Affinage

HS3ST1

Heparan sulfate glucosamine 3-O-sulfotransferase 1 · UniProt O14792

Length
307 aa
Mass
35.8 kDa
Annotated
2026-04-28
81 papers in source corpus 28 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HS3ST1 encodes heparan sulfate D-glucosaminyl 3-O-sulfotransferase-1 (3-OST-1), a Golgi-localized type II membrane enzyme that catalyzes the transfer of sulfate from PAPS to the 3-OH position of specific glucosamine residues in heparan sulfate, generating the rare 3-O-sulfated pentasaccharide motif required for high-affinity antithrombin binding (PMID:9988767, PMID:9988768). The sulfotransferase domain is the self-contained unit determining isoform-specific substrate selectivity, with Arg268 governing substrate discrimination and Glu86 essential for catalysis, as established by crystal structure analysis and mutagenesis (PMID:22431632, PMID:41914643, PMID:11563988). Although Hs3st1 knockout mice lack anticoagulant heparan sulfate yet maintain normal hemostasis, they lose antithrombin's anti-inflammatory activity and exhibit a proinflammatory phenotype, while HS3ST1-generated 3-O-sulfated heparan sulfate also mediates tau and ApoE cellular uptake relevant to Alzheimer's disease, modulates neuropilin-1/semaphorin signaling, and regulates EGFR and HB-EGF signaling in cancer contexts (PMID:12671048, PMID:28126521, PMID:31692167, PMID:37014788, PMID:26731579, PMID:37463954). HS3ST1 expression is negatively regulated by the transcription factor ZNF263, and its 3-O-sulfated products are elevated sevenfold in Alzheimer's disease brains, where they promote pathological tau spread (PMID:32277030, PMID:37235665).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 High

    Identifying HS3ST1 as the enzyme responsible for the rate-limiting 3-O-sulfation step that converts inactive heparan sulfate to antithrombin-binding anticoagulant heparan sulfate established the molecular basis for a long-known but enzymatically uncharacterized biosynthetic modification.

    Evidence cDNA cloning with recombinant expression in COS-7 cells, radiolabeled PAPS sulfotransferase assays, and disaccharide analysis

    PMID:9988767 PMID:9988768

    Open questions at the time
    • No structural information on the enzyme or its substrate-binding mode
    • In vivo relevance of the anticoagulant HS product not yet tested
  2. 2001 High

    Domain-swap chimeras demonstrated that the C-terminal sulfotransferase domain alone dictates 3-OST-1's unique 300-fold preference for generating antithrombin-binding sites over other 3-OST isoforms, resolving how isoform specificity is encoded.

    Evidence Domain-swap chimeras between 3-OST-1 and 3-OST-3A expressed in COS-7 and CHO cells with antithrombin-binding and HSV-1 entry readouts

    PMID:11563988 PMID:9988768

    Open questions at the time
    • Specific residues responsible for substrate discrimination not yet identified
    • Upstream biosynthetic requirements not fully defined
  3. 2001 High

    Genetic epistasis in CHO cells revealed that 6-O-sulfotransferase-1 acts upstream of 3-OST-1 in the anticoagulant HS pathway, establishing the ordered biosynthetic logic.

    Evidence Chemical mutagenesis screen in 3-OST-1-transduced CHO cells with 6-OST-1 rescue and LC-MS disaccharide analysis

    PMID:11551899

    Open questions at the time
    • Whether other 6-OST isoforms can substitute remains untested
    • Full combinatorial sulfation code for the antithrombin-binding pentasaccharide not delineated
  4. 2003 High

    Hs3st1 knockout mice resolved a central paradox: despite dramatic loss of anticoagulant HS, hemostasis was normal, demonstrating that bulk HSAT is dispensable for coagulation homeostasis and pointing to non-anticoagulant functions.

    Evidence Hs3st1−/− mice assessed by ferric chloride carotid injury, fibrin accumulation, thrombin-antithrombin complex measurements

    PMID:12671048

    Open questions at the time
    • Cause of background-specific lethality and growth retardation unexplained
    • Alternative in vivo roles of HSAT not yet explored
  5. 2012 High

    The crystal structure of the 3-OST-1 ternary complex with PAP and a heptasaccharide substrate identified Arg268 as the key specificity-determining residue, providing an atomic-level explanation for isoform-specific substrate recognition.

    Evidence X-ray crystallography of the ternary complex with site-directed mutagenesis validation

    PMID:22431632

    Open questions at the time
    • No full-length structure including the transmembrane and stem regions
    • How Golgi membrane context influences activity is unknown
  6. 2013 High

    Golgi-targeted 3-OST-1 produced functional antithrombin-binding sites while also upregulating other sulfation marks, revealing that 3-O-sulfation is integrated with coordinated HS biosynthetic regulation in the Golgi.

