Affinage

HS3ST1

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

Length
307 aa
Mass
35.8 kDa
Annotated
2026-06-10
83 papers in source corpus 25 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

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 integral membrane enzyme that transfers a sulfo group from PAPS to the 3-OH position of specific glucosamine residues in heparan sulfate, the rate-limiting step that converts non-anticoagulant HS into anticoagulant HS bearing the antithrombin-binding motif (PMID:9988767, PMID:9988768, PMID:24247246). Isoform-specific substrate selectivity resides entirely within its self-contained C-terminal sulfotransferase domain rather than its divergent N-terminus (PMID:11563988), and the catalytic mechanism has been defined structurally by a ternary complex of the enzyme with PAP and a heptasaccharide together with mutagenesis identifying Arg268 as a key substrate-binding residue and Glu86 as catalytically essential—an E86Q substitution behaving as a dominant-negative that abolishes activity while retaining binding (PMID:22431632, PMID:41914643). Correct Golgi targeting is required to generate the high-affinity antithrombin-binding site, and 6-O-sulfotransferase-1 acts downstream as a co-limiting enzyme in anticoagulant HS biosynthesis (PMID:11551899, PMID:24247246). The 3-O-sulfated motif serves as a high-affinity ligand for multiple proteins: antithrombin, where HS3ST1-derived HS is dispensable for normal hemostasis but is required for antithrombin's anti-inflammatory and endothelial barrier-protective activity (PMID:12671048, PMID:12975616, PMID:28126521); tau, where 3-O-sulfation promotes cell-surface binding and internalization of monomeric and aggregated tau and is elevated in Alzheimer's disease brain (PMID:31692167, PMID:36564747, PMID:37235665); and ApoE (PMID:37014788). HS3ST1 transcription is repressed by the zinc-finger factor ZNF263, whose loss elevates 3-O-sulfation and antithrombin binding (PMID:32277030). Beyond coagulation and neurodegeneration, HS3ST1-generated anticoagulant HS in epithelial basement membranes suppresses an inflammatory, pro-metastatic phenotype in pancreatic ductal adenocarcinoma by enabling antithrombin to inhibit tissue factor/factor VIIa-driven thrombin generation (PMID:40924474), and HS3ST1-derived 3-O-sulfated HS modulates growth-factor signaling, facilitating EGF/EGFR-ERK signaling in castration-resistant prostate cancer and HB-EGF/STAT3 signaling in renal epithelial cells (PMID:30794825, PMID:37463954).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1999 High

    Established the molecular identity and enzymatic activity of HS3ST1, answering what reaction the gene product catalyzes and why its activity is biologically distinct from related sulfotransferases.

    Evidence cDNA expression in COS-7 cells with radiolabeled PAPS sulfotransferase assay and disaccharide analysis

    PMID:9988767 PMID:9988768

    Open questions at the time
    • Domain responsible for substrate selectivity not yet localized
    • Subcellular localization not directly demonstrated
    • In vivo function unknown
  2. 2000 Medium

    Demonstrated directly that 3-OST-1 modification converts low-affinity to high-affinity antithrombin binding, linking a single sulfation event to a defined recognition outcome.

    Evidence Surface plasmon resonance on biotinylated HS biochip with enzymatic modification

    PMID:11006120

    Open questions at the time
    • Single lab/study
    • Structural basis of recognition not resolved
  3. 2001 High

    Localized isoform-specific substrate selectivity to the sulfotransferase domain, showing the divergent N-terminus does not dictate which HS sites are modified.

    Evidence Domain-swap chimera expression in COS-7 with antithrombin-binding and HSV-1 entry readouts

    PMID:11563988

    Open questions at the time
    • Specific residues within domain not yet identified
    • Structural model absent
  4. 2001 High

    Placed 3-OST-1 within the anticoagulant HS biosynthetic pathway by identifying 6-OST-1 as a co-limiting downstream enzyme.

