View source for 7c3m


==Structure of FERM protein==
<StructureSection load='7c3m' size='340' side='right'caption='[[7c3m]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7c3m]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7C3M OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7C3M FirstGlance]. <br>
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FERMT3, KIND3, MIG2B, URP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7c3m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c3m OCA], [http://pdbe.org/7c3m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7c3m RCSB], [http://www.ebi.ac.uk/pdbsum/7c3m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7c3m ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/URP2_HUMAN URP2_HUMAN]] Leukocyte adhesion deficiency type III. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:19064721</ref> <ref>PMID:19234463</ref> <ref>PMID:19234460</ref> <ref>PMID:18779414</ref> <ref>PMID:19617577</ref>  
== Function ==
[[http://www.uniprot.org/uniprot/URP2_HUMAN URP2_HUMAN]] Plays a central role in cell adhesion in hematopoietic cells. Acts by activating the integrin beta-1-3 (ITGB1, ITGB2 and ITGB3). Required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells. Required for activation of integrin beta-2 (ITGB2) in polymorphonuclear granulocytes (PMNs) (By similarity).<ref>PMID:18280249</ref> <ref>PMID:19064721</ref> <ref>PMID:19234463</ref> <ref>PMID:19234460</ref>   Isoform 2 may act as a repressor of NF-kappa-B and apoptosis.<ref>PMID:18280249</ref> <ref>PMID:19064721</ref> <ref>PMID:19234463</ref> <ref>PMID:19234460</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Kindlin-1, -2, and -3 directly bind integrin beta cytoplasmic tails to regulate integrin activation and signaling. Despite their functional significance and links to several diseases, structural information on full-length kindlin proteins remains unknown. Here, we report the crystal structure of human full-length kindlin-3, which reveals a novel homotrimer state. Unlike kindlin-3 monomer, which is the major population in insect and mammalian cell expression systems, kindlin-3 trimer does not bind integrin beta cytoplasmic tail as the integrin-binding pocket in the F3 subdomain of 1 protomer is occluded by the pleckstrin homology (PH) domain of another protomer, suggesting that kindlin-3 is auto-inhibited upon trimer formation. This is also supported by functional assays in which kindlin-3 knockout K562 erythroleukemia cells reconstituted with the mutant kindlin-3 containing trimer-disrupting mutations exhibited an increase in integrin-mediated adhesion and spreading on fibronectin compared with those reconstituted with wild-type kindlin-3. Taken together, our findings reveal a novel mechanism of kindlin auto-inhibition that involves its homotrimer formation.

Structural basis of human full-length kindlin-3 homotrimer in an auto-inhibited state.,Bu W, Levitskaya Z, Loh ZY, Jin S, Basu S, Ero R, Yan X, Wang M, Ngan SFC, Sze SK, Tan SM, Gao YG PLoS Biol. 2020 Jul 9;18(7):e3000755. doi: 10.1371/journal.pbio.3000755., eCollection 2020 Jul. PMID:32644996<ref>PMID:32644996</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7c3m" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Basu, S]]
[[Category: Bu, W]]
[[Category: Ero, R]]
[[Category: Gao, Y G]]
[[Category: Jin, S]]
[[Category: Loh, Z Y]]
[[Category: Park, J E]]
[[Category: Sze, S K]]
[[Category: Tan, S M]]
[[Category: Wang, M]]
[[Category: Yan, X]]
[[Category: Ferm protein]]
[[Category: Integrin]]
[[Category: Kindlin]]
[[Category: Signaling protein]]