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==Crystal structure of CNNM3 cyclic nucleotide-binding homology domain==
<StructureSection load='6dfd' size='340' side='right'caption='[[6dfd]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6dfd]] 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=6DFD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DFD 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]] 1.901&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=6dfd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dfd OCA], [https://pdbe.org/6dfd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dfd RCSB], [https://www.ebi.ac.uk/pdbsum/6dfd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dfd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CNNM3_HUMAN CNNM3_HUMAN] Probable metal transporter.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Proteins of the family of CBS domain divalent metal cation transport mediators (CNNMs, also called ancient conserved domain proteins, ACDPs) are represented by four integral membrane proteins that have been proposed to function as Mg(2+) transporters. CNNMs are associated with a number of genetic diseases affecting ion movement and cancer via their association with highly oncogenic phosphatases of regenerating liver (PRL). Structurally, CNNMs contain an N-terminal extracellular domain, a transmembrane domain (DUF21), and a large cytosolic region containing a cystathionine-beta-synthase (CBS) domain and a putative cyclic nucleotide-binding homology (CNBH) domain. Although the CBS domain has been extensively characterized, little is known about the CNBH domain. Here, we determined the first crystal structures of the CNBH domains of CNNM2 and CNNM3 at 2.6 and 1.9 A resolutions. Contrary to expectation, these domains did not bind cyclic nucleotides, but mediated dimerization both in crystals and in solution. Analytical ultracentrifugation experiments revealed an inverse correlation between the propensity of the CNBH domains to dimerize and the ability of CNNMs to mediate Mg(2+) efflux. CNBH domains from active family members were observed as both dimers and monomers, whereas the inactive member, CNNM3, was observed only as a dimer. Mutational analysis revealed that the CNBH domain was required for Mg(2+) efflux activity of CNNM4. This work provides a structural basis for understanding the function of CNNM proteins in Mg(2+) transport and associated diseases.

The cyclic nucleotide-binding homology domain of the integral membrane protein CNNM mediates dimerization and is required for Mg(2+) efflux activity.,Chen YS, Kozlov G, Fakih R, Funato Y, Miki H, Gehring K J Biol Chem. 2018 Oct 19. pii: RA118.005672. doi: 10.1074/jbc.RA118.005672. PMID:30341174<ref>PMID:30341174</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6dfd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gehring K]]
[[Category: Kozlov G]]