Calpamodulin
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Calpamodulin
Calpain-6 (also known as calpamodulin) is a protein in humans that is encoded by the ''CAPN6'' gene. Calpains are a ubiquitous, well-conserved family of calcium-dependent, cysteine proteases. In the MEROPS protease enzyme classification system, they are members of clan CA (papain-like proteases). The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large subunit possesses a cysteine protease domain, and both subunits possess calcium-binding domains. Calpains have been implicated in neurodegenerative processes, as their activation can be triggered by calcium influx and oxidative stress. The protein encoded by this gene is highly expressed in the placenta. Its C-terminal region lacks any homology to the calmodulin-like domain of other calpains. The protein lacks a critical catalytic triad residue in its active site (cysteine nucleophile mutated to lysine) and thus is suggested to be proteolytically inactive. The protein may ...
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Catalytic Triad
A catalytic triad is a set of three coordinated amino acids that can be found in the active site of some enzymes. Catalytic triads are most commonly found in hydrolase and transferase enzymes (e.g. proteases, amidases, esterases, acylases, lipases and β-lactamases). An acid- base-nucleophile triad is a common motif for generating a nucleophilic residue for covalent catalysis. The residues form a charge-relay network to polarise and activate the nucleophile, which attacks the substrate, forming a covalent intermediate which is then hydrolysed to release the product and regenerate free enzyme. The nucleophile is most commonly a serine or cysteine amino acid, but occasionally threonine or even selenocysteine. The 3D structure of the enzyme brings together the triad residues in a precise orientation, even though they may be far apart in the sequence (primary structure). As well as divergent evolution of function (and even the triad's nucleophile), catalytic triads show some ...
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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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Placenta
The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate maternal and fetal circulations, and is an important endocrine organ, producing hormones that regulate both maternal and fetal physiology during pregnancy. The placenta connects to the fetus via the umbilical cord, and on the opposite aspect to the maternal uterus in a species-dependent manner. In humans, a thin layer of maternal decidual (endometrial) tissue comes away with the placenta when it is expelled from the uterus following birth (sometimes incorrectly referred to as the 'maternal part' of the placenta). Placentas are a defining characteristic of placental mammals, but are also found in marsupials and some non-mammals with varying levels of development. Mammalian placentas probably first evolved about 150 million to 200 million years ...
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Apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between eight and fourteen years old, approximately twenty to thirty billion cells die per day. In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis is a highly regulated and controlled process that confers advantages during an organism's life cycle. For example, the separation of fingers and toes in a developing human embryo occurs because cells between the digits undergo apoptosis. Unlike necrosis, apoptosis produces cell fragments called apoptotic ...
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Neoplasm
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, when it may be called a tumor. ICD-10 classifies neoplasms into four main groups: benign neoplasms, in situ neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior. Malignant neoplasms are also simply known as cancers and are the focus of oncology. Prior to the abnormal growth of tissue, as neoplasia, cells often undergo an abnormal pattern of growth, such as metaplasia or dysplasia. However, metaplasia or dysplasia does not always progress to neoplasia and can occur in other conditions as well. The word is from Ancient Greek 'new' and 'formation, creation'. Types A neoplasm can be benign, potentially ma ...
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Calmodulin
Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is an intracellular target of the secondary messenger Ca2+, and the binding of Ca2+ is required for the activation of calmodulin. Once bound to Ca2+, calmodulin acts as part of a calcium signal transduction pathway by modifying its interactions with various target proteins such as kinases or phosphatases. Structure Calmodulin is a small, highly conserved protein that is 148 amino acids long (16.7 kDa). The protein has two approximately symmetrical globular domains (the N- and C- domains) each containing a pair of EF hand motifs separated by a flexible linker region for a total of four Ca2+ binding sites, two in each globular domain. In the Ca2+-free state, the helices that form the four EF-hands are collapsed in a compact orientation, and the central linker is disordered; in the Ca2+-saturated state, th ...
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Homology (biology)
In biology, homology is similarity due to shared ancestry between a pair of structures or genes in different taxa. A common example of homologous structures is the forelimbs of vertebrates, where the wings of bats and birds, the arms of primates, the front flippers of whales and the forelegs of four-legged vertebrates like dogs and crocodiles are all derived from the same ancestral tetrapod structure. Evolutionary biology explains homologous structures adapted to different purposes as the result of descent with modification from a common ancestor. The term was first applied to biology in a non-evolutionary context by the anatomist Richard Owen in 1843. Homology was later explained by Charles Darwin's theory of evolution in 1859, but had been observed before this, from Aristotle onwards, and it was explicitly analysed by Pierre Belon in 1555. In developmental biology, organs that developed in the embryo in the same manner and from similar origins, such as from matching p ...
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C-terminus
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is translated from messenger RNA, it is created from N-terminus to C-terminus. The convention for writing peptide sequences is to put the C-terminal end on the right and write the sequence from N- to C-terminus. Chemistry Each amino acid has a carboxyl group and an amine group. Amino acids link to one another to form a chain by a dehydration reaction which joins the amine group of one amino acid to the carboxyl group of the next. Thus polypeptide chains have an end with an unbound carboxyl group, the C-terminus, and an end with an unbound amine group, the N-terminus. Proteins are naturally synthesized starting from the N-terminus and ending at the C-terminus. Function C-terminal retention signals While the N-terminus of a protein often c ...
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Oxidative Stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Oxidative stress from Cellular respiration, oxidative metabolism causes base damage, as well as DNA damage (naturally occurring), strand breaks in DNA. Base damage is mostly indirect and caused by the reactive oxygen species generated, e.g., O2− (superoxide radical), OH (hydroxyl radical) and H2O2 (hydrogen peroxide). Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of cellular signaling. In humans, oxidative stress is thought to be involved in the ...
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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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Calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to its heavier homologues strontium and barium. It is the fifth most abundant element in Earth's crust, and the third most abundant metal, after iron and aluminium. The most common calcium compound on Earth is calcium carbonate, found in limestone and the fossilised remnants of early sea life; gypsum, anhydrite, fluorite, and apatite are also sources of calcium. The name derives from Latin ''calx'' "lime", which was obtained from heating limestone. Some calcium compounds were known to the ancients, though their chemistry was unknown until the seventeenth century. Pure calcium was isolated in 1808 via electrolysis of its oxide by Humphry Davy, who named the element. Calcium compounds are widely used in many industries: in foods and pharma ...
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Neurodegeneration
A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies (like proteinopathy) and induced cell death. These similarities suggest that ...
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