HMGA1
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HMGA1
High-mobility group protein HMG-I/HMG-Y is a protein that in humans is encoded by the ''HMGA1'' gene. Function This gene encodes a non-histone chromatin protein involved in many cellular processes, including regulation of inducible gene transcription, DNA replication, heterochromatin organization, integration of retroviruses into chromosomes, and the metastatic progression of cancer cells. HMGA1 proteins are quite small (~10-12 kDa) and basic molecules, and consist of three AT-hooks with the RGRP (Arg-Gly-Arg-Pro) core motif, a novel cross-linking domain located between the second and third AT-hook, and a C-terminal acidic tail characteristic for the HMG family comprising HMGA, HMGB and HMGN proteins. HMGA1-GFP fusion proteins are highly dynamic in vivo (determined using FRAP analysis), but in contrast also show nanomolar affinity to AT-rich DNA in vitro (determined biochemically), which might be explained due to the extensive post-transcriptional modifications in vivo. ...
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HMGA
HMGA is a family of high mobility group proteins characterized by an AT-hook. They code for a "small, nonhistone, chromatin-associated protein that has no intrinsic transcriptional activity but can modulate transcription by altering the chromatin architecture". Mammals have two orthologs: HMGA1 and HMGA2. Genomic distribution In mouse embryonic stem cells it has been demonstrated that both HMGA proteins binds uniformly to the DNA due to their AT-hook domains, with a slight preference for AT-rich regions/ Such regions tend to lack coding genes, an observation that argues against a direct role in transcriptional control and in agreement with previous studies, suggest that these proteins have a structural role in the chromatin, similar to histone. Association with human traits Variations in HMGA2 to have a moderate association with adult height. See also * HMGA1 High-mobility group protein HMG-I/HMG-Y is a protein that in humans is encoded by the ''HMGA1'' gene. Function ...
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High Mobility Group
High-Mobility Group or HMG is a group of chromosomal proteins that are involved in the regulation of DNA-dependent processes such as transcription, replication, recombination, and DNA repair. Families The HMG proteins are subdivided into 3 superfamilies each containing a characteristic functional domain: * HMGA – contains an AT-hook domain ** HMGA1 ** HMGA2 * HMGB – contains a HMG-box domain ** HMGB1 ** HMGB2 ** HMGB3 ** HMGB4 * HMGN – contains a nucleosomal binding domain ** HMGN1 ** HMGN2 ** HMGN3 ** HMGN4 ** HMGN5 Proteins containing any of these embedded in their sequence are known as HMG motif proteins. HMG-box proteins are found in a variety of eukaryotic organisms. They were originally isolated from mammalian cells, and named according to their electrophoretic mobility in polyacrylamide gels. Other families with HMG-box domain * SOX gene family ** Sex-Determining Region Y Protein ** SOX1, SOX2, etc. * TCF/LEF family (T cell factor/lymphoid enhancer factor fa ...
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Sp1 Transcription Factor
Transcription factor Sp1, also known as specificity protein 1* is a protein that in humans is encoded by the SP1 gene. Function The protein encoded by this gene is a zinc finger transcription factor that binds to GC-rich motifs of many promoters. The encoded protein is involved in many cellular processes, including cell differentiation, cell growth, apoptosis, immune responses, response to DNA damage, and chromatin remodeling. Post-translational modifications such as phosphorylation, acetylation, ''O''-GlcNAcylation, and proteolytic processing significantly affect the activity of this protein, which can be an activator or a repressor. In the SV40 virus, Sp1 binds to the GC boxes in the regulatory region (RR) of the genome. Structure SP1 belongs to the Sp/KLF family of transcription factors. The protein is 785 amino acids long, with a molecular weight of 81 kDa. The SP1 transcription factor contains two glutamine-rich activation domains at its N-terminus that are believ ...
