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PAS Domain
A Per-Arnt-Sim (PAS) domain is a protein domain found in all kingdoms of life. Generally, the PAS domain acts as a molecular sensor, whereby small molecules and other proteins associate via binding of the PAS domain. Due to this sensing capability, the PAS domain has been shown as the key structural motif involved in protein-protein interactions of the circadian clock, and it is also a common motif found in signaling proteins, where it functions as a signaling sensor. Discovery PAS domains are found in a large number of organisms from bacteria to mammals. The PAS domain was named after the three proteins in which it was first discovered: * Per – period circadian protein * Arnt – aryl hydrocarbon receptor nuclear translocator protein * Sim – single-minded protein Since the initial discovery of the PAS domain, a large quantity of PAS domain binding sites have been discovered in bacteria and eukaryotes. A subset called PAS LOV proteins are responsive to oxygen, light a ...
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N-terminus
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amine group is bonded to the carboxylic group of another amino acid, making it a chain. That leaves a free carboxylic group at one end of the peptide, called the C-terminus, and a free amine group on the other end called the N-terminus. By convention, peptide sequences are written N-terminus to C-terminus, left to right (in LTR writing systems). This correlates the translation direction to the text direction, because when a protein is translated from messenger RNA, it is created from the N-terminus to the C-terminus, as amino acids are added to the carboxyl end of the protein. Chemistry Each amino acid has an amine group and a carboxylic group. Amino acids link to one another by peptide bonds which form through a dehydration reaction that ...
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Cyclic Di-GMP
Cyclic di-GMP (also called cyclic diguanylate and c-di-GMP) is a second messenger used in signal transduction in a wide variety of bacteria. Cyclic di-GMP is not known to be used by archaea, and has only been observed in eukaryotes in ''Dictyostelium''. The biological role of cyclic di-GMP was first uncovered when it was identified as an allosteric activator of a cellulose synthase found in ''Gluconacetobacter xylinus'' in order to produce microbial cellulose. In structure, it is a cycle containing only two guanine bases linked by ribose and phosphate. Contact with surfaces increases c-di-GMP which increases transcription, translation, and post translation of exopolysaccharides (EPSs) and other extracellular polymeric substance matrix components (see the review by Jenal et al 2017). In bacteria, certain signals are communicated by synthesizing or degrading cyclic di-GMP. Cyclic di-GMP is synthesized by proteins with diguanylate cyclase activity. These proteins typically have a ...
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Hypoxia-inducible Factors
Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or Hypoxia (medical), hypoxia. They are only present in ParaHoxozoa, parahoxozoan animals. Discovery The HIF transcriptional complex was discovered in 1995 by Gregg L. Semenza and postdoctoral fellow Guang Wang. In 2016, William Kaelin Jr., Peter J. Ratcliffe and Gregg L. Semenza were presented the Lasker Award for their work in elucidating the role of HIF-1 in oxygen sensing and its role in surviving low oxygen conditions. In 2019, the same three individuals were jointly awarded the Nobel Prize in Physiology or Medicine for their work in elucidating how HIF senses and adapts cellular response to oxygen availability. Structure Most, if not all, oxygen-breathing species express the conservation (genetics), highly conserved transcriptional complex HIF-1, which is a heterodimer composed of an alpha and a beta subunit, the latter being a const ...
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NPAS2
Neuronal PAS domain protein 2 (NPAS2) also known as member of PAS protein 4 (MOP4) is a transcription factor protein that in humans is encoded by the ''NPAS2'' gene. NPAS2 is paralogous to CLOCK, and both are key proteins involved in the maintenance of circadian rhythms in mammals. In the brain, NPAS2 functions as a generator and maintainer of mammalian circadian rhythms. More specifically, NPAS2 is an activator of transcription and translation of core clock and clock-controlled genes through its role in a negative feedback loop in the suprachiasmatic nucleus (SCN), the brain region responsible for the control of circadian rhythms. Discovery The mammalian and mouse ''Npas2'' gene was first sequenced and characterized in 199Dr. Steven McKnight'slab and published by Yu-Dong Zhou et al. The gene’s cDNAs encoding mouse and human forms of NPAS2 were isolated and sequenced. RNA blotting assays were used to demonstrate the selective presence of the gene in brain and spinal cord tissue ...
