1.
Cell surface receptor
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Cell surface receptors are receptors that are embedded in the membranes of cells. They act in signaling by receiving extracellular molecules. They are specialized integral membrane proteins that allow communication between the cell and the extracellular space, in the process of signal transduction, ligand binding affects a cascading chemical change through the cell membrane. Transmembrane receptors are classified based on their tertiary structure. But, if the structure is yet undiscovered, then they can be classified based on experimentally verifiable membrane topology. The simplest polypeptide chains are found to cross the lipid bilayer once, while others, such as the G-protein coupled receptors, there are various kinds, such as glycoprotein and lipoprotein. Hundreds of different receptors are known and many more have yet to be studied, many membrane receptors include transmembrane proteins. Each cell membrane can have several kinds of receptor, in varying surface distribution. A specific receptor may also be distributed on different membrane surfaces, depending on the membrane sort. Since receptors usually cluster on the surface, the placement of every receptor on each membrane surface is heterogeneous. Two current models have been proposed to explain transmembrane receptors mechanism, dimerization, This dimerization model suggests that prior to ligand binding, receptors exist in a monomeric form. When contact occurs with a ligand, receptors bind together to form a dimer, prior to ligand binding, the extracellular protein loses flexibility while the intracellular portion gains it. Like any integral membrane protein, a receptor may be divided into three domains. The extracellular domain juts externally from the cell or organelle, if the polypeptide chain crosses the bilayer several times, the external domain comprises loops entwined through the membrane. By definition, a main function is to recognize and respond to a type of ligand. For example, a neurotransmitter, hormone, or atomic ions may bind to the extracellular domain as a ligand coupled to receptor. Klotho is an enzyme which effects a receptor to recognize the ligand, in the majority of receptors with known structures, transmembrane alpha helices constitute most of the transmembrane component. In certain receptors, such as the nicotinic receptor, the transmembrane domain forms a protein pore through the membrane
2.
Rhodopsin-like receptors
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Rhodopsin-like receptors are a family of proteins that comprise the largest group of G protein-coupled receptors. G-protein-coupled receptors, GPCRs, constitute a vast protein family that encompasses a range of functions. They show considerable diversity at the level, on the basis of which they can be separated into distinct groups. There is a database for GPCRs. Rhodopsin-like GPCRs have been classified into the following 19 subgroups based on a phylogenetic analysis
3.
Adenosine receptor
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The adenosine receptors are a class of purinergic G protein-coupled receptors with adenosine as endogenous ligand. In humans, there are four types of adenosine receptors, each is encoded by a separate gene and has different functions, although with some overlap. The adenosine A1 receptor has been found to be throughout the entire body. This receptor has a function on most of the tissues in which it is expressed. In the brain, it slows metabolic activity by a combination of actions, presynaptically, it reduces synaptic vesicle release while post synaptically it has been found to stabilize the magnesium on the NMDA receptor. Specific A1 antagonists include 8-Cyclopentyl-1, 3-dipropylxanthine, and Cyclopentyltheophylline or 8-cyclopentyl-1, 3-dipropylxanthine, tecadenoson is an effective A1 adenosine agonist, as is selodenoson. The A1, together with A2A receptors of endogenous adenosine play a role in regulating myocardial oxygen consumption, stimulation of the A1 receptor has a myocardial depressant effect by decreasing the conduction of electrical impulses and suppressing pacemaker cell function, resulting in a decrease in heart rate. This makes adenosine a useful medication for treating and diagnosing tachyarrhythmias and this effect on the A1 receptor also explains why there is a brief moment of cardiac standstill when adenosine is administered as a rapid IV push during cardiac resuscitation. The rapid infusion causes a momentary myocardial stunning effect, in normal physiological states, this serves as a protective mechanism. Theophylline and caffeine are nonselective adenosine antagonists that are used to stimulate respiration in premature infants, adenosine receptors play a key role in the homeostasis of bone. The A1 receptor has shown to stimulate osteoclast differentiation and function. Studies have found that blockade of the A1 Receptor suppresses the osteoclast function, as with the A1, the A2A receptors are believed to play a role in regulating myocardial oxygen consumption and coronary blood flow. The activity of A2A adenosine receptor, a G-protein coupled receptor family member, is mediated by G proteins that activate adenylyl cyclase and it is abundant in basal ganglia, vasculature and platelets and it is a major target of caffeine. The A2A receptor is responsible for regulating blood flow by vasodilating the coronary arteries, which increases blood flow to the myocardium. Just as in A1 receptors, this serves as a protective mechanism. Specific antagonists include istradefylline and SCH-58261, while specific agonists include CGS-21680, the role of A2A receptor opposes that of A1 in that it inhibits osteoclast differentiation and activates osteoblasts. Studies have shown it to be effective in decreasing inflammatory osteolysis in inflamed bone and this role could potentiate new therapeutic treatment in aid of bone regeneration and increasing bone volume. This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine and this protein also interacts with netrin-1, which is involved in axon elongation
4.
