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Bromodomain-containing Protein
A bromodomain is an approximately 110 amino acid protein domain that recognizes acetylated lysine residues, such as those on the ''N''-terminal tails of histones. Bromodomains, as the "readers" of lysine acetylation, are responsible in transducing the signal carried by acetylated lysine residues and translating it into various normal or abnormal phenotypes. Their affinity is higher for regions where multiple acetylation sites exist in proximity. This recognition is often a prerequisite for protein-histone association and chromatin remodeling. The domain itself adopts an all-α protein fold, a bundle of four alpha helices each separated by loop regions of variable lengths that form a hydrophobic pocket that recognizes the acetyl lysine. Discovery The bromodomain was identified as a novel structural motif by John W. Tamkun and colleagues studying the drosophila gene ''Brahma''/''brm'', and showed sequence similarity to genes involved in transcriptional activation. The name "brom ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ribbon Diagram
Ribbon diagrams, also known as Richardson diagrams, are three-dimensional space, 3D schematic representations of protein structure and are one of the most common methods of protein depiction used today. The ribbon shows the overall path and organization of the protein backbone in 3D, and serves as a visual framework on which to hang details of the full atomic structure, such as the balls for the oxygen atoms bound to the active site of myoglobin in the adjacent image. Ribbon diagrams are generated by interpolating a smooth curve through the polypeptide backbone. Alpha helix, α-helices are shown as coiled ribbons or thick tubes, Beta strand, β-strands as arrows, and non-repetitive coils or loops as lines or thin tubes. The direction of the Peptide, polypeptide chain is shown locally by the arrows, and may be indicated overall by a colour ramp along the length of the ribbon. Ribbon diagrams are simple yet powerful, expressing the visual basics of a molecular structure (twist, fold ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BRD2
Bromodomain-containing protein 2 is a protein that in humans is encoded by the ''BRD2'' gene. BRD2 is part of the Bromodomain and Extra-Terminal motif (BET) protein family that also contains BRD3, BRD4, and BRDT in mammals Early descriptions demonstrated that BRD2 gene product is a mitogen-activated kinase which localizes to the nucleus. The gene maps to the major histocompatibility complex (MHC) class II region on chromosome 6p21.3 but sequence comparison suggests that the protein is not involved in the immune response. Homology to the ''Drosophila'' gene female sterile homeotic suggests that this human gene may be part of a signal transduction pathway involved in growth control. Functions *BRD2 has been implicated in cancer. *BRD2 loss in mice causes obesity without diabetes for unknown reasons. *BRD2 may have functional overlap with close homolog BRD3. *BRD2 function is blocked by BET inhibitors. Interactions BRD2 has been shown to interact with E2F2, and many transcription ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chromodomain
A chromodomain (''chromatin organization modifier'') is a protein structural domain of about 40–50 amino acid residues commonly found in proteins associated with the remodeling and manipulation of chromatin. The domain is highly conserved among both plants and animals, and is represented in a large number of different proteins in many genomes, such as that of the mouse. Some chromodomain-containing genes have multiple alternative splicing isoforms that omit the chromodomain entirely. In mammals, chromodomain-containing proteins are responsible for aspects of gene regulation related to chromatin remodeling and formation of heterochromatin regions. Chromodomain-containing proteins also bind methylated histones and appear in the RNA-induced transcriptional silencing RNA-induced transcriptional silencing (RITS) is a form of RNA interference by which short RNA molecules – such as small interfering RNA (siRNA) – trigger the downregulation of transcription of a particular g ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BET Inhibitors
BET inhibitors are a class of drugs that reversibly bind the bromodomains of Bromodomain and Extra-Terminal motif (BET) proteins BRD2, BRD3, BRD4, and BRDT, and prevent protein-protein interaction between BET proteins and acetylated histones and transcription factors. Discovery and development Thienodiazepine BET inhibitors were discovered by scientists at Yoshitomi Pharmaceuticals (now Mitsubishi Tanabe Pharma) in the early 1990s, and their potential both as anti-inflammatories and anti-cancer agents noted. However, these molecules remained largely unknown until 2010 when both the use of JQ1 in NUT midline carcinoma and of I-BET 762 in sepsis were published. Since this time a number of molecules have been described that are capable of targeting BET bromodomains. BET inhibitors have been described that are able to discriminate between the first and second bromodomains of BET proteins (BD1 vs BD2). However, no BET inhibitor has yet been described that can reliably distinguish ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Multiple Sclerosis
Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This damage disrupts the ability of parts of the nervous system to transmit signals, resulting in a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems. Specific symptoms can include double vision, blindness in one eye, muscle weakness, and trouble with sensation or coordination. MS takes several forms, with new symptoms either occurring in isolated attacks (relapsing forms) or building up over time (progressive forms). In the relapsing forms of MS, between attacks, symptoms may disappear completely, although some permanent neurological problems often remain, especially as the disease advances. While the cause is unclear, the underlying mechanism is thought to be either destruction by the immune system ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Remyelination
