1a6z

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{{STRUCTURE_1a6z| PDB=1a6z | SCENE= }}
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==HFE (HUMAN) HEMOCHROMATOSIS PROTEIN==
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===HFE (HUMAN) HEMOCHROMATOSIS PROTEIN===
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<StructureSection load='1a6z' size='340' side='right' caption='[[1a6z]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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{{ABSTRACT_PUBMED_9546397}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1a6z]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A6Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1A6Z FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HFE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1a6z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a6z OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1a6z RCSB], [http://www.ebi.ac.uk/pdbsum/1a6z PDBsum]</span></td></tr>
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<table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/HFE_HUMAN HFE_HUMAN]] Defects in HFE are a cause of hemochromatosis (HFE) [MIM:[http://omim.org/entry/235200 235200]]. A disorder of iron metabolism characterized by iron overload. Excess iron is deposited in a variety of organs leading to their failure, and resulting in serious illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis, and hypogonadotropic hypogonadism. Severe effects of the disease usually do not appear until after decades of progressive iron loading.<ref>PMID:8696333</ref> <ref>PMID:9106528</ref> <ref>PMID:9024376</ref> <ref>PMID:9620340</ref> <ref>PMID:10194428</ref> <ref>PMID:10575540</ref> <ref>PMID:10401000</ref> <ref>PMID:10094552</ref> [:]<ref>PMID:11423500</ref> <ref>PMID:11446670</ref> <ref>PMID:12542741</ref> <ref>PMID:12737937</ref> <ref>PMID:14633868</ref> <ref>PMID:12584229</ref> <ref>PMID:15046077</ref> <ref>PMID:15965644</ref> <ref>PMID:18157833</ref> Defects in HFE are associated with variegate porphyria (VP) [MIM:[http://omim.org/entry/176200 176200]]. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. VP is the most common form of porphyria in South Africa. It is characterized by skin hyperpigmentation and hypertrichosis, abdominal pain, tachycardia, hypertension and neuromuscular disturbances. High fecal levels of protoporphyrin and coproporphyrin, increased urine uroporphyrins and iron overload are typical markers of the disease. Note=Iron overload due to HFE mutations is a precipitating or exacerbating factor in variegate porphyria. Defects in HFE are associated with susceptibility to microvascular complications of diabetes type 7 (MVCD7) [MIM:[http://omim.org/entry/612635 612635]]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/HFE_HUMAN HFE_HUMAN]] Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin.<ref>PMID:9465039</ref> [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a6/1a6z_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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HFE is an MHC-related protein that is mutated in the iron-overload disease hereditary hemochromatosis. HFE binds to transferrin receptor (TfR) and reduces its affinity for iron-loaded transferrin, implicating HFE in iron metabolism. The 2.6 A crystal structure of HFE reveals the locations of hemochromatosis mutations and a patch of histidines that could be involved in pH-dependent interactions. We also demonstrate that soluble TfR and HFE bind tightly at the basic pH of the cell surface, but not at the acidic pH of intracellular vesicles. TfR:HFE stoichiometry (2:1) differs from TfR:transferrin stoichiometry (2:2), implying a different mode of binding for HFE and transferrin to TfR, consistent with our demonstration that HFE, transferrin, and TfR form a ternary complex.
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==Disease==
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Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor.,Lebron JA, Bennett MJ, Vaughn DE, Chirino AJ, Snow PM, Mintier GA, Feder JN, Bjorkman PJ Cell. 1998 Apr 3;93(1):111-23. PMID:9546397<ref>PMID:9546397</ref>
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[[http://www.uniprot.org/uniprot/HFE_HUMAN HFE_HUMAN]] Defects in HFE are a cause of hemochromatosis (HFE) [MIM:[http://omim.org/entry/235200 235200]]. A disorder of iron metabolism characterized by iron overload. Excess iron is deposited in a variety of organs leading to their failure, and resulting in serious illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis, and hypogonadotropic hypogonadism. Severe effects of the disease usually do not appear until after decades of progressive iron loading.<ref>PMID:8696333</ref><ref>PMID:9106528</ref><ref>PMID:9024376</ref><ref>PMID:9620340</ref><ref>PMID:10194428</ref><ref>PMID:10575540</ref><ref>PMID:10401000</ref><ref>PMID:10094552</ref>[:]<ref>PMID:11423500</ref><ref>PMID:11446670</ref><ref>PMID:12542741</ref><ref>PMID:12737937</ref><ref>PMID:14633868</ref><ref>PMID:12584229</ref><ref>PMID:15046077</ref><ref>PMID:15965644</ref><ref>PMID:18157833</ref> Defects in HFE are associated with variegate porphyria (VP) [MIM:[http://omim.org/entry/176200 176200]]. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. VP is the most common form of porphyria in South Africa. It is characterized by skin hyperpigmentation and hypertrichosis, abdominal pain, tachycardia, hypertension and neuromuscular disturbances. High fecal levels of protoporphyrin and coproporphyrin, increased urine uroporphyrins and iron overload are typical markers of the disease. Note=Iron overload due to HFE mutations is a precipitating or exacerbating factor in variegate porphyria. Defects in HFE are associated with susceptibility to microvascular complications of diabetes type 7 (MVCD7) [MIM:[http://omim.org/entry/612635 612635]]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref><ref>PMID:1336137</ref><ref>PMID:7554280</ref><ref>PMID:4586824</ref><ref>PMID:8084451</ref><ref>PMID:12119416</ref><ref>PMID:12796775</ref><ref>PMID:16901902</ref><ref>PMID:16491088</ref><ref>PMID:17646174</ref><ref>PMID:18835253</ref><ref>PMID:18395224</ref><ref>PMID:19284997</ref>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/HFE_HUMAN HFE_HUMAN]] Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin.<ref>PMID:9465039</ref> [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
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</div>
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==About this Structure==
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[[1a6z]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A6Z OCA].
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==See Also==
==See Also==
*[[Beta-2 microglobulin|Beta-2 microglobulin]]
*[[Beta-2 microglobulin|Beta-2 microglobulin]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:009546397</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Bennett, M J.]]
[[Category: Bennett, M J.]]

Revision as of 17:22, 29 September 2014

HFE (HUMAN) HEMOCHROMATOSIS PROTEIN

1a6z, resolution 2.60Å

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