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