Misplaced Pages

#599400

29-512: HFE may refer to: Science and technology [ edit ] HFE (gene) , a gene that encodes the Human hemochromatosis protein Hello from Earth , an interstellar radio message Hidden Field Equations , a cryptosystem H-parameter model (h FE ), the current gain of a bipolar junction transistor Human factors engineering Hydrofluoroether ,

58-558: A missense mutation in Hfe (C282Y). These mice correspond to humans with hemochromatosis who are homozygous for HFE C282Y. These mice develop iron loading that is less severe than that of Hfe −/− mice. The black rhinoceros ( Diceros bicornis ) can develop iron overload. To determine whether the HFE gene of black rhinoceroses has undergone mutation as an adaptive mechanism to improve iron absorption from iron-poor diets, Beutler et al. sequenced

87-579: A gene of interest in mice (or other experimental animals) as a means of studying function of the gene and its protein. Such mice are called “ knockouts ” with respect to the deleted gene. Hfe is the mouse equivalent of the human hemochromatosis gene HFE . The protein encoded by HFE is Hfe. Mice homozygous (two abnormal gene copies) for a targeted knockout of all six transcribed Hfe exons are designated Hfe −/−. Iron-related traits of Hfe −/− mice, including increased iron absorption and hepatic iron loading, are inherited in an autosomal recessive pattern. Thus,

116-593: A highly conserved region involved in the interaction of HFE and TfR1. Transmembrane protein The peptide sequence that spans the membrane, or the transmembrane segment , is largely hydrophobic and can be visualized using the hydropathy plot . Depending on the number of transmembrane segments, transmembrane proteins can be classified as single-pass membrane proteins , or as multipass membrane proteins. Some other integral membrane proteins are called monotopic , meaning that they are also permanently attached to

145-499: A signal-anchor sequence, with type II being targeted to the ER lumen with its C-terminal domain, while type III have their N-terminal domains targeted to the ER lumen. Type IV is subdivided into IV-A, with their N-terminal domains targeted to the cytosol and IV-B, with an N-terminal domain targeted to the lumen. The implications for the division in the four types are especially manifest at the time of translocation and ER-bound translation, when

174-619: A solvent Transport [ edit ] Hefei Luogang International Airport , in Anhui, China, now defunct Hefei Xinqiao International Airport , in Anhui, China Hertford East railway station , in England Other uses [ edit ] Health First Europe Herschend Family Entertainment Corporation , an American entertainment company Horizontal Fiscal Equalisation , in Australia Topics referred to by

203-476: A transmembrane region that anchors the protein in the cell membrane, and a short cytoplasmic tail. HFE expression is subjected to alternative splicing . The predominant HFE full-length transcript has ~4.2 kb. Alternative HFE splicing variants may serve as iron regulatory mechanisms in specific cells or tissues. HFE is prominent in small intestinal absorptive cells, gastric epithelial cells, tissue macrophages , and blood monocytes and granulocytes , and

232-491: Is cosmopolitan but occurs with greatest frequency in individuals of European descent. Allele frequencies of H63D in ethnically diverse western European populations are 10-29%. and in North American non-Hispanic whites are 14-15%. At least 42 mutations involving HFE introns and exons have been discovered, most of them in persons with hemochromatosis or their family members. Most of these mutations are rare. Many of

261-555: Is different from Wikidata All article disambiguation pages All disambiguation pages HFE (gene) 1DE4 , 1A6Z 3077 15216 ENSG00000010704 ENSMUSG00000006611 Q30201 P70387 NM_139005 NM_139006 NM_139007 NM_139008 NM_139009 NM_139010 NM_139011 NM_001384164 NM_010424 NM_001347493 NP_620576 NP_620577 NP_620578 NP_620579 NP_620580 NP_001371093 NP_001334422 NP_034554 Human homeostatic iron regulator protein, also known as

