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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 transc ...
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BRD3
Bromodomain-containing protein 3 (BRD3) also known as RING3-like protein (RING3L) is a protein that in humans is encoded by the BRD3 gene. This gene was identified based on its homology to the gene encoding the RING3 (BRD2) protein, a serine/threonine kinase. The gene maps to 9q34, a region which contains several major histocompatibility complex (MHC) genes. Structure BRD3 is a member of the Bromodomain and Extra-Terminal motif (BET) protein family. Like other BET family members it contains two tandem homologous bromodomains and an "Extra-Terminal" motif. BRD3, similar to BRD2, does not have a long C-terminal domain as BET family proteins BRD4 and BRDT do. Function Like other BET protein family members, BRD3 associates with acetylated lysine residues on histones and transcription factors. BRD3 has been implicated in nucleosome remodeling in the context of transcription. In addition, BRD3 has been shown to interact with RNA molecules and form protein-RNA aggregates. ...
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BET Inhibitor
BET inhibitors are a class of drugs that reversibly bind the bromodomains of BET protein, 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 di ...
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BRD4
Bromodomain-containing protein 4 is a protein that in humans is encoded by the ''BRD4'' gene. BRD4 is a member of the BET (bromodomain and extra terminal domain) family, which also includes BRD2, BRD3, and BRDT. BRD4, similar to other BET family members, contains two bromodomains that recognize acetylated lysine residues. BRD4 also has an extended C-terminal domain with little sequence homology to other BET family members. Structure The two bromodomains in BRD4, termed BD1 and BD2, consist of 4 alpha-helices linked by 2 loops. The ET domain structure is made up of 3 alpha-helices and a loop. The C-terminal domain of BRD4 has been implicated in promoting gene transcription through interaction with the transcription elongation factor P-TEFb and RNA polymerase II. Function The protein encoded by this gene is homologous to the murine protein MCAP, which associates with chromosomes during mitosis, and to the human BRD2 (RING3) protein, a serine/threonine kinase. Each of t ...
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BRDT
Bromodomain testis-specific protein is a protein that in humans is encoded by the ''BRDT'' gene. It is a member of the Bromodomain and Extra-terminal motif (BET) protein family. BRDT is similar to the RING3 protein family. It possesses 2 bromodomain motifs and a PEST sequence (a cluster of proline, glutamic acid, serine, and threonine residues), characteristic of proteins that undergo rapid intracellular degradation. The bromodomain is found in proteins that regulate transcription. Two transcript variants encoding the same protein have been found for this gene. The use of three different mouse models (Brdt knock-out mice, mice expressing a non-functional Brdt and mice expressing a mutated Brdt lacking its first bromodomain) showed that Brdt drives a meiotic and post-meiotic gene expression program. It also controls the genome-wide post-meiotic genome reorganization that occurs after histone hyperacetylation in elongating spermatids. Model organisms Model organisms have been ...
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E2F2
Transcription factor E2F2 is a protein that in humans is encoded by the ''E2F2'' gene. Function The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein and another 2 members, E2F1 and E2F3, have an additional cyclin binding domain. This protein binds specifically to retinoblastoma protein pRB in a cell-cycle dependent manner, and it e ...
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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 resid ...
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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 g ...
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MHC Class II
MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, and B cells. These cells are important in initiating immune responses. The antigens presented by class II peptides are derived from extracellular proteins (not cytosolic as in MHC class I). Loading of a MHC class II molecule occurs by phagocytosis; extracellular proteins are endocytosed, digested in lysosomes, and the resulting epitopic peptide fragments are loaded onto MHC class II molecules prior to their migration to the cell surface. In humans, the MHC class II protein complex is encoded by the human leukocyte antigen gene complex (HLA). HLAs corresponding to MHC class II are HLA-DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, and HLA-DR. Mutations in the HLA gene complex can lead to bare lymphocyte syndrome (BLS), which is a ty ...
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Human Leukocyte Antigen
The human leukocyte antigen (HLA) system or complex is a complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for the regulation of the immune system. The HLA system is also known as the human version of the major histocompatibility complex (MHC) found in many animals. Mutations in HLA genes may be linked to autoimmune disease such as type I diabetes, and celiac disease. The HLA gene complex resides on a 3 Mbp stretch within chromosome 6, p-arm at 21.3. HLA genes are highly polymorphic, which means that they have many different alleles, allowing them to fine-tune the adaptive immune system. The proteins encoded by certain genes are also known as ''antigens'', as a result of their historic discovery as factors in organ transplants. HLAs corresponding to MHC class I ( A, B, and C), all of which are the HLA Class1 group, present peptides from inside the cell. For example, if the cell is infected by a virus, the HLA system brings f ...
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Drosophila
''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit. They should not be confused with the Tephritidae, a related family, which are also called fruit flies (sometimes referred to as "true fruit flies"); tephritids feed primarily on unripe or ripe fruit, with many species being regarded as destructive agricultural pests, especially the Mediterranean fruit fly. One species of ''Drosophila'' in particular, '' D. melanogaster'', has been heavily used in research in genetics and is a common model organism in developmental biology. The terms "fruit fly" and "''Drosophila''" are often used synonymously with ''D. melanogaster'' in modern biological literature. The entire genus, however, contains more than 1,500 species and is very diverse in appea ...
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Signal Transduction Pathway
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellular response. Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term sensor is used. The changes elicited by ligand binding (or signal sensing) in a receptor give rise to a biochemical cascade, which is a chain of biochemical events known as a signaling pathway. When signaling pathways interact with one another they form networks, which allow cellular responses to be coordinated, often by combinatorial signaling events. At the molecular level, such responses include changes in the transcription or translation of genes, and post-translational and conformational changes in proteins, as well as changes in their location. These molecular events are the basic mechanisms controlling cell growth ...
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