Chromosome 8 (human)
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Chromosome 8 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome, chromosome 8 spans about 145 million base pairs and represents between 4.5 and 5. 0% of the total DNA in cells. Identifying genes on each chromosome is an area of genetic research. Because researchers use different approaches to genome annotation their predictions of the number of genes on each chromosome varies, in January 2017, two estimates differed by 5%, with one estimate giving 2,152 genes, and the other estimate giving 2,047 genes. About 8% of its genes are involved in development and function. A unique feature of 8p is a region of about 15 megabases that appears to have a mutation rate. This region shows an significant divergence between human and chimpanzee, suggesting that its high rates have contributed to the evolution of the human brain. The following are some of the located on chromosome 8, AEG1, Astrocyte Elevated Gene ANK1, ankyrin 1
5.
Chromosome 1 (human)
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Chromosome 1 is the designation for the largest human chromosome. Humans have two copies of chromosome 1, as they do all of the autosomes, which are the non-sex chromosomes. Chromosome 1 spans about 249 million nucleotide pairs, which are the basic units of information for DNA. It represents about 9% of the total DNA in human cells, identifying genes on each chromosome is an active area of genetic research. Because researchers use different approaches to genome annotation their predictions of the number of genes on each chromosome varies, in January 2017, two estimates differed by 12%, with one estimate giving 5,078 genes, and the other estimate giving 4,474 genes. It was the last completed chromosome, sequenced two decades after the beginning of the Human Genome Project, some of these diseases are hearing loss, Alzheimer disease, glaucoma and breast cancer. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases, patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. The following diseases are some of those related to genes on chromosome 1, reuters Wed May 17,2006 Final genome chapter published BBC NEWS
6.
Chromosome 6 (human)
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Chromosome 6 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome, chromosome 6 spans more than 170 million base pairs and represents between 5.5 and 6% of the total DNA in cells. It contains the Major Histocompatibility Complex, which contains over 100 genes related to the immune response, identifying genes on each chromosome is an active area of genetic research. Because researchers use different approaches to genome annotation their predictions of the number of genes on each chromosome varies, in January 2017, two estimates differed by 16%, with one estimate giving 3,000 genes, and the other estimate giving 2,516 genes. In 2003, the entirety of chromosome 6 was manually annotated for proteins, resulting in the identification of 1,557 genes, the human leukocyte antigen lies on chromosome 6, and encodes cell-surface antigen-presenting proteins among other functions
7.
Neurotransmitter receptor
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A neurotransmitter receptor is a membrane receptor protein that is activated by a neurotransmitter. A membrane protein interacts with the bilayer that encloses the cell and a membrane receptor protein interacts with a chemical in the cells external environment. Membrane receptor proteins, in neuronal and glial cells, allow cells to communicate with one another through chemical signals, in postsynaptic cells, neurotransmitter receptors receive signals that trigger an electrical signal, by regulating the activity of ion channels. The influx of ions through ion channels opened due to the binding of neurotransmitters to specific receptors can change the potential of a neuron. This can result in a signal that runs along the axon and is passed along at a synapse to another neuron, on presynaptic cells, there can be receptor sites specific to the neurotransmitters released by that cell, which provide feedback and mediate excessive neurotransmitter release from it. There are two types of receptors, ligand-gated receptors or ionotropic receptors and G protein-coupled receptors or metabotropic receptors. Ligand-gated receptors can be excited by neurotransmitters like glutamate and aspartate and these receptors can also be inhibited by neurotransmitters like GABA and glycine. Conversely, G protein-coupled receptors are neither excitatory nor inhibitory, rather, they modulate the actions of excitatory and inhibitory neurotransmitters. Most neurotransmitters receptors are G-protein coupled, ligand-gated ion channels are one type of ionotropic receptor or channel-linked receptor. They are a group of ion channels that are opened or closed in response to the binding of a chemical messenger. The binding site of endogenous ligands on LGICs protein complexes are located on a different portion of the protein compared to where the ion conduction pore is located. LGICs are also different from voltage-gated ion channels, and stretch-activated ion channels, G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates, and animals. G protein-coupled receptors are involved in diseases, and are also the target of approximately 30% of all modern medicinal drugs. There are two principal signal transduction pathways involving the G protein-coupled receptors, the signal pathway and the phosphatidylinositol signal pathway. When a ligand binds to the GPCR it causes a change in the GPCR. The GPCR can then activate an associated G-protein by exchanging its bound GDP for a GTP, Neurotransmitter receptors are subject to ligand-induced desensitization, That is, they can become unresponsive upon prolonged exposure to their neurotransmitter. In addition to being found in cells, neurotransmitter receptors are also found in various immune. Many neurotransmitter receptors are categorized as a receptor or G protein-coupled receptor because they span the cell membrane not once
8.
