Platelet aggregation

Inhibits fibrinogen interaction with platelets. Acts by binding to the glycoprotein IIb-IIIa receptor (ITGA2B/ITGB3) on the platelet surface and inhibits aggregation induced by ADP, thrombin, platelet-activating factor and collagen. Also inhibits T24 and SK-Mel-28 cell adhesion to fibronectin with IC(50) of 4.4 uM and 33 nM, respectively. Disintegrin batroxostatin Protein, Bothrops atrox, Recombinant (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 15.2 kDa and the accession number is P18618.

Platelet endothelial aggregation receptor-1 (PEAR1), an epidermal growth factor repeat-containing transmembrane receptor, is known to participate in platelet contact-induced activation. Platelet endothelial aggregation receptor 1 (PEAR1) triggers platelet aggregation and is expressed in platelets and endothelial cells.PEAR1 encodes the Platelet-Endothelial Aggregation Receptor 1, a contact receptor involved in platelet function and megakaryocyte and endothelial cell proliferation. PEAR1 expression during megakaryocyte differentiation is controlled by DNA methylation at its first CpG island.

Thrombin-like snake venom serine protease that clots fibrinogen by releasing fibrinopeptide A from the alpha chain of fibrinogen (FGA), induces platelet aggregation through its interaction with GPIb (GP1BA/GP1BB), and activates factor VIII (F8). SVTLE Protein, Bothrops jararaca, Recombinant (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 33.0 kDa and the accession number is P81661.

Non-hemorrhagic metalloproteinase that hydrolyzes the alpha chains of fibrinogen, as well as fibrin, fibronectin and casein. Beta and gamma chains are also hydrolyzed, but more slowly. Thrombolytic activity is also observed. Induces detachment of endothelial cells followed by death, and inhibits endothelial cell adhesion to fibronectin. Induces edema in mouse paw. Inhibits ADP-induced platelet aggregation on human platelet-rich plasma with an IC(50) of 2.8 uM. SVMP Protein, Bothrops leucurus, Recombinant (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 30.5 kDa and the accession number is P84907.

Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion. Present at the cell surface of oocytes and plays a key role in sperm-egg fusion, possibly by organizing multiprotein complexes and the morphology of the membrane required for the fusion. In myoblasts, associates with CD81 and PTGFRN and inhibits myotube fusion during muscle regeneration. In macrophages, associates with CD9 and beta-1 and beta-2 integrins, and prevents macrophage fusion into multinucleated giant cells specialized in ingesting complement-opsonized large particles. Also prevents the fusion between mononuclear cell progenitors into osteoclasts in charge of bone resorption. Acts as a receptor for PSG17. Involved in platelet activation and aggregation. Regulates paranodal junction formation. Involved in cell adhesion, cell motility and tumor metastasis. Also regulates integrin-dependent migration of macrophages, particularly relevant for inflammatory response in the lung.

In the nervous system, could hydrolyze ATP and other nucleotides to regulate purinergic neurotransmission. Could also be implicated in the prevention of platelet aggregation by hydrolyzing platelet-activating ADP to AMP. Hydrolyzes ATP and ADP equally well.

In the nervous system, could hydrolyze ATP and other nucleotides to regulate purinergic neurotransmission. Could also be implicated in the prevention of platelet aggregation by hydrolyzing platelet-activating ADP to AMP. Hydrolyzes ATP and ADP equally well.

