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Ankyrin Repeats
Ankyrins are a family of proteins that mediate the attachment of integral membrane proteins to the spectrin-actin based membrane cytoskeleton. Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral membrane proteins. This linkage is required to maintain the integrity of the plasma membranes and to anchor specific ion channels, ion exchangers and ion transporters in the plasma membrane. The name is derived from the Greek language, Greek word wikt:ἄγκυρα, ἄγκυρα (''ankyra'') for "anchor". Structure Ankyrins contain four functional Structural domain, domains: an N-terminal domain that contains 24 tandem ankyrin repeats, a central domain that binds to spectrin, a death domain that binds to proteins involved in apoptosis, and a C-terminal regulatory domain that is highly variable between different ankyrin proteins. Membrane protein recognition The 24 tandem ankyrin repeats are responsible for the recognition of a wide range of ...
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ANK1
Ankyrin 1, also known as ANK-1, and erythrocyte ankyrin, is a protein that in humans is encoded by the ''ANK1'' gene. Tissue distribution The protein encoded by this gene, Ankyrin 1, is the prototype of the ankyrin family, was first discovered in erythrocytes, but since has also been found in brain and muscles. Genetics Complex patterns of alternative splicing in the regulatory domain, giving rise to different isoforms of ankyrin 1 have been described, however, the precise functions of the various isoforms are not known. Alternative polyadenylation accounting for the different sized erythrocytic ankyrin 1 mRNAs, has also been reported. Truncated muscle-specific isoforms of ankyrin 1 resulting from usage of an alternate promoter have also been identified. Disease linkage Mutations in erythrocytic ankyrin 1 have been associated in approximately half of all patients with hereditary spherocytosis. ANK1 shows altered methylation and expression in Alzheimer's disease. A gene expre ...
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Alternative Splicing
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be included within or excluded from the final, processed messenger RNA (mRNA) produced from that gene. This means the exons are joined in different combinations, leading to different (alternative) mRNA strands. Consequently, the proteins translated from alternatively spliced mRNAs will contain differences in their amino acid sequence and, often, in their biological functions (see Figure). Biologically relevant alternative splicing occurs as a normal phenomenon in eukaryotes, where it increases the number of proteins that can be encoded by the genome. In humans, it is widely believed that ~95% of multi-exonic genes are alternatively spliced to produce functional alternative products from the same gene but many scientists believe that most o ...
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Peripheral Membrane Proteins
Peripheral membrane proteins, or extrinsic membrane proteins, are membrane proteins that adhere only temporarily to the biological membrane with which they are associated. These proteins attach to integral membrane proteins, or penetrate the peripheral regions of the lipid bilayer. The regulatory protein subunits of many ion channels and transmembrane receptors, for example, may be defined as peripheral membrane proteins. In contrast to integral membrane proteins, peripheral membrane proteins tend to collect in the water-soluble component, or fraction, of all the proteins extracted during a protein purification procedure. Proteins with GPI anchors are an exception to this rule and can have purification properties similar to those of integral membrane proteins. The reversible attachment of proteins to biological membranes has shown to regulate cell signaling and many other important cellular events, through a variety of mechanisms. For example, the close association between many enzy ...
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DARPin
DARPins (an acronym for designed ankyrin repeat proteins) are genetically engineered antibody mimetic proteins typically exhibiting highly specific and high-affinity target protein binding. They are derived from natural ankyrin repeat proteins, one of the most common classes of binding proteins in nature, which are responsible for diverse functions such as cell signaling, regulation and structural integrity of the cell. DARPins consist of at least three, repeat motifs or modules, of which the most N- and the most C-terminal modules are referred to as "caps", since they shield the hydrophobic core of the protein. The number of internal modules is indicated as number (e.g. N1C, N2C, N3C, ...) while the caps are indicated with "N" or "C", respectively. The molecular mass of e.g. 14 or 18 kDa (kilodaltons) for four- (N2C) or five- (N3C) repeat DARPins is rather small for a biologic (ca 10% of the size of an IgG). DARPins constitute a new class of potent, specific and versatile sma ...
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Bipolar Disorder
Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with psychosis, it is called mania; if it is less severe, it is called hypomania. During mania, an individual behaves or feels abnormally energetic, happy or irritable, and they often make impulsive decisions with little regard for the consequences. There is usually also a reduced need for sleep during manic phases. During periods of depression, the individual may experience crying and have a negative outlook on life and poor eye contact with others. The risk of suicide is high; over a period of 20 years, 6% of those with bipolar disorder died by suicide, while 30–40% engaged in self-harm. Other mental health issues, such as anxiety disorders and substance use disorders, are commonly associated with bipolar disorder. While the causes of ...