    Evidence Retroviral 3-OST-1 transduction, mutagenesis screen, 6-OST-1 rescue, and HPLC-MS disaccharide analysis in CHO cells

    PMID:11551899

    Open questions at the time
    • Ordering of sulfation steps in vivo not fully resolved
    • Other pathway enzymes not characterized here
  5. 2002 Medium

    Defined the kinetic parameters and demonstrated a soluble active enzyme could be produced, establishing tractable biochemistry for the catalytic mechanism.

    Evidence E. coli expression, purification, radiochemical kinetic assay with [35S]PAPS; companion homology modeling

    PMID:11811991 PMID:11811992

    Open questions at the time
    • Modeling predictions not experimentally validated in these studies
    • Single lab
  6. 2003 High

    Tested the physiological requirement for anticoagulant HS in vivo, revealing it is dispensable for hemostasis and pointing to alternative biological roles.

    Evidence Hs3st1 knockout mice with enzyme assays, ferric chloride carotid injury, fibrin accumulation, and thrombin-antithrombin measurements

    PMID:12671048 PMID:12975616

    Open questions at the time
    • Alternative biological function of the structures unidentified at the time
    • Cause of background-specific lethality unexplained
  7. 2012 High

    Provided a definitive structural basis for catalysis and isoform-specific substrate recognition through a ternary complex structure.

    Evidence X-ray crystallography of 3-OST-1 with PAP and heptasaccharide plus site-directed mutagenesis of Arg268

    PMID:22431632

    Open questions at the time
    • Catalytic residue contributions not all mapped here
    • Conformational dynamics during turnover not addressed
  8. 2012 Medium

    Linked HS3ST1 activity to glucose-stimulated insulin secretion, extending its function beyond the antithrombin axis.

    Evidence siRNA knockdown in MIN6T3 cells with glucose-induced insulin secretion assay and chlorate sulfation inhibition

    PMID:24843591

    Open questions at the time
    • Single lab single phenotype
    • Molecular target of HS in beta-cell secretion unknown
    • Not validated in vivo
  9. 2013 High

    Connected correct Golgi localization to functional anticoagulant site formation and revealed concerted regulation of other HS sulfation enzymes.

    Evidence Golgi-targeted vs untargeted HS3ST1 stable CHO transfection with anti-factor Xa activity, immunofluorescence, and disaccharide analysis

    PMID:24247246

    Open questions at the time
    • Mechanism coordinating other sulfotransferase upregulation unknown
    • Single lab
  10. 2017 High

    Identified neuropilin-1 as a 3-O-sulfated HS-binding partner while showing isoform specialization (Hs3st2, not Hs3st1, for growth cone collapse).

    Evidence Affinity chromatography, SPR, growth cone collapse and endothelial sprouting assays in isoform-specific knockout neurons

    PMID:26731579

    Open questions at the time
    • Distinct in vivo role of Hs3st1 versus Hs3st2 not fully delineated
  11. 2017 High

    Resolved the principal physiological role of HS3ST1-derived HS as the mediator of antithrombin's anti-inflammatory activity, with human genetic support linking reduced expression to coronary artery disease.

    Evidence Hs3st1 knockout LPS septic shock model, intravital microscopy, coronary arteriole assays, and human candidate-gene/eQTL study

    PMID:28126521

    Open questions at the time
    • Endothelial signaling downstream of AT not fully mapped
    • Causality of the human variant beyond association not established
  12. 2019 Medium

    Implicated HS3ST1 in growth-factor signaling, with overexpression prolonging HB-EGF-induced STAT3 activation and pro-fibrotic cytokines repressing its expression.

    Evidence Stable HS3ST1 overexpression in HKC8 renal cells with pSTAT3 time-course and qRT-PCR in TGFβ-treated cells

    PMID:30794825

    Open questions at the time
    • Gain-of-function only; loss-of-function not tested
    • Direct HS-receptor interaction not demonstrated
    • Single lab
  13. 2019 High

    Established that 3-O-sulfation enhances tau binding and internalization, providing a glycan-based entry route relevant to tau propagation.

