P-selectin
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P-selectin
P-selectin is a type-1 transmembrane protein that in humans is encoded by the SELP gene. P-selectin functions as a cell adhesion molecule (CAM) on the surfaces of activated endothelial cells, which line the inner surface of blood vessels, and activated platelets. In unactivated endothelial cells, it is stored in granules called Weibel-Palade bodies. In unactivated platelets P-selectin is stored in α-granules. Other names for P-selectin include CD62P, Granule Membrane Protein 140 (GMP-140), and Platelet Activation-Dependent Granule to External Membrane Protein (PADGEM). It was first identified in endothelial cells in 1989. Gene and regulation P-selectin is located on chromosome 1q21-q24, spans > 50 kb and contains 17 exons in humans. P-selectin is constitutively expressed in megakaryocytes (the precursor of platelets) and endothelial cells. P-selectin expression is induced by two distinct mechanisms. First, P-selectin is synthesized by megakaryocytes and endothelial cells ...
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PSGL-1
Selectin P ligand, also known as SELPLG or CD162 (cluster of differentiation 162), is a human gene. SELPLG codes for PSGL-1, the high affinity counter-receptor for P-selectin on myeloid cells and stimulated T lymphocytes. As such, it plays a critical role in the tethering of these cells to activated platelets or endothelia expressing P-selectin. The organization of the SELPLG gene closely resembles that of CD43 and the human platelet glycoprotein GpIb-alpha both of which have an intron in the 5-prime-noncoding region, a long second exon containing the complete coding region, and TATA-less promoters. P-selectin glycoprotein ligand-1 (PSGL-1) is a glycoprotein found on white blood cells and endothelial cells that binds to P-selectin (P stands for platelet), which is one of a family of selectins that includes E-selectin (endothelial) and L-selectin (leukocyte). Selectins are part of the broader family of cell adhesion molecules. PSGL-1 can bind to all three members of the family but ...
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E-selectin
E-selectin, also known as CD62 antigen-like family member E (CD62E), endothelial-leukocyte adhesion molecule 1 (ELAM-1), or leukocyte-endothelial cell adhesion molecule 2 (LECAM2), is a selectin cell adhesion molecule expressed only on endothelial cells activated by cytokines. Like other selectins, it plays an important part in inflammation. In humans, E-selectin is encoded by the ''SELE'' gene. Structure E selectin has a cassette structure: an N-terminal, C-type lectin domain, an EGF (epidermal-growth-factor)-like domain, 6 Sushi domain (SCR repeat) units, a transmembrane domain (TM) and an intracellular cytoplasmic tail (cyto). The three-dimensional structure of the ligand-binding region of human E-selectin has been determined at 2.0 Å resolution in 1994. The structure reveals limited contact between the two domains and a coordination of Ca2+ not predicted from other C-type lectins. Structure/function analysis indicates a defined region and specific amino-acid side chains t ...
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Weibel–Palade Body
Weibel–Palade bodies (WPBs) are the storage granules of endothelial cells, the cells that form the inner lining of the blood vessels and heart. They manufacture, store and release two principal molecules, von Willebrand factor and P-selectin, and thus play a dual role in hemostasis and inflammation. Etymology Weibel–Palade bodies were initially described by the Swiss anatomist Ewald R. Weibel and the Romanian physiologist George Emil Palade in 1964. Palade won Nobel Prize in Physiology and Medicine in 1974 for his work on the function of organelles in cells. Constituents There are two major components stored within Weibel–Palade bodies. One is von Willebrand factor (vWF), a multimeric protein that plays a major role in blood coagulation. Storage of long polymers of vWF gives this specialized lysosomal structure an oblong shape and striated appearance on electron microscope. The other is P-selectin, which plays a central role in the ability of inflamed endothelial cells to r ...
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EGF-like Domain
The EGF-like domain is an evolutionary conserved protein domain, which derives its name from the epidermal growth factor where it was first described. It comprises about 30 to 40 amino-acid residues and has been found in a large number of mostly animal proteins. Most occurrences of the EGF-like domain are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted. An exception to this is the prostaglandin-endoperoxide synthase. The EGF-like domain includes 6 cysteine residues which in the epidermal growth factor have been shown to form 3 disulfide bonds. The structures of 4-disulfide EGF-domains have been solved from the laminin and integrin proteins. The main structure of EGF-like domains is a two-stranded β-sheet followed by a loop to a short C-terminal, two-stranded β-sheet. These two β-sheets are usually denoted as the major (N-terminal) and minor (C-terminal) sheets. EGF-like domains frequently occur in numerous tandem copies in pro ...
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Granule (cell Biology)
In cell biology, a granule is a small particle. It can be any structure barely visible by light microscopy. The term is most often used to describe a secretory vesicle. In leukocytes A group of leukocytes, called granulocytes, contain granules and play an important role in the immune system. The granules of certain cells, such as natural killer cells, contain components which can lead to the lysis of neighboring cells. The granules of leukocytes are classified as azurophilic granules or specific granules. Leukocyte granules are released in response to immunological stimuli during a process known as degranulation. In platelets The granules of platelets are classified as dense granules and alpha granules. α-Granules are unique to platelets and are the most abundant of the platelet granules, numbering 50–80 per platelet 2. These granules measure 200–500 nm in diameter and account for about 10% of platelet volume. They contain mainly proteins, both membrane-associated ...