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ELISA
The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presence of a ligand (commonly a protein) in a liquid sample using antibodies directed against the protein to be measured. ELISA has been used as a diagnostic tool in medicine, plant pathology, and biotechnology, as well as a quality control check in various industries. In the most simple form of an ELISA, antigens from the sample to be tested are attached to a surface. Then, a matching antibody is applied over the surface so it can bind the antigen. This antibody is linked to an enzyme and then any unbound antibodies are removed. In the final step, a substance containing the enzyme's substrate is added. If there was binding, the subsequent reaction produces a detectable signal, most commonly a color change. Performing an ELISA involves at least ...
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SPR (gene)
Sepiapterin reductase is an enzyme that in humans is encoded by the ''SPR'' gene. Function Sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase; EC 1.1.1.153) catalyzes the NADPH-dependent reduction of various carbonyl substances, including derivatives of pteridines, and belongs to a group of enzymes called aldo-keto reductases. SPR plays an important role in the biosynthesis of tetrahydrobiopterin. Reaction Sepiapterin reductase (SPR) catalyzes the chemical reaction L-erythro-7,8-dihydrobiopterin + NADP+ \rightleftharpoons sepiapterin + NADPH + H+ Thus, the two substrates of this enzyme are L-erythro-7,8-dihydrobiopterin and NADP+, whereas its three products are sepiapterin, NADPH, and a single hydrogen ion (H+). This enzyme belongs to the family of oxidoreductases, to be specific, those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is 7,8-dihydrobiopterin:NADP+ oxidoreductase. This enzyme p ...
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KAHRP
KAHRP (knob-associated histidine-rich protein) is a protein expressed by ''Plasmodium falciparum'' infecting erythrocytes. KAHRP is a major component of knobs, feature found on Plasmodium falciparum infected erythrocytes. It has been suggested that KAHRP may play a role in trafficking or docking PfEMP1, major malarial cytoadherence protein to the erythrocyte membrane; however, these findings were disputed by recent NMR and fluorescence anisotropy studies showing no interaction between PfEMP1 and KAHRP. Instead, KAHRP was shown to interact with Ankyrin, more precisely the D3 subunit of the Membrane-binding domain of Ankyrin type 1. This interaction was suggested via SPR, ELISA, and Pulldown studies, however, it has not been confirmed by NMR, ITC, crystallography Crystallography is the experimental science of determining the arrangement of atoms in crystalline solids. Crystallography is a fundamental subject in the fields of materials science and solid-state physics (conde ...
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Cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is composed of similar proteins in the various organisms. It is composed of three main components, microfilaments, intermediate filaments and microtubules, and these are all capable of rapid growth or disassembly dependent on the cell's requirements. A multitude of functions can be performed by the cytoskeleton. Its primary function is to give the cell its shape and mechanical resistance to deformation, and through association with extracellular connective tissue and other cells it stabilizes entire tissues. The cytoskeleton can also contract, thereby deforming the cell and the cell's environment and allowing cells to migrate. Moreover, it is involved in many cell signaling pathways and in the uptake of extracellular material ( endocytosis), the ...
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Inositol Triphosphate Receptor
Inositol trisphosphate receptor (InsP3R) is a membrane glycoprotein complex acting as a Ca2+ channel activated by inositol trisphosphate (InsP3). InsP3R is very diverse among organisms, and is necessary for the control of cellular and physiological processes including cell division, cell proliferation, apoptosis, fertilization, development, behavior, learning and memory. Inositol triphosphate receptor represents a dominant second messenger leading to the release of Ca2+ from intracellular store sites. There is strong evidence suggesting that the InsP3R plays an important role in the conversion of external stimuli to intracellular Ca2+ signals characterized by complex patterns relative to both space and time, such as Ca2+ waves and oscillations. Discovery The InsP3 receptor was first purified from rat cerebellum by neuroscientists Surachai Supattapone and Solomon Snyder at Johns Hopkins University School of Medicine. The cDNA of the InsP3 receptor was first cloned in the lab ...
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CD44
The CD44 antigen is a cell-surface glycoprotein involved in cell–cell interactions, cell adhesion and migration. In humans, the CD44 antigen is encoded by the ''CD44'' gene on chromosome 11. CD44 has been referred to as HCAM (homing cell adhesion molecule), Pgp-1 (phagocytic glycoprotein-1), Hermes antigen, lymphocyte homing receptor, ECM-III, and HUTCH-1. Tissue distribution and isoforms CD44 is expressed in a large number of mammalian cell types. The standard isoform, designated CD44s, comprising exons 1–5 and 16–20 is expressed in most cell types. CD44 splice variants containing variable exons are designated CD44v. Some epithelial cells also express a larger isoform (CD44E), which includes exons v8–10. Function CD44 participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. CD44 is a receptor for hyaluronic acid and can also interact with other ligands, such as osteop ...
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