Mutation:BRCA1: Difference between revisions

Sequence

⎈ mutations with manual annotation; pathogenic; benign; not yet reviewed;

wild type Show which residues have mutations:

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-==Your Heading Here (maybe something like 'Structure')==
+<StructureSection load='' size='340' side='right' caption='' scene=''>
-<StructureSection load='1t15' size='340' side='right' caption='Caption for this structure' scene=''>
+<div id='openPageText'>
-This is a default text for your page '''A'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.
-You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.
-== Function ==
+A number of germline mutations in BRCA1 are known to substantially increase a carrier’s risk of breast and ovarian cancer. Human BRCA1 is a large protein and appears to be mostly disordered except for the N terminal RING domain and tandem BRCT domains at the C terminus. Many cancer risk mutations truncate the protein, consistent with low or absent in vivo protein levels. There are also a number of missense mutations in the structured regions. Most of these are too rare for clinical significance to have been established, and inspection of the structural context as well as analysis of sequence conservation may help distinguish those which are pathogenic from the benign ones.
+<ref>PMID: 15133502</ref>
-== Disease ==
+Mutations are assigned pathogenic or benign status according to the BRCA exchange (https://brcaexchange.org/)  and Clinvar annotations. Six of the seven BRCA Exchange established pathogenic mutations in the RING domain act by destabilizing its three-dimensional structure. Five (C39R, H41R, C44Y, C44S and C61G) disrupt liganding to a zinc atom. The two zinc atoms are critical to the integrity of the small domain linking the two helices, so that loss of liganding is disruptive. A sixth mutation, T37K, introduces a large, positively charged residue into the interior of the zinc binding domain, causing destabilization both through over-packing and through costly desolvation of the charged epsilon amino group. The seventh mutation, L22S, lies in the interface between the RING domain and the obligatory BARD1 binding partner. That mutation introduces a buried hydroxyl group with no internal hydrogen bonds to compensate for the desolvation cost, and also creates an internal cavity approximately the size of two methyl groups, so weakening the protein-protein interaction.
-== Relevance ==
+== Authorship ==
+Data on these pages are compiled by [[User:Yizhou_Yin|Yizhou Yin]], [[User:Lipika_Ray|Lipika Ray Pal]] and [[User:John_Moult|John Moult]] (IBBR, University of Maryland, USA). The mutation interface is built by [[User:Jaime_Prilusky|Jaime Prilusky]] and [[User:Joel_L._Sussman|Joel Sussman]] (Weizmann Institute, Israel) and [[User:Angel_Herraez|Angel Herráez]] (Universidad de Alcalá, Spain). The work is supported by NIH R01 GM120364.
-== Structural highlights ==
-This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
+</div>
 </StructureSection>
 == References ==
 <references/>
+[[Category: Mutations]]