SPINK6
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SPINK6
Serine protease inhibitor Kazal-type 6 (SPINK6) is a protein encoded by the ''SPINK6'' gene in humans. It is a potent inhibitor of epidermal proteases involved in maintaining skin homeostasis, including KLK5, KLK7 and KLK14. ''SPINK6'' is a member of a gene family cluster located on chromosome 5q33.1, which includes ''SPINK5'' and ''SPINK9 Lympho-epithelial Kazal-type related inhibitor 2 (LEKTI-2) is a protein encoded by the ''SPINK9'' gene in humans. ''SPINK9'' is a member of a gene family cluster located on chromosome 5q33.1, which includes '' SPINK5'' and '' SPINK6''. LEKTI-2 is ...''. See also * Kazal-type serine protease inhibitor domain References Proteins {{gene-5-stub ...
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KLK7
Kallikrein-related peptidase 7 (KLK7) is a serine protease that in humans is encoded by the ''KLK7'' gene. KLK7 was initially purified from the epidermis and characterised as stratum corneum chymotryptic enzyme (SCCE). It was later identified as the seventh member of the human kallikrein family, which includes fifteen homologous serine proteases located on chromosome 19 (19q13). Gene Alternative splicing of the ''KLK7'' gene results in two transcript variants encoding the same protein. Function KLK7 is secreted as an inactive zymogen in the stratum granulosum layer of the epidermis, requiring proteolytic cleavage of the short N-terminal pro-region to liberate activated enzyme. This may be performed by KLK5 or matriptase, which are ''in vitro'' activators of KLK7. Once active, KLK7 is able to cleave desmocollin and corneodesmosin. These proteins constitute the extracellular component of corneodesmosomes, intercellular cohesive structures which link the intermediate filaments ...
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Chromosome 5
Chromosome 5 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 5 spans about 181 million base pairs (the building blocks of DNA) and represents almost 6% of the total DNA in cells. Chromosome 5 is the 5th largest human chromosome, yet has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of non-coding and syntenic conservation with non-mammalian vertebrates, suggesting they are functionally constrained. Because chromosome 5 is responsible for many forms of growth and development (cell divisions) changes may cause cancers. One example would be acute myeloid leukemia (AML). Genes Number of genes The following are some of the gene count estimates of human chromosome 5. Because researchers use different approaches to genome annotation their predictions of the number of genes on each chromosome varies (for technical details, see gene prediction ...
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SPINK5
Lympho-epithelial Kazal-type-related inhibitor (LEKTI) also known as serine protease inhibitor Kazal-type 5 (SPINK5) is a protein that in humans is encoded by the ''SPINK5'' gene. Structure and function LEKTI is a large multidomain serine protease inhibitor expressed in stratified epithelial tissue. It consists of 15 domains that are cleaved into smaller, functional fragments by the protease furin. Only two of these domains (2 and 15) contain 6 evenly spaced cysteines responsible for 3 intramolecular disulfide bonds characteristic of Kazal-type related inhibitors. The remaining domains contain 4 cysteines. These disulfide bonds force the molecule into a rigid conformation that enables the protein to interact with a target protease via an extended beta-sheet. All domains (excepting 1, 2 and 15) contain an arginine at P1, indicating trypsin-like proteases are the likely targets. In the epidermis, LEKTI is implicated in the regulation of desquamation via its ability to selective ...
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SPINK9
Lympho-epithelial Kazal-type related inhibitor 2 (LEKTI-2) is a protein encoded by the ''SPINK9'' gene in humans. ''SPINK9'' is a member of a gene family cluster located on chromosome 5q33.1, which includes ''SPINK5'' and ''SPINK6''. LEKTI-2 is an inhibitor of KLK5. Desquamation The outer layer of the epidermis is called the stratum corneum. In the stratum corneum terminally differentiated corneocytes are held together by corneodesmosomes. In order for desquamation to occur, corneodesmosomes need to be fully degraded. KLK5 and KLK7 are two serine proteases that degrade corneodesmosomes. LEKTI-2 regulates corneodesmosome degradation by inhibiting KLK5. In acral (palm and sole) skin, where desquamation needs to be delayed, ''SPINK9'' expression is strongly upregulated. The resulting high level of LEKTI-2 delays corneodesmosome degradation, thereby allowing the epidermis to form a thick protective stratum corneum layer. Clinical Significance SPINK9 is overexpressed in lichen simplex ...
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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 residue ...
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Epidermis (skin)
The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water released from the body into the atmosphere through transepidermal water loss. The epidermis is composed of multiple layers of flattened cells that overlie a base layer (stratum basale) composed of columnar cells arranged perpendicularly. The layers of cells develop from stem cells in the basal layer. The human epidermis is a familiar example of epithelium, particularly a stratified squamous epithelium. The word epidermis is derived through Latin , itself and . Something related to or part of the epidermis is termed epidermal. Structure Cellular components The epidermis primarily consists of keratinocytes ( proliferating basal and differentiated suprabasal), which comprise 90% of its cells, but also contains melanocytes, Langerhans c ...
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Proteases
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products. They do this by cleaving the peptide bonds within proteins by hydrolysis, a reaction where water breaks bonds. Proteases are involved in many biological functions, including digestion of ingested proteins, protein catabolism (breakdown of old proteins), and cell signaling. In the absence of functional accelerants, proteolysis would be very slow, taking hundreds of years. Proteases can be found in all forms of life and viruses. They have independently evolved multiple times, and different classes of protease can perform the same reaction by completely different catalytic mechanisms. Hierarchy of proteases Based on catalytic residue Proteases can be classified into seven broad groups: * Serine proteases - ...
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KLK5
Kallikrein-5, formerly known as stratum corneum tryptic enzyme (SCTE), is a serine protease expressed in the epidermis. In humans it is encoded by the ''KLK5'' gene. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Its expression is up-regulated by estrogens and progestins. Alternative splicing results in multiple transcript variants encoding the same protein. KLK5 has been suggested to regulate cell shedding (desquamation) in conjunction with KLK7 and KLK14, given its ability to degrade proteins which form the extracellular component of cell junctions in the stratum corneum. It is proposed that KLK5 regulates this process since it is able to self-activate in addition to activating KLK7 and KLK14. References Further reading * * * * * * * * * * * * * * * * * External links * The MEROPS MEROPS is an online database for peptidases (also known as proteases, proteinases and proteolytic enzymes) and their inhibitors. The c ...
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KLK14
Kallikrein-14 is a protein that in humans is encoded by the ''KLK14'' gene. Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer, skin disorders and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Apart from its common transcript, an additional transcript variant has been described but its difference in function and full length nature has not been determined. KLK14 displays optimal trypsin-like activity at an alkaline pH of 8.0 and remains active in the pH ranges of 5.0 - 9.0 and is produced as a zymogen, but can function also in a chymotrypsin-like fashion. Activation of KLK14 is mediated by KLK5 and after KLK14 activation, it further amplifies the activity of KLK proteases by a positive feedback loop via cleavage of pro-KLK5, which is a central play ...
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