    Evidence HS microarray, SPR with defined oligosaccharides, Hs3st1−/− cell binding/uptake assays, and NMR mapping to tau R2/PRR2 domains

    PMID:31692167

    Open questions at the time
    • Cell-surface receptor mediating uptake not identified
    • In vivo relevance to tau spread not tested here
  14. 2020 High

    Identified ZNF263 as a transcriptional repressor of HS3ST1, explaining a regulatory mechanism controlling 3-O-sulfation output.

    Evidence CRISPR knockout and siRNA knockdown of ZNF263 with qRT-PCR, antithrombin binding, factor Xa inhibition, and neuropilin-1 binding readouts

    PMID:32277030

    Open questions at the time
    • Direct ZNF263 binding to the HS3ST1 promoter not detailed
    • Upstream regulators of ZNF263 unknown
  15. 2020 Medium

    Showed HS3ST1-derived 3-O-sulfated HS is exploited by Plasmodium HRPII, which competes with antithrombin to disrupt endothelial barrier protection.

    Evidence siRNA HS3ST1 knockdown in endothelial cells with barrier permeability, VE-cadherin phosphorylation, and AT competition assays

    PMID:31858717

    Open questions at the time
    • Single lab
    • Structural basis of HRPII/AT competition not resolved
  16. 2023 High

    Defined ApoE as a 3-O-sulfated HS-binding ligand whose cell-surface binding and uptake depend on HS3ST1.

    Evidence Glycan microarray, SPR, NMR titration, and HS3ST1 KO cell binding/uptake assays

    PMID:37014788

    Open questions at the time
    • Isoform-specific (E2/E3/E4) functional consequences not distinguished
    • In vivo significance not tested
  17. 2023 High

    Extended the tau axis by showing HS3ST1-generated 3-O-sulfated HS drives uptake of tau aggregates and identifying a disease-elevated 3-O-sulfated structure in Alzheimer's brain.

    Evidence HS3ST1 KO cells with LC-MS/MS confirmation, tau aggregate uptake and AT competition assays, and synthetic 14-mer inhibition tests

    PMID:36564747 PMID:37235665

    Open questions at the time
    • Causal contribution to disease progression in vivo not established
    • Receptor co-factor for aggregate uptake unidentified
  18. 2023 Medium

    Demonstrated an oncogenic signaling role in castration-resistant prostate cancer, where HS3ST1-derived HS facilitates EGF binding and EGFR-ERK activation for hormone-independent growth.

    Evidence HS3ST1 siRNA knockdown in C4-2 cells with EGF binding, EGFR-ERK1/2 phosphorylation, proliferation assays, and castrated-mouse xenografts with gefitinib

    PMID:37463954

    Open questions at the time
    • Single lab
    • Direct HS-EGF/EGFR structural interaction not defined
  19. 2025 High

    Revealed a tumor-suppressive role in pancreatic cancer, with HS3ST1-generated anticoagulant HS in epithelial basement membranes restraining inflammation and metastasis via antithrombin-mediated inhibition of thrombin generation.

    Evidence HS3ST1 inactivation in PDAC cells, mouse metastasis model, antithrombin binding, tissue factor/factor VIIa thrombin generation assay, and human tissue immunostaining

    PMID:40924474

    Open questions at the time
    • Signaling linking thrombin to the inflammatory/metastatic phenotype not fully mapped
    • Therapeutic implications untested
  20. 2025 Medium

    Engineered hyperactive 3-OST-1 mutants with increased substrate affinity, advancing biotechnological production of anticoagulant heparin.