Hepatocellular carcinoma (HCC) is a major contributor to cancer-related deaths due to its often late stage diagnosis, and dermcidin (DCD) may have the potential to be used as a serum biomarker for HCC for more timely diagnoses. Human dermcidin (DCD) is an antimicrobial peptide secreted constitutively by sweat glands. And the role of DCD in ischemic heart disease has drawn increasing attention in particular its relationship with insulin secretion and glycemic control, nitric oxide (NO) synthesis and hypertension, platelet aggregation and acute myocardial infarction (AMI).

cGMP-dependent 3',5'-cyclic phosphodiesterase, also known as cyclic GMP-stimulated phosphodiesterase and PDE2A, is a peripheral membrane protein that belongs to the cyclic nucleotide phosphodiesterase family and PDE2 subfamily. Phosphodiesterases (PDEs) comprise a family of enzymes that regulate the levels of cyclic nucleotides, key second messengers that mediate a diverse array of functions. Phosphodiesterases (PDEs) modulate signaling by cyclic nucleotides in diverse processes such as cardiac contractility, platelet aggregation, lipolysis, glycogenolysis, and smooth muscle contraction. PDE2A is an evolutionarily conserved cGMP-stimulated cAMP and cGMP PDE. PDE2A contains two GAF domains. PDE2A is expressed in brain and to a lesser extent in heart, placenta, lung, skeletal muscle, kidney and pancreas. PDE2A is a cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. PDE2A is involved in the regulation of blood pressure and fluid homeostasis by the atrial natriuretic peptide (ANP), making PDE2-type enzymes important targets for drug discovery.

PDE1C belongs to the cyclic nucleotide phosphodiesterase family, PDE1 subfamily. Phosphodiesterases (PDEs) are a family of related phosphohydrolyases that selectively catalyze the hydrolysis of 3' cyclic phosphate bonds in adenosine and/or guanine 3',5' cyclic monophosphate (cAMP and/or cGMP). They regulate the cellular levels, localization and duration of action of these second messengers by controlling the rate of their degradation. PDEs are expressed ubiquitously, with each subtype having a specific tissue distribution. These enzymes are involved in many signal transduction pathways and their functions include vascular smooth muscle proliferation and contraction, cardiac contractility, platelet aggregation, hormone secretion, immune cell activation, and they are involved in learning and memory. PDE1C has a high affinity for both cAMP and cGMP. It is expressed in several tissues, including brain and heart. As a cyclic nucleotide phosphodiesterase, PDE1C has a dual-specificity for the second messengers cAMP and cGMP.

Metalloproteinase that binds to von Willebrand factor (VWF) and induces its interaction with GPIb (GP1BA), resulting in platelet aggregation. SVMP Protein, Bothrops jararaca, Recombinant (His & KSI) is expressed in E. coli expression system with N-6xHis-KSI tag. The predicted molecular weight is 18.0 kDa and the accession number is P22028.

Released during platelet aggregation. Neutralizes the anticoagulant effect of heparin because it binds more strongly to heparin than to the chondroitin-4-sulfate chains of the carrier molecule. Chemotactic for neutrophils and monocytes. Inhibits endothelial cell proliferation. CXCL4 Protein, Pig, Recombinant (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 17.1 kDa and the accession number is P30034.

The growth arrest-specific 6 gene (GAS6) is a member of the family of plasma vitamin K-dependent proteins, which are able to bind to phospholipids using an N-terminal gamma-carboxyglutamic acid domain. GAS6 is a vitamin K-dependent protein, plays a role in the survival, proliferation, migration, differentiation, adhesion, and apoptosis of cells. The growth arrest-specific 6 (GAS6) has been implicated in systemic inflammation and coagulation. Growth arrest-specific 6 (GAS6), plays a role in tumor progression by regulating growth in many cancers. GAS6, expressed by osteoblasts in the bone marrow, plays a significant role in the regulation of PCa cell survival during chemotherapy, which will have important implications for targeting metastatic disease. The GAS6/TYRO3-AXL-MERTK (TAM) signaling pathway is essential for full and sustained platelet activation, as well as thrombus stabilization. Inhibition of this pathway decreases platelet aggregation, shape change, clot retraction, aggregate formation under flow conditions, and surface expression of activation markers. It had been show that GAS6 signaling regulates invasion, proliferation, chemotherapy-induced apoptosis of prostate cancer (PCa) cells, and GAS6 secreted from osteoblasts in the bone marrow environment plays a critical role in establishing prostate tumor cell dormancy.

