders, viral infections, and coagulation abnormalities have been linked to changes in N-sulfation.
How can I study heparan sulfate N-sulfotransferase activity in the lab?
Common methods include radioactive PAPS transfer assays, HPLC disaccharide analysis, and CRISPR-Cas9 knockout of NDST genes.
What CRISPR models are available for NDST genes?
Knockout, point mutation, knock-in, and overexpression models can be generated in various cell lines to study NDST function.
What is the difference between N-deacetylase and N-sulfotransferase activities?
N-deacetylase removes acetyl groups from GlcNAc, while N-sulfotransferase adds sulfate to the exposed nitrogen; both are domains of the same NDST enzyme.
Can heparan sulfate N-sulfotransferase be targeted therapeutically?
Yes, modulating N-sulfation is a potential strategy for cancer, antiviral, and anticoagulant therapies, though further research is needed.
Conclusion
Heparan sulfate N-sulfotransferase activity (GO:0015016) is a fundamental enzymatic step in heparan sulfate biosynthesis, governing the structural and functional diversity of HSPGs. Its importance spans development, cancer, infection, and coagulation, making it a focal point for biomedical research. Advances in CRISPR-based genome editing and analytical methods continue to unravel the complexities of NDST regulation and its impact on human health. EDITGENE is committed to supporting this research with high-quality CRISPR models and services.
References
- 1. Xi X et al.. 2023. Improvement of the stability and catalytic efficiency of heparan sulfate N-sulfotransferase for preparing N-sulfated heparosan.. J Ind Microbiol Biotechnol 50(1) PMID: 37327079
- 2. Grobe K et al.. 2002. Heparan sulfate and development: differential roles of the N-acetylglucosamine N-deacetylase/N-sulfotransferase isozymes.. Biochim Biophys Acta 1573(3):209-15 PMID: 12417402
- 3. Berninsone P et al.. 1998. Heparan sulfate/heparin N-deacetylase/N-sulfotransferase. The N-sulfotransferase activity domain is at the carboxyl half of the holoenzyme.. J Biol Chem 273(40):25556-9 PMID: 9748218
- 4. Clausen TM et al.. 2025. Antithrombin-binding heparan sulfate is ubiquitously expressed in epithelial cells and suppresses pancreatic tumorigenesis.. J Clin Invest 135(22) PMID: 40924474
- 5. Dou W et al.. 2015. Role of Deacetylase Activity of N-Deacetylase/N-Sulfotransferase 1 in Forming N-Sulfated Domain in Heparan Sulfate.. J Biol Chem 290(33):20427-37 PMID: 26109066
- 6. Duncan MB et al.. 2006. Characterization of the N-deacetylase domain from the heparan sulfate N-deacetylase/N-sulfotransferase 2.. Biochem Biophys Res Commun 339(4):1232-7 PMID: 16343444
- 7. Ohka S et al.. 2021. Heparan sulfate 3-O-sulfotransferase 4 is genetically associated with herpes zoster and enhances varicella-zoster virus-mediated fusogenic activity.. Mol Pain 17:17448069211052171 PMID: 34904858
