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Hemojuvelin
Hemojuvelin (HJV), also known as repulsive guidance molecule C (RGMc) or hemochromatosis type 2 protein (HFE2), is a membrane-bound and soluble protein in mammals that is responsible for the iron overload condition known as juvenile hemochromatosis in humans, a severe form of hemochromatosis. In humans, the hemojuvelin protein is encoded by the ''HFE2'' gene. Hemojuvelin is a member of the repulsive guidance molecule family of proteins. Both RGMa and RGMb are found in the nervous system, while hemojuvelin is found in skeletal muscle and the liver. Function For many years the signal transduction pathways that regulate systemic iron homeostasis have been unknown. However it has been demonstrated that hemojuvelin interacts with bone morphogenetic protein (BMP), possibly as a co-receptor, and may signal via the SMAD pathway to regulate hepcidin expression. Associations with BMP2 and BMP4 have been described. Mouse HJV knock-out models confirmed that HJV is the gene resp ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Repulsive Guidance Molecule
Repulsive guidance molecules (RGMs) are members of a three gene family (in vertebrates) composed of RGMA, RGMa, RGMB, RGMb, and hemojuvelin, RGMc (also called hemojuvelin). RGMa has been implicated to play an important role in the Neural development, developing brain and in the Granulation tissue, scar tissue that forms after a Traumatic brain injury, brain injury. For example, RGMa helps guide retinal ganglion cell (RGC) axons to the Midbrain tectum, tectum in the Mesencephalon, midbrain. It has also been demonstrated that after induced spinal cord injury RGMa accumulates in the scar tissue around the lesion. Further research has shown that RGMa is an inhibitor of axonal outgrowth. Taken together, these findings highlight the importance of RGMa in Axon guidance, axonal guidance and outgrowth. Family members References {{DEFAULTSORT:Repulsive Guidance Molecule Proteins Developmental biology ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Proprotein Convertase
Proprotein convertases (PPCs) are a family of proteins that activate other proteins. Many proteins are inactive when they are first synthesized, because they contain chains of amino acids that block their activity. Proprotein convertases remove those chains and activate the protein. The prototypical proprotein convertase is furin. Proprotein convertases have medical significance, because they are involved in many important biological processes, such as cholesterol synthesis. Compounds called proprotein convertase inhibitors can block their action, and block the target proteins from becoming active. Many proprotein convertases, especially furin and PACE4, are involved in pathological processes such as viral infection, inflammation, hypercholesterolemia, and cancer, and have been postulated as therapeutic targets for some of these diseases. History The phenomenon of prohormone conversion was discovered by Donald F. Steiner while examining the biosynthesis of insulin in 1967. At th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Furin
Furin is a protease, a proteolytic enzyme that in humans and other animals is encoded by the ''FURIN'' gene. Some proteins are inactive when they are first synthesized, and must have sections removed in order to become active. Furin cleaves these sections and activates the proteins. It was named furin because it was in the upstream region of an oncogene known as FES. The gene was known as FUR (FES Upstream Region) and therefore the protein was named furin. Furin is also known as PACE (Paired basic Amino acid Cleaving Enzyme). A member of family S8, furin is a subtilisin-like peptidase. Function The protein encoded by this gene is an enzyme that belongs to the subtilisin-like proprotein convertase family. The members of this family are proprotein convertases that process latent precursor proteins into their biologically active products. This encoded protein is a calcium-dependent serine endoprotease that can efficiently cleave precursor proteins at their paired basic amino acid ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Juvenile Hemochromatosis
Juvenile hemochromatosis, also known as hemochromatosis type 2, is a rare form of hereditary hemochromatosis, which emerges in young individuals, typically between 15 and 30 years of age, but occasionally later. It is characterized by an inability to control how much iron is absorbed by the body, in turn leading to iron overload, where excess iron accumulates in many areas of the body and causes damage to the places it accumulates. It is a genetic disorder that can be caused by mutations in either the HJV (also called HFE2) or HAMP genes, and is inherited in an autosomal recessive fashion. Depending on which of these genes is affected, the disease can be further subdivided into types 2A and 2B. Signs and Symptoms The most common symptoms of juvenile hemochromatosis are as follows: * Weakness * Lethargy * Hyperpigmentation (darkening of the skin) * Arthropathy (joint disease) * Diabetes * Heart disease ( dilated cardiomyopathy). Complications of heart disease are the mai ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hepcidin
Hepcidin is a protein that in humans is encoded by the ''HAMP'' gene. Hepcidin is a key regulator of the entry of iron into the circulation in mammals. During conditions in which the hepcidin level is abnormally high, such as inflammation, serum iron falls due to iron trapping within macrophages and liver cells and decreased gut iron absorption. This typically leads to anemia due to an inadequate amount of serum iron being available for developing red blood cells. When the hepcidin level is abnormally low such as in hemochromatosis, iron overload occurs due to increased ferroportin mediated iron efflux from storage and increased gut iron absorption. Structure Hepcidin exists as a preprohormone (84 amino acids), prohormone (60 amino acids), and hormone (25 amino acids). Twenty- and 22-amino acid metabolites of hepcidin also exist in the urine. Deletion of 5 ''N''-terminal amino acids results in loss of function. The conversion of prohepcidin to hepcidin is mediated by the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HAMP