    Evidence Rational mutagenesis (W72R, H144R), enzyme kinetics, molecular dynamics simulations, and anti-factor Xa assays

    PMID:40267027

    Open questions at the time
    • Molecular dynamics component is computational
    • Single lab
    • Not tested in cellular contexts
  21. 2026 High

    Pinpointed Glu86 as the catalytic residue and created a dominant-negative tool, while delivering a sensitive assay to quantify endogenous 3-OST-1 activity.

    Evidence E86Q site-directed mutagenesis, quantitative LC-MS/MS activity assay with 13C standards, and cellular dominant-negative expression

    PMID:41914643

    Open questions at the time
    • In vivo use of the dominant-negative not demonstrated
    • Full catalytic mechanism beyond Glu86 not enumerated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HS3ST1-derived 3-O-sulfated HS engages distinct cell-surface co-receptors to direct opposing outcomes (anti-inflammatory protection versus tau/ApoE internalization versus growth-factor signaling) in different tissues remains unresolved.
  • No unifying model for tissue-specific ligand selection
  • Co-receptors for tau/ApoE uptake unidentified
  • In vivo significance of growth-factor and insulin-secretion roles untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 7 GO:0140098 catalytic activity, acting on RNA 4
Localization
GO:0005794 Golgi apparatus 2
Pathway
R-HSA-109582 Hemostasis 3 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 HS3ST1 (3-OST-1) encodes heparan sulfate D-glucosaminyl 3-O-sulfotransferase-1, a type II integral membrane protein with a self-contained C-terminal sulfotransferase domain (~260 residues) and a divergent N-terminal region. Expression in COS-7 cells confirmed 3-O-sulfation of specific glucosaminyl residues within heparan sulfate and conversion of non-anticoagulant to anticoagulant heparan sulfate (HSact). 3-OST-1 showed 300-fold greater HSact conversion activity than 3-OST-2 and 3-OST-3A isoforms. cDNA expression in COS-7 cells, radiolabeled PAPS sulfotransferase assay, disaccharide analysis, Northern blot The Journal of biological chemistry High 9988767 9988768
2001 The sequence-specific properties of 3-OST-1 (preferential generation of antithrombin-binding sites) reside entirely within the sulphotransferase domain and are not influenced by the divergent N-terminal region. Domain-swap chimeras (N-terminal of 3-OST-3A fused to sulphotransferase domain of 3-OST-1, and vice versa) demonstrated that the sulphotransferase domain alone determines isoform-specific substrate selectivity. cDNA domain-swap chimera expression in COS-7 cells, antithrombin-binding site generation assay, HSV-1 entry assay in CHO transfectants The Biochemical journal High 11563988
2000 3-OST-1 enzymatically modifies heparan sulfate immobilized on a biochip by introducing a 3-O-sulfo group, converting low-affinity antithrombin III (ATIII) binding to high-affinity binding, as detected by surface plasmon resonance. This demonstrates the specific structural modification required for ATIII recognition. Surface plasmon resonance (SPR) on streptavidin biochip with biotinylated heparan sulfate, enzymatic modification with 3-OST-1 and PAPS Biochemical and biophysical research communications Medium 11006120
2002 Recombinant human 3-OST-1 expressed in E. coli is a soluble, active enzyme with Km values in the low micromolar range (KmHS = 4.3 µM; KmPAPS = 38.6 µM) and Vmax of ~18–21 pmol sulfate/min/pmol enzyme, comparable to baculovirus-expressed enzyme. This established the kinetic parameters of the catalytic mechanism. Expression in E. coli, purification, radiochemical in vitro sulfotransferase kinetic assay with [35S]PAPS Biochemical and biophysical research communications Medium 11811991
