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==SALSA / DMBT1 / GP340 SRCR domain 8 soaked in calcium and magnesium==
<StructureSection load='6san' size='340' side='right'caption='[[6san]], [[Resolution|resolution]] 1.36&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6san]] is a 2 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=6SAN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SAN 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]] 1.36&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=6san FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6san OCA], [https://pdbe.org/6san PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6san RCSB], [https://www.ebi.ac.uk/pdbsum/6san PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6san ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/DMBT1_HUMAN DMBT1_HUMAN] The gene represented in this entry is involved in disease pathogenesis. Homozygous deletions may be the predominant mechanism of DMBT1 inactivation playing a role in carcinogenesis. DMBT1 is deleted in medulloblastoma and glioblastoma cell lines; point mutations have also been reported in patients with glioma. A loss or reduction of DMBT1 expression has been seen in esophageal, gastric, lung and colorectal carcinomas as well.
== Function ==
[https://www.uniprot.org/uniprot/DMBT1_HUMAN DMBT1_HUMAN] May be considered as a candidate tumor suppressor gene for brain, lung, esophageal, gastric, and colorectal cancers. May play roles in mucosal defense system, cellular immune defense and epithelial differentiation. May play a role as an opsonin receptor for SFTPD and SPAR in macrophage tissues throughout the body, including epithelial cells lining the gastrointestinal tract. May play a role in liver regeneration. May be an important factor in fate decision and differentiation of transit-amplifying ductular (oval) cells within the hepatic lineage. Required for terminal differentiation of columnar epithelial cells during early embryogenesis. May function as a binding protein in saliva for the regulation of taste sensation. Binds to HIV-1 envelope protein and has been shown to both inhibit and facilitate viral transmission. Displays a broad calcium-dependent binding spectrum against both Gram-positive and Gram-negative bacteria, suggesting a role in defense against bacterial pathogens. Binds to a range of poly-sulfated and poly-phosphorylated ligands which may explain its broad bacterial-binding specificity. Inhibits cytoinvasion of S.enterica. Associates with the actin cytoskeleton and is involved in its remodeling during regulated exocytosis. Interacts with pancreatic zymogens in a pH-dependent manner and may act as a Golgi cargo receptor in the regulated secretory pathway of the pancreatic acinar cell.<ref>PMID:10485905</ref> <ref>PMID:11007786</ref> <ref>PMID:11751412</ref> <ref>PMID:16796526</ref> <ref>PMID:17548659</ref> <ref>PMID:17709527</ref> <ref>PMID:19189310</ref> <ref>PMID:9288095</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The scavenger receptor cysteine-rich (SRCR) family of proteins comprises more than 20 membrane-associated and secreted molecules. Characterised by the presence of one or more copies of the approximately 110 amino-acid SRCR domain, this class of proteins have widespread functions as antimicrobial molecules, scavenger receptors, and signalling receptors. Despite the high level of structural conservation of SRCR domains, no unifying mechanism for ligand interaction has been described. The SRCR protein SALSA, also known as DMBT1/gp340, is a key player in mucosal immunology. Based on detailed structural data of SALSA SRCR domains 1 and 8, we here reveal a novel universal ligand-binding mechanism for SALSA ligands. The binding interface incorporates a dual cation-binding site, which is highly conserved across the SRCR superfamily. Along with the well-described cation dependency on most SRCR domain-ligand interactions, our data suggest that the binding mechanism described for the SALSA SRCR domains is applicable to all SRCR domains. We thus propose to have identified in SALSA a conserved functional mechanism for the SRCR class of proteins.

Structures of SALSA/DMBT1 SRCR domains reveal the conserved ligand-binding mechanism of the ancient SRCR fold.,Reichhardt MP, Loimaranta V, Lea SM, Johnson S Life Sci Alliance. 2020 Feb 25;3(4). pii: 3/4/e201900502. doi:, 10.26508/lsa.201900502. Print 2020 Apr. PMID:32098784<ref>PMID:32098784</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6san" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Johnson S]]
[[Category: Lea SM]]
[[Category: Loimaranta V]]
[[Category: Reichhardt MP]]