Hepcidin is a protein that in humans is encoded by the ''HAMP'' gene. Hepcidin is a key regulator of the entry of iron into the circulation in mammals. During conditions in which the hepcidin level is abnormally high, such as inflammation, serum iron falls due to iron trapping within macrophages and liver cells and decreased gut iron absorption. This typically leads to anemia due to an inadequate amount of serum iron being available for developing red blood cells. When the hepcidin level is abnormally low such as in hemochromatosis, iron overload occurs due to increased ferroportin mediated iron efflux from storage and increased gut iron absorption. Structure Hepcidin exists as a preprohormone (84 amino acids), prohormone (60 amino acids), and hormone (25 amino acids). Twenty- and 22-amino acid metabolites of hepcidin also exist in the urine. Deletion of 5 ''N''-terminal amino acids results in loss of function. The conversion of prohepcidin to hepcidin is mediated ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Iron Metabolism
Human iron metabolism is the set of chemical reactions that maintain human homeostasis of iron at the systemic and cellular level. Iron is both necessary to the body and potentially toxic. Controlling iron levels in the body is a critically important part of many aspects of human health and disease. Hematologists have been especially interested in systemic iron metabolism because iron is essential for red blood cells, where most of the human body's iron is contained. Understanding iron metabolism is also important for understanding diseases of iron overload, such as hereditary hemochromatosis, and iron deficiency, such as iron-deficiency anemia. Importance of iron regulation Iron is an essential bioelement for most forms of life, from bacteria to mammals. Its importance lies in its ability to mediate electron transfer. In the ferrous state (Fe2+), iron acts as an electron donor, while in the ferric state (Fe3+) it acts as an acceptor. Thus, iron plays a vital role in the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TGF Beta
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other signaling proteins. TGFB proteins are produced by all white blood cell lineages. Activated TGF-β complexes with other factors to form a serine/threonine kinase complex that binds to TGF-β receptors. TGF-β receptors are composed of both type 1 and type 2 receptor subunits. After the binding of TGF-β, the type 2 receptor kinase phosphorylates and activates the type 1 receptor kinase that activates a signaling cascade. This leads to the activation of different downstream substrates and regulatory proteins, inducing transcription of different target genes that function in differentiation, chemotaxis, proliferation, and activation of many immune cells. TGF-β is secreted by many cell types, including macrophages, in a latent form in whic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ETS Transcription Factor Family
In the field of molecular biology, the ETS (E26 transformation-specific or E-twenty-six. (Erythroblast Transformation Specific)) family is one of the largest families of transcription factors and is unique to animals. There are 29 genes in humans, 28 in the mouse, 10 in ''Caenorhabditis elegans'' and 9 in ''Drosophila.'' The founding member of this family was identified as a gene transduced by the leukemia virus, E26. The members of the family have been implicated in the development of different tissues as well as cancer progression. Subfamilies The ETS (Erythroblast Transformation Specific)family is divided into 12 subfamilies, which are listed below: Structure All ETS (Erythroblast Transformation Specific) family members are identified through a highly conserved DNA binding domain, the ETS domain, which is a winged helix-turn-helix structure that binds to DNA sites with a central GGA(A/T) DNA sequence. As well as DNA-binding functions, evidence suggests that the ETS dom ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Iron
Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in front of oxygen (32.1% and 30.1%, respectively), forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust. In its metallic state, iron is rare in the Earth's crust, limited mainly to deposition by meteorites. Iron ores, by contrast, are among the most abundant in the Earth's crust, although extracting usable metal from them requires kilns or furnaces capable of reaching or higher, about higher than that required to smelt copper. Humans started to master that process in Eurasia during the 2nd millennium BCE and the use of iron tools and weapons began to displace copper alloys, in some regions, only around 1200 BCE. That event is considered the transition from the Bronze Age to the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
RGMA
Repulsive guidance molecule A (RGMa) is a bone morphogenetic protein (BMP) co-receptor of the repulsive guidance molecule family. Together with BMPR1A and BMPR1B, as well as ACVR2A and BMPR2, it binds BMPs thereby activating the intracellular SMAD1/5/8 signalling pathway. In humans this protein is encoded by the ''RGMA'' gene. Function RGMa is a repulsive guidance molecule for retinal axons. Furthermore, neogenin functions as a receptor for RGM. Neogenin overexpression and RGM downexpression in the developing embryonic neural tube induces apoptosis. The apoptotic activity of neogenin in the neural tube is associated with cleavage of its cytoplasmic domain by caspases. RGMA belongs to a family of repulsive guidance molecules that are (glycosylphosphatidylinositol)-linked cell-membrane-associated proteins. The three proteins, RGMa (this protein), RGMb and RGMc are 40-50% identical to each other, and share similarities in predicted protein domains and overall structure. A ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
RGMB
Repulsive guidance molecule B (RGMb), also known as DRAGON (DRG11-responsive axonal guidance and outgrowth of neurite), is a bone morphogenetic protein (BMP) co-receptor of the repulsive guidance molecule family. In humans this protein is encoded by the ''RGMB'' gene. Function RGMB is a glycosylphosphatidylinositol (GPI)-anchored member of the repulsive guidance molecule family (see also RGMA and RGMC) and contributes to the patterning of the developing nervous system. There is a potential association between RGMs and cancer bone metastasis, as RGMs coordinate bone morphogenetic protein (BMP) signaling. RGMB may act as a negative regulator ''in vitro'' in breast cancer and prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that su ... through BMP signalling. Furthermore, a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