2002 Structure-based homology modeling of 3-OST-1 identified key structural motifs and specific amino acids predicted to be important for enzymatic function and substrate recognition, providing a structural framework for the 3-O-sulfotransferase catalytic mechanism. Computational homology modeling using crystallographic data of related enzymes, structural analysis tools Biochemical and biophysical research communications Low 11811992
2001 6-O-sulfotransferase-1 (6-OST-1) is a limiting enzyme in the anticoagulant heparan sulfate (HSact) biosynthetic pathway downstream of 3-OST-1. In CHO cells expressing 3-OST-1, a mutant deficient in 6-O-sulfation failed to produce HSact; transfection with 6-OST-1 rescued HSact production to ~50%. Both 3-O- and 6-O-sulfation can each be the terminal step in HSact biosynthesis. Retroviral transduction of 3-OST-1 into CHO cells, chemical mutagenesis screen, 6-OST-1 transfection rescue, in vitro modification with purified 6-OST-1, capillary HPLC-MS disaccharide analysis The Journal of biological chemistry High 11551899
2003 Hs3st1 knockout mice are devoid of 3-OST-1 enzyme activity in plasma and tissues, showing dramatic reductions in tissue HSact. However, hemostasis is normal (normal fibrin accumulation, normal carotid artery occlusion times, normal thrombin-antithrombin complexes). Instead, Hs3st1−/− mice exhibit genetic background-specific lethality and intrauterine growth retardation, indicating that bulk HSact is dispensable for normal hemostasis and that 3-OST-1-derived structures serve alternative biological roles. Hs3st1 knockout mouse generation, enzyme activity assay in plasma and tissue extracts, ferric chloride carotid artery injury assay, tissue fibrin accumulation under normoxic and hypoxic conditions, thrombin-antithrombin complex measurement The Journal of clinical investigation High 12671048 12975616
2012 Crystal structure of the ternary complex of 3-OST-1 with 3'-phosphoadenosine 5'-phosphate (PAP) and a heptasaccharide substrate was determined. Comparison to 3-OST-3 structures revealed distinct substrate-binding modes and saccharide conformations for each isoform. Site-directed mutagenesis identified Arg268 in 3-OST-1 (and Lys259, Thr256, Trp283 in 3-OST-3) as key residues for substrate binding and isoform specificity. X-ray crystallography (ternary complex), site-directed mutagenesis, structural comparison to 3-OST-3 crystal structures Proceedings of the National Academy of Sciences of the United States of America High 22431632
2013 Golgi-targeted HS3ST1 localizes to the Golgi and produces a single type of antithrombin (AT)-binding site in CHO cells with high anti-factor Xa activity (137 ± 36 units/mg). Untargeted HS3ST1 is broadly distributed throughout CHO cells and produces no detectable AT-binding sites. Stable HS3ST1 overexpression also upregulates 2-O-, 6-O-, and N-sulfo group-containing disaccharides, revealing a concerted interplay between HS biosynthetic enzymes. Stable CHO cell transfection with Golgi-targeted vs. untargeted HS3ST1, anti-factor Xa anticoagulant activity assay, immunofluorescence localization, disaccharide composition analysis by AMAC-LCMS The Journal of biological chemistry High 24247246
2017 3-O-sulfation of heparan sulfate catalyzed by Hs3st1 enhances binding of neuropilin-1 to heparan sulfate. 3-O-sulfated heparan sulfate dodecamers inhibited neuropilin-1-dependent semaphorin-3a-induced growth cone collapse of neurons and enhanced inhibition of endothelial cell sprouting. The effect was specific to Hs3st2 (not Hs3st1) for growth cone collapse in neurons from isoform-specific knockout mice. Affinity chromatography with 3-O-sulfated HS columns, SPR binding assay, thermal denaturation protection assay, growth cone collapse assay with Hs3st1−/− and Hs3st2−/− neuron cultures, endothelial cell sprouting assay ACS chemical biology High 26731579