Podoplanin belongs to the podoplanin family, also known as Glycoprotein 38. Podoplanin is synthesized as a 172 amino acid (aa) precursor with a 22 aa signal sequence, a 119 aa extracellular domain (ECD), a 21 aa transmembrane region, and a short, 10 aa cytoplasmic tail. Detected at high levels in lung and brain, at lower levels in kidney, stomach, liver, spleen and esophagus, and not detected in skin and small intestine. Expressed in epithelial cells of choroid plexus, ependyma, glomerulus and alveolus, in mesothelial cells and in endothelia of lymphatic vessels. Also expressed in stromal cells of peripheral lymphoid tissue and thymic epithelial cells. Detected in carcinoma cell lines and cultured fibroblasts. Expressed at higher levels in colon carcinomas than in normal colon tissue. It can interacts with CLEC1B; the interaction is independent of CLEC1B glycosylation and activates CLEC1B. It may be involved in cell migration and/or actin cytoskeleton organization. When expressed in keratinocytes, induces changes in cell morphology with transfected cells showing an elongated shape, numerous membrane protrusions, major reorganization of the actin cytoskeleton, increased motility and decreased cell adhesion. Required for normal lung cell proliferation and alveolus formation at birth. Ligand for CLEC1B, a platelet receptor. Induces platelet aggregation. Does not have any effect on folic acid or amino acid transport. Does not function as a water channel or as a regulator of aquaporin-type water channels.

Tyrosine-protein kinase Mer (MERTK) is a single-pass type I membrane protein which belongs to the MER/AXL/TYRO3 receptor kinase family. MERTK include two fibronectin type-III domains, two Ig-like C2-type domains, and one tyrosine kinase domain. It can’t be expressed in normal B- and T-lymphocytes, but it is usually expressed in numerous neoplastic B- and T-cell lines. MERTK could regulate many physiological processes, such as cell survival, migration, differentiation. It was demonstrated that the MERTK plays critical role in the engulfment and efficient clearance of apoptotic cells, platelet aggregation, and cytoskeleton reorganization. Not only these, it also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3. In addition, MERTK could regulate rod outer segments fragments phagocytosis in the retinal pigment epithelium (RPE)， deficiency in MERTK are the cause of retinitis pigmentosa.

Protein Disulfide-Isomerase A6 (PDIA6) is a 48.5kDa protein that belongs to the protein disulfide isomerase family (PDI). PDIA6 is an enzyme in the endoplasmic reticulum in eukaryotes which catalyzes the formation and breakage of disulfide bonds between cysteine residues within proteins as they fold. The PDIA6 expressed in platelets, its functions as a chaperone that inhibits aggregation of misfolded proteins. PDIA6 is part a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGT1A1. PDIA6 also plays a role in platelet aggregation and activation by agonists such as convulxin, collagen and thrombin.

Elicits platelet aggregation by the binding to the C-type lectin domain family 1 member B (CLEC1B/CLEC2). Binding leads to tyrosine phosphorylation in the cytoplasmic tail of CLEC1B, which promotes the binding of spleen tyrosine kinase (Syk), subsequent activation of PLC-gamma-2, and platelet activation and aggregation. Binding to GPIbalpha (GP1BA) and alpha-2/beta-1 (ITGA2/ITGB1) may also induce aggregation, but this is controversial. Snaclec rhodocytin subunit alpha Protein, Calloselasma rhodostoma, Recombinant (His) is expressed in yeast with N-6xHis tag. The predicted molecular weight is 17.8 kDa and the accession number is Q9I841.

Elicits platelet aggregation by the binding to the C-type lectin domain family 1 member B (CLEC1B/CLEC2). Binding leads to tyrosine phosphorylation in the cytoplasmic tail of CLEC1B, which promotes the binding of spleen tyrosine kinase (Syk), subsequent activation of PLCgamma2, and platelet activation and aggregation. Binding to GPIbalpha (GP1BA) and alpha2/beta-1 (ITGA2/ITGB1) may also induce aggregation, but this is controversial. Snaclec rhodocytin subunit beta Protein, Calloselasma rhodostoma, Recombinant (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 21.8 kDa and the accession number is Q9I840.