    Evidence Subcellular targeting constructs in CHO cells with flow cytometry, anti-factor Xa assay, and AMAC-LCMS disaccharide analysis

    PMID:24247246

    Open questions at the time
    • Mechanism of cross-regulation among HS biosynthetic enzymes not elucidated
  7. 2016 High

    Discovery that 3-O-sulfated HS produced by Hs3st1 enhances neuropilin-1 binding and modulates semaphorin-3a-induced growth cone collapse in neurons established a new non-anticoagulant signaling role for the 3-O-sulfate modification.

    Evidence Affinity chromatography, binding assays, neuronal growth cone collapse assays using Hs3st1−/− and Hs3st2−/− mouse neurons, endothelial sprouting assay

    PMID:26731579

    Open questions at the time
    • In vivo neuronal phenotype in Hs3st1−/− mice not systematically characterized
    • Whether 3-O-sulfation alters semaphorin-neuropilin complex structure is unknown
  8. 2017 High

    Hs3st1 knockout mice lost antithrombin's anti-inflammatory activity during septic shock while retaining normal coagulation, definitively reassigning the primary in vivo function of HSAT from anticoagulation to anti-inflammation.

    Evidence LPS-induced septic shock in Hs3st1−/− mice with leukocyte adhesion, coronary arteriole dilation assays, and human SNP association study

    PMID:28126521

    Open questions at the time
    • Mechanism by which HSAT-bound antithrombin suppresses inflammation at the molecular level not defined
    • Whether the rs16881446 SNP is causal or a marker remains unresolved
  9. 2019 High

    3-O-sulfated HS produced by HS3ST1 was shown to enhance tau protein binding and cellular internalization, opening an entirely new disease-relevant axis for this modification in Alzheimer's pathology.

    Evidence HS microarray, SPR, Hs3st1−/− cell tau binding and uptake assays, NMR titration mapping tau-binding epitope

    PMID:31692167

    Open questions at the time
    • In vivo contribution to tau spread in brain not yet demonstrated
    • Receptor or co-receptor mediating 3-O-S-dependent tau internalization not identified
  10. 2020 High

    Identification of ZNF263 as a transcriptional repressor of HS3ST1 revealed an upstream regulatory mechanism controlling the abundance of 3-O-sulfated HS, with functional consequences for antithrombin binding and neuropilin-1 interaction.

    Evidence CRISPR knockout and siRNA knockdown of ZNF263 in cell lines and primary cells with qPCR, antithrombin binding, factor Xa inhibition, and neuropilin-1 binding assays

    PMID:32277030

    Open questions at the time
    • Direct ZNF263 binding site on the HS3ST1 promoter not mapped
    • Whether ZNF263 regulation is tissue-specific in vivo is unknown
  11. 2023 High

    3-O-sulfated HS was found to be elevated sevenfold in Alzheimer's disease brains compared to controls, and all ApoE isoforms recognized this modification, linking HS3ST1 activity to two major AD risk pathways (tau and ApoE).

    Evidence LC-MS/MS of AD and control brain HS, synthetic 14-mer tau uptake inhibition, glycan microarray and SPR for ApoE binding, HS3ST1 KO cell validation

    PMID:37014788 PMID:37235665

    Open questions at the time
    • Whether HS3ST1 upregulation is a cause or consequence of AD pathology is unknown
    • Therapeutic potential of 3-O-sulfated HS mimetics for blocking tau/ApoE binding untested in vivo
  12. 2025 High

    HS3ST1 inactivation in pancreatic cancer cells eliminated HSAT from basement membranes and increased metastasis, establishing that loss of 3-O-sulfated HS removes an antithrombin-dependent anti-metastatic barrier.

    Evidence HS3ST1 inactivation in PDAC cells, mouse metastasis model, antithrombin binding and thrombin generation assays, patient plasma HSAT measurement

    PMID:40924474

    Open questions at the time
    • Whether HSAT loss is a general feature of epithelial cancers beyond PDAC is unknown
    • Mechanism linking HSAT loss to inflammatory phenotype in tumor cells not defined
  13. 2026 High

    Identification of E86 as the catalytic residue via dominant-negative E86Q mutagenesis provided the first active-site mechanism for 3-OST-1, complementing the structural understanding from the Arg268 specificity determinant.

