SLC40A1

The protein encoded by this gene is a cell membrane protein that may be involved in iron export from duodenal epithelial cells. Defects in this gene are a cause of hemochromatosis type 4 (HFE4).

Full Name

Solute Carrier Family 40 Member 1

Function

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).

Biological Process

Biological Process apoptotic processIEA:Ensembl
Biological Process cellular iron ion homeostasisManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process endothelium developmentIEA:Ensembl
Biological Process establishment of localization in cellIEA:Ensembl
Biological Process iron ion export across plasma membraneISS:ARUK-UCL
Biological Process iron ion homeostasisManual Assertion Based On ExperimentIBA:GO_Central
Biological Process iron ion transmembrane transportManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process lymphocyte homeostasisIEA:Ensembl
Biological Process multicellular organismal iron ion homeostasisISS:BHF-UCL
Biological Process negative regulation of apoptotic processIEA:Ensembl
Biological Process positive regulation of transcription by RNA polymerase IIIEA:Ensembl
Biological Process regulation of transcription from RNA polymerase II promoter in response to ironIEA:Ensembl
Biological Process spleen trabecula formationIEA:Ensembl
Biological Process transcription by RNA polymerase IIIEA:Ensembl

Cellular Location

Cell membrane
Localized to the basolateral membrane of polarized epithelial cells.

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.

PTM

Polyubiquitinated by RNF217; leading to proteasomal degradation. Ubiquitination is necessary for its internalization by hepcidin/HAMP (PubMed:22682227).