2acm
From Proteopedia
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| - | [[Image:2acm.png|left|200px]] | ||
| - | + | ==Solution structure of the SEA domain of human mucin 1 (MUC1)== | |
| + | <StructureSection load='2acm' size='340' side='right'caption='[[2acm]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2acm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ACM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ACM FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2acm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2acm OCA], [https://pdbe.org/2acm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2acm RCSB], [https://www.ebi.ac.uk/pdbsum/2acm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2acm ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/MUC1_HUMAN MUC1_HUMAN] Note=MUC1/CA 15-3 is used as a serological clinical marker of breast cancer to monitor response to breast cancer treatment and disease recurrence (PubMed:20816948). Decreased levels over time may be indicative of a positive response to treatment. Conversely, increased levels may indicate disease progression. At an early stage disease, only 21% of patients exhibit high MUC1/CA 15-3 levels, that is why CA 15-3 is not a useful screening test. Most antibodies target the highly immunodominant core peptide domain of 20 amino acid (APDTRPAPGSTAPPAHGVTS) tandem repeats. Some antibodies recognize glycosylated epitopes. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MUC1_HUMAN MUC1_HUMAN] The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack.<ref>PMID:9139698</ref> <ref>PMID:11877440</ref> <ref>PMID:14688481</ref> <ref>PMID:15710329</ref> <ref>PMID:16288032</ref> <ref>PMID:15513966</ref> <ref>PMID:17524503</ref> <ref>PMID:17308127</ref> <ref>PMID:16983337</ref> The beta subunit contains a C-terminal domain which is involved in cell signaling, through phosphorylations and protein-protein interactions. Modulates signaling in ERK, SRC and NF-kappa-B pathways. In activated T-cells, influences directly or indirectly the Ras/MAPK pathway. Promotes tumor progression. Regulates TP53-mediated transcription and determines cell fate in the genotoxic stress response. Binds, together with KLF4, the PE21 promoter element of TP53 and represses TP53 activity.<ref>PMID:9139698</ref> <ref>PMID:11877440</ref> <ref>PMID:14688481</ref> <ref>PMID:15710329</ref> <ref>PMID:16288032</ref> <ref>PMID:15513966</ref> <ref>PMID:17524503</ref> <ref>PMID:17308127</ref> <ref>PMID:16983337</ref> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ac/2acm_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </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/main_output.php?pdb_ID=2acm ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The single cell layer of the lungs and the gastrointestinal tract is protected by the mucus formed by large glycoproteins called mucins. Transmembrane mucins typically contain 110-residue SEA domains located next to the membrane. These domains undergo post-translational cleavage between glycine and serine in a characteristic GSVVV sequence, but the two peptides remain tightly associated. We show that the SEA domain of the human MUC1 transmembrane mucin undergoes a novel type of autoproteolysis, which is catalyzed by conformational stress and the conserved serine hydroxyl. We propose that self-cleaving SEA domains have evolved to dissociate as a result of mechanical rather than chemical stress at the apical cell membrane and that this protects epithelial cells from rupture. We further suggest that the cell can register mechanical shear at the mucosal surface if the dissociation is signaled via loss of a SEA-binding protein. | ||
| - | + | Autoproteolysis coupled to protein folding in the SEA domain of the membrane-bound MUC1 mucin.,Macao B, Johansson DG, Hansson GC, Hard T Nat Struct Mol Biol. 2006 Jan;13(1):71-6. Epub 2005 Dec 20. PMID:16369486<ref>PMID:16369486</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2acm" style="background-color:#fffaf0;"></div> | |
| - | + | == References == | |
| - | + | <references/> | |
| - | == | + | __TOC__ |
| - | < | + | </StructureSection> |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Hansson GC]] |
| - | [[Category: | + | [[Category: Hard T]] |
| - | [[Category: | + | [[Category: Johansson DGA]] |
| - | [[Category: | + | [[Category: Macao B]] |
| - | + | ||
Current revision
Solution structure of the SEA domain of human mucin 1 (MUC1)
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