    Evidence E86Q site-directed mutagenesis with LC-MS/MS enzymatic activity quantification and cell-based 3-O-sulfated HS measurement

    PMID:41914643

    Open questions at the time
    • Full catalytic mechanism (acid-base vs. direct transfer) not defined
    • Whether E86Q dominant-negative approach works in vivo for functional studies not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include the structural basis for how 3-O-sulfated HS engages tau and ApoE at the cell surface, the identity of the internalization receptor/co-receptor for 3-O-S-dependent cargo uptake, whether HS3ST1 upregulation drives or follows AD pathology in vivo, and the full catalytic mechanism of 3-OST-1.
  • No structural model of 3-O-sulfated HS in complex with tau or ApoE receptor
  • Internalization receptor for 3-O-S-dependent tau/ApoE uptake not identified
  • Causal role of HS3ST1 in AD progression not demonstrated in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 5
Localization
GO:0005794 Golgi apparatus 1
Partners
ANTITHROMBINAPOEHS6ST1NRP1TAUZNF263

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 HS3ST1 (3-OST-1) encodes a heparan sulfate D-glucosaminyl 3-O-sulfotransferase that transfers sulfate from PAPS to the 3-OH position of specific glucosamine residues within heparan sulfate, converting nonanticoagulant heparan sulfate (HSinact) to anticoagulant heparan sulfate (HSact); it is a type II integral membrane protein with a carboxyl-terminal sulfotransferase domain as the self-contained functional unit. cDNA cloning, expression in COS-7 cells, radiolabeled PAPS sulfotransferase activity assay, disaccharide analysis The Journal of biological chemistry High 9988767 9988768
1999 3-OST-1 exhibits distinct substrate specificity compared to other 3-OST isoforms: it is 300-fold more efficient than 3-OST-2 or 3-OST-3A at generating anticoagulant heparan sulfate binding sites for antithrombin; the sulphotransferase domain alone determines this isoform-specific sequence selectivity, as shown by domain-swap chimeras. COS-7 cell expression, PAPS sulfotransferase activity assay, HSact conversion assay, domain-swap chimera analysis The Journal of biological chemistry High 11563988 9988768
2001 The sulphotransferase domain of 3-OST-1 is a portable, self-contained unit that determines its sequence specificity for generating antithrombin-binding sites; swapping the sulphotransferase domain of 3-OST-1 into 3-OST-3A context (N3A-ST1 chimera) conferred 3-OST-1-like antithrombin-binding activity, while swapping the N-terminal region had no effect on specificity. Domain-swap chimeras expressed in COS-7 cells, antithrombin-binding site generation assay, CHO cell transfection with HSV-1 entry susceptibility assay The Biochemical journal High 11563988
2001 6-O-sulfotransferase-1 (6-OST-1) acts as a limiting enzyme upstream of 3-OST-1 in the anticoagulant heparan sulfate biosynthetic pathway; 3-OST-1 introduced into CHO cells via retroviral transduction confers HSact production, and chemical mutagenesis of these cells showed 6-OST-1 deficiency blocked HSact generation, which was rescued by 6-OST-1 transfection. Retroviral transduction of 3-OST-1 into CHO cells, chemical mutagenesis screen, in vitro 6-OST-1 modification assay, capillary HPLC-MS disaccharide analysis The Journal of biological chemistry High 11551899
2002 Recombinant human 3-OST-1 expressed in E. coli is soluble and catalytically active, with apparent Km values of 4.3 µM for heparan sulfate and 38.6 µM for PAPS, and Vmax ~18-21 pmol sulfate/min/pmol enzyme, comparable to baculovirus-expressed enzyme. E. coli recombinant expression, radiochemical sulfotransferase assay with [35S]PAPS and bovine kidney heparan sulfate Biochemical and biophysical research communications High 11811991
2002 Structure-function analysis by homology modeling of 3-OST-1 identified specific structural motifs and amino acid residues likely critical for enzymatic function of the sulphotransferase domain. Homology modeling based on crystal structures of related enzymes, structural analysis tools Biochemical and biophysical research communications Low 11811992
2003 Hs3st1 knockout mice (Hs3st1-/-) lack 3-OST-1 enzyme activity in plasma and tissues and show dramatic reductions in anticoagulant heparan sulfate (HSact), yet exhibit normal hemostasis (normal fibrin accumulation, normal carotid artery occlusion times, normal thrombin-antithrombin complexes), demonstrating that bulk HSact is not essential for normal hemostasis in vivo. Unexpectedly, these mice exhibited genetic background-specific lethality and intrauterine growth retardation without coagulopathy, suggesting 3-OST-1-derived structures serve additional biological roles. Hs3st1-/- knockout mouse generation, enzyme activity assays, ferric chloride carotid artery injury model, fibrin accumulation assay under normoxia/hypoxia, thrombin-antithrombin complex measurement The Journal of clinical investigation High 12671048