290-429: Is technically difficult. There are relatively few examples of the successful refolding experiments, as for bacteriorhodopsin . In vivo , all such proteins are normally folded co-translationally within the large transmembrane translocon . The translocon channel provides a highly heterogeneous environment for the nascent transmembrane α-helices. A relatively polar amphiphilic α-helix can adopt a transmembrane orientation in

319-400: Is thought that β-barrel membrane proteins come from one ancestor even having different number of sheets which could be added or doubled during evolution. Some studies show a huge sequence conservation among different organisms and also conserved amino acids which hold the structure and help with folding. Note: n and S are, respectively, the number of beta-strands and the "shear number" of

SECTION 10

#1732772168600

348-451: The HFE protein ( H igh FE 2+), is a transmembrane protein that in humans is encoded by the HFE gene . The HFE gene is located on short arm of chromosome 6 at location 6p22.2 The protein encoded by this gene is an integral membrane protein that is similar to MHC class I -type proteins and associates with beta-2 microglobulin (beta2M). It is thought that this protein functions to regulate circulating iron uptake by regulating

377-470: The Hfe −/− mouse model simulates important genetic and physiological abnormalities of HFE hemochromatosis. Other knockout mice were created to delete the second and third HFE exons (corresponding to α1 and α2 domains of Hfe). Mice homozygous for this deletion also had increased duodenal iron absorption, elevated plasma iron and transferrin saturation levels, and iron overload, mainly in hepatocytes . Mice have also been created that are homozygous for

406-521: The detergent . For example, the "unfolded" bacteriorhodopsin in SDS micelles has four transmembrane α-helices folded, while the rest of the protein is situated at the micelle-water interface and can adopt different types of non-native amphiphilic structures. Free energy differences between such detergent-denatured and native states are similar to stabilities of water-soluble proteins (< 10 kcal/mol). Refolding of α-helical transmembrane proteins in vitro

435-468: The molten globule states, formation of non-native disulfide bonds , or unfolding of peripheral regions and nonregular loops that are locally less stable. It is also important to properly define the unfolded state . The unfolded state of membrane proteins in detergent micelles is different from that in the thermal denaturation experiments. This state represents a combination of folded hydrophobic α-helices and partially unfolded segments covered by

464-513: The position of the protein N- and C-termini on the different sides of the lipid bilayer . Types I, II, III and IV are single-pass molecules . Type I transmembrane proteins are anchored to the lipid membrane with a stop-transfer anchor sequence and have their N-terminal domains targeted to the endoplasmic reticulum (ER) lumen during synthesis (and the extracellular space, if mature forms are located on cell membranes ). Type II and III are anchored with

493-403: The entire HFE coding region of four species of rhinoceros (two browsing and two grazing species). Although HFE was well conserved across the species, numerous nucleotide differences were found between rhinoceros and human or mouse, some of which changed deduced amino acids. Only one allele, p.S88T in the black rhinoceros, was a candidate that might adversely affect HFE function. p.S88T occurs in

522-511: The factors modifying Wilson's disease phenotype , making the symptoms of the disease appear earlier. Allele frequencies of HFE C282Y in ethnically diverse western European white populations are 5-14% and in North American non-Hispanic whites are 6-7%. C282Y exists as a polymorphism only in Western European white and derivative populations, although C282Y may have arisen independently in non-whites outside Europe. HFE H63D

551-430: The interaction of the transferrin receptor with transferrin . The HFE gene contains 7 exons spanning 12 kb. The full-length transcript represents 6 exons. HFE protein is composed of 343 amino acids . There are several components, in sequence: a signal peptide (initial part of the protein), an extracellular transferrin receptor-binding region (α1 and α2), a portion that resembles immunoglobulin molecules (α3),

