heparan

Converts D-glucuronic acid residues adjacent to N-sulfate sugar residues to L-iduronic acid residues, both in maturing heparan sulfate (HS) and heparin chains. This is important for further modifications that determine the specificity of interactions between these glycosaminoglycans and proteins. GLCE Protein, Human, Recombinant (His) is expressed in E. coli expression system with N-6xHis tag. The predicted molecular weight is 70.9 kDa and the accession number is O94923.

Syndecan-2 is a member of the Syndecans family comprised of type I transmembrane heparan sulfate proteoglycans (HSPG) that are involved in the regulation of many cellular processes. Four sub-types of mammalian Syndecans have been reported and among them. Syndecan-2 plays a role in the cancer development. It can affect the basal and chemotherapy-induced apoptosis in osteosarcoma. It can also suppress MMP2 activation, suppressing metastasis.

NDST1 Protein, Human, Recombinant (His & SUMO) is expressed in E. coli expression system with N-6xHis-SUMO tag. The predicted molecular weight is 73.5 kDa and the accession number is P52848.

HSPG2 Protein, Human, Recombinant (His & Myc) is expressed in HEK293.

HS3ST1 Protein, Human, Recombinant (His) is expressed in Baculovirus insect cells with His tag. The predicted molecular weight is 36 kDa and the accession number is AAH57803.1.

Exostosin-like 2 (EXTL2) is a member of the exostosin (EXT)-related family which contains five members: EXT1, EXT2, EXTL1, EXTL2, and EXTL3. Studies have shown that EXT gene family members have the activities of heparan sulfate-synthesizing glycosyltransferases. EXT1 and EXT2, which have been identified as causal genes for hereditary multiple exostoses, have HS-GlcAT-II and GlcNAcT-II activities. EXTL1 has GlcNAcT-II activity and EXTL3 has GlcNAcT-I and -II activities. EXTL2 has GlcNAcT-I and N-acetylgalactosaminyltransferase activities, and transfers a GlcNAc residue to the tetrasaccharide linkage region when this region is phosphorylated by a xylose kinase 1 (FAM20B) and thereby terminate chain elongation. In mice, lack of EXTL2 causes glycosaminoglycan (GAG) overproduction and structural changes of GAGs associated with pathological processes.

Inactive precursor that is cleaved to give rise to the mature F1 and F2 fusion glycoproteins.; Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and plasma cell membrane fusion, the coiled coil regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm. This fusion is pH independent and occurs at the plasma or endosomal membrane. The trimer of F1-F2 (F protein) also facilitates the attachment to host cell by binding to host heparan sulfate.; Major determinant of the species specificity of RSV infection. The trimer of F1-F2 (F protein) also facilitates the attachment to host cell by binding to host heparan sulfate.

Osteonectin, also known as SPOCK1, is an extracellular heparan chondroitin sulfate proteoglycan. Members of this family are known as testicans, also called SPOCKs. They are characterized structurally by an N-terminal testican-specific domain, a follistatin-like region, a calcium-binding domain, a thyroglobulin-like domain, and an acidic C-terminal domain with two putative glycosaminoglycan attachment sites. SPOCKs are enriched in brain and have been shown to regulate neuronal attachment and outgrowth. They contain inhibitory regions in several domains targeted to different classes of protease, and in some cases may act as protease inhibitors. Osteonectin contains 1 Kazal-like domain and 1 thyroglobulin type-1 domain. Up to now, little is known about osteonectin’s function. It may play a role in cell-cell and cell-matrix interactions. Osteonectin also may contribute to various neuronal mechanisms in the central nervous system.

HGF, is a pleiotropic protein in the Plasminogen subfamily of S1 peptidases and contains 4 kringle domains, 1 PAN domain and 1 peptidase S1 domain. HGF is secreted as an inactive 728 amino acid (aa) single chain propeptide. It is cleaved after the fourth Kringle domain by a serine protease to form bioactive disulfide-linked HGF with a 60 kDa alpha and 30 kDa beta chain. HGF binds heparan-sulfate proteoglycans and the widely expressed receptor tyrosine kinase, HGF R c-MET. HGF regulates epithelial morphogenesis by inducing cell scattering and branching tubulogenesis. It can also alter epithelium morphology by the induction of nectin-1 alpha ectodomain shedding, an adhesion protein component of adherens junctions. HGF regulates cell growth, cell motility, and morphogenesis by activating a tyrosine kinase signaling cascade after binding to the proto oncogenic c-Met receptor. HGF is secreted by mesenchymal cells and acts as a multi-functional cytokine on cells of mainly epithelial origin. Its ability to stimulate mitogenesis, cell motility, and matrix invasion gives it a central role in angiogenesis, tumorogenesis, and tissue regeneration.

