SLC40A1 Membrane Protein Introduction

Introduction of SLC40A1

Ferroportin-1, alternatively known as solute carrier family 40 member 1 (SLC40A1) or iron-regulated transporter 1 (IREG1), is a transmembrane protein that in human is encoded by SLC40A1 gene. SLC40A1 belongs to the Ferroportin (FPN) family, which transports iron from the intracellular to the extracellular. Members of the FPN family are composed of 400-800 amino acid residues, with a highly conserved histidine at residue position 32 (H32), and show 8-11 putative transmembrane segments (TMs). SLC40A1 is expressed in placenta, spleen, intestine, and muscle.

Basic Information of SLC40A1
Protein Name	Solute carrier family 40 member 1
Gene Name	SLC40A1
Aliases	Ferroportin-1, Iron-regulated transporter 1
Organism	Homo sapiens (Human)
UniProt ID	Q9NP59
Transmembrane Times	11
Length (aa)	571
Sequence	MTRAGDHNRQRGCCGSLADYLTSAKFLLYLGHSLSTWGDRMWHFAVSVFLVELYGNSLLLTAVYGLVVAGSVLVLGAIIGDWVDKNARLKVAQTSLVVQNVSVILCGIILMMVFLHKHELLTMYHGWVLTSCYILIITIANIANLASTATAITIQRDWIVVVAGEDRSKLANMNATIRRIDQLTNILAPMAVGQIMTFGSPVIGCGFISGWNLVSMCVEYVLLWKVYQKTPALAVKAGLKEEETELKQLNLHKDTEPKPLEGTHLMGVKDSNIHELEHEQEPTCASQMAEPFRTFRDGWVSYYNQPVFLAGMGLAFLYMTVLGFDCITTGYAYTQGLSGSILSILMGASAITGIMGTVAFTWLRRKCGLVRTGLISGLAQLSCLILCVISVFMPGSPLDLSVSPFEDIRSRFIQGESITPTKIPEITTEIYMSNGSNSANIVPETSPESVPIISVSLLFAGVIAARIGLWSFDLTVTQLLQENVIESERGIINGVQNSMNYLLDLLHFIMVILAPNPEAFGLLVLISVSFVAMGHIMYFRFAQNTLGNKLFACGPDAKEVRKENQANTSVV

Function of SLC40A1 Membrane Protein

SLC40A1 plays a critical role in neural tube closure and forebrain patterning. It has been shown that intact iron transport mechanisms are essential to normal neural tube closure, and the product and activity of SLC40A1 are necessary along the whole anterior-posterior axis of the animal to ensure correct closure of the neural tube. It can also act as a manganese exporter. Since SLC40A1 extrudes Fe²⁺ from the cell, it is supposed to function via cation (H⁺ or Na⁺) antiport. Once iron is absorbed into the cells of the intestine, SLC40A1 permits iron to be transported out of those cells and into the bloodstream. SLC40A1 may also play a role in iron export from the duodenal epithelial cell and in the transfer of iron between maternal and fetal circulation. It has been proved to mediate iron efflux in the presence of a ferroxidase (hephaestin and/or ceruloplasmin). Furthermore, SLC40A1 plays a critical role in early embryonic development. The loss of SLC40A1 in the extraembryonic visceral endoderm leads to embryonic death.

SLC40A1 Membrane Protein Introduction Fig.1 A schematic drawing of the 11-transmembrane (TM) model of ferroportin (Fpn). (Yeh, 2011)

Application of SLC40A1 Membrane Protein in Literature

Shan Z., et al. Suppression of ferroportin expression by cadmium stimulates proliferation, EMT, and migration in triple-negative breast cancer cells. Toxicol Appl Pharmacol. 2018, 356: 36-43. PubMed ID: 30030096

Results of this study indicate that Cd-induced stimulation of MDA-MB-231 cell proliferation, EMT, and migration is caused by suppression of FPN expression and associated disruption of iron homeostasis.
Helgudottir S.S., et al. Hepcidin Mediates Transcriptional Changes in Ferroportin mRNA in Differentiated Neuronal-Like PC12 Cells Subjected to Iron Challenge. Mol Neurobiol. 2018, 56(4): 2362-2374. PubMed ID: 30027341

This article reveals a transcriptional induction of Fpn in response to changes in cellular iron levels.
Lim D., et al. The hepcidin-ferroportin axis controls the iron content of Salmonella-containing vacuoles in macrophages. Nat Commun. 2018, 9(1): 2091. PubMed ID: 29844422

This study suggests that FPN is necessary to provide sufficient iron to the SCV, where iron acts as a cofactor for the generation of antimicrobial ROS rather than as a nutrient for Salmonella.
Wang L., et al. Deletion of ferroportin in murine myeloid cells increases iron accumulation and stimulates osteoclastogenesis in vitro and in vivo. J Biol Chem. 2018, 293(24): 9248-9264. PubMed ID: 29724825

The results of this study indicate that FPN-regulated intracellular iron levels are essential for mitochondrial metabolism, osteoclastogenesis, and skeletal homeostasis in mice.
Zhang D.L., et al. Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk. Science. 2018, 359(6383): 1520-1523. PubMed ID: 29599243

Results of this study suggest that FPN protects RBCs from oxidative stress and malaria infection.

SLC40A1 Preparation Options

Creative Biolabs offers SLC40A1 membrane protein preparation services via our Magic™ membrane protein production platform, which enables robust reconstitution forms as well as multiple active formats for membrane proteins with fast turnaround times. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-SLC40A1 antibody development services.

To prepare the soluble and functional target protein of your interest, Creative Biolabs has extensive experience in membrane protein preparation and is willing to provide customized services. Our scientists have established an effective way to conduct membrane protein studies for our worldwide clients. Please feel free to contact us for more details.

Reference

Yeh K Y, et al. (2011). Interactions between ferroportin and hephaestin in rat enterocytes are reduced after iron ingestion. Gastroenterology. 141(1), pp.292-299.

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