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Dioxins And Dioxin-like Compounds
Dioxins and dioxin-like compounds (DLCs) are a group of chemical compounds that are persistent organic pollutants (POPs) in the environment. They are mostly by-products of burning or various industrial processes - or, in case of dioxin-like PCBs and PBBs, unwanted minor components of intentionally produced mixtures. Some of them are highly toxic, but the toxicity among them varies 30,000-fold. They are grouped together because their mechanism of action is the same. They activate the aryl hydrocarbon receptor (AH receptor), albeit with very different binding affinities, leading to high differences in toxicity and other effects. They include: * Polychlorinated dibenzo''-p-''dioxins (PCDDs), or simply dioxins. PCDDs are derivatives of dibenzo''-p-''dioxin. There are 75 PCDD congeners, differing in the number and location of chlorine atoms, and 7 of them are specifically toxic, the most toxic being 2,3,7,8-tetrachlorodibenzodioxin (TCDD). * Polychlorinated dibenzofurans (PCDFs), or ...
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Chaperonin
HSP60, also known as chaperonins (Cpn), is a family of heat shock proteins originally sorted by their 60kDa molecular mass. They prevent misfolding of proteins during stressful situations such as high heat, by assisting protein folding. HSP60 belong to a large class of molecules that assist protein folding, called molecular chaperones. Newly made proteins usually must fold from a linear chain of amino acids into a three-dimensional tertiary structure. The energy to fold proteins is supplied by non-covalent interactions between the amino acid side chains of each protein, and by solvent effects. Most proteins spontaneously fold into their most stable three-dimensional conformation, which is usually also their functional conformation, but occasionally proteins mis-fold. Molecular chaperones catalyze protein refolding by accelerating partial unfolding of misfolded proteins, aided by energy supplied by the hydrolysis of adenosine triphosphate (ATP). Chaperonin proteins may also tag ...
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Cryptochrome
Cryptochromes (from the Greek κρυπτός χρώμα, "hidden colour") are a class of flavoproteins found in plants and animals that are sensitive to blue light. They are involved in the circadian rhythms and the sensing of magnetic fields in a number of species. The name ''cryptochrome'' was proposed as a ''portmanteau'' combining the '' chromatic'' nature of the photoreceptor, and the ''cryptogamic'' organisms on which many blue-light studies were carried out. The two genes ''Cry1'' and ''Cry2'' code the two cryptochrome proteins CRY1 and CRY2. In insects and plants, CRY1 regulates the circadian clock in a light-dependent fashion, whereas in mammals, CRY1 and CRY2 act as light-independent inhibitors of CLOCK-BMAL1 components of the circadian clock. In plants, blue-light photoreception can be used to cue developmental signals. Besides chlorophylls, cryptochromes are the only proteins known to form photoinduced radical-pairs ''in vivo''. These appear to enable some animal ...
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ARNTL
Aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL) or brain and muscle ARNT-Like 1 (BMAL1) is a protein that in humans is encoded by the gene on chromosome 11, region p15.3. It's also known as ''BMAL1'', ''MOP3'', and, less commonly, ''bHLHe5'', ''BMAL'', ''BMAL1C'', ''JAP3'', ''PASD3'', and ''TIC''. ''ARNTL'' encodes a transcription factor with a basic helix-loop-helix (bHLH) and two PAS domains. The human ''ARNTL'' gene has a predicted 24 exons, located on the p15 band of the 11th chromosome. The ARNTL protein is 626 amino acids long and plays a key role as one of the positive elements in the mammalian auto-regulatory transcription-translation negative feedback loop (TTFL), which is responsible for generating molecular circadian rhythms. Research has revealed that ''ARNTL'' is the only clock gene without which the circadian clock fails to function in humans. ''ARNTL'' has also been identified as a candidate gene for susceptibility to hypertension, diabetes, ...
