| Structural highlights
8dl7 is a 4 chain structure with sequence from Homo sapiens, Mus musculus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | 2GX, 3FB, ACA, EOE, POV, SOW, SQ6, SQI |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
S40A1_HUMAN Hemochromatosis type 4. The disease is caused by variants affecting the gene represented in this entry.
Function
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][1] [2] [3] [4]
References
- ↑ Schimanski LM, Drakesmith H, Merryweather-Clarke AT, Viprakasit V, Edwards JP, Sweetland E, Bastin JM, Cowley D, Chinthammitr Y, Robson KJ, Townsend AR. In vitro functional analysis of human ferroportin (FPN) and hemochromatosis-associated FPN mutations. Blood. 2005 May 15;105(10):4096-102. doi: 10.1182/blood-2004-11-4502. Epub 2005 , Feb 3. PMID:15692071 doi:https://dx.doi.org/10.1182/blood-2004-11-4502
- ↑ Qiao B, Sugianto P, Fung E, Del-Castillo-Rueda A, Moran-Jimenez MJ, Ganz T, Nemeth E. Hepcidin-induced endocytosis of ferroportin is dependent on ferroportin ubiquitination. Cell Metab. 2012 Jun 6;15(6):918-24. doi: 10.1016/j.cmet.2012.03.018. PMID:22682227 doi:https://dx.doi.org/10.1016/j.cmet.2012.03.018
- ↑ Aschemeyer S, Qiao B, Stefanova D, Valore EV, Sek AC, Ruwe TA, Vieth KR, Jung G, Casu C, Rivella S, Jormakka M, Mackenzie B, Ganz T, Nemeth E. Structure-function analysis of ferroportin defines the binding site and an alternative mechanism of action of hepcidin. Blood. 2018 Feb 22;131(8):899-910. doi: 10.1182/blood-2017-05-786590. Epub 2017 , Dec 13. PMID:29237594 doi:https://dx.doi.org/10.1182/blood-2017-05-786590
- ↑ Billesbolle CB, Azumaya CM, Kretsch RC, Powers AS, Gonen S, Schneider S, Arvedson T, Dror RO, Cheng Y, Manglik A. Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms. Nature. 2020 Aug 19. pii: 10.1038/s41586-020-2668-z. doi:, 10.1038/s41586-020-2668-z. PMID:32814342 doi:https://dx.doi.org/10.1038/s41586-020-2668-z
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