Locus (genetics)
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A locus in genetics is the position on a chromosome. Each chromosome carries many genes, humans estimated haploid protein coding genes are 19, 000-20,000, a variant of the similar DNA sequence located at a given locus is called an allele. The ordered list of known for a particular genome is called a gene map. Gene mapping is the process of determining the locus for a biological trait. The chromosomal locus of a gene might be written 3p22.1, here 3 means chromosome 3, p means p-arm. And 22 refers to region 2, band 2 and this is read as two two, not as twenty-two. So the entire locus is read as three P two two point one, the cytogenetic bands are counting from the centromere out toward the telomeres. A range of loci is specified in a similar way. For example, the locus of gene OCA1 may be written 11q1. 4-q2.1, meaning it is on the arm of chromosome 11. The ends of a chromosome are labeled pter and qter, a centisome is defined as 1% of a chromosome length. Chromosomal translocation Cytogenetic notation Karyotype Null allele Michael, R. Cummings, belmont, California, Brooks/Cole Overview at ornl. gov Chromosome Banding and Nomenclature from NCBI
9.
Adrenergic receptor
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The adrenergic receptors are a class of G protein-coupled receptors that are targets of the catecholamines, especially norepinephrine and epinephrine. Many cells possess these receptors, and the binding of a catecholamine to the receptor will generally stimulate the nervous system. By the turn of the 19th century, it was agreed that the stimulation of sympathetic nerves could cause different effects on body tissues, the second hypothesis found support from 1906 to 1913, when Henry Dale explored the effects of adrenaline, injected into animals, on blood pressure. Usually, adrenaline would increase the pressure of these animals. Although, if the animal had been exposed to ergotoxine, the pressure decreased. This mixed response, with the same compound causing either contraction or relaxation, was conceived of as the response of different types of junctions to the same compound and this again supported the argument that the muscles had two different mechanisms by which they could respond to the same compound. In June of that year, Raymond Ahlquist, Professor of Pharmacology at Medical College of Georgia, in it, he explicitly named the different responses as due to what he called α receptors and β receptors, and that the only sympathetic transmitter was adrenaline. While the latter conclusion was subsequently shown to be incorrect, his receptor nomenclature, there are two main groups of adrenergic receptors, α and β, with several subtypes. α receptors have the subtypes α1 and α2, phenylephrine is a selective agonist of the α receptor. β receptors have the subtypes β1, β2 and β3, all three are linked to Gs proteins, which in turn are linked to adenylate cyclase. Agonist binding thus causes a rise in the concentration of the second messenger cAMP. Downstream effectors of cAMP include cAMP-dependent protein kinase, which some of the intracellular events following hormone binding. Epinephrine reacts with both α- and β-adrenoreceptors, causing vasoconstriction and vasodilation, respectively, the result is that high levels of circulating epinephrine cause vasoconstriction. At lower levels of circulating epinephrine, β-adrenoreceptor stimulation dominates, producing vasodilation followed by decrease of peripheral vascular resistance, Smooth muscle behavior is variable depending on anatomical location. Smooth muscle contraction/relaxation is generalized below, one important note is the differential effects of increased cAMP in smooth muscle compared to cardiac muscle. Increased cAMP will promote relaxation in smooth muscle, while promoting increased contractility, at one time, there was a subtype known as C, but was found to be identical to one of the previously discovered subtypes. To avoid confusion, naming was continued with the letter D. α receptors have several functions in common, common effects include, Vasoconstriction of veins Decrease motility of smooth muscle in gastrointestinal tract α1-adrenergic receptors are members of the Gq protein-coupled receptor superfamily. Upon activation, a heterotrimeric G protein, Gq, activates phospholipase C, the PLC cleaves phosphatidylinositol 4, 5-bisphosphate, which in turn causes an increase in inositol triphosphate and diacylglycerol
10.
