2.8.2.30	evolution	both isozymes, HS3ST3B and HS3ST2 (EC 2.8.2.29), are differently expressed in monocytes and macrophages depending on the inflammatory environment	760623	
2.8.2.30	evolution	HS3STs represent the largest family of HS-modifying enzymes, and yet the reaction of 3-O-sulfation is the rarest maturation step, when compared to other sulfations. Seven HS3STs have been characterized in human, for which the expression is dependent on cell type and tissue environment	761164	
2.8.2.30	evolution	there are several isoforms in every gene family except that HS2ST gene family has only one isoform	761220	
2.8.2.30	malfunction	enhanced 3-O-sulfation increases binding to antithrombin, which enhances Factor Xa inhibition, and binding of neuropilin-1	762294	
2.8.2.30	malfunction	expression of the genes encoding HS-modifying enzymes is frequently dysregulated in cancer and other diseases. The enzymes show either anti-oncogenic or tumor-promoting effects. Hypermethylation in proximal regions of the HS3ST3A1 gene in chondrosarcoma. Exposure to a demethylating agent restores its expression, confirming that aberrant methylation has affected its transcription. Re-expression of HS3ST3A reduces the proliferative and migratory properties of chondrosarcoma cells, suggesting that silencing of this enzyme may have contributed to tumor cell growth and invasiveness. The HS3ST3A1 gene is epigenetically repressed in breast cancer cell lines representative of the different molecular subgroups, except in the human epidermal growth factor receptor 2-positive (HER2+) cell lines. Re-expression of the enzyme in luminal A-type MCF-7 and triple negative MDA-MB-231 cell lines reduces cell proliferation in vitro. HS3ST3A is also anti-proliferative in MDA-MB-231 cells. Overexpression of HS3ST3A does not have any effects on the proliferation of MDA-MB-231 cells	761164	
2.8.2.30	malfunction	expression of the genes encoding HS-modifying enzymes is frequently dysregulated in cancer and other diseases. The enzymes show either anti-oncogenic or tumor-promoting effects. Re-expression of HS3ST3B in MDA-MB-231 cells leads to an increase in cell viability and invasion, MDA-MB-231 cells carrying HS3ST3B expression display a significant increase in proliferation and survival. High expression of HS3ST3B in U937 leukemia cells enhances cell proliferation and survival, while its silencing has opposite effects	761164	
2.8.2.30	malfunction	HS3ST3B1 is significantly upregulated in non-small cell lung cancer cell (NSCLC) tissues compared with matched normal tissues. Its expression is also upregulated in mesenchymal phenotype of NSCLC lines compared with epithelial phenotype. When TGF-beta is applied to induce the epithelial phenotype to mesenchymal phenotype, HS3ST3B1 is upregulated compared with previous epithelial cell lines. When HS3ST3B1 is knocked down by specific small interfering RNA in the mesenchymal phenotype, mesenchymal phenotype is transformed to epithelial phenotype. HS3ST3B1 can be targeted by miR-218 in non-small cell lung cancer cells (NSCLC)	761577	
2.8.2.30	malfunction	in HER2+ patients, high level expression of 3-OST3A in tumors is associated with reduced relapse-free survival	762063	
2.8.2.30	malfunction	knocking down enzyme receptor in fibroblasts cells significantly reduces HSV-1 entry and glycoprotein D binding to cells	726544	
2.8.2.30	metabolism	heparan sulfate (HS) 3-O-sulfation can be catalysed by seven 3-sulfotransferases (HS3STs) in humans, but nevertheless it is the rarest modification in heparan sulfate (HS). Isozymes HS3ST2 (EC 2.8.2.29) and HS3ST3B exhibit the same activity in vitro. But they are differently expressed in macrophages depending on cell environment, which suggests that they may be involved in distinct cellular processes	760623	
2.8.2.30	metabolism	heparan sulfate (HS) is a type of glycosaminoglycan consisting of variably sulfated glucuronic acid or iduronic acid-Nacetylglucosamine repeating disaccharide units, and it can bind plenty of growth factors such as FGF2 and its receptor FGFR1, thereby regulating cancer cell signaling. Divergent fine structures of HS are generated by sulfation catalyzed by HS Ndeacetylase/N-, 2-O-, 6-O-, 3-O-sulfotransferases (correspondingly abbreviated as NDST, HS2ST, HS6ST, HS3ST), epimerization catalyzed by HS C5-epimerase at the Golgi lumen and further desulfation catalyzed by HS 6-O-endosulfatase at the cell surface. There are several isoforms in every gene family except that HS2ST gene family has only one isoform	761220	
2.8.2.30	metabolism	HS3ST-mediated 3-O-sulfation leads to at least two distinct forms of 3-O-sulfated motifs. HS3ST1 and HS3ST5 participate in the generation of anticoagulant-active HS/heparin sequences for antithrombin-III, while HS3ST2, HS3ST3A, HS3ST3B, HS3ST4, and HS3ST6 are described to provide the HS-binding motifs for the glycoprotein gD of herpes simplex virus-1 (HSV-1). HS3ST regulations in cancer cells, cell proliferation, and tumor progression, overview	761164	
2.8.2.30	metabolism	regulation of HS3ST3B1 by miR-218 in cells	761577	
2.8.2.30	metabolism	the sulfation at the 3-OH position of glucosamine is an important modification in forming structural domains for heparan sulfate to enable its biological functions. Seven 3-O-sulfotransferase isoforms in the human genome are involved in the biosynthesis of 3-O-sulfated heparan sulfate	761349	
