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2.A.100.1.4
Solute carrier family 40 member 1 (Ferroportin-1; FPN1, SLC40A1, FPN, IREG1, SLC11A3)) (Iron-regulated transporter 1).  Transports iron, cobalt, zinc and manganese, magnesium, and maybe copper (Madejczyk and Ballatori 2012).  Regulated by its inhibitor, the processed liver antimicrobial peptide, hepcidin (TC# 8.A.37.1.2).  Tryptophan 42, a hemochromatosis type 4 disease residue, plays a role in iron export and iron homeostasis as well as hepcidin binding (Le Gac et al. 2013).  This protein has been modeled using the MSF EmrD of E. coli (TC# 2.A.1.2.9) (Le Gac et al. 2013). Defects can be corrected by adding the small molecule, hinokitiol (Cioffi et al. 2015; Grillo et al. 2017). The R178Q mutation is a recurrent cause of hemochromatosis and is associated with a novel pathogenic mechanism (Ka et al. 2018). The function of the "gating residues" in the mechanism of iron export have been modeled and studied (Guellec et al. 2019). Optimal conditions for Western blotting for this and other proteins requires that the sample not be boiled (Tsuji 2020).  Ferroptosis resists intracellular Vibrio splendidus AJ01 mediated by ferroportin in sea cucumber Apostichopus japonicus (Wang et al. 2024).  Alternative splicing generates a novel ferroportin isoform with a shorter C-terminal and intact iron- and hepcidin-binding properties (Juneja et al. 2024).  Dual loss and gain of function of the FPN1 iron exporter results in the ferroportin disease phenotype (Uguen et al. 2024).

Accession Number:Q9NP59
Protein Name:Solute carrier family 40 member 1
Length:571
Molecular Weight:62542.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:11
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate magnesium(2+), cobalt(2+), copper(2+), iron(2+), zinc(2+), manganese(2+)

Cross database links:

Entrez Gene ID: 30061   
Pfam: PF06963   
KEGG: hsa:30061   

Gene Ontology

GO:0005737 C:cytoplasm
GO:0005887 C:integral to plasma membrane
GO:0008021 C:synaptic vesicle
GO:0005381 F:iron ion transmembrane transporter activity
GO:0009653 P:anatomical structure morphogenesis
GO:0006915 P:apoptotic process
GO:0006879 P:cellular iron ion homeostasis
GO:0003158 P:endothelium development
GO:0002260 P:lymphocyte homeostasis
GO:0060586 P:multicellular organismal iron ion homeostasis
GO:0060345 P:spleen trabecula formation

References (21)

[1] “A novel mammalian iron-regulated protein involved in intracellular iron metabolism.”  Abboud S.et.al.   10747949
[2] “A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation.”  McKie A.T.et.al.   10882071
[3] “Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter.”  Donovan A.et.al.   10693807
[4] “Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.”  Wiemann S.et.al.   11230166
[5] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[6] “Analysis of genes implicated in iron regulation in individuals presenting with primary iron overload.”  Zaahl M.G.et.al.   15338274
[7] “Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra.”  Yu L.-R.et.al.   17924679
[8] “Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene.”  Montosi G.et.al.   11518736
[9] “A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis.”  Njajou O.T.et.al.   11431687
[10] “Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis.”  Wallace D.F.et.al.   12091366
[11] “Autosomal dominant reticuloendothelial iron overload associated with a 3-base pair deletion in the ferroportin 1 gene (SLC11A3).”  Devalia V.et.al.   12091367
[12] “A valine deletion of ferroportin 1: a common mutation in hemochromastosis type 4.”  Roetto A.et.al.   12123233
[13] “Genetic hyperferritinaemia and reticuloendothelial iron overload associated with a three base pair deletion in the coding region of the ferroportin gene (SLC11A3).”  Cazzola M.et.al.   12406098
[14] “Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (SLC11A3) mutations.”  Hetet G.et.al.   12730114
[15] “Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene.”  Gordeuk V.R.et.al.   14636642
[16] “A novel mutation in ferroportin1 is associated with haemochromatosis in a Solomon Islands patient.”  Arden K.E.et.al.   12865285
[17] “Autosomal dominant reticuloendothelial iron overload (HFE type 4) due to a new missense mutation in the FERROPORTIN 1 gene (SLC11A3) in a large French-Canadian family.”  Rivard S.R.et.al.   12857562
[18] “Novel mutation in ferroportin 1 gene is associated with autosomal dominant iron overload.”  Jouanolle A.-M.et.al.   12873829
[19] “The ferroportin disease.”  Pietrangelo A.et.al.   14757427
[20] “Recent advances in understanding haemochromatosis: a transition state.”  Robson K.J.H.et.al.   15466004
[21] “Genetic and clinical heterogeneity of ferroportin disease.”  Cremonesi L.et.al.   16351644
Structure:
6W4S   6WBV     

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence 
1:	MTRAGDHNRQ RGCCGSLADY LTSAKFLLYL GHSLSTWGDR MWHFAVSVFL VELYGNSLLL 
61:	TAVYGLVVAG SVLVLGAIIG DWVDKNARLK VAQTSLVVQN VSVILCGIIL MMVFLHKHEL 
121:	LTMYHGWVLT SCYILIITIA NIANLASTAT AITIQRDWIV VVAGEDRSKL ANMNATIRRI 
181:	DQLTNILAPM AVGQIMTFGS PVIGCGFISG WNLVSMCVEY VLLWKVYQKT PALAVKAGLK 
241:	EEETELKQLN LHKDTEPKPL EGTHLMGVKD SNIHELEHEQ EPTCASQMAE PFRTFRDGWV 
301:	SYYNQPVFLA GMGLAFLYMT VLGFDCITTG YAYTQGLSGS ILSILMGASA ITGIMGTVAF 
361:	TWLRRKCGLV RTGLISGLAQ LSCLILCVIS VFMPGSPLDL SVSPFEDIRS RFIQGESITP 
421:	TKIPEITTEI YMSNGSNSAN IVPETSPESV PIISVSLLFA GVIAARIGLW SFDLTVTQLL 
481:	QENVIESERG IINGVQNSMN YLLDLLHFIM VILAPNPEAF GLLVLISVSF VAMGHIMYFR 
541:	FAQNTLGNKL FACGPDAKEV RKENQANTSV V