HRAS
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HRAS
GTPase HRas, from "Harvey Rat sarcoma virus", also known as transforming protein p21 is an enzyme that in humans is encoded by the gene. The ''HRAS'' gene is located on the short (p) arm of chromosome 11 at position 15.5, from base pair 522,241 to base pair 525,549. HRas is a small G protein in the Ras subfamily of the Ras superfamily of small GTPases. Once bound to Guanosine triphosphate, H-Ras will activate a Raf kinase like c-Raf, the next step in the MAPK/ERK pathway. Function GTPase HRas is involved in regulating cell division in response to growth factor stimulation. Growth factors act by binding cell surface receptors that span the cell's plasma membrane. Once activated, receptors stimulate signal transduction events in the cytoplasm, a process by which proteins and second messengers relay signals from outside the cell to the cell nucleus and instructs the cell to grow or divide. The HRAS protein is a GTPase and is an early player in many signal transduction pathways an ...
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Ras (protein)
Ras, from "Rat sarcoma virus", is a family of related proteins that are expressed in all animal cell lineages and organs. All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signals within cells (cellular signal transduction). Ras is the prototypical member of the Ras superfamily of proteins, which are all related in three-dimensional structure and regulate diverse cell behaviours. When Ras is 'switched on' by incoming signals, it subsequently switches on other proteins, which ultimately turn on genes involved in cell growth, differentiation, and survival. Mutations in Ras genes can lead to the production of permanently activated Ras proteins, which can cause unintended and overactive signaling inside the cell, even in the absence of incoming signals. Because these signals result in cell growth and division, overactive Ras signaling can ultimately lead to cancer. The three Ras genes in humans (''HRAS'', ''KRAS'', an ...
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Ras Subfamily
Ras, from "Rat sarcoma virus", is a family of related proteins that are expressed in all animal cell lineages and organs. All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signals within cells (cellular signal transduction). Ras is the prototypical member of the Ras superfamily of proteins, which are all related in three-dimensional structure and regulate diverse cell behaviours. When Ras is 'switched on' by incoming signals, it subsequently switches on other proteins, which ultimately turn on genes involved in cell growth, differentiation, and survival. Mutations in Ras genes can lead to the production of permanently activated Ras proteins, which can cause unintended and overactive signaling inside the cell, even in the absence of incoming signals. Because these signals result in cell growth and division, overactive Ras signaling can ultimately lead to cancer. The three Ras genes in humans (''HRAS'', ''KRAS'', a ...
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Costello Syndrome
Costello syndrome, also called faciocutaneoskeletal syndrome or FCS syndrome, is a rare genetic disorder that affects many parts of the body. It is characterized by delayed development and intellectual disabilities, distinctive facial features, unusually flexible joints, and loose folds of extra skin, especially on the hands and feet.James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. . Heart abnormalities are common, including a very fast heartbeat (tachycardia), structural heart defects, and overgrowth of the heart muscle (hypertrophic cardiomyopathy). Infants with Costello syndrome may be large at birth, but grow more slowly than other children and have difficulty feeding. Later in life, people with this condition have relatively short stature and many have reduced levels of growth hormones. It is a RASopathy. Beginning in early childhood, people with specific mutations on the Costello syndrome gene ...
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Ras Superfamily
The Ras superfamily, derived from "Rat sarcoma virus", is a protein superfamily of small GTPases. Members of the superfamily are divided into families and subfamilies based on their structure, sequence and function. The five main families are Ras, Rho, Ran, Rab and Arf GTPases. The Ras family itself is further divided into 6 subfamilies: Ras, Ral, Rap, Rheb, Rad and Rit. ''Miro'' is a recent contributor to the superfamily. Each subfamily shares the common core G domain, which provides essential GTPase and nucleotide exchange activity. The surrounding sequence helps determine the functional specificity of the small GTPase, for example the 'Insert Loop', common to the Rho subfamily, specifically contributes to binding to effector proteins such as WASP. In general, the Ras family is responsible for cell proliferation: Rho for cell morphology, Ran for nuclear transport, and Rab and Arf for vesicle transport. Subfamilies and members The following is a list of human proteins belongi ...
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KRAS
''KRAS'' (Kirsten rat sarcoma virus) is a gene that provides instructions for making a protein called K-Ras, a part of the RAS/MAPK pathway. The protein relays signals from outside the cell to the cell's nucleus. These signals instruct the cell to grow and divide ( proliferate) or to mature and take on specialized functions ( differentiate). It is called ''KRAS'' because it was first identified as a viral oncogene in the Kirsten RAt Sarcoma virus. The oncogene identified was derived from a cellular genome, so , when found in a cellular genome, is called a proto-oncogene. The K-Ras protein is a GTPase, a class of enzymes which convert the nucleotide guanosine triphosphate (GTP) into guanosine diphosphate (GDP). In this way the K-Ras protein acts like a switch that is turned on and off by the GTP and GDP molecules. To transmit signals, it must be turned on by attaching (binding) to a molecule of GTP. The K-Ras protein is turned off (inactivated) when it converts the GTP to GDP. ...