2000 3-OST-1 enzymatically modifies heparan sulfate on a biochip by introducing the critical 3-O-sulfo group into the pentasaccharide sequence, converting low-affinity ATIII-binding HS to high-affinity ATIII-binding HS, as demonstrated by surface plasmon resonance. Biochip-bound heparan sulfate, enzymatic modification with 3-OST-1 and PAPS, surface plasmon resonance spectroscopy Biochemical and biophysical research communications High 11006120
2012 Crystal structure of the ternary complex of 3-OST-1 with 3'-phosphoadenosine 5'-phosphate and a heptasaccharide substrate was solved, revealing the substrate-binding mode and showing that Arg268 in 3-OST-1 is a key residue for substrate specificity distinguishing it from 3-OST-3; saccharide substrates display distinct conformations when interacting with different 3-OST isoforms. X-ray crystallography of ternary complex, site-directed mutagenesis of active-site residues Proceedings of the National Academy of Sciences of the United States of America High 22431632
2013 Golgi-targeted HS3ST1 (but not untargeted HS3ST1) localizes to the Golgi apparatus and produces antithrombin III-binding sites with high anti-factor Xa activity in CHO cells; overexpression of HS3ST1 also upregulates 2-O-, 6-O-, and N-sulfo group-containing disaccharides, indicating concerted interplay among HS biosynthetic enzymes. Subcellular targeting constructs expressed in CHO cells, flow cytometry ATIII binding assay, anti-factor Xa assay, AMAC-LCMS disaccharide analysis The Journal of biological chemistry High 24247246
2017 HS3ST1 genotype controls endothelial cell production of HSAT+ (antithrombin-binding heparan sulfate); in Hs3st1-/- mice, antithrombin lost its anti-inflammatory activity and instead exerted pro-inflammatory effects in LPS-induced septic shock, demonstrating that HSAT+ is required for AT's anti-inflammatory but not anticoagulant activity. An intronic SNP (rs16881446) in HS3ST1 associated with reduced expression in endothelial cells and with coronary artery disease severity. Hs3st1-/- knockout mouse model, LPS-induced septic shock model, leukocyte firm adhesion assay, isolated coronary arteriole dilation assay, human candidate-gene association study, endothelial cell gene expression Matrix biology : journal of the International Society for Matrix Biology High 28126521
2016 3-O-sulfation of heparan sulfate by Hs3st1 (but not Hs3st2) enhanced binding of neuropilin-1 to heparan sulfate; 3-O-sulfated HS dodecamers inhibited neuropilin-1-dependent semaphorin-3a-induced growth cone collapse in dorsal root ganglion neurons from wild-type but not Hs3st1-deficient mice, and inhibited endothelial cell sprouting. Affinity chromatography with 3-O-sulfated HS columns, ELISA binding assay, thermal shift assay, neuronal growth cone collapse assay using Hs3st1-/- and Hs3st2-/- mouse neurons, endothelial cell sprouting assay ACS chemical biology High 26731579
2019 3-O-sulfation of heparan sulfate generated by HS3ST1 significantly enhances tau binding to cell-surface heparan sulfate and tau cellular internalization; Hs3st1-/- cells showed reduced 3-O-sulfate levels, diminished cell-surface tau binding, and reduced tau internalization; NMR titrations mapped 3-O-S binding to the R2 and PRR2 regions of tau. HS microarray, surface plasmon resonance, Hs3st1-/- cell lines, tau cell-surface binding and internalization assays, NMR titration, competitive inhibition with soluble 3-O-S HS 12-mer Angewandte Chemie (International ed. in English) High 31692167
2022 3-O-sulfation of heparan sulfate produced by HS3ST1 contributes to the cellular uptake of tau aggregates; HS3ST1-/- cells showed reduced tau aggregate uptake, confirmed by LC-MS/MS quantification of 3-O-sulfated HS products; antithrombin III competition reduced tau uptake, and 3-O-sulfated HS showed higher affinity for aggregated tau. HS3ST1-/- cell lines, tau aggregate uptake assay, LC-MS/MS with 13C-labeled HS calibrants, antithrombin III competition assay BMC molecular and cell biology High 36564747
2023 HS3ST1-encoded 3-OST-1 produces a specific 3-O-sulfated heparan sulfate that is elevated sevenfold in Alzheimer's disease brains; this specific 3-O-sulfated HS (identified by LC-MS/MS) enhances tau internalization, and its addition as a synthetic 14-mer inhibited tau cellular uptake, implicating HS3ST1 overexpression in tau pathology spread. LC-MS/MS analysis of brain HS from AD patients and controls, recombinant sulfotransferase modification, Hs3st1 knockout mouse HS analysis, synthetic 14-mer inhibition of tau internalization Science advances High 37235665
2023 All ApoE isoforms (ApoE2, ApoE3, ApoE4) recognize 3-O-sulfated heparan sulfate produced by HS3ST1; knockout of HS3ST1 in cells reduced ApoE cell-surface binding and uptake; NMR titration localized ApoE/3-O-S binding to the vicinity of the canonical HS binding motif. Glycan microarray, surface plasmon resonance, HS3ST1 knockout cells, ApoE binding and uptake assays, NMR titration Angewandte Chemie (International ed. in English) High 37014788