N-Acetylglucosamine-6-Sulfatase is a member of the Sulfatase family. N-Acetylglucosamine-6-Sulfatase is required for the lysosomal degradation of the Glycosaminoglycans (GAG) Heparan Sulfate and Keratan Sulfate. N-Acetylglucosamine-6-Sulfatase hydrolyzes the 6-Sulfate groups of the N-Acetyl-D-Glucosamine 6-Sulfate units of Heparan Sulfate and Keratan Sulfate. N-Acetylglucosamine-6-Sulfatase binds 1 Calcium ion per subunit. N-Acetylglucosamine-6-Sulfatase deficiency are the cause of Mucopolysaccharidosis Type 3D (MPS3D), an inborn error leading to lysosomal accumulation of heparan sulfate. MPS3D has profound mental deterioration, hyperactivity, and relatively mild somatic manifestations.

Glypican-1 is a cell membrane protein and belongs to the glypican family. The protein may act as a catalyst in increasing the rate of conversion of prion protein PRPN(C) to PRNP(Sc) via associating (via the heparan sulfate side chains) with both forms of PRPN, targeting them to lipid rafts and facilitating their interaction. It is required for proper skeletal muscle differentiation by sequestering FGF2 in lipid rafts preventing its binding to receptors (FGFRs) and inhibiting the FGF-mediated signaling.

Catalyzes the formation of UDP-alpha-D-glucuronate, a constituent of complex glycosaminoglycans. Required for the biosynthesis of chondroitin sulfate and heparan sulfate. Required for embryonic development via its role in the biosynthesis of glycosaminoglycans. Required for proper brain and neuronal development.

Cell surface receptor that binds to glycosaminoglycans, including chondroitin sulfate proteoglycans and heparan sulfate proteoglycans. Binding to chondroitin sulfate and heparan sulfate proteoglycans has opposite effects on PTPRS oligomerization and regulation of neurite outgrowth. Contributes to the inhibition of neurite and axonal outgrowth by chondroitin sulfate proteoglycans, also after nerve transection. Plays a role in stimulating neurite outgrowth in response to the heparan sulfate proteoglycan GPC2. Required for normal brain development, especially for normal development of the pituitary gland and the olfactory bulb. Functions as tyrosine phosphatase. Mediates dephosphorylation of NTRK1, NTRK2 and NTRK3. Plays a role in down-regulation of signaling cascades that lead to the activation of Akt and MAP kinases. Down-regulates TLR9-mediated activation of NF-kappa-B, as well as production of TNF, interferon alpha and interferon beta.

Glypican-5 (GPC5), is a cell membrane protein that belongs to the glypican family. The glypicans compose a family of glycosylphosphatidylinositol-anchored heparan sulfate proteoglycans that may play a role in the control of cell division and growth regulation. So far, six members (Glypican-1 GPC1, Glypican-2 GPC2, Glypican-3 GPC3, Glypican-4 GPC4, Glypican-5 GPC5, Glypican-6 GPC6) of this family are known in the vertebrates. In the adult, Glypican-5 is primarily expressed in the brain. It is also detected in the fetal brain, lung, and liver. Glypican-5 enhances the intracellular signaling of FGF2 and HGF. It alters the cellular distribution of FGF2. The properties of Glypican-5 make it an attractive target for therapeutic intervention in rhabdomyosarcomas and other tumors that amplify and or overexpress its gene. Glypican-5 is overexpressed in lymphoma cell lines that had shown amplification. It is a likely target for amplification, and that over-expression of GPC5 may contribute to the development and or progression of lymphomas and other tumors.

CD48 is a GPI-linked protein in the CD2 family of immunoglobulin superfamily proteins. CD48 is expressed on most lineage-committed hematopoietic cells but not on hematopoietic stem cells or multipotent hematopoietic progenitors. Among dendritic cells (DC), CD48 is selectively expressed on circulating myeloid DC and resident bone marrow and thymus DC. CD2, 2B4, and heparan sulfate function as CD48 ligands. CD48 is competent to transduce signals and can also trigger signaling through CD2 or 2B4. CD48 expressed on NK cells is coactivating, whereas CD48 expressed on other cell types inhibits NK cell activation.