Receptor for extracellular adenine nucleotides such as ADP. In platelets, binding to ADP leads to mobilization of intracellular calcium ions via activation of phospholipase C, a change in platelet shape, and ultimately platelet aggregation. P2Y1 Protein, Human, Recombinant (His) is expressed in E. coli expression system with C-6xHis tag. The predicted molecular weight is 12.4 kDa and the accession number is P47900.

Platelet factor 4 (PF4), also known as chemokine (C-X-C motif) ligand 4 (CXCL4), is a small cytokine belonging to the CXC chemokine family. CXCL4/PF4 is released from the alpha-granules of activated platelets and binds with high affinity to heparin. Its major physiologic role appears to be neutralization of heparin-like molecules on the endothelial surface of blood vessels, thereby inhibiting local antithrombin III activity and promoting coagulation. As a strong chemoattractant for neutrophils and fibroblasts, CXCL4/PF4 probably has a role in inflammation and wound repair. This protein is released during platelet aggregation. CXCL4/PF4 neutralizes the anticoagulant effect of heparin because it binds more strongly to heparin than to the chondroitin-4-sulfate chains of the carrier molecule. CXCL4 is chemotactic for neutrophils and monocytes. It inhibits endothelial cell proliferation, the short form is a more potent inhibitor than the longer form. CXCL4/PF4 is up-regulated in human liver fibrosis and that it plays a nonredundant, functional role in experimental liver fibrosis by mediating stellate cell proliferation, migration, and intrahepatic immune cell recruitment.

Histones are a complex family of highly conserved basic proteins responsible for packaging chromosomal DNA into nucleosomes. Histone proteins exhibit two levels of diversity: 1. evolutionary diversity between species and 2. subtype diversity in a class(H1, H2A, H2B, H3 or H4) within a species. It has become more and more evident that histone modifications are key players in the regulation of chromatin states and dynamics as well as in gene expression. Therefore, histone modifications and the enzymatic machinery that set them are crucial regulators that can control cellular proliferation, differentiation, plasticity, and malignancy processes. However, extracellular histones are a double-edged sword because they also damage host tissue and may cause death. Histones bound to platelets, induced calcium influx, and recruited plasma adhesion proteins such as fibrinogen to induce platelet aggregation. Histone H2B proteins have been studied in a variety of species and are easily detected in most species. The reversible ubiquitylation of histone H2B has long been implicated in transcriptional activation and gene silencing. Phosphorylation of H2B serine 32 occurs in normal cycling and mitogen-stimulated cells. Notably, this phosphorylation is elevated in skin cancer cell lines and tissues compared with normal counterparts. HIST2H2BE is a member of the histone H2B family and generates two transcripts through the use of the conserved stem-loop termination motif, and the polyA addition motif.

Podoplanin is a type-1 transmembrane protein that belongs to Podoplanin family. PDPN expressed in various specialized cell types throughout the body. It highly expressed in placenta, lung, skeletal muscle and brain, weakly expressed in brain, kidney and liver. In placenta, PDPN expressed on the apical plasma membrane of endothelium, in lung, expressed in alveolar epithelium. PDPN physiological function is related to its mucin-type character. PDPN may be involved in cell migration and/or actin cytoskeleton organization. When expressed in keratinocytes, induces changes in cell morphology with transfected cells showing an elongated shape, numerous membrane protrusions, and major reorganization of the actin cytoskeleton, increased motility and decreased cell adhesion. It requires for normal lung cell proliferation and alveolus formation at birth and Induces platelet aggregation. Nevertheless, it doesn’t have any effect on amino acid transport and the aquaporin-type water channels.