2.8.2.30	metabolism	ZNF263, a C2H2 zinc finger protein, is a negative transcriptional regulator of heparin and heparan sulfate biosynthesis, which shows distinctively low expression in mast cells compared with other (non-heparin-producing) immune cells. ZNF263 is a transcriptional repressor, and its inactivation or silencing enhances mRNA expression of HS3ST1 (EC 2.8.2.23) and HS3ST3A1, enzymes involved in the formation of binding sites for antithrombin and neuropilin-1 (NRP1) and glycoprotein D of herpes simplex virus, respectively. Heparan sulfate (HS) biosynthetic genes exhibit the ZNF263 consensus motif	762294	
2.8.2.30	additional information	to date, only a few ligands are known to selectively interact with 3-O-sulfated motifs, whereas hundreds of HS-binding proteins have been identified	761164	
2.8.2.30	physiological function	3-O-sulfotransferase-3 isoform mediates Herpes simplex virus type 1 entry and spread	726544	
2.8.2.30	physiological function	3-OST3A exerts dual activities acting as tumor-suppressor in MCF-7 and MDA-MB-231 cells, or as an oncogenic factor in SKBR-3 cells	739207	
2.8.2.30	physiological function	CHO-K1 cells expressing 3-OST-3 isoform induce membrane protrusions during herpes simplex virus type-1 entry. Enzyme expression is associated with enhanced filopodia induction	726083	
2.8.2.30	physiological function	heparan sulfate D-glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1) participates in the biosynthetic steps of heparan sulfate (HS) and targets vascular endothelial growth factor (VEGF) in acute myeloid leukemia (AML) cells, thus contributing to angiogenesis and proliferation of AML cells. HS3ST3B1 plays a role in angiogenesis and the proliferation of cancer cells. Heparan sulfate D-glucosamine 3-O-sulfotransferase 3B1 is a regulator of transforming growth factor-beta-mediated epithelial-to-mesenchymal transition and regulated by miR-218 in nonsmall cell lung cancer	761577	
2.8.2.30	physiological function	heparan sulfate proteoglycans modified by zebrafish encoded glucosaminyl 3-O sulfotransferase-3 generate a receptor for herpes simplex virus type-1 entry and spread	726083	
2.8.2.30	physiological function	heparan sulfate sulfotransferase 3-OST3A (HS3ST3A) is a tumor regulator and a prognostic marker in breast cancer. Heparan sulfate (HS) proteoglycan chains are key components of the breast tumor microenvironment that critically influence the behavior of cancer cells. It is established that abnormal synthesis and processing of HS play a prominent role in tumorigenesis. HS function is mainly controlled by sulfotransferases, cellular and pathophysiological significance for the 3-O-sulfotransferase 3-OST3A (HS3ST3A), catalyzing the final maturation step of HS, in breast cancer, overview. OST3A exert dual activities acting as tumor-suppressor in lumA-michigan cancer foundation (MCF)-7 and triple negative-MD Anderson (MDA) metastatic breast (MB)-231 cells, or as an oncogenic factor in HER2+-SKBR3 cells. Mechanistically, fluorescence-resonance energy transfer-fluorescence-lifetime imaging microscopy experiments indicate that the effects of 3-OST3A in MCF-7 cells are mediated by altered interactions between HS and fibroblast growth factor-7 (FGF-7). This interplay between HS and FGF-7 modulates downstream ERK, AKT and p38 cascades, suggesting that altering 3-O-sulfation affects FGFR2IIIb-mediated signaling	762063	
2.8.2.30	physiological function	isoform 3-OST-3 mediates herpes simplex virus-1 entry and spread	738938	
2.8.2.30	physiological function	isoform HS3ST3B1 positively contributes to acute myeloid leukemia progression. The enzyme increases vascular endothelial growth factor expression and release by leukemia cells and promotes the activation of the Notch-1-Jagged-1, PI3K-AKT and ERK pathways	738745	
2.8.2.30	physiological function	isozyme HS3ST3A may have a restricted substrate specificity, making it incapable of synthesizing 3-O-sulfated heparan sulfate (HS) with a tumor-promoting property in MDA-MB-231 cells	761164	
2.8.2.30	physiological function	isozymes HS3ST2, HS3ST3B, and HS3ST4 may exhibit a broader selectivity. In pancreatic cancer cells, high level expression of HS3ST3B is reported to induce epithelial-mesenchymal transition (EMT) and to enhance cell invasiveness in vitro. HS3ST3B is related to an increase in the production of vascular endothelial growth factor (VEGF) and activation of downstream signalling pathways. The tumor-promoting effects of HS3ST2, HS3ST3B, and HS3ST4 are related to sustained activation of Src, Akt, and NF-kappaB, and upregulation of the anti-apoptotic proteins survivin and XIAP. Importantly, all these signalling molecules have been well described to play a critical role in promoting tumor growth and resistance to apoptosis. The tumor-promoting effect of HS3ST3B in leukemia cells is dependent on an autocrine activation of VEGF-dependent signalling pathways. HS3ST3B is described as a regulator of TGF-beta-mediated EMT in NSCLC cells. The tumor-promoting properties of HS3ST3B can be dependent on the formation of signalling complexes containing Nrp1	761164	
2.8.2.30	physiological function	the enzyme is a epithelial-mesenchymal transition inducer in pancreatic cancer. Overexpression of isoform 3-OST-3B1 upregulates Snail expression and triggers its nuclear translocation. The enzyme promotes in vivo angiogenic response	724692	
2.8.2.30	physiological function	the enzyme is involved in bone marrow mesenchymal stromal cell differentiation	737733	
2.8.2.30	physiological function	the enzyme plays a role in pre-eclampsia-associated placental dysfunction	739264	
2.8.2.30	physiological function	the enzyme shows a potent inhibitory effect on hepatitis B virus replication and protein expression	726527