Runt Domain
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Runt Domain
The Runt domain is an evolutionary conserved protein domain. The AML1/RUNX1 gene is rearranged by the t(8;21) translocation in acute myeloid leukemia. The gene is highly similar to the ''Drosophila melanogaster'' segmentation gene runt and to the mouse transcription factor PEBP2 alpha subunit gene. The region of shared similarity, known as the Runt domain, is responsible for DNA-binding and protein-protein interaction. In addition to the highly conserved Runt domain, the AML-1 gene product carries a putative ATP-binding site (GRSGRGKS), and has a C-terminal region rich in proline and serine residues. The protein (known as acute myeloid leukemia 1 protein, oncogene AML-1, core-binding factor (CBF), alpha-B subunit, etc.) binds to the core site, 5'-pygpyggt-3', of a number of enhancers and promoters. The protein is a heterodimer of alpha- and beta-subunits. The alpha-subunit binds DNA as a monomer, and appears to have a role in the development of normal hematopoiesis. CBF ...
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Protein Domain
In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of several domains, and a domain may appear in a variety of different proteins. Molecular evolution uses domains as building blocks and these may be recombined in different arrangements to create proteins with different functions. In general, domains vary in length from between about 50 amino acids up to 250 amino acids in length. The shortest domains, such as zinc fingers, are stabilized by metal ions or disulfide bridges. Domains often form functional units, such as the calcium-binding EF hand domain of calmodulin. Because they are independently stable, domains can be "swapped" by genetic engineering between one protein and another to make chimeric proteins. Background The concept of the domain was first proposed in 1973 by Wetlaufer aft ...
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RUNX1
Runt-related transcription factor 1 (RUNX1) also known as acute myeloid leukemia 1 protein (AML1) or core-binding factor subunit alpha-2 (CBFA2) is a protein that in humans is encoded by the ''RUNX1'' gene. RUNX1 is a transcription factor that regulates the differentiation of hematopoietic stem cells into mature blood cells. In addition it plays a major role in the development of the neurons that transmit pain. It belongs to the Runt-related transcription factor (RUNX) family of genes which are also called core binding factor-α (CBFα). RUNX proteins form a heterodimeric complex with CBFβ which confers increased DNA binding and stability to the complex. Chromosomal translocations involving the ''RUNX1'' gene are associated with several types of leukemia including M2 AML. Mutations in ''RUNX1'' are implicated in cases of breast cancer. Gene and protein In humans, the gene RUNX1 is 260 kilobases (kb) in length, and is located on chromosome 21 (21q22.12). The gene can be t ...
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Drosophila Melanogaster
''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly" or "pomace fly". Starting with Charles W. Woodworth's 1901 proposal of the use of this species as a model organism, ''D. melanogaster'' continues to be widely used for biological research in genetics, physiology, microbial pathogenesis, and life history evolution. As of 2017, five Nobel Prizes have been awarded to drosophilists for their work using the insect. ''D. melanogaster'' is typically used in research owing to its rapid life cycle, relatively simple genetics with only four pairs of chromosomes, and large number of offspring per generation. It was originally an African species, with all non-African lineages having a common origin. Its geographic range includes all continents, including islands. ''D. melanogaster'' is a common pest in homes, restaurants, and othe ...
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RUNX2
Runt-related transcription factor 2 (RUNX2) also known as core-binding factor subunit alpha-1 (CBF-alpha-1) is a protein that in humans is encoded by the ''RUNX2'' gene. RUNX2 is a key transcription factor associated with osteoblast differentiation. It has also been suggested that Runx2 plays a cell proliferation regulatory role in cell cycle entry and exit in osteoblasts, as well as endothelial cells. Runx2 suppresses pre-osteoblast proliferation by affecting cell cycle progression in the G1 phase. In osteoblasts, the levels of Runx2 is highest in G1 phase and is lowest in S, G2, and M. The comprehensive cell cycle regulatory mechanisms that Runx2 may play are still unknown, although it is generally accepted that the varying activity and levels of Runx2 throughout the cell cycle contribute to cell cycle entry and exit, as well as cell cycle progression. These functions are especially important when discussing bone cancer, particularly osteosarcoma development, that can be a ...
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RUNX3
Runt-related transcription factor 3 is a protein that in humans is encoded by the ''RUNX3'' gene. Function This gene encodes a member of the runt domain-containing family of transcription factors. A heterodimer of this protein and a beta subunit forms a complex that binds to the core DNA sequence 5'-YGYGGT-3' found in a number of enhancers and promoters, and can either activate or suppress transcription. It also interacts with other transcription factors. It functions as a tumor suppressor, and the gene is frequently deleted or transcriptionally silenced in cancer. Multiple transcript variants encoding different isoforms have been found for this gene. In melanocytic cells RUNX3 gene expression may be regulated by MITF. Knockout mouse Runx3 null mouse gastric mucosa exhibits hyperplasia due to stimulated proliferation and suppressed apoptosis in epithelial cells, and the cells are resistant to TGF-beta stimulation. The RUNX3 controversy In 2011 serious doubt was cast ove ...
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Pair-rule Gene
A pair-rule gene is a type of gene involved in the development of the segmented embryos of insects. Pair-rule genes are expressed as a result of differing concentrations of gap gene proteins, which encode transcription factors controlling pair-rule gene expression. Pair-rule genes are defined by the effect of a mutation in that gene, which causes the loss of the normal developmental pattern in alternating segments. Pair-rule genes were first described by Christiane Nüsslein-Volhard and Eric Wieschaus in 1980. They used a genetic screen to identify genes required for embryonic development in the fruit fly ''Drosophila melanogaster''. In normal unmutated ''Drosophila,'' each segment produces bristles called denticles in a band arranged on the side of the segment closer to the head (the anterior). They found five genes – ''even-skipped, hairy, odd-skipped, paired'' and ''runt'' – where mutations caused the deletion of a particular region of every alternate segment. For example, ...
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