2020 ZNF263, a C2H2 zinc finger transcription factor, negatively regulates HS3ST1 expression; CRISPR-mediated or siRNA knockdown of ZNF263 dramatically increased HS3ST1 expression, enhanced 3-O-sulfation, increased antithrombin binding, enhanced Factor Xa inhibition, and increased neuropilin-1 binding. CRISPR targeting and siRNA knockdown of ZNF263 in mammalian cell lines and human primary cells, qPCR, antithrombin binding assay, Factor Xa inhibition assay, neuropilin-1 binding assay Proceedings of the National Academy of Sciences of the United States of America High 32277030
2012 Hs3st1 silencing in pancreatic beta-cell line MIN6T3 cells reduced glucose-induced insulin secretion (GIIS), implicating the 3-O-sulfate group on heparan sulfate produced by Hs3st1 in the insulin secretory pathway upstream of membrane depolarization. siRNA knockdown of Hs3st1, glucose-induced insulin secretion assay, sodium chlorate inhibition experiments, qRT-PCR Journal of diabetes investigation Medium 24843591
2023 HS3ST1 promotes NSCLC cell malignant behaviors by inhibiting SPOP expression, which normally mediates degradation of FADD, thereby activating the NF-κB pathway; HS3ST1 knockdown suppressed tumor growth in vitro and in vivo. HS3ST1 knockdown/overexpression in NSCLC cell lines, in vivo xenograft model, SPOP/FADD/NF-κB pathway analysis BioMed research international Low 35909476 38188779
2023 In castration-resistant prostate cancer cells (C4-2), EGF-activated EGFR-ERK1/2 signaling under hormone-depleted conditions depends on 3-O-sulfated heparan sulfate produced by HS3ST1; HS3ST1 knockdown suppressed hormone-independent growth, inhibited EGF binding to the cell surface, and blocked EGFR-ERK1/2 activation. HS3ST1 knockdown in C4-2 cells, hormone-depletion culture conditions, EGF binding assay, EGFR-ERK1/2 phosphorylation, xenograft mouse model with gefitinib Scientific reports Medium 37463954
2025 HS3ST1 is required for antithrombin-binding heparan sulfate (HSAT) expression in epithelial basement membranes; inactivation of HS3ST1 in pancreatic ductal adenocarcinoma cells eliminated HSAT, induced an inflammatory phenotype, suppressed apoptosis markers, and increased metastasis in experimental mouse models; HSAT-positive cells bind antithrombin, which inhibits tissue factor/factor VIIa-dependent thrombin generation. HS3ST1 inactivation in PDAC cells, immunostaining, mouse PDAC metastasis model, AT binding assay, thrombin generation assay, plasma HSAT measurement from PDAC patients The Journal of clinical investigation High 40924474
2019 HS3ST1 overexpression in renal epithelial cells (HKC8-HS3ST1) prolonged STAT3 phosphorylation in response to HB-EGF compared to a transient response in control cells, indicating that HS 3-O-sulfation produced by HS3ST1 modulates HB-EGF signaling in renal epithelial cells. HS3ST1 overexpression in HKC8 cells, HB-EGF stimulation, STAT3 phosphorylation time-course assay Biochimica et biophysica acta. General subjects Medium 30794825
2026 The 3-OST-1 E86Q mutant acts as a dominant-negative inhibitor: it retains substrate and PAPS donor binding but abolishes catalytic activity, reducing wild-type 3-OST-1-like activity by >80% in vitro and significantly decreasing 3-O-sulfated HS products in cells without affecting overall HS abundance, identifying E86 as critical for catalysis. E86Q site-directed mutagenesis, LC-MS/MS enzymatic activity assay with 13C-labeled internal standards, cell-based 3-O-sulfated HS quantification Glycobiology High 41914643
2005 In glomerular epithelial cells expressing both 3-OST-1 and 3-OST-3A, anticoagulant heparan sulfate production is regulated by an extremely limiting precursor pool rather than by limiting 3-OST-1 levels alone; Hs3st1-/- kidney sections showed continued HSPG synthesis by non-3-OST-1 isoforms in vivo, demonstrating cell-type-specific regulatory mechanisms. Radiolabeled antithrombin probing of kidney cryosections, cultured glomerular epithelial cell HS structural analysis, Hs3st1-/- mouse kidney section probing, disaccharide and transcript analyses The Journal of biological chemistry Medium 16107334
2010 Hs3st1-/- mice exhibit a strong proinflammatory phenotype that is unresponsive to antithrombin's anti-inflammatory activity, establishing that the predominant function of HSAT+ (produced by HS3ST1) is to mediate antithrombin's anti-inflammatory rather than anticoagulant activity. Hs3st1-/- knockout mouse, inflammatory model, antithrombin treatment experiments Progress in molecular biology and translational science Medium 20807645
2020 siRNA knockdown of HS3ST1 (3-O-sulfotransferase 1) in endothelial cells downregulated the pro-inflammatory function of Plasmodium falciparum HRPII, supporting the hypothesis that HRPII competitively inhibits the interaction of antithrombin with 3-O-sulfate-containing vascular glycosaminoglycans produced by HS3ST1. siRNA knockdown of 3-OST-1 in endothelial cells, barrier permeability assay, AT-HRPII competition assay Journal of thrombosis and haemostasis : JTH Medium 31858717
2024 HS3ST1 interacts with GPC4 (glypican-4) as shown by immunoprecipitation, and HS3ST1-mediated glycolysis is promoted by GPC4; hypoxia-derived exosomal lncRNA OIP5-AS1 enhances this HS3ST1-GPC4-mediated glycolysis via miR-200c-3p in lung adenocarcinoma cells. Co-immunoprecipitation of HS3ST1 and GPC4, cell viability, colony formation, xenograft animal models Cancers Low 38398086