2017 In Hs3st1−/− mice, antithrombin (AT) treatment during LPS-induced septic shock induced pro-inflammatory rather than anti-inflammatory effects: increased LPS-lethality, increased leukocyte firm adhesion to endothelium, and vasoconstriction of coronary arterioles (opposite of effects in wild-type mice). In humans, the rs16881446G allele in HS3ST1 was associated with reduced HS3ST1 expression in primary endothelial cells and with increased severity of coronary artery disease. This establishes that the primary function of HS3ST1-derived HSAT+ is to mediate AT's anti-inflammatory activity. Hs3st1−/− mouse LPS challenge model, intravital microscopy for leukocyte adhesion, ex vivo coronary arteriole dilation assay, human candidate-gene association study in >2000 patients, eQTL analysis in primary endothelial cells Matrix biology : journal of the International Society for Matrix Biology High 28126521
2019 3-O-sulfation of heparan sulfate (catalyzed by HS3ST1/3-OST-1) significantly enhances tau binding to heparan sulfate. In Hs3st1−/− cells, reduced 3-O-sulfation diminished both cell-surface binding and internalization of tau. NMR titrations mapped 3-O-S binding sites on tau to the microtubule binding repeat 2 (R2) and proline-rich region 2 (PRR2) domains. HS microarray, SPR binding assay with structurally defined oligosaccharides, Hs3st1−/− cell-based tau binding and uptake assay, NMR titration Angewandte Chemie (International ed. in English) High 31692167
2020 ZNF263, a C2H2 zinc finger transcription factor, represses HS3ST1 transcription. CRISPR-mediated knockout or siRNA knockdown of ZNF263 dramatically increased HS3ST1 expression, leading to enhanced 3-O-sulfation, increased antithrombin binding, increased Factor Xa inhibition, and increased neuropilin-1 binding. ZNF263 is expressed at distinctively low levels in mast cells (heparin-producing cells). CRISPR KO and siRNA knockdown of ZNF263 in mammalian cell lines and primary human cells, qRT-PCR, antithrombin binding flow cytometry, Factor Xa inhibition assay, transcriptomics analysis of mast cell expression Proceedings of the National Academy of Sciences of the United States of America High 32277030
2022 3-O-sulfation of heparan sulfate, as generated by HS3ST1, contributes to cellular internalization of tau aggregates. In HS3ST1−/− cells (confirmed by LC-MS/MS), uptake of tau aggregates was reduced. Aggregated tau shows higher affinity for 3-O-sulfated HS than non-3-O-sulfated HS, and competition with antithrombin III (which binds 3-O-sulfated HS) reduced tau uptake. HS3ST1 KO cell line, LC-MS/MS with 13C-labeled HS calibrants to confirm 3-O-sulfation loss, tau aggregate uptake assay, antithrombin III competition assay BMC molecular and cell biology High 36564747
2023 A specific 3-O-sulfated heparan sulfate disaccharide structure made by 3-OST-1 (encoded by HS3ST1) is increased sevenfold in Alzheimer's disease brains versus controls. This structure was identified by LC-MS/MS and confirmed using recombinant sulfotransferases and Hs3st1 knockout mouse HS. A synthetic 14-mer carrying this 3-O-sulfated domain showed stronger inhibition of tau internalization than a 14-mer lacking it. LC-MS/MS analysis of brain HS, recombinant enzyme modification assay, Hs3st1−/− mouse HS analysis, synthetic tetradecasaccharide inhibition assay for tau internalization Science advances High 37235665
2023 ApoE (all isoforms: ApoE2, ApoE3, ApoE4) recognizes and binds 3-O-sulfated heparan sulfate. In HS3ST1 knockout cells, cell-surface binding and uptake of ApoE were reduced. NMR titration localized ApoE/3-O-S binding to the vicinity of the canonical HS binding motif in ApoE. Glycan microarray, SPR binding assay, NMR titration, HS3ST1 KO cell-based ApoE binding and uptake assay Angewandte Chemie (International ed. in English) High 37014788
2012 HS3ST1 (Hs3st1) is involved in the insulin secretion pathway in pancreatic β-cells. siRNA-mediated silencing of Hs3st1 reduced glucose-induced insulin secretion (GIIS) in MIN6T3 cells, acting upstream of membrane depolarization. siRNA knockdown of Hs3st1 in MIN6T3 cells, glucose-induced insulin secretion assay, sodium chlorate inhibition of sulfation, qRT-PCR Journal of diabetes investigation Medium 24843591