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Timeless (gene)
Timeless (''tim'') is a gene in multiple species but is most notable for its role in ''Drosophila'' for encoding TIM, an essential protein that regulates circadian rhythm. ''Timeless'' mRNA and protein oscillate rhythmically with time as part of a transcription-translation negative feedback loop involving the '' period'' (''per'') gene and its protein. Discovery In 1994, ''timeless'' was discovered through forward genetic screening performed by Jeffery L. Price while working in the lab of Michael W. Young. This gene was found when they noticed an arrhythmic ''tim''01 mutant via a P element screen. The tim01 mutation caused arrhythmic behavior, defined by the lack of ability to establish proper circadian rhythms. In 1995, the timeless gene was cloned by Amita Sehgal and partners in the lab of Michael W. Young. Unlike the Drosophila ''timeless'' gene, homologs have been discovered in other species that are non-essential for circadian rhythm. The discovery of ''timeless'' foll ...
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Cycle (gene)
''Cycle'' (''cyc'') is a gene in ''Drosophila melanogaster'' that encodes the CYCLE protein (CYC). The ''Cycle'' gene ''(''c''yc)'' is expressed in a variety of cell types in a circadian manner. It is involved in controlling both the sleep-wake cycle and circadian regulation of gene expression by promoting transcription in a negative feedback mechanism. The c''yc'' gene is located on the left arm of chromosome 3 and codes for a transcription factor containing a basic helix-loop-helix (bHLH) domain and a PAS domain. The 2.17 kb c''yc'' gene is divided into 5 coding exons totaling 1,625 base pairs which code for 413 aminos acid residues. Currently 19 alleles are known for c''yc'' ., accessdate=10 April 2013 Orthologs performing the same function in other species include ARNTL and ARNTL2. Function ''Cycle'' is primarily known for its role in the genetic transcription-translation feedback loop that generates circadian rhythms in ''Drosophila''. In the cell nucleus, the CYCLE pr ...
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CLOCK
A clock or a timepiece is a device used to measure and indicate time. The clock is one of the oldest human inventions, meeting the need to measure intervals of time shorter than the natural units such as the day, the lunar month and the year. Devices operating on several physical processes have been used over the millennia. Some predecessors to the modern clock may be considered as "clocks" that are based on movement in nature: A sundial shows the time by displaying the position of a shadow on a flat surface. There is a range of duration timers, a well-known example being the hourglass. Water clocks, along with the sundials, are possibly the oldest time-measuring instruments. A major advance occurred with the invention of the verge escapement, which made possible the first mechanical clocks around 1300 in Europe, which kept time with oscillating timekeepers like balance wheels., pp. 103–104., p. 31. Traditionally, in horology, the term ''clock'' was used for a stri ...
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Annual Review Of Cell And Developmental Biology
The ''Annual Review of Cell and Developmental Biology'' is a peer-reviewed scientific journal published by Annual Reviews since 1985. It releases an annual volume of review articles relevant to the fields of cell biology and developmental biology. Its editor has been Ruth Lehmann since 2018; as of 2022, its impact factor is 11.902. History Beginning in 1969, scientists began to propose that the nonprofit publishing company Annual Reviews add a journal title that published review articles relevant to cell biology. Marilyn Farquhar, the 1982 president of the American Society for Cell Biology, also thought such a journal would be useful. In 1983, Farquhar and other scientists attended a meeting at Annual Reviews to plan the topics and authors for the first volume. The ''Annual Review of Cell Biology'' published its first volume in 1985, with George E. Palade as the inaugural editor. Beginning with the eleventh volume, published in 1995, the journal was published under its current ...
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