Glycoprotein VI (GPVI) is a 63 kDa platelet/megakaryocyte-specific type I transmembrane glycoprotein of the immunoglobulin superfamily that is an important collagen receptor and initiator of platelet activation, aggregation and thrombin generation. GPVI is also a secondary receptor required for platelet spreading on laminin. GPVI associates with the Fc receptor gamma -chain via charged aa in the TM domains of GPVI (arginine) and the FcR gamma (aspartic acid). Collagen binding by the GPVI Ig-like domains initiates signaling through the FcR gamma ITAM sequence. Dimerization of GPVI (2:2 with FcR gamma ) and N-glycosylation greatly enhances collagen binding. Type I and III collagens are strong thrombus-forming components in the vascular subendothelium and atherosclerotic plaques. GPVI initiates binding to fibrillar collagens under flow conditions, then activates integrin alpha 2 beta 1 which binds collagen more tightly. GPVI deficiencies cause only a mild bleeding tendency, probably because integrin alpha 2 beta 1 is able to minimally initiate collagen binding. Normal human GPVI concentration can vary widely and affect maximum thrombin generation. Engagement of GPVI by collagens or other agonists, including autoantibodies, causes calmodulin-regulated metalloproteinase cleavage of the 57 kDa ECD and depletes surface GPVI.

Elicits platelet aggregation by the binding to the C-type lectin domain family 1 member B (CLEC1B/CLEC2). Binding leads to tyrosine phosphorylation in the cytoplasmic tail of CLEC1B, which promotes the binding of spleen tyrosine kinase (Syk), subsequent activation of PLCgamma2, and platelet activation and aggregation. Binding to GPIbalpha (GP1BA) and alpha2/beta-1 (ITGA2/ITGB1) may also induce aggregation, but this is controversial. Snaclec rhodocytin subunit beta Protein, Calloselasma rhodostoma, Recombinant (His) is expressed in yeast with N-6xHis tag. The predicted molecular weight is 16.4 kDa and the accession number is Q9I840.

Elicits platelet aggregation by the binding to the C-type lectin domain family 1 member B (CLEC1B/CLEC2). Binding leads to tyrosine phosphorylation in the cytoplasmic tail of CLEC1B, which promotes the binding of spleen tyrosine kinase (Syk), subsequent activation of PLC-gamma-2, and platelet activation and aggregation. Binding to GPIbalpha (GP1BA) and alpha-2/beta-1 (ITGA2/ITGB1) may also induce aggregation, but this is controversial. Snaclec rhodocytin subunit alpha Protein, Calloselasma rhodostoma, Recombinant (His & SUMO) is expressed in E. coli expression system with N-6xHis-SUMO tag. The predicted molecular weight is 31.8 kDa and the accession number is Q9I841.

Histones are a complex family of highly conserved basic proteins responsible for packaging chromosomal DNA into nucleosomes. There are subtype diversities: H1, H2A, H2B, and H3 or H4. It has become more and more evident that histone modifications are key players in the regulation of chromatin states and dynamics as well as in gene expression. Therefore, histone modifications and the enzymatic machinery that set them are crucial regulators that can control cellular proliferation, differentiation, plasticity, and malignancy processes. However, extracellular histones are a double-edged sword because they also damage host tissue and may cause death. Histones bound to platelets, induced calcium influx, and recruited plasma adhesion proteins such as fibrinogen to induce platelet aggregation. Histone cluster 3, H2a also known as histone H2A (HIST3H2A) is a member of histones. Covalent modification of histones is important in regulating chromatin dynamics and transcription. One example of such modification is ubiquitination, which mainly occurs on histones H2A and H2B. E3 ubiquitin ligase complex is specific for histone H2A (HIST3H2A). Reducing the expression of Ring2 results in a dramatic decrease in the level of ubiquitinated H2A in HeLa cells. DNA damage induces monoubiquitylation of histone H2A (HIST3H2A) in the vicinity of DNA lesions.