Remyelination is the process of propagating oligodendrocyte precursor cells to form oligodendrocytes to create new myelin sheaths on demyelinated axons in the CNS. This is a process naturally regulated in the body and tends to be very efficient in a healthy CNS. The process creates a thinner myelin sheath than normal, but it helps to protect the axon from further damage, from overall degeneration, and proves to increase conductance once again. The processes underlying remyelination are under investigation in the hope of finding treatments for demyelinating diseases, such as multiple sclerosis. Function Remyelination is activated and regulated by a variety of factors surrounding lesion sites that control the migration and differentiation of Oligodendrocyte Precursor Cells. Remyelination looks different from developmental myelination in the structure of the myelin formed. Reasons for this are unclear, but proper function of the axon is restored regardless. Perhaps of most interest ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BRD9
Bromodomain-containing protein 9 is a protein that in humans is encoded by the ''BRD9'' gene. Structure and interaction BRD9 contains a bromodomain. It is closely related to BRD7. BRD9 is present in some SWI/SNF ATPase remodeling complexes. Role in cancer The BRD9 gene is frequently present in variable copy number in lung cancer. Small molecule inhibition Small molecules capable of binding to the bromodomain of BRD9 have been developed. See also Bromodomain A bromodomain is an approximately 110 amino acid protein domain that recognizes acetylated lysine residues, such as those on the ''N''-terminal tails of histones. Bromodomains, as the "readers" of lysine acetylation, are responsible in transducin ... References Human proteins {{gene-5-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BRD7
Bromodomain-containing protein 7 is a protein that in humans is encoded by the ''BRD7'' gene. Interactions BRD7 has been shown to interact with IRF2 and HNRPUL1. Azoospermia BRD7 protein is a transcription regulator that is normally highly expressed in the testis, particularly in meiotic pachytene and diplotene spermatocytes and in round spermatids. However, in the testes of patients exhibiting spermatogenesis arrest and azoospermia, BRD7 protein expression is observed to be absent or reduced. Homozygous knockout mice RD7(-/-)are infertile and have increased DNA damage and apoptosis in their germline In biology and genetics, the germline is the population of a multicellular organism's cells that pass on their genetic material to the progeny (offspring). In other words, they are the cells that form the egg, sperm and the fertilised egg. They .... References External links * Further reading * * * * * * * * * * * * * * * * {{refend [Baidu] |
PCAF
P300/CBP-associated factor (PCAF), also known as K(lysine) acetyltransferase 2B (KAT2B), is a human gene and transcriptional coactivator associated with p53. Structure Several domains of PCAF can act independently or in unison to enable its functions. PCAF has separate acetyltransferase and E3 ubiquitin ligase domains as well as a bromodomain for interaction with other proteins. PCAF also possesses sites for its own acetylation and ubiquitination. Function CBP and p300 are large nuclear proteins that bind to many sequence-specific factors involved in cell growth and/or differentiation, including c-jun and the adenoviral oncoprotein E1A. The protein encoded by the PCAF gene associates with p300/CBP. It has in vitro and in vivo binding activity with CBP and p300, and competes with E1A for binding sites in p300/CBP. It has histone acetyl transferase activity with core histones and nucleosome core particles, indicating that this protein plays a direct role in transcriptional reg ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
EP300
Histone acetyltransferase p300 also known as p300 HAT or E1A-associated protein p300 (where E1A = adenovirus early region 1A) also known as EP300 or p300 is an enzyme that, in humans, is encoded by the ''EP300'' gene. It functions as histone acetyltransferase that regulates transcription of genes via chromatin remodeling by allowing histone proteins to wrap DNA less tightly. This enzyme plays an essential role in regulating cell growth and division, prompting cells to mature and assume specialized functions (differentiate), and preventing the growth of cancerous tumors. The p300 protein appears to be critical for normal development before and after birth. The EP300 gene is located on the long (q) arm of the human chromosome 22 at position 13.2. This gene encodes the adenovirus E1A-associated cellular p300 transcriptional co-activator protein. EP300 is closely related to another gene, CREB binding protein, which is found on human chromosome 16. Function p300 HAT functions ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Histone Acetyltransferases
Histone acetyltransferases (HATs) are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl-CoA to form ε-''N''-acetyllysine. DNA is wrapped around histones, and, by transferring an acetyl group to the histones, genes can be turned on and off. In general, histone acetylation increases gene expression. In general, histone acetylation is linked to transcriptional activation and associated with euchromatin. Euchromatin, which is less densely compact, allows transcription factors to bind more easily to regulatory sites on DNA, causing transcriptional activation. When it was first discovered, it was thought that acetylation of lysine neutralizes the positive charge normally present, thus reducing affinity between histone and (negatively charged) DNA, which renders DNA more accessible to transcription factors. Research has emerged, since, to show that lysine acetylation and other posttranslational modifications of histo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ASH1L
ASH1L (also called huASH1, ASH1, ASH1L1, ASH1-like, or KMT2H) is a histone-lysine N-methyltransferase enzyme encoded by the ASH1L gene located at chromosomal band 1q22. ASH1L is the human homolog of Drosophila Ash1 (absent, small, or homeotic-like). Gene Ash1 was discovered as a gene causing an imaginal disc mutant phenotype in Drosophila. Ash1 is a member of the trithorax-group (trxG) of proteins, a group of transcriptional activators that are involved in regulating Hox gene expression and body segment identity. Drosophila Ash1 interacts with trithorax to regulate ultrabithorax expression. The human ASH1L gene spans 227.5 kb on chromosome 1, band q22. This region is rearranged in a variety of human cancers such as leukemia, non-Hodgkin’s lymphoma, and some solid tumors. The gene is expressed in multiple tissues, with highest levels in brain, kidney, and heart, as a 10.5-kb mRNA transcript. Structure Human ASH1L protein is 2969 amino acids long with a molecular weight ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
