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JARID1A
Lysine-specific demethylase 5A is an enzyme that in humans is encoded by the ''KDM5A'' gene. Function The protein encoded by this gene is a ubiquitously expressed nuclear protein. It binds directly, with several other proteins, to retinoblastoma protein which regulates cell proliferation. It was formerly known as Retinoblastoma Binding Protein 2 (RBP2). This protein also interacts with rhombotin-2 which functions distinctly in erythropoiesis and in T-cell leukemogenesis. Rhombotin-2 is thought to either directly affect the activity of the encoded protein or may indirectly modulate the functions of the retinoblastoma protein by binding to this protein. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. The ''Drosophila'' homolog, LID, was found to be an H3K4 histone demethylase that binds to Myc, c-Myc. It was recently renamed to Lysine Demethylase 5 (KDM5). Enzymatically can be designated as a trimethyllysine dioxygenase, which ...
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Estrogen Receptor Alpha
Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein) that is activated by the sex hormone estrogen. In humans, ERα is encoded by the gene ''ESR1'' (EStrogen Receptor 1). Structure The estrogen receptor (ER) is a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription. Alternative splicing results in several ESR1 mRNA transcripts, which differ primarily in their 5-prime untranslated regions. The translated receptors show less variability. Ligands Agonists Non-selective * Endogenous estrogens (e.g., estradiol, estrone, estriol, estetrol) * Natural estrogens (e.g., conjugated equine estrogens) * Synthetic estrogens (e.g., ethinylestradiol, diethylstilbestrol) Selective Agonists of ERα selective over ERβ include: * Propylp ...
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LMO2
LIM domain only 2 (rhombotin-like 1), also known as LMO2, RBTNL1, RBTN2, RHOM2, LIM Domain Only Protein 2, TTG2, and T-Cell Translocation Protein 2, is a protein which in humans is encoded by the ''LMO2'' gene. Function LMO2 encodes a cysteine-rich, two LIM domain protein that is required for yolk sac erythropoiesis. The LMO2 protein has a central and crucial role in hematopoietic development and is highly conserved. Clinical significance Aberrant ''LMO2'' expression is a significant feature of T cell acute lymphoblastic leukaemia with multiple described mechanisms of activation. The LMO2 transcription start site is located approximately 25 kb downstream from the 11p13 T-cell translocation cluster (11p13 ttc), where a number of T-cell acute lymphoblastic leukemia-specific translocations occur. An upstream noncoding DNA element is also the site of recurrent mutations in T cell acute lymphoblastic leukaemia, leading the recruitment of the transcription factor MYB and signif ...
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Retinoblastoma Protein
The retinoblastoma protein (protein name abbreviated pRb; gene name abbreviated ''Rb'', ''RB'' or ''RB1'') is a proto-oncogenic tumor suppressor protein that is dysfunctional in several major cancers. One function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide. When the cell is ready to divide, pRb is phosphorylated, inactivating it, and the cell cycle is allowed to progress. It is also a recruiter of several chromatin remodeling enzymes such as methylases and acetylases. pRb belongs to the pocket protein family, whose members have a pocket for the functional binding of other proteins. Should an oncogenic protein, such as those produced by cells infected by high-risk types of human papillomavirus, bind and inactivate pRb, this can lead to cancer. The ''RB'' gene may have been responsible for the evolution of multicellularity in several lineages of life including animals. Name and genetics In humans, the prote ...
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Enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. Almost all metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called ''enzymology'' and the field of pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Other biocatalysts are catalytic RNA molecules, called ribozymes. Enzymes' specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the reaction ra ...
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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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Demethylase
Demethylases are enzymes that remove methyl (CH3) groups from nucleic acids, proteins (particularly histones), and other molecules. Demethylases are important epigenetic proteins, as they are responsible for transcriptional regulation of the genome by controlling the methylation of DNA and histones, and by extension, the chromatin state at specific gene loci. Histone lysine demethylation Histone methylation was initially considered an effectively irreversible process as the half-life of the histone methylation was approximately equal to the histone half-life. Histone lysine demethylase LSD1 (later classified as KDM1A) was first identified in 2004 as a nuclear amine oxidase homolog. Two main classes of histone lysine demethylases exist, defined by their mechanisms: flavin adenine dinucleotide (FAD)-dependent amine oxidases and α-ketoglutarate-dependent hydroxylases. Histone lysine demethylases possess a variety of domains that are responsible for histone recognition, DNA ...