Source papers

Stage 0 corpus · 81 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Multiple isoforms of heparan sulfate D-glucosaminyl 3-O-sulfotransferase. Isolation, characterization, and expression of human cdnas and identification of distinct genomic loci. The Journal of biological chemistry 195 9988767
2011 Selectin ligand sialyl-Lewis x antigen drives metastasis of hormone-dependent breast cancers. Cancer research 156 22025563
1999 Expression of heparan sulfate D-glucosaminyl 3-O-sulfotransferase isoforms reveals novel substrate specificities. The Journal of biological chemistry 150 9988768
2003 Normal levels of anticoagulant heparan sulfate are not essential for normal hemostasis. The Journal of clinical investigation 122 12671048
2020 Transdifferentiation of tumor infiltrating innate lymphoid cells during progression of colorectal cancer. Cell research 120 32367039
2015 Polygenic Overlap Between C-Reactive Protein, Plasma Lipids, and Alzheimer Disease. Circulation 112 25862742
2017 Heparan Sulfate Microarray Reveals That Heparan Sulfate-Protein Binding Exhibits Different Ligand Requirements. Journal of the American Chemical Society 103 28651046
1999 Heparan sulfate D-glucosaminyl 3-O-sulfotransferase-3A sulfates N-unsubstituted glucosamine residues. The Journal of biological chemistry 87 10608887
2019 3-O-Sulfation of Heparan Sulfate Enhances Tau Interaction and Cellular Uptake. Angewandte Chemie (International ed. in English) 85 31692167
2001 6-O-sulfotransferase-1 represents a critical enzyme in the anticoagulant heparan sulfate biosynthetic pathway. The Journal of biological chemistry 71 11551899
2010 Quantitative and qualitative alterations of heparan sulfate in fibrogenic liver diseases and hepatocellular cancer. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 66 20124094
2016 Expanding the 3-O-Sulfate Proteome--Enhanced Binding of Neuropilin-1 to 3-O-Sulfated Heparan Sulfate Modulates Its Activity. ACS chemical biology 62 26731579
2012 Metabolic engineering of Chinese hamster ovary cells: towards a bioengineered heparin. Metabolic engineering 62 22326251
2005 Developmental and regional expression of heparan sulfate sulfotransferase genes in the mouse brain. Glycobiology 57 15944372
2002 Mice deficient in heparan sulfate 3-O-sulfotransferase-1: normal hemostasis with unexpected perinatal phenotypes. Glycoconjugate journal 54 12975616
2012 Dissecting the substrate recognition of 3-O-sulfotransferase for the biosynthesis of anticoagulant heparin. Proceedings of the National Academy of Sciences of the United States of America 53 22431632
2000 Enzymatic modification of heparan sulfate on a biochip promotes its interaction with antithrombin III. Biochemical and biophysical research communications 51 11006120
2018 Meta-analysis of Alzheimer's disease on 9,751 samples from Norway and IGAP study identifies four risk loci. Scientific reports 48 30591712
2010 Anticoagulant heparan sulfate to not clot--or not? Progress in molecular biology and translational science 46 20807645
2008 Tetrasulfated disaccharide unit in heparan sulfate: enzymatic formation and tissue distribution. The Journal of biological chemistry 43 18757372
2003 Biosynthesis of 3-O-sulfated heparan sulfate: unique substrate specificity of heparan sulfate 3-O-sulfotransferase isoform 5. Glycobiology 42 12907690
2007 Soluble 3-O-sulfated heparan sulfate can trigger herpes simplex virus type 1 entry into resistant Chinese hamster ovary (CHO-K1) cells. The Journal of general virology 38 17374750
2020 ZNF263 is a transcriptional regulator of heparin and heparan sulfate biosynthesis. Proceedings of the National Academy of Sciences of the United States of America 32 32277030
2013 Bioengineered Chinese hamster ovary cells with Golgi-targeted 3-O-sulfotransferase-1 biosynthesize heparan sulfate with an antithrombin-binding site. The Journal of biological chemistry 32 24247246
2017 Heparan Sulfate Biosynthetic System Is Inhibited in Human Glioma Due to EXT1/2 and HS6ST1/2 Down-Regulation. International journal of molecular sciences 31 29104277
2001 Portable sulphotransferase domain determines sequence specificity of heparan sulphate 3-O-sulphotransferases. The Biochemical journal 31 11563988
2023 Increased 3-O-sulfated heparan sulfate in Alzheimer's disease brain is associated with genetic risk gene HS3ST1. Science advances 29 37235665