UniProt
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UniProt is a freely accessible database of protein sequence and functional information, many entries being derived from genome sequencing projects. It contains an amount of information about the biological function of proteins derived from the research literature. The UniProt consortium comprises the European Bioinformatics Institute, the Swiss Institute of Bioinformatics, EBI, located at the Wellcome Trust Genome Campus in Hinxton, UK, hosts a large resource of bioinformatics databases and services. SIB, located in Geneva, Switzerland, maintains the ExPASy servers that are a resource for proteomics tools. In 2002, EBI, SIB, and PIR joined forces as the UniProt consortium, each consortium member is heavily involved in protein database maintenance and annotation. Until recently, EBI and SIB together produced the Swiss-Prot and TrEMBL databases and these databases coexisted with differing protein sequence coverage and annotation priorities. Swiss-Prot aimed to provide reliable protein sequences associated with a level of annotation. Recognizing that sequence data were being generated at a pace exceeding Swiss-Prots ability to keep up, meanwhile, PIR maintained the PIR-PSD and related databases, including iProClass, a database of protein sequences and curated families. The consortium members pooled their resources and expertise, and launched UniProt in December 2003. UniProt provides four core databases, UniProtKB, UniParc, UniRef, UniProt Knowledgebase is a protein database partially curated by experts, consisting of two sections, UniProtKB/Swiss-Prot and UniProtKB/TrEMBL. As of 19 March 2014, release 2014_03 of UniProtKB/Swiss-Prot contains 542,782 sequence entries, UniProtKB/Swiss-Prot is a manually annotated, non-redundant protein sequence database. It combines information extracted from literature and biocurator-evaluated computational analysis. The aim of UniProtKB/Swiss-Prot is to all known relevant information about a particular protein. Annotation is regularly reviewed to keep up with current scientific findings, the manual annotation of an entry involves detailed analysis of the protein sequence and of the scientific literature. Sequences from the gene and the same species are merged into the same database entry. Differences between sequences are identified, and their cause documented, a range of sequence analysis tools is used in the annotation of UniProtKB/Swiss-Prot entries. Computer-predictions are manually evaluated, and relevant results selected for inclusion in the entry and these predictions include post-translational modifications, transmembrane domains and topology, signal peptides, domain identification, and protein family classification. Relevant publications are identified by searching databases such as PubMed, the full text of each paper is read, and information is extracted and added to the entry
11.
Rhodopsin
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Rhodopsin is a light-sensitive receptor protein involved in visual phototransduction. It is named after ancient Greek ῥόδον for “rose”, due to its pinkish color, Rhodopsin is a biological pigment found in the rods of the retina and is a G-protein-coupled receptor. Rhodopsin is extremely sensitive to light, and thus enables vision in low-light conditions, when rhodopsin is exposed to light, it immediately photobleaches. In humans, it is regenerated fully in about 30 minutes, Rhodopsin was discovered by Franz Christian Boll in 1876. Rhodopsin consists of a protein moiety also called scotopsin, which binds covalently a cofactor called retinal, opsins are G protein coupled receptors and have seven transmembrane domains. The seven transmembrane domains form a pocket, where the retinal binds to a residue in the seventh transmembrane domain. The retinal lies horizontally to the cell membrane, and the cell membrane lipid bilayer embeds half of the rhodopsin. Thousands of rhodopsin molecules are found in outer segment disc of the host rod cell. Retinol is produced in the retina from Vitamin A, from dietary beta-carotene, Rhodopsin of the rods most strongly absorbs green-blue light and, therefore, appears reddish-purple, which is why it is also called visual purple. It is responsible for vision in the dark. Several closely related opsins exist that only in a few amino acids. Humans have eight different other opsins besides rhodopsin, as well as cryptochrome, the photopsins are found in the different types of the cone cells of the retina and are the basis of color vision. They have absorption maxima for yellowish-green, green, and bluish-violet light, the remaining opsin is found in photosensitive ganglion cells and absorbs blue light most strongly. In rhodopsin, the group of retinal is covalently linked to the amino group of a lysine residue on the protein in a protonated Schiff base. The intermediates formed during this process were first investigated in the laboratory of George Wald, the photoisomerization dynamics has been subsequently investigated with time-resolved IR spectroscopy and UV/Vis spectroscopy. A first photoproduct called photorhodopsin forms within 200 femtoseconds after irradiation and this intermediate can be trapped and studied at cryogenic temperatures, and was initially referred to as prelumirhodopsin. In subsequent intermediates lumirhodopsin and metarhodopsin I, the Schiffs base linkage to all-trans retinal remains protonated, the structure of rhodopsin has been studied in detail via x-ray crystallography on rhodopsin crystals. Several models attempt to explain how the group can change its conformation without clashing with the enveloping rhodopsin protein pocket