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Trimethyllysine Dioxygenase
In enzymology, a trimethyllysine dioxygenase (TMLH; ) is an enzyme that catalyzes the chemical reaction :N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2 \rightleftharpoons 3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2 TMLH is a member of the alpha-ketoglutarate-dependent hydroxylases superfamily. The 3 substrates of this enzyme are N6,N6,N6-trimethyl-L-lysine, 2-oxoglutarate, and O2, whereas its 3 products are 3-hydroxy-N6,N6,N6-trimethyl-L-lysine, succinate, and CO2. This enzyme belongs to the family of oxidoreductases, specifically those acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2 with 2-oxoglutarate as one donor, and incorporation of one atom o oxygen into each donor. The systematic name of this enzyme class is N6,N6,N6-trimethyl-L-lysine,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating). Other names in common use include trimethyllysine alpha-ketoglutarate di ...
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Alpha-ketoglutarate-dependent Hydroxylase
Alpha-ketoglutarate-dependent hydroxylases are a major class of non-heme iron proteins that catalyse a wide range of reactions. These reactions include hydroxylation reactions, demethylations, ring expansions, ring closures, and desaturations. Functionally, the αKG-dependent hydroxylases are comparable to cytochrome P450 enzymes. Both use O2 and reducing equivalents as cosubstrates and both generate water. Biological function αKG-dependent hydroxylases have diverse roles. In microorganisms such as bacteria, αKG-dependent dioxygenases are involved in many biosynthetic and metabolic pathways; for example, in ''E. coli'', the AlkB enzyme is associated with the repair of damaged DNA. In plants, αKG-dependent dioxygenases are involved in diverse reactions in plant metabolism. These include flavonoid biosynthesis, and ethylene biosyntheses. In mammals and humans, αKG-dependent dioxygenase have functional roles in biosyntheses (e.g. collagen biosynthesis and L-carnitine biosynthe ...
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H3K4me3
H3K4me3 is an epigenetic modification to the DNA packaging protein Histone H3 that indicates tri-methylation at the 4th lysine residue of the histone H3 protein and is often involved in the regulation of gene expression. The name denotes the addition of three methyl groups ( trimethylation) to the lysine 4 on the histone H3 protein. H3 is used to package DNA in eukaryotic cells (including human cells), and modifications to the histone alter the accessibility of genes for transcription. H3K4me3 is commonly associated with the activation of transcription of nearby genes. H3K4 trimethylation regulates gene expression through chromatin remodeling by the NURF complex. This makes the DNA in the chromatin more accessible for transcription factors, allowing the genes to be transcribed and expressed in the cell. More specifically, H3K4me3 is found to positively regulate transcription by bringing histone acetylases and nucleosome remodelling enzymes (NURF). H3K4me3 also plays an impor ...
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Transcription Factors
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the desired cells at the right time and in the right amount throughout the life of the cell and the organism. Groups of TFs function in a coordinated fashion to direct cell division, cell growth, and cell death throughout life; cell migration and organization (body plan) during embryonic development; and intermittently in response to signals from outside the cell, such as a hormone. There are up to 1600 TFs in the human genome. Transcription factors are members of the proteome as well as regulome. TFs work alone or with other proteins in a complex, by promoting (as an activator), or blocking (as a repressor) the recruitment of RNA po ...
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Human 2OG Oxygenases
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, and language. Humans are highly social and tend to live in complex social structures composed of many cooperating and competing groups, from families and kinship networks to political states. Social interactions between humans have established a wide variety of values, social norms, and rituals, which bolster human society. Its intelligence and its desire to understand and influence the environment and to explain and manipulate phenomena have motivated humanity's development of science, philosophy, mythology, religion, and other fields of study. Although some scientists equate the term ''humans'' with all members of the genus ''Homo'', in common usage, it generally refers to ''Homo sapiens'', the only extant member. Anatomically modern hu ...
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