2019 HS3ST1 overexpression in renal epithelial cells (HKC8-HS3ST1) leads to prolonged STAT3 phosphorylation in response to HB-EGF (heparin-binding EGF-like growth factor), compared to transient STAT3 phosphorylation in control cells. Pro-fibrotic factors TGFβ1 and TGFβ2/IL1β significantly downregulate HS3ST1 expression in renal epithelial cells and fibroblasts. Stable overexpression of HS3ST1 in HKC8 cells, HB-EGF stimulation with STAT3 phosphorylation time-course, qRT-PCR for HS3ST1 in TGFβ-treated cells Biochimica et biophysica acta. General subjects Medium 30794825
2023 In castration-resistant prostate cancer (CRPC) cells (C4-2) under hormone depletion, HS3ST1 produces 3-O-sulfated heparan sulfate that facilitates EGF binding to the cell surface and activation of EGFR-ERK1/2 signaling, enabling hormone-independent growth. HS3ST1 knockdown suppressed hormone-independent cell growth, EGF binding, and EGFR-ERK1/2 activation. HS3ST1 siRNA knockdown in C4-2 cells, EGF binding assay, EGFR-ERK1/2 phosphorylation assay, cell proliferation assay under hormone-depleted conditions, in vivo xenograft in castrated mice with gefitinib treatment Scientific reports Medium 37463954
2025 HS3ST1-generated HSAT (antithrombin-binding heparan sulfate) is expressed in basement membranes of epithelial cells, not only in endothelium. Inactivation of HS3ST1 in pancreatic ductal adenocarcinoma (PDAC) cells eliminated HSAT expression, induced an inflammatory phenotype, suppressed apoptosis markers, and increased metastasis in a mouse PDAC model. HSAT-positive cells bind antithrombin, which inhibits thrombin generation by tissue factor/factor VIIa. HS3ST1 inactivation in PDAC cells, mouse experimental metastasis model, antithrombin binding assay, tissue factor/factor VIIa thrombin generation assay, immunostaining of human tissues The Journal of clinical investigation High 40924474
2020 HRPII from Plasmodium falciparum competes with antithrombin for binding to 3-O-sulfated heparan sulfate on endothelial cells, disrupting AT's anti-inflammatory/barrier-protective signaling. siRNA knockdown of HS3ST1 (3-OST-1) in endothelial cells downregulated HRPII's pro-inflammatory effects, supporting the mechanism that HRPII's action depends on competition at the 3-O-sulfated HS/AT interface. siRNA knockdown of HS3ST1 in endothelial cells, endothelial barrier permeability assay, Src-dependent VE-cadherin phosphorylation assay, competition experiments with AT Journal of thrombosis and haemostasis : JTH Medium 31858717
2026 An E86Q active-site mutant of 3-OST-1 acts as a dominant-negative inhibitor: it retains substrate and donor binding but abolishes catalytic activity, reducing wild-type 3-OST-1 activity by >80% in vitro and significantly decreasing 3-O-sulfated HS products in cells without affecting total HS abundance. An LC-MS/MS assay was developed that can quantify endogenous 3-OST-1 activity at nanogram sensitivity. Site-directed mutagenesis (E86Q), in vitro LC-MS/MS activity assay with 13C-labeled internal standards, cellular overexpression of dominant-negative mutant, heparinase digestion and AMAC derivatization Glycobiology High 41914643
2025 Rational design of 3-OST-1 mutants W72R and H144R, individually and as double mutant W72R/H144R, increased enzyme activity 1.7-, 1.1-, and 2.2-fold respectively over wild-type. Enhanced activity resulted from increased substrate affinity, as shown by enzyme kinetics and molecular dynamics simulations. The mutant-modified heparin showed superior anticoagulant properties. Rational mutagenesis, enzyme kinetic assays (Km, Vmax), molecular dynamics simulations, anti-factor Xa anticoagulant activity assay Journal of agricultural and food chemistry Medium 40267027

