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==NMR structure of calcium-loaded STIM1 EF-SAM==
==NMR structure of calcium-loaded STIM1 EF-SAM==
<StructureSection load='2k60' size='340' side='right' caption='[[2k60]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
<StructureSection load='2k60' size='340' side='right'caption='[[2k60]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2k60]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K60 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2K60 FirstGlance]. <br>
<table><tr><td colspan='2'>[[2k60]] is a 1 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=2K60 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K60 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">STIM1, GOK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2k60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k60 OCA], [http://pdbe.org/2k60 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2k60 RCSB], [http://www.ebi.ac.uk/pdbsum/2k60 PDBsum]</span></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=2k60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k60 OCA], [https://pdbe.org/2k60 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k60 RCSB], [https://www.ebi.ac.uk/pdbsum/2k60 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k60 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/STIM1_HUMAN STIM1_HUMAN]] Defects in STIM1 are the cause of immune dysfunction with T-cell inactivation due to calcium entry defect type 2 (IDTICED2) [MIM:[http://omim.org/entry/612783 612783]]. IDTICED2 is an immune disorder characterized by recurrent infections, impaired T-cell activation and proliferative response, decreased T-cell production of cytokines, lymphadenopathy, and normal lymphocytes counts and serum immunoglobulin levels. Additional features include thrombocytopenia, autoimmune hemolytic anemia, non-progressive myopathy, partial iris hypoplasia, hepatosplenomegaly and defective enamel dentition.<ref>PMID:19420366</ref>
[https://www.uniprot.org/uniprot/STIM1_HUMAN STIM1_HUMAN] Defects in STIM1 are the cause of immune dysfunction with T-cell inactivation due to calcium entry defect type 2 (IDTICED2) [MIM:[https://omim.org/entry/612783 612783]. IDTICED2 is an immune disorder characterized by recurrent infections, impaired T-cell activation and proliferative response, decreased T-cell production of cytokines, lymphadenopathy, and normal lymphocytes counts and serum immunoglobulin levels. Additional features include thrombocytopenia, autoimmune hemolytic anemia, non-progressive myopathy, partial iris hypoplasia, hepatosplenomegaly and defective enamel dentition.<ref>PMID:19420366</ref>  
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/STIM1_HUMAN STIM1_HUMAN]] Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Acts as Ca(2+) sensor in the endoplasmic reticulum via its EF-hand domain. Upon Ca(2+) depletion, translocates from the endoplasmic reticulum to the plasma membrane where it activates the Ca(2+) release-activated Ca(2+) (CRAC) channel subunit, TMEM142A/ORAI1.<ref>PMID:9377559</ref> <ref>PMID:16005298</ref> <ref>PMID:15866891</ref> <ref>PMID:16208375</ref> <ref>PMID:16807233</ref> <ref>PMID:16766533</ref> <ref>PMID:16733527</ref> <ref>PMID:16537481</ref> <ref>PMID:22464749</ref>
[https://www.uniprot.org/uniprot/STIM1_HUMAN STIM1_HUMAN] Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Acts as Ca(2+) sensor in the endoplasmic reticulum via its EF-hand domain. Upon Ca(2+) depletion, translocates from the endoplasmic reticulum to the plasma membrane where it activates the Ca(2+) release-activated Ca(2+) (CRAC) channel subunit, TMEM142A/ORAI1.<ref>PMID:9377559</ref> <ref>PMID:16005298</ref> <ref>PMID:15866891</ref> <ref>PMID:16208375</ref> <ref>PMID:16807233</ref> <ref>PMID:16766533</ref> <ref>PMID:16733527</ref> <ref>PMID:16537481</ref> <ref>PMID:22464749</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k6/2k60_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k6/2k60_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </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/chain_selection.php?pdb_ID=2ata ConSurf].
</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=2k60 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Stromal interaction molecule-1 (STIM1) activates store-operated Ca2+ entry (SOCE) in response to diminished luminal Ca2+ levels. Here, we present the atomic structure of the Ca2+-sensing region of STIM1 consisting of the EF-hand and sterile alpha motif (SAM) domains (EF-SAM). The canonical EF-hand is paired with a previously unidentified EF-hand. Together, the EF-hand pair mediates mutually indispensable hydrophobic interactions between the EF-hand and SAM domains. Structurally critical mutations in the canonical EF-hand, "hidden" EF-hand, or SAM domain disrupt Ca2+ sensitivity in oligomerization via destabilization of the entire EF-SAM entity. In mammalian cells, EF-SAM destabilization mutations within full-length STIM1 induce punctae formation and activate SOCE independent of luminal Ca2+. We provide atomic resolution insight into the molecular basis for STIM1-mediated SOCE initiation and show that the folded/unfolded state of the Ca2+-sensing region of STIM is crucial to SOCE regulation.
Structural and mechanistic insights into STIM1-mediated initiation of store-operated calcium entry.,Stathopulos PB, Zheng L, Li GY, Plevin MJ, Ikura M Cell. 2008 Oct 3;135(1):110-22. PMID:18854159<ref>PMID:18854159</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2k60" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Ikura, M]]
[[Category: Large Structures]]
[[Category: Stathopulos, P B]]
[[Category: Ikura M]]
[[Category: Calcium transport]]
[[Category: Stathopulos PB]]
[[Category: Ef-hand]]
[[Category: Ef-sam]]
[[Category: Endoplasmic reticulum luminal calcium sensor]]
[[Category: Glycoprotein]]
[[Category: Ion transport]]
[[Category: Membrane]]
[[Category: Phosphoprotein]]
[[Category: Sam domain]]
[[Category: Signaling protein]]
[[Category: Soce]]
[[Category: Stim1]]
[[Category: Store operated calcium entry regulator]]
[[Category: Stromal interaction molecule]]
[[Category: Transmembrane]]
[[Category: Transport]]
[[Category: Transport protein]]

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