UniProt:Q9NP59 SLC40A1

chain
  • chain:1-571
checksum E4D6B5594C904959
comment
  • 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).CATALYTIC ACTIVITY Fe(2+)(in) = Fe(2+)(out)SUBUNIT Identified in a complex with STOM (PubMed:23219802). Interacts with HAMP; affinity of the peptide hormone HAMP for SLC40A1 increases by 80-fold in the presence of iron and the interaction promotes SLC40A1 ubiquitination and degradation (PubMed:22682227, PubMed:29237594, PubMed:32814342). Part of a complex composed of SLC40A1/ferroportin, TF/transferrin and HEPH/hephaestin that transfers iron from cells to transferrin (PubMed:37277838).INTERACTION Localized to the basolateral membrane of hepatocytoma WIF-B cells.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).PTM 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).DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the ferroportin (FP) (TC 2.A.100) family. SLC40A subfamily.CAUTION Manganese Mn(2+) transport by SLC40A1 remains controversial. Some in vitro studies have suggested that SLC40A1 transports minimal amounts of Mn(2+) (PubMed:22178646, PubMed:30247984). Other groups have suggested that it does not (PubMed:24304836, PubMed:29792530). The affinity of SLC40A1 for Mn(2+) is extremely low compared with iron, implying that any SLC40A1-mediated Mn(2+) transport in vivo would likely be trivial (PubMed:24304836). A recent study examined the role of SLC40A1 in Mn(2+) homeostasis by using Tmprss6-O mice, which express high levels of hepcidin/HAMP and therefore have very low SLC40A1 levels in their tissues. These mice show frank iron deficiency and reduced iron levels in most tissues, but manganese levels are largely unaffected (By similarity). These studies suggest that manganese is probably not the physiological substrate of SLC40A1.
created [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10
crossReference
databaseName UniProt
dbId 153505
description
  • recommendedName: fullName evidence="33"Ferroportin alternativeName: Ferroportin-1 alternativeName: Iron-regulated transporter 1 alternativeName: fullName evidence="35"Solute carrier family 40 member 1
displayName UniProt:Q9NP59 SLC40A1
geneName
  • SLC40A1
  • FPN
  • FPN1
  • IREG1
  • SLC11A3
  • MSTP079
identifier Q9NP59
isSequenceChanged false
keyword
  • 3D-structure
  • Cell membrane
  • Disease variant
  • Glycoprotein
  • Ion transport
  • Iron
  • Iron transport
  • Membrane
  • Metal-binding
  • Proteomics identification
  • Reference proteome
  • Transmembrane
  • Transmembrane helix
  • Transport
  • Ubl conjugation
modified [InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType Protein
name
  • SLC40A1
otherIdentifier
  • 11715788_a_at
  • 11715789_a_at
  • 16906419
  • 223044_PM_at
  • 223044_at
  • 2591858
  • 2591859
  • 2591860
  • 2591861
  • 2591862
  • 2591864
  • 2591865
  • 2591866
  • 2591867
  • 2591868
  • 2591874
  • 2591875
  • 2591876
  • 2591877
  • 2591878
  • 2591882
  • 2591883
  • 2591884
  • 2591887
  • 2591888
  • 2591889
  • 2591890
  • 2591891
  • 2591893
  • 2591894
  • 30061
  • 45826_at
  • 47365_at
  • 8057677
  • A_23_P102391
  • GE58603
  • GO:0002260
  • GO:0002376
  • GO:0003158
  • GO:0005381
  • GO:0005515
  • GO:0005654
  • GO:0005737
  • GO:0005829
  • GO:0005886
  • GO:0006351
  • GO:0006355
  • GO:0006366
  • GO:0006811
  • GO:0006826
  • GO:0006879
  • GO:0006915
  • GO:0008021
  • GO:0015093
  • GO:0016020
  • GO:0016323
  • GO:0017046
  • GO:0031410
  • GO:0034755
  • GO:0042802
  • GO:0043066
  • GO:0045944
  • GO:0046872
  • GO:0048536
  • GO:0048856
  • GO:0051649
  • GO:0055085
  • GO:0060345
  • GO:0060586
  • GO:1903988
  • HMNXSV003009430
  • ILMN_1761833
  • ILMN_2053103
  • PH_hs_0024808
  • TC02002614.hg
  • TC02004748.hg
  • g12053382_3p_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • S40A1_HUMAN
  • Q6FI62
  • Q7Z4F8
  • Q8IVB2
  • Q9NRL0
sequenceLength 571
species [Species:48887] Homo sapiens
stId uniprot:Q9NP59
url http://purl.uniprot.org/uniprot/Q9NP59
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