View source for 5dse


==Crystal Structure of the TTC7B/Hyccin Complex==
<StructureSection load='5dse' size='340' side='right'caption='[[5dse]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5dse]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DSE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DSE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5dse FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dse OCA], [https://pdbe.org/5dse PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dse RCSB], [https://www.ebi.ac.uk/pdbsum/5dse PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dse ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/HYCCI_HUMAN HYCCI_HUMAN] Hypomyelination - congenital cataract. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/HYCCI_HUMAN HYCCI_HUMAN] May have a role in the beta-catenin/Lef signaling pathway. May have a role in the process of myelination of the central and peripheral nervous system.<ref>PMID:16951682</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Genetic defects in myelin formation and maintenance cause leukodystrophies, a group of white matter diseases whose mechanistic underpinnings are poorly understood. Hypomyelination and congenital cataract (HCC), one of these disorders, is caused by mutations in FAM126A, a gene of unknown function. We show that FAM126A, also known as hyccin, regulates the synthesis of phosphatidylinositol 4-phosphate (PtdIns(4)P), a determinant of plasma membrane identity. HCC patient fibroblasts exhibit reduced PtdIns(4)P levels. FAM126A is an intrinsic component of the plasma membrane phosphatidylinositol 4-kinase complex that comprises PI4KIIIalpha and its adaptors TTC7 and EFR3 (refs ,). A FAM126A-TTC7 co-crystal structure reveals an all-alpha-helical heterodimer with a large protein-protein interface and a conserved surface that may mediate binding to PI4KIIIalpha. Absence of FAM126A, the predominant FAM126 isoform in oligodendrocytes, destabilizes the PI4KIIIalpha complex in mouse brain and patient fibroblasts. We propose that HCC pathogenesis involves defects in PtdIns(4)P production in oligodendrocytes, whose specialized function requires massive plasma membrane expansion and thus generation of PtdIns(4)P and downstream phosphoinositides. Our results point to a role for FAM126A in supporting myelination, an important process in development and also following acute exacerbations in multiple sclerosis.

The leukodystrophy protein FAM126A (hyccin) regulates PtdIns(4)P synthesis at the plasma membrane.,Baskin JM, Wu X, Christiano R, Oh MS, Schauder CM, Gazzerro E, Messa M, Baldassari S, Assereto S, Biancheri R, Zara F, Minetti C, Raimondi A, Simons M, Walther TC, Reinisch KM, De Camilli P Nat Cell Biol. 2015 Nov 16. doi: 10.1038/ncb3271. PMID:26571211<ref>PMID:26571211</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5dse" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Baskin JM]]
[[Category: De Camilli P]]
[[Category: Reinisch KM]]
[[Category: Wu X]]