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CLDN14
Claudin-14 is a protein that in humans is encoded by the ''CLDN14'' gene. It belongs to a related family of proteins called claudins. The protein encoded by CLDN14 is an integral membrane protein and a component of tight junctions, one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets. Tight junctions form continuous seals around cells and serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are composed of sets of continuous networking protein strands in the outer surface of the cell membrane, with complementary grooves in the inwardly facing extracytoplasmic leaflet. The CLDN14 protein also binds to WW domain of Yes-associated protein. Defects in CLDN14 are the cause of an autosomal recessive form of nonsyndromic sensorineural deafness. Two transcript variants encoding the same protein have been found for this gene. There are also suggestions that CLDN14 plays a role in tumour angi ...
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Claudin
Claudins are a family of proteins which, along with occludin, are the most important components of the tight junctions ( zonulae occludentes). Tight junctions establish the paracellular barrier that controls the flow of molecules in the intercellular space between the cells of an epithelium. They have four transmembrane domains, with the N-terminus and the C-terminus in the cytoplasm. Structure Claudins are small (20–24/27 kilodalton (kDa)) transmembrane proteins which are found in many organisms, ranging from nematodes to human beings. They all have a very similar structure. Claudins span the cellular membrane 4 times, with the N-terminal end and the C-terminal end both located in the cytoplasm, and two extracellular loops which show the highest degree of conservation. Claudins have both cis and trans interactions between cell membranes. Cis-interactions is when claudins on the same membrane interact, one way they interact is by transmembrane domain having molecular inte ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid resid ...
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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 g ...
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Integral Membrane Protein
An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All ''transmembrane proteins'' are IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a significant fraction of the proteins encoded in an organism's genome. Proteins that cross the membrane are surrounded by annular lipids, which are defined as lipids that are in direct contact with a membrane protein. Such proteins can only be separated from the membranes by using detergents, nonpolar solvents, or sometimes denaturing agents. Structure Three-dimensional structures of ~160 different integral membrane proteins have been determined at atomic resolution by X-ray crystallography or nuclear magnetic resonance spectroscopy. They are challenging subjects for study owing to the difficulties associated with extraction and crystallization. In addition, structures of many water-soluble protein domains of IMPs are available in the Prote ...
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Tight Junctions
Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein junctional complexes whose canonical function is to prevent leakage of solutes and water and seals between the epithelial cells. They also play a critical role maintaining the structure and permeability of endothelial cells. Tight junctions may also serve as leaky pathways by forming selective channels for small cations, anions, or water. The corresponding junctions that occur in invertebrates are septate junctions. Structure Tight junctions are composed of a branching network of sealing strands, each strand acting independently from the others. Therefore, the efficiency of the junction in preventing ion passage increases exponentially with the number of strands. Each strand is formed from a row of transmembrane proteins embedded in both plasma membranes, with extracellular domains joining one another directly. There are at least 40 different protei ...
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Cell Adhesion
Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indirect interaction, where cells attach to surrounding extracellular matrix, a gel-like structure containing molecules released by cells into spaces between them. Cells adhesion occurs from the interactions between cell-adhesion molecules (CAMs), transmembrane proteins located on the cell surface. Cell adhesion links cells in different ways and can be involved in signal transduction for cells to detect and respond to changes in the surroundings. Other cellular processes regulated by cell adhesion include cell migration and tissue development in multicellular organisms. Alterations in cell adhesion can disrupt important cellular processes and lead to a variety of diseases, including cancer and arthritis. Cell adhesion is also essential for inf ...
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Epithelial
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellular matrix. Epithelial tissues line the outer surfaces of organs and blood vessels throughout the body, as well as the inner surfaces of cavities in many internal organs. An example is the epidermis, the outermost layer of the skin. There are three principal shapes of epithelial cell: squamous (scaly), columnar, and cuboidal. These can be arranged in a singular layer of cells as simple epithelium, either squamous, columnar, or cuboidal, or in layers of two or more cells deep as stratified (layered), or ''compound'', either squamous, columnar or cuboidal. In some tissues, a layer of columnar cells may appear to be stratified due to the placement of the nuclei. This sort of tissue is called pseudostratified. All glands are made up of epith ...
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Endothelial
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. Endothelial cells form the barrier between vessels and tissue and control the flow of substances and fluid into and out of a tissue. Endothelial cells in direct contact with blood are called vascular endothelial cells whereas those in direct contact with lymph are known as lymphatic endothelial cells. Vascular endothelial cells line the entire circulatory system, from the heart to the smallest capillaries. These cells have unique functions that include fluid filtration, such as in the glomerulus of the kidney, blood vessel tone, hemostasis, neutrophil recruitment, and hormone trafficking. Endothelium of the interior surfaces of the heart chambers is called endocardium. An impaired function can lead to serious health issues throu ...
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WW Domain
The WW domain, (also known as the rsp5-domain or WWP repeating motif) is a modular protein domain that mediates specific interactions with protein ligands. This domain is found in a number of unrelated signaling and structural proteins and may be repeated up to four times in some proteins. Apart from binding preferentially to proteins that are proline-rich, with particular proline-motifs, PP-P- PY, some WW domains bind to phosphoserine- phosphothreonine-containing motifs. Structure and ligands The WW domain is one of the smallest protein modules, composed of only 40 amino acids, which mediates specific protein-protein interactions with short proline-rich or proline-containing motifs. Named after the presence of two conserved tryptophans (W), which are spaced 20-22 amino acids apart within the sequence, the WW domain folds into a meandering triple-stranded beta sheet. The identification of the WW domain was facilitated by the analysis of two splice isoforms of YAP gen ...
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YAP1
YAP1 (yes-associated protein 1), also known as YAP or YAP65, is a protein that acts as a transcription coregulator that promotes transcription of genes involved in cellular proliferation and suppressing apoptotic genes. YAP1 is a component in the hippo signaling pathway which regulates organ size, regeneration, and tumorigenesis. YAP1 was first identified by virtue of its ability to associate with the SH3 domain of Yes and Src protein tyrosine kinases. ''YAP1'' is a potent oncogene, which is amplified in various human cancers. Structure Cloning of the YAP1 gene facilitated the identification of a modular protein domain, known as the WW domain. Two splice isoforms of the YAP1 gene product were initially identified, named YAP1-1 and YAP1-2, which differed by the presence of an extra 38 amino acids that encoded the WW domain. Apart from the WW domain, the modular structure of YAP1 contains a proline-rich region at the very amino terminus, which is followed by a TID (TEAD tran ...
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Sensorineural Deafness
Sensorineural hearing loss (SNHL) is a type of hearing loss in which the root cause lies in the inner ear or sensory organ (cochlea and associated structures) or the vestibulocochlear nerve (Cranial nerves, cranial nerve VIII). SNHL accounts for about 90% of reported hearing loss . SNHL is usually permanent and can be mild, moderate, severe, profound, or total. Various other descriptors can be used depending on the shape of the audiogram, such as high frequency, low frequency, U-shaped, notched, peaked, or flat. ''Sensory'' hearing loss often occurs as a consequence of damaged or deficient cochlear hair cells. Hair cells may be abnormal at birth or damaged during the lifetime of an individual. There are both external causes of damage, including Ear infection, infection, and Ototoxicity, ototoxic drugs, as well as intrinsic causes, including genetic mutations. A common cause or exacerbating factor in SNHL is prolonged exposure to environmental noise, or noise-induced hearing loss. ...
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Transcript Variants
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 ...
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