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Chromosome 11 (human)
Chromosome 11 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome. Chromosome 11 spans about 135 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the total DNA in cells. The shorter arm (p arm) is termed 11p while the longer arm (q arm) is 11q. At about 21.5 genes per megabase, chromosome 11 is one of the most gene-rich, and disease-rich, chromosomes in the human genome. More than 40% of the 856 olfactory receptor genes in the human genome are located in 28 single-gene and multi-gene clusters along the chromosome. Gene Number of genes The following are some of the gene count estimates of human chromosome 11. Because researchers use different approaches to genome annotation their predictions of the number of genes on each chromosome varies (for technical details, see gene prediction). Among various projects, the collaborative consensus coding sequence project ( CCDS) takes an extremely ...
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RasGAP
RAS p21 protein activator 1 or RasGAP (Ras GTPase activating protein), also known as RASA1, is a 120-kDa cytosolic human protein that provides two principal activities: * Inactivation of Ras from its active GTP-bound form to its inactive GDP-bound form by enhancing the endogenous GTPase activity of Ras, via its C-terminal GAP domain * Mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains The protein encoded by this gene is located in the cytoplasm and is part of the GAP1 family of GTPase-activating proteins. The gene product stimulates the GTPase activity of normal RAS p21 but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with ...
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Neuroblastoma RAS Viral Oncogene Homolog
NRAS is an enzyme that in humans is encoded by the ''NRAS'' gene. It was discovered by a small team of researchers led by Robin Weiss at the Institute of Cancer Research in London. It was the third ''RAS'' gene to be discovered, and was named ''NRAS'', for its initial identification in human neuroblastoma cells. Function The N-ras proto-oncogene is a member of the Ras gene family. It is mapped on chromosome 1, and it is activated in HL60, a promyelocytic leukemia line. The order of nearby genes is as follows: cen—CD2—NGFB—NRAS—tel. The mammalian Ras gene family consists of the Harvey and Kirsten Ras genes (''HRAS'' and ''KRAS''), an inactive pseudogene of each (c-Hras2 and c-Kras1) and the N-Ras gene. They differ significantly only in the C-terminal 40 amino acids. These Ras genes have GTP/GDP binding and GTPase activity, and their normal function may be as G-like regulatory proteins involved in the normal control of cell growth. The N-Ras gene specifies two main tra ...
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SOS1
Son of sevenless homolog 1 is a protein that in humans is encoded by the ''SOS1'' gene. Function SOS1 is a guanine nucleotide exchange factor (GEF) which interacts with RAS proteins to phosphorylate GDP into GTP, or from an inactive state to an active state to signal cell proliferation. RAS genes (e.g., MIM 190020) encode membrane-bound guanine nucleotide-binding proteins that function in the transduction of signals that control cell growth and differentiation. Binding of GTP activates RAS proteins, and subsequent hydrolysis of the bound GTP to GDP and phosphate inactivates signaling by these proteins. GTP binding can be catalyzed by guanine nucleotide exchange factors for RAS, and GTP hydrolysis can be accelerated by GTPase-activating proteins (GAPs). The first exchange factor to be identified for RAS was the S. cerevisiae Cdc25 gene product. Genetic analysis indicated that CDC25 is essential for activation of RAS proteins. In ''Drosophila'', the protein encoded by the 'son of s ...
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C-Raf
RAF proto-oncogene serine/threonine-protein kinase, also known as proto-oncogene c-RAF or simply c-Raf or even Raf-1, is an enzyme that in humans is encoded by the ''RAF1'' gene. The c-Raf protein is part of the ERK1/2 pathway as a MAP kinase (MAP3K) that functions downstream of the Ras subfamily of membrane associated GTPases. C-Raf is a member of the Raf kinase family of serine/threonine-specific protein kinases, from the TKL (Tyrosine-kinase-like) group of kinases. Discovery The first Raf gene, v-Raf was found in 1983. It was isolated from the murine retrovirus bearing the number 3611. It was soon demonstrated to be capable to transform rodent fibroblasts to cancerous cell lines, so this gene was given the name Virus-induced Rapidly Accelerated Fibrosarcoma (V-RAF). A year later, another transforming gene was found in the avian retrovirus MH2, named v-Mil - that turned out to be highly similar to v-Raf. Researchers were able to demonstrate that these genes encode enzymes th ...
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MAPK/ERK Pathway
The MAPK/ERK pathway (also known as the Ras-Raf-MEK-ERK pathway) is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. The signal starts when a signaling molecule binds to the receptor on the cell surface and ends when the DNA in the nucleus expresses a protein and produces some change in the cell, such as cell division. The pathway includes many proteins, such as mitogen-activated protein kinases (MAPKs), originally called extracellular signal-regulated kinases (ERKs), which communicate by adding phosphate groups to a neighboring protein ( phosphorylating it), thereby acting as an "on" or "off" switch. When one of the proteins in the pathway is mutated, it can become stuck in the "on" or "off" position, a necessary step in the development of many cancers. In fact, components of the MAPK/ERK pathway were first discovered in cancer cells, and drugs that reverse the "on" or "off" switch are ...
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Guanosine Diphosphate
Guanosine diphosphate, abbreviated GDP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside guanosine. GDP consists of a pyrophosphate group, a pentose sugar ribose, and the nucleobase guanine. GDP is the product of GTP dephosphorylation by GTPases, e.g., the G-proteins that are involved in signal transduction. GDP is converted into GTP with the help of pyruvate kinase and phosphoenolpyruvate. See also * DNA *Guanosine triphosphate *Nucleoside *Nucleotide *Oligonucleotide *RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ... References {{DEFAULTSORT:Guanosine phosphate2 Nucleotides Phosphate esters Purines Pyrophosphates ...
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