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CEBPB
CCAAT/enhancer-binding protein beta is a protein that in humans is encoded by the ''CEBPB'' gene. Function The protein encoded by this intronless gene is a bZIP transcription factor that can bind as a homodimer to certain DNA regulatory regions. It can also form heterodimers with the related proteins CEBP-alpha, CEBP-delta, and CEBP-gamma. The encoded protein is important in the regulation of genes involved in immune and inflammatory responses and has been shown to bind to the IL-1 response element in the IL-6 gene, as well as to regulatory regions of several acute-phase and cytokine genes. In addition, the encoded protein can bind the promoter and upstream element and stimulate the expression of the collagen type I gene. CEBP-beta is critical for normal macrophage functioning, an important immune cell sub-type; mice unable to express CEBP-beta have macrophages that cannot differentiate (specialize) and thus are unable to perform all their biological functions - includi ...
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AT-hook
The second AT-hook of HMGA1 (black ribbon) bound to the minor-groove of AT-rich DNA. The amino-acid side chains and nucleotides have been hidden. The AT-hook is a DNA-binding motif present in many proteins, including the high mobility group (HMG) proteins, DNA-binding proteins from plants and hBRG1 protein, a central ATPase of the human switching/sucrose non-fermenting (SWI/SNF) remodeling complex. This motif consists of a conserved, palindromic, core sequence of proline-arginine-glycine-arginine-proline, although some AT-hooks contain only a single proline in the core sequence. AT-hooks also include a variable number of positively charged lysine and arginine residues on either side of the core sequence. The AT-hook binds to the minor groove of adenine-thymine (AT) rich DNA, hence the AT in the name. The rest of the name derives from a predicted asparagine/aspartate "hook" in the earliest AT-hooks reported in 1990. In 1997 structural studies using NMR Nuclear magnetic re ...
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Posttranslational Modification
Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribosomes translating mRNA into polypeptide chains, which may then undergo PTM to form the mature protein product. PTMs are important components in cell signal transduction, signaling, as for example when prohormones are converted to hormones. Post-translational modifications can occur on the amino acid side chains or at the protein's C-terminus, C- or N-terminus, N- termini. They can extend the chemical repertoire of the 20 standard amino acids by modifying an existing functional group or introducing a new one such as phosphorylation, phosphate. Phosphorylation is a highly effective mechanism for regulating the activity of enzymes and is the most common post-translational modification. Many eukaryotic and prokaryotic proteins also have carbohydra ...
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Insulin Receptor
The insulin receptor (IR) is a transmembrane receptor that is activated by insulin, IGF-I, IGF-II and belongs to the large class of receptor tyrosine kinase. Metabolically, the insulin receptor plays a key role in the regulation of glucose homeostasis, a functional process that under degenerate conditions may result in a range of clinical manifestations including diabetes and cancer. Insulin signalling controls access to blood glucose in body cells. When insulin falls, especially in those with high insulin sensitivity, body cells begin only to have access to lipids that do not require transport across the membrane. So, in this way, insulin is the key regulator of fat metabolism as well. Biochemically, the insulin receptor is encoded by a single gene , from which alternate splicing during transcription results in either IR-A or IR-B isoforms. Downstream post-translational events of either isoform result in the formation of a proteolytically cleaved α and β subunit, which upon com ...
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Diabetic
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased appetite. If left untreated, diabetes can cause many health complications. Acute complications can include diabetic ketoacidosis, hyperosmolar hyperglycemic state, or death. Serious long-term complications include cardiovascular disease, stroke, chronic kidney disease, foot ulcers, damage to the nerves, damage to the eyes, and cognitive impairment. Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body not responding properly to the insulin produced. Insulin is a hormone which is responsible for helping glucose from food get into cells to be used for energy. There are three main types of diabetes mellitus: * Type 1 diabetes results from failure of the pancreas to produce enough insulin due to loss of ...
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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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Post-transcriptional Modification
Transcriptional modification or co-transcriptional modification is a set of biological processes common to most eukaryotic cells by which an RNA primary transcript is chemically altered following transcription from a gene to produce a mature, functional RNA molecule that can then leave the nucleus and perform any of a variety of different functions in the cell. There are many types of post-transcriptional modifications achieved through a diverse class of molecular mechanisms. One example is the conversion of precursor messenger RNA transcripts into mature messenger RNA that is subsequently capable of being translated into protein. This process includes three major steps that significantly modify the chemical structure of the RNA molecule: the addition of a 5' cap, the addition of a 3' polyadenylated tail, and RNA splicing. Such processing is vital for the correct translation of eukaryotic genomes because the initial precursor mRNA produced by transcription often contains both exo ...
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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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