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Cell Adhesion Molecule
Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each other and to their surroundings. CAMs are crucial components in maintaining tissue structure and function. In fully developed animals, these molecules play an integral role in generating force and movement and consequently ensuring that organs are able to execute their functions normally. In addition to serving as "molecular glue", CAMs play important roles in the cellular mechanisms of growth, contact inhibition, and apoptosis. Aberrant expression of CAMs may result in a wide range of pathologies, ranging from frostbite to cancer. Structure CAMs are typically single-pass transmembrane receptors and are composed of three conserved domains: an intracellular domain that interacts with the cytoskeleton, a transmembrane domain, and an extrac ...
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Granule (cell Biology)
In cell biology, a granule is a small particle. It can be any structure barely visible by light microscopy. The term is most often used to describe a secretory vesicle. In leukocytes A group of leukocytes, called granulocytes, contain granules and play an important role in the immune system. The granules of certain cells, such as natural killer cells, contain components which can lead to the lysis of neighboring cells. The granules of leukocytes are classified as azurophilic granules or specific granules. Leukocyte granules are released in response to immunological stimuli during a process known as degranulation. In platelets The granules of platelets are classified as dense granules and alpha granules. α-Granules are unique to platelets and are the most abundant of the platelet granules, numbering 50–80 per platelet 2. These granules measure 200–500 nm in diameter and account for about 10% of platelet volume. They contain mainly proteins, both membrane-associated ...
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Platelets
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby initiating a blood clot. Platelets have no cell nucleus; they are fragments of cytoplasm that are derived from the megakaryocytes of the bone marrow or lung, which then enter the circulation. Platelets are found only in mammals, whereas in other vertebrates (e.g. birds, amphibians), thrombocytes circulate as intact mononuclear cells. One major function of platelets is to contribute to hemostasis: the process of stopping bleeding at the site of interrupted endothelium. They gather at the site and, unless the interruption is physically too large, they plug the hole. First, platelets attach to substances outside the interrupted endothelium: ''adhesion''. Second, they change shape, turn on receptors and secrete chemical messengers: ''activatio ...
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Platelet Alpha-granule
Alpha granules, (α-granules) also known as platelet alpha-granules are a cellular component of platelets. Platelets contain different types of granules that perform different functions, and include alpha granules, dense granules, and lysosomes. Of these, alpha granules are the most common, making up between 50% to 80% of the secretory granules. Alpha granules contain several growth factors. Contents Contents include insulin-like growth factor 1, platelet-derived growth factors, TGF beta, platelet factor 4 (which is a heparin-binding chemokine) and other clotting proteins (such as thrombospondin, fibronectin, factor V, and von Willebrand factor). The alpha granules express the adhesion molecule P-selectin and CD63. These are transferred to the membrane after synthesis. The other type of granules within platelets are called dense granules. Clinical significance A deficiency of alpha granules is known as gray platelet syndrome Gray platelet syndrome (GPS), or platelet alpha-gra ...
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Platelet Alpha-granule
Alpha granules, (α-granules) also known as platelet alpha-granules are a cellular component of platelets. Platelets contain different types of granules that perform different functions, and include alpha granules, dense granules, and lysosomes. Of these, alpha granules are the most common, making up between 50% to 80% of the secretory granules. Alpha granules contain several growth factors. Contents Contents include insulin-like growth factor 1, platelet-derived growth factors, TGF beta, platelet factor 4 (which is a heparin-binding chemokine) and other clotting proteins (such as thrombospondin, fibronectin, factor V, and von Willebrand factor). The alpha granules express the adhesion molecule P-selectin and CD63. These are transferred to the membrane after synthesis. The other type of granules within platelets are called dense granules. Clinical significance A deficiency of alpha granules is known as gray platelet syndrome Gray platelet syndrome (GPS), or platelet alpha-gra ...
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Gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and noncoding genes. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as gen ...
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CUB Domain
CUB domain is an evolutionarily conserved protein domain. The CUB domain (for complement C1r/C1s, Uegf, Bmp1) is a structural motif of approximately 110 residues found almost exclusively in extracellular and plasma membrane-associated proteins, many of which are developmentally regulated. These proteins are involved in a diverse range of functions, including complement activation, developmental patterning, tissue repair, axon guidance and angiogenesis, cell signalling, fertilisation, haemostasis, inflammation, neurotransmission, receptor-mediated endocytosis, and tumour suppression. Many CUB-containing proteins are peptidases belonging to MEROPS peptidase families M12A (astacin) and S1A (chymotrypsin). Examples Proteins containing a CUB domain include: * Mammalian complement subcomponents C1s/C1r, which form the calcium-dependent complex C1, the first component of the classical pathway of the complement system. * '' Cricetidae sp.'' (Hamster) serine protease Casp, which ...
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