CD138 (syndecan-1, Sdc-1) is a member of the syndecan family that comprises heparan sulfate proteoglycans. CD138 is significant for cell-cell and cell-matrix interactions.CD138 plays a crucial role in carcinogenesis and is an attractive target for anticancer treatment with heparanase inhibitors and anti-CD138 antibodies for immunotherapy.

Major attachment protein that mediates binding of the virus to cell surface heparan sulfate or chondroitin sulfate. Plays also a role in host immune evasion by inhibiting the host complement cascade activation. Human herpesvirus 2 (HHV-2) (strain HG52) Envelope glycoprotein C (His) is expressed in E. coli expression system with N-10xHis tag. The predicted molecular weight is 50.5 kDa and the accession number is Q89730.

Iduronate 2-Sulfatase, also known as IDS, is a member of the highly conserved sulfatase family of enzymes that catalyze the hydrolysis of O- and N-sulfate esters from a variety of substrates. The human Iduronate 2-Sulfatase IDS consists of a signal peptide, a propeptide, and a mature chain that may be further processed into two chains. Among the identified 18 human sulfatases, Iduronate 2-Sulfatase IDS is required for the lysosomal degradation of the glycosaminoglycans (GAG), heparan sulfate, and dermatan sulfate. Multiple mutations in this X-chromosome localized gene result in Iduronate 2-Sulfatase IDS enzymatic deficiency and lead to the sex-linked Mucopolysaccharidosis Type II (MPS II ), also known as Hunter Syndrome characterized by the lysosomal accumulation of the GAG and their excretion in urine. MPS II has a wide spectrum of clinical manifestations ranging from mild to severe due to the level of Iduronate 2-Sulfatase IDS enzyme. Retroviral-mediated Iduronate 2-Sulfatase IDS gene transfer into lymphoid cells would be a promising gene therapeutic strategy.

C-type lectin domain family 3 member A (CLEC3A) is a poorly characterized protein belonging to the superfamily of C-type lectins. Elevated CLEC3A expression may correlate with breast IDC metastatic potential and indicated a poor prognosis in breast IDC. CLEC3A knockdown inhibited BC cell growth and metastasis might be through suppressing PI3K AKT signaling activity. That CLEC3A is a promising therapeutic target for BC in the future. Matrilysin (MMP-7) plays important roles in tumor progression. Previous studies have suggested that MMP-7 binds to tumor cell surface and promotes their metastatic potential. C-type lectin domain family 3 member A (CLEC3A) as a membrane-bound substrate of MMP-7. CLEC3A binds to heparan sulfate proteoglycans on cell surface, leading to the enhancement of cell adhesion to integrin ligands on ECM. It can be speculated that the cleavage of CLEC3A by MMP-7 weakens the stable adhesion of tumor cells to the matrix and promotes their migration in tumor microenvironments.

Envelope protein that binds to heparan sulfate on the cell surface and might provide virion attachment to target cell. Vaccinia virus (strain Copenhagen) Ag35 Protein (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 40.3 kDa and the accession number is P20497.

APRIL (a proliferation-inducing ligand), also known as TNFSF13, TALL2, TRDL1, and CD256, is a member of the TNF ligand superfamily. It is synthesized as a 32 kDa proprotein which is cleaved by furin in the Golgi to release the active 17 kDa soluble molecule. Secreted human APRIL, which consists almost entirely of a single TNF homology domain, shares 85% amino acid sequence identity with mouse and rat APRIL. Both APRIL and its close relative BAFF bind and signal through the TNF superfamily receptors TACI and BCMA, while BAFF additionally functions through BAFF R. APRIL binds to heparan sulfate proteoglycans (HSPGs) independently of its binding to TACI and BCMA. APRIL can form bioactive heterotrimers with BAFF, and these circulate in the serum of patients with rheumatic immune disorders. APRIL enhances the proliferation and survival of plasma cells and also promotes T cell-dependent humoral responses. APRIL levels are elevated in the serum during coronary artery disease, and it is also elevated in many cancers primarily due to expression by tumor-infiltratin neutrophils.