2021 Genome-wide association study and functional validation implicates JADE1 in tauopathy. Acta neuropathologica 29 34719765
2020 Autoinflammation in addition to combined immunodeficiency: SLC29A3 gene defect. Molecular immunology 29 32151906
2018 Identification of specific and common diagnostic antibody markers for gastrointestinal cancers by SEREX screening using testis cDNA phage library. Oncotarget 29 29719626
2021 Development and Validation of a Hypoxia-Related Signature for Predicting Survival Outcomes in Patients With Bladder Cancer. Frontiers in genetics 26 34122523
2004 Mapping critical biological motifs and biosynthetic pathways of heparan sulfate. Glycobiology 26 15033939
2023 Apolipoprotein E Recognizes Alzheimer's Disease Associated 3-O Sulfation of Heparan Sulfate. Angewandte Chemie (International ed. in English) 25 37014788
2005 Synthesis of anticoagulantly active heparan sulfate proteoglycans by glomerular epithelial cells involves multiple 3-O-sulfotransferase isoforms and a limiting precursor pool. The Journal of biological chemistry 25 16107334
2017 HS3ST1 genotype regulates antithrombin's inflammomodulatory tone and associates with atherosclerosis. Matrix biology : journal of the International Society for Matrix Biology 23 28126521
2017 Therapeutic Response to Paroxetine in Major Depressive Disorder Predicted by DNA Methylation. Neuropsychobiology 23 29131015
2015 Tissue-specificity of heparan sulfate biosynthetic machinery in cancer. Cell adhesion & migration 21 26120938
2008 Glycanogenomics: a qPCR-approach to investigate biological glycan function. Biochemical and biophysical research communications 21 18692483
2010 Direct effects of IL-4/IL-13 and the nematode Nippostrongylus brasiliensis on intestinal epithelial cells in vitro. Parasite immunology 20 20500673
2023 Genetic associations with age at dementia onset in the PSEN1 E280A Colombian kindred. Alzheimer's & dementia : the journal of the Alzheimer's Association 18 36951251
2014 Transcriptional Activity of Heparan Sulfate Biosynthetic Machinery is Specifically Impaired in Benign Prostate Hyperplasia and Prostate Cancer. Frontiers in oncology 18 24782989
2014 Comprehensive analysis of herpes simplex virus 1 (HSV-1) entry mediated by zebrafish 3-O-Sulfotransferase isoforms: implications for the development of a zebrafish model of HSV-1 infection. Journal of virology 17 25142596
2011 A synthetic heparan sulfate oligosaccharide library reveals the novel enzymatic action of D-glucosaminyl 3-O-sulfotransferase-3a. Molecular bioSystems 16 22116385
2022 The 3-O sulfation of heparan sulfate proteoglycans contributes to the cellular internalization of tau aggregates. BMC molecular and cell biology 14 36564747
2020 Combinatorial virtual library screening analysis of antithrombin binding oligosaccharide motif generation by heparan sulfate 3-O-Sulfotransferase 1. Computational and structural biotechnology journal 14 32346466
2013 Bioengineering murine mastocytoma cells to produce anticoagulant heparin. Glycobiology 14 24326668
2023 Hemolysis is associated with altered heparan sulfate of the endothelial glycocalyx and with local complement activation in thrombotic microangiopathies. Kidney international 12 37164260
2020 Plasmodium falciparum histidine rich protein HRPII inhibits the anti-inflammatory function of antithrombin. Journal of thrombosis and haemostasis : JTH 12 31858717
2012 Toward a bioengineered heparin: challenges and strategies for metabolic engineering of mammalian cells. Bioengineered 12 22714556
2012 Involvement of heparan sulfate 3-O-sulfotransferase isoform-1 in the insulin secretion pathway. Journal of diabetes investigation 12 24843591
2015 Proteoglycan expression correlates with the phenotype of malignant and non-malignant EBV-positive B-cell lines. Oncotarget 11 26527314
2013 Expression of low endotoxin 3-O-sulfotransferase in Bacillus subtilis and Bacillus megaterium. Applied biochemistry and biotechnology 11 23912211
2002 Expression in Escherichia coli, purification and kinetic characterization of human heparan sulfate 3-O-sulfotransferase-1. Biochemical and biophysical research communications 11 11811991
2024 Hypoxia-Derived Exosomes Promote Lung Adenocarcinoma by Regulating HS3ST1-GPC4-Mediated Glycolysis. Cancers 10 38398086