Source papers

Stage 0 corpus · 83 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 196 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 152 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 121 32367039
2015 Polygenic Overlap Between C-Reactive Protein, Plasma Lipids, and Alzheimer Disease. Circulation 113 25862742
2017 Heparan Sulfate Microarray Reveals That Heparan Sulfate-Protein Binding Exhibits Different Ligand Requirements. Journal of the American Chemical Society 103 28651046
2019 3-O-Sulfation of Heparan Sulfate Enhances Tau Interaction and Cellular Uptake. Angewandte Chemie (International ed. in English) 87 31692167
1999 Heparan sulfate D-glucosaminyl 3-O-sulfotransferase-3A sulfates N-unsubstituted glucosamine residues. The Journal of biological chemistry 87 10608887
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 55 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
2018 Meta-analysis of Alzheimer's disease on 9,751 samples from Norway and IGAP study identifies four risk loci. Scientific reports 52 30591712
2000 Enzymatic modification of heparan sulfate on a biochip promotes its interaction with antithrombin III. Biochemical and biophysical research communications 51 11006120
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
2017 Heparan Sulfate Biosynthetic System Is Inhibited in Human Glioma Due to EXT1/2 and HS6ST1/2 Down-Regulation. International journal of molecular sciences 32 29104277
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
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 30 37235665
2018 Identification of specific and common diagnostic antibody markers for gastrointestinal cancers by SEREX screening using testis cDNA phage library. Oncotarget 30 29719626
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
2023 Apolipoprotein E Recognizes Alzheimer's Disease Associated 3-O Sulfation of Heparan Sulfate. Angewandte Chemie (International ed. in English) 28 37014788
2021 Development and Validation of a Hypoxia-Related Signature for Predicting Survival Outcomes in Patients With Bladder Cancer. Frontiers in genetics 27 34122523
2004 Mapping critical biological motifs and biosynthetic pathways of heparan sulfate. Glycobiology 26 15033939
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 24 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 19 36951251
2014 Transcriptional Activity of Heparan Sulfate Biosynthetic Machinery is Specifically Impaired in Benign Prostate Hyperplasia and Prostate Cancer. Frontiers in oncology 18 24782989
2023 Hemolysis is associated with altered heparan sulfate of the endothelial glycocalyx and with local complement activation in thrombotic microangiopathies. Kidney international 17 37164260
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
2022 The 3-O sulfation of heparan sulfate proteoglycans contributes to the cellular internalization of tau aggregates. BMC molecular and cell biology 16 36564747
2011 A synthetic heparan sulfate oligosaccharide library reveals the novel enzymatic action of D-glucosaminyl 3-O-sulfotransferase-3a. Molecular bioSystems 16 22116385
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
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 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 3 39605742
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 Rational Design and Engineering of 3-O-Sulfotransferase 1 Based on Enzyme Affinity for Improved Enzymatic Heparin Preparation. Journal of agricultural and food chemistry 2 40267027
2025 Antithrombin-binding heparan sulfate is ubiquitously expressed in epithelial cells and suppresses pancreatic tumorigenesis. The Journal of clinical investigation 2 40924474
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 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
2026 HS3ST1 regulates pulmonary inflammation and is a determinant of clinical outcomes after trauma and hemorrhagic shock. bioRxiv : the preprint server for biology 0 42182247
2026 Sporadic cone-rod dystrophy caused by a heterozygous RAB28 p.Ser23Phe pathogenic variant and a de novo 4p16.1p15.33 deletion. BMC medical genomics 0 42231409
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

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