Human VEGF121, also known as Vascular endothelial growth factor A, VEGFA, Vascular permeability factor, VPF and VEGF, is a homodimeric, heparin-binding glycoprotein which belongs to the platelet-derived growth factor (PDGF) vascular endothelial growth factor (VEGF) family. VEGF-A is a glycosylated mitogen that specifically acts on endothelial cells and has various effects, including mediating increased vascular permeability, inducing angiogenesis, vasculogenesis, permeabilization of blood vessels and endothelial cell growth, increasing microvascular permeability, promoting cell migration and inhibiting apoptosis. Alternatively spliced transcript variants of VEGF-A encod either secreted or cell-associated isoforms. The lymphangiogenesis may be promoted by upregulation of VEGF121, which may in turn act in part via induction of VEGF-C. It binds to the FLT1 VEGFR1 and KDR VEGFR2 receptors, heparan sulfate and heparin. NRP1 Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth.

Insulin-like growth factor-binding protein 7(IGFBP-7) is a secreted glycosylated protein that contains three protein domain modules. IGFBP7 contains an N-terminal IGFBP domain, followed by a Kazal-type serine proteinase inhibitor domain and a C-terminal immunoglobulin-like C2-type domain. Human and mouse IGFBP7 are highly homologous and share 94% aa sequence identity. It is expressed in many normal tissues and in cancer cells. It is abundantly expressed in high endothelial venules (HEVs) of blood vessels in the secondary lymphoid tissues. It binds IGF and insulin with very low affinity and has been shown to enhance the mitogenic actions of IGF and insulin. IGFBP7 also has IGF insulin-independent activities. It interacts with heparan sulfate proteoglycans, type IV collagen, and specific chemokines. It supports weak cell adhesion, promotes cell spreading on type IV collagen, and stimulates the production of the potent vasodilator PGI2. It modulates tumor cell growth and has also been implicated in angiogenesis.

Ceruloplasmin is a blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron transport across the cell membrane. Provides Cu(2+) ions for the ascorbate-mediated deaminase degradation of the heparan sulfate chains of GPC1. May also play a role in fetal lung development or pulmonary antioxidant defense. Ceruloplasmin Protein, Human, Recombinant (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 35.4 kDa and the accession number is P00450.

FGF19, also known as FGF-19, is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF19 interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by KL, KLB and heparan sulfate glycosaminoglycans that function as coreceptors. It interacts with KL and KLB directly. However, it interacts with FGFR4 in the presence of heparin, KL or KLB. FGF19 is involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression, following positive regulation of the JNK and ERK1 2 cascades. It also stimulates glucose uptake in adipocytes.

The Glypicans are a small multigene family of GPI-linked proteoglycans that play a key role in growth factor signaling. Human Glypican 1 (GPC1) is synthesized as a 558 amino acid (aa) preproprecursor that contains a 23 aa signal sequence, a 507 aa mature segment, and a 28 aa C-terminal prosegment. There are two potential N-linked and four potential O-linked sites for glycosylation or glycanation. There are potentially two heparan sulfate (HS) modifications on GPC1 that could contribute to a native molecular weight of approximately 200 kDa. Mature human GPC1 shares 91% aa identity with mature mouse GPC1. Cells known to express GPC1 include neurons, smooth and skeletal muscle cells, keratinocytes, osteoblasts, Schwann cells, immature dendritic cells, and tumor, plus tumorassociated vascular endothelial cells. The function of GPC1 is complex and varied. As a proteoglycan, it appears to make use of its HS adduct to impact select growth factor activity. This is accomplished by having juxtramembrane HS attachment sites, and a flexible, GPI-linkage.

Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Similar to integrins, fibronectin binds extracellular matrix components such as collagen, fibrin, and heparan sulfate proteoglycans. Fibronectin plays a major role in cell adhesion, growth, migration, and differentiation, and it is important for processes such as wound healing and embryonic development. Altered fibronectin expression, degradation, and organization has been associated with a number of pathologies, including cancer and fibrosis. Anastellin binds fibronectin and induces fibril formation. This fibronectin polymer, named superfibronectin, exhibits enhanced adhesive properties. Both anastellin and superfibronectin inhibit tumor growth, angiogenesis and metastasis. Anastellin activates p38 MAPK and inhibits lysophospholipid signaling.