580-859: The membrane, but do not pass through it. There are two basic types of transmembrane proteins: alpha-helical and beta barrels . Alpha-helical proteins are present in the inner membranes of bacterial cells or the plasma membrane of eukaryotic cells, and sometimes in the bacterial outer membrane . This is the major category of transmembrane proteins. In humans, 27% of all proteins have been estimated to be alpha-helical membrane proteins. Beta-barrel proteins are so far found only in outer membranes of gram-negative bacteria , cell walls of gram-positive bacteria , outer membranes of mitochondria and chloroplasts , or can be secreted as pore-forming toxins . All beta-barrel transmembrane proteins have simplest up-and-down topology, which may reflect their common evolutionary origin and similar folding mechanism. In addition to

609-424: The mutations cause or probably cause hemochromatosis phenotypes, often in compound heterozygosity with HFE C282Y. Other mutations are either synonymous or their effect on iron phenotypes, if any, has not been demonstrated. The HFE protein interacts with the transferrin receptor TFRC . Its primary mode of action is the regulation of the iron storage hormone hepcidin . It is possible to delete part or all of

SECTION 20

#1732772168600

638-462: The positive inside rule and other methods have been developed. Transmembrane alpha-helical (α-helical) proteins are unusually stable judging from thermal denaturation studies, because they do not unfold completely within the membranes (the complete unfolding would require breaking down too many α-helical H-bonds in the nonpolar media). On the other hand, these proteins easily misfold , due to non-native aggregation in membranes, transition to

667-463: The protein domains, there are unusual transmembrane elements formed by peptides. A typical example is gramicidin A , a peptide that forms a dimeric transmembrane β-helix. This peptide is secreted by gram-positive bacteria as an antibiotic . A transmembrane polyproline-II helix has not been reported in natural proteins. Nonetheless, this structure was experimentally observed in specifically designed artificial peptides. This classification refers to

696-690: The protein has to be passed through the ER membrane in a direction dependent on the type. Membrane protein structures can be determined by X-ray crystallography , electron microscopy or NMR spectroscopy . The most common tertiary structures of these proteins are transmembrane helix bundle and beta barrel . The portion of the membrane proteins that are attached to the lipid bilayer (see annular lipid shell ) consist mostly of hydrophobic amino acids. Membrane proteins which have hydrophobic surfaces, are relatively flexible and are expressed at relatively low levels. This creates difficulties in obtaining enough protein and then growing crystals. Hence, despite

725-403: The same term [REDACTED] This disambiguation page lists articles associated with the title HFE . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=HFE&oldid=1220083739 " Category : Disambiguation pages Hidden categories: Short description

754-432: The significant functional importance of membrane proteins, determining atomic resolution structures for these proteins is more difficult than globular proteins. As of January 2013 less than 0.1% of protein structures determined were membrane proteins despite being 20–30% of the total proteome. Due to this difficulty and the importance of this class of proteins methods of protein structure prediction based on hydropathy plots,

783-516: The syncytiotrophoblast, an iron transport tissue in the placenta. The iron storage disorder hereditary hemochromatosis (HHC) is an autosomal recessive genetic disorder that usually results from defects in this gene. The disease-causing genetic variant most commonly associated with hemochromatosis is p. C282Y. About 1/200 of people of Northern European origin have two copies of this variant; they, particularly males, are at high risk of developing hemochromatosis. This variant may also be one of

812-443: The translocon (although it would be at the membrane surface or unfolded in vitro ), because its polar residues can face the central water-filled channel of the translocon. Such mechanism is necessary for incorporation of polar α-helices into structures of transmembrane proteins. The amphiphilic helices remain attached to the translocon until the protein is completely synthesized and folded. If the protein remains unfolded and attached to

841-464: The translocon for too long, it is degraded by specific "quality control" cellular systems. Stability of beta barrel (β-barrel) transmembrane proteins is similar to stability of water-soluble proteins, based on chemical denaturation studies. Some of them are very stable even in chaotropic agents and high temperature. Their folding in vivo is facilitated by water-soluble chaperones , such as protein Skp. It

#599400