8dl6

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[8dl6]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DL6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DL6 FirstGlance]. <br>
<table><tr><td colspan='2'>[[8dl6]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DL6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DL6 FirstGlance]. <br>
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</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>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</td></tr>
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<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'>[https://proteopedia.org/fgij/fg.htm?mol=8dl6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dl6 OCA], [https://pdbe.org/8dl6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dl6 RCSB], [https://www.ebi.ac.uk/pdbsum/8dl6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dl6 ProSAT]</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=8dl6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dl6 OCA], [https://pdbe.org/8dl6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dl6 RCSB], [https://www.ebi.ac.uk/pdbsum/8dl6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dl6 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[https://www.uniprot.org/uniprot/S40A1_HUMAN S40A1_HUMAN] Hemochromatosis type 4. The disease is caused by variants affecting the gene represented in this entry.
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[https://www.uniprot.org/uniprot/S40A1_HUMAN S40A1_HUMAN] SLC40A1-related hemochromatosis;Ferroportin disease. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
== Function ==
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[https://www.uniprot.org/uniprot/S40A1_HUMAN S40A1_HUMAN] Major iron transporter that plays a key role in balancing cellular and systemic iron levels (PubMed:29237594, PubMed:22682227, PubMed:15692071). Transports iron from intestinal, splenic, and hepatic cells into the blood to provide iron to other tissues (By similarity). Controls therefore dietary iron uptake, iron recycling by macrophages, and release of iron stores in hepatocytes (By similarity). When iron is in excess, hepcidin/HAMP levels increase resulting in a degradation of ferroportin/SLC40A1 limiting the iron efflux to plasma (PubMed:22682227, PubMed:29237594, PubMed:32814342).[UniProtKB:Q9JHI9]<ref>PMID:15692071</ref> <ref>PMID:22682227</ref> <ref>PMID:29237594</ref> <ref>PMID:32814342</ref>
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[https://www.uniprot.org/uniprot/S40A1_HUMAN S40A1_HUMAN] Transports Fe(2+) from the inside of a cell to the outside of the cell, playing a key role for maintaining systemic iron homeostasis (PubMed:15692071, PubMed:22178646, PubMed:22682227, PubMed:24304836, PubMed:29237594, PubMed:29599243, PubMed:30247984). Transports iron from intestinal, splenic, hepatic cells, macrophages and erythrocytes into the blood to provide iron to other tissues (By similarity). Controls therefore dietary iron uptake, iron recycling by macrophages and erythrocytes, and release of iron stores in hepatocytes (By similarity). When iron is in excess in serum, circulating HAMP/hepcidin levels increase resulting in a degradation of SLC40A1, thus limiting the iron efflux to plasma (PubMed:22682227, PubMed:29237594, PubMed:32814342).[UniProtKB:Q9JHI9]<ref>PMID:15692071</ref> <ref>PMID:22178646</ref> <ref>PMID:22682227</ref> <ref>PMID:24304836</ref> <ref>PMID:29237594</ref> <ref>PMID:29599243</ref> <ref>PMID:30247984</ref> <ref>PMID:32814342</ref>
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== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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Ferroportin (Fpn) is a transporter that releases ferrous ion (Fe(2+)) from cells and is important for homeostasis of iron in circulation. Export of one Fe(2+) by Fpn is coupled to import of two H(+) to maintain charge balance. Here we show that human Fpn (HsFpn) binds to and mediates Ca(2+) transport. We determine the structure of Ca(2+)-bound HsFpn and identify a single Ca(2+) binding site distinct from the Fe(2+) binding sites. Further studies validate the Ca(2+) binding site and show that Ca(2+) transport is not coupled to transport of another ion. In addition, Ca(2+) transport is significantly inhibited in the presence of Fe(2+) but not vice versa. Function of Fpn as a Ca(2+) uniporter may allow regulation of iron homeostasis by Ca(2+).
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Ferroportin (Fpn) is a transporter that releases ferrous ion (Fe(2+)) from cells and is important for homeostasis of iron in circulation. Export of one Fe(2+) by Fpn is coupled to import of two H(+) to maintain charge balance. Here, we show that human Fpn (HsFpn) binds to and mediates Ca(2+) transport. We determine the structure of Ca(2+)-bound HsFpn and identify a single Ca(2+) binding site distinct from the Fe(2+) binding sites. Further studies validate the Ca(2+) binding site and show that Ca(2+) transport is not coupled to transport of another ion. In addition, Ca(2+) transport is significantly inhibited in the presence of Fe(2+) but not vice versa. Function of Fpn as a Ca(2+) uniporter may allow regulation of iron homeostasis by Ca(2+).
Mechanism of Ca(2+) transport by ferroportin.,Shen J, Wilbon AS, Zhou M, Pan Y Elife. 2023 Jan 17;12:e82947. doi: 10.7554/eLife.82947. PMID:36648329<ref>PMID:36648329</ref>
Mechanism of Ca(2+) transport by ferroportin.,Shen J, Wilbon AS, Zhou M, Pan Y Elife. 2023 Jan 17;12:e82947. doi: 10.7554/eLife.82947. PMID:36648329<ref>PMID:36648329</ref>

Current revision

Cryo-EM structure of human ferroportin/slc40 bound to Ca2+ in nanodisc

PDB ID 8dl6

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