2023 Genome-wide identification of potential odontogenic genes involved in the dental epithelium-mesenchymal interaction during early odontogenesis. BMC genomics 10 37013486
2021 The construction of a dual-functional strain that produces both polysaccharides and sulfotransferases. Biotechnology letters 10 34176028
2019 Heparan sulfate in chronic kidney diseases: Exploring the role of 3-O-sulfation. Biochimica et biophysica acta. General subjects 10 30794825
2023 Switching mechanism from AR to EGFR signaling via 3-O-sulfated heparan sulfate in castration-resistant prostate cancer. Scientific reports 9 37463954
2013 Members of 3-O-Sulfotransferases (3-OST) Family: A Valuable Tool from Zebrafish to Humans for Understanding Herpes Simplex Virus Entry. The open virology journal 9 23358893
2002 Identification of structural motifs and amino acids within the structure of human heparan sulfate 3-O-sulfotransferase that mediate enzymatic function. Biochemical and biophysical research communications 9 11811992
2023 Identification of potential diagnostic biomarkers and therapeutic targets for endometriosis based on bioinformatics and machine learning analysis. Journal of assisted reproduction and genetics 7 37555920
2019 Identification of Important Invasion-Related Genes in Non-functional Pituitary Adenomas. Journal of molecular neuroscience : MN 7 30982163
2018 Increased soluble heterologous expression of a rat brain 3-O-sulfotransferase 1 - A key enzyme for heparin biosynthesis. Protein expression and purification 6 29894802
2022 HS3ST1 Promotes Non-Small-Cell Lung Cancer Progression by Targeting the SPOP/FADD/NF-κB Pathway. BioMed research international 5 35909476
2025 Sex- and age- differences in the expression of critical blood-brain barrier regulators: a physiological context. Biology of sex differences 4 40898358
2014 Modulation of heparan sulfate biosynthesis by sodium butyrate in recombinant CHO cells. Cytotechnology 4 24468831
2024 Genetic variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfate diversity. Essays in biochemistry 3 39630030
2022 Preparation and characterization of 2-deacetyl-3-O-sulfo-heparosan and its antitumor effects via the fibroblast growth factor receptor pathway. International journal of biological macromolecules 3 34998873
2025 Genetic Markers of Postmortem Brain Iron. Journal of neurochemistry 2 39918201
2025 Design and verification of a 25 K multiple-SNP liquid-capture chip by target sequencing for dairy goat. BMC genomics 2 40234771
2025 Excitatory cortical neurons from CDKL5 deficiency disorder patient-derived organoids show early hyperexcitability not identified in neurogenin2 induced neurons. Neurobiology of disease 2 40930428
2024 Excitatory Cortical Neurons from CDKL5 Deficiency Disorder Patient-Derived Organoids Show Early Hyperexcitability Not Identified in Neurogenin2 Induced Neurons. bioRxiv : the preprint server for biology 2 39605742
2025 Antithrombin-binding heparan sulfate is ubiquitously expressed in epithelial cells and suppresses pancreatic tumorigenesis. The Journal of clinical investigation 1 40924474
2024 Differential regulation of heparan sulfate biosynthesis in fibroblasts cocultured with normal vs. cancerous prostate cells. Frontiers in immunology 1 39318629
2026 Machine learning-based predictive models and subtypes patterns in peripheral blood of schizophrenia based on a machine learning computational framework. Schizophrenia (Heidelberg, Germany) 0 41876515
2026 Development of a specific and sensitive LC-MS/MS method to quantify Heparan Sulfate 3-O-Sulfotransferase-1 activity. Glycobiology 0 41914643
2025 Rational Design and Engineering of 3-O-Sulfotransferase 1 Based on Enzyme Affinity for Improved Enzymatic Heparin Preparation. Journal of agricultural and food chemistry 0 40267027
2025 Exploring the Cellular and Molecular Landscape of Idiopathic Pulmonary Fibrosis: Integrative Multi-Omics and Single-Cell Analysis. Biomedicines 0 41007698
2025 Repurposing cephalosporins as excellent anticancer agents and chemosensitizers for inflammation-driven cancer therapy. Scientific reports 0 41272089
2024 Hypoxia-related signature to risk stratify patients for the benefit of immune checkpoint inhibitors therapy in head and neck squamous cell carcinoma: An experimental study. Medicine 0 39093745
2023 Retracted: HS3ST1 Promotes Non-Small-Cell Lung Cancer Progression by Targeting the SPOP/FADD/NF-κB Pathway. BioMed research international 0 38188779