SLC40A1
Function
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).
Involvement in disease
Hemochromatosis 4
HFE4
A disorder of iron metabolism characterized by iron overload. Excess iron is deposited in a variety of organs leading to their failure, and resulting in serious illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis, and hypogonadotropic hypogonadism. Severe effects of the disease usually do not appear until after decades of progressive iron loading.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Polyubiquitinated by RNF217; leading to proteasomal degradation (By similarity). Under conditions of high systemic iron levels, both the hormone peptide hepcidin/HAMP and holo(iron bound)-transferrin/TF induce the ubiquitination, internalization and proteasomal degradation of SLC40A1 to control iron release from cells (PubMed:22682227, PubMed:37277838).
Sequence Similarities
Belongs to the ferroportin (FP) (TC 2.A.100) family. SLC40A subfamily.
Tissue Specificity
Detected in erythrocytes (at protein level) (PubMed:23219802). Expressed in placenta, intestine, muscle and spleen (PubMed:10747949). Highly expressed in mature red blood (PubMed:29599243).
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Basolateral cell membrane
- Multi-pass membrane protein
- Localized to the basolateral membrane of hepatocytoma WIF-B cells.
Alternative names
FPN, FPN1, IREG1, SLC11A3, MSTP079, SLC40A1, Ferroportin, Ferroportin-1, Iron-regulated transporter 1, Solute carrier family 40 member 1