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{{Infobox_gene}}
{{Infobox_gene}}
'''Ferroportin-1,''' also known as '''solute carrier family 40 member 1 (SLC40A1)''' or '''iron-regulated transporter 1 (IREG1),''' is a [[protein]] that in humans is encoded by the ''SLC40A1'' [[gene]], and is part of the '''Ferroportin (Fpn)''' '''Family''' ([http://www.tcdb.org/search/result.php?tc=2.A.100 TC# 2.A.100]).<ref name="Donovan_2000">{{cite journal |vauthors=Donovan A, Brownlie A, Zhou Y, Shepard J, Pratt SJ, Moynihan J, Paw BH, Drejer A, Barut B, Zapata A, Law TC, Brugnara C, Lux SE, Pinkus GS, Pinkus JL, Kingsley PD, Palis J, Fleming MD, Andrews NC, Zon LI | title = Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter | journal = Nature | volume = 403 | issue = 6771 | pages = 776–81 |date=February 2000 | pmid = 10693807 | doi = 10.1038/35001596 }}</ref> Ferroportin is a [[transmembrane protein]] that transports [[iron]] from the inside of a [[cell (biology)|cell]] to the outside of the cell. After iron is absorbed into the cells of the intestine, ferroportin allows that iron to be transported out of those cells and into the bloodstream.
'''Ferroportin-1,''' also known as '''solute carrier family 40 member 1 (SLC40A1)''' or '''iron-regulated transporter 1 (IREG1),''' is a [[protein]] that in humans is encoded by the ''SLC40A1'' [[gene]], and is part of the '''Ferroportin (Fpn)''' '''Family''' ([http://www.tcdb.org/search/result.php?tc=2.A.100 TC# 2.A.100]).<ref name="Donovan_2000">{{cite journal | vauthors = Donovan A, Brownlie A, Zhou Y, Shepard J, Pratt SJ, Moynihan J, Paw BH, Drejer A, Barut B, Zapata A, Law TC, Brugnara C, Lux SE, Pinkus GS, Pinkus JL, Kingsley PD, Palis J, Fleming MD, Andrews NC, Zon LI | title = Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter | journal = Nature | volume = 403 | issue = 6771 | pages = 776–81 | date = February 2000 | pmid = 10693807 | doi = 10.1038/35001596 | bibcode = 2000Natur.403..776D }}</ref> Ferroportin is a [[transmembrane protein]] that transports [[iron]] from the inside of a [[cell (biology)|cell]] to the outside of the cell. After iron is absorbed into the cells of the intestine, ferroportin allows that iron to be transported out of those cells and into the bloodstream. Ferroportin is the only known iron exporter.<ref>{{cite journal |last1=Ward |first1=DM |last2=Kaplan |first2=J |title=Ferroportin-mediated iron transport: expression and regulation. |journal=Biochimica et Biophysica Acta |date=September 2012 |volume=1823 |issue=9 |pages=1426–33 |doi=10.1016/j.bbamcr.2012.03.004 |pmid=22440327|pmc=3718258 }}</ref>


== Structure ==
== Structure ==


Members of the FPN family consist of 400-800 [[amino acid]] residues,<ref name="url_SLC11A3_NCBI">{{cite web | url = https://www.ncbi.nlm.nih.gov/protein/AAF80986.1?report=gpwithparts&log$=seqview | title = SLC11A3 iron transporter [Homo sapiens] | work = Protein - NCBI }}</ref> with a [[conserved sequence|highly conserved]] [[histidine]] at residue position 32 (H32), and exhibit 8-11 putative [[Transmembrane domain|transmembrane segments]] (TMSs). When H32 is mutated, lower activity in its iron transport role is observed.<ref name="pmid17289807">{{cite journal |vauthors=Zohn IE, De Domenico I, Pollock A, Ward DM, Goodman JF, Liang X, Sanchez AJ, Niswander L, Kaplan J | title = The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease | journal = Blood | volume = 109 | issue = 10 | pages = 4174–80 |date=May 2007 | pmid = 17289807 | pmc = 1885502 | doi = 10.1182/blood-2007-01-066068 }}</ref> Ferroportin can also function as a manganese exporter.<ref>{{Cite journal|last=Madejczyk|first=Michael S.|last2=Ballatori|first2=Nazzareno|date=2012-03-01|title=The iron transporter ferroportin can also function as a manganese exporter|journal=Biochimica et Biophysica Acta|volume=1818|issue=3|pages=651–657|doi=10.1016/j.bbamem.2011.12.002|issn=0006-3002|pmid=22178646}}</ref> Because ferroportin extrudes Fe<sup>2+</sup> from the cell, ferroportin is presumed to function by cation (H<sup>+</sup> or Na<sup>+</sup>) [[Antiporter|antiport]].
Members of the FPN family consist of 400-800 [[amino acid]] residues,<ref name="url_SLC11A3_NCBI">{{cite web | url = https://www.ncbi.nlm.nih.gov/protein/AAF80986.1?report=gpwithparts&log$=seqview | title = SLC11A3 iron transporter [Homo sapiens] | work = Protein - NCBI }}</ref> with a [[conserved sequence|highly conserved]] [[histidine]] at residue position 32 (H32), and exhibit 8-11 putative [[Transmembrane domain|transmembrane segments]] (TMSs). When H32 is mutated, lower activity in its iron transport role is observed.<ref name="pmid17289807">{{cite journal | vauthors = Zohn IE, De Domenico I, Pollock A, Ward DM, Goodman JF, Liang X, Sanchez AJ, Niswander L, Kaplan J | title = The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease | journal = Blood | volume = 109 | issue = 10 | pages = 4174–80 | date = May 2007 | pmid = 17289807 | pmc = 1885502 | doi = 10.1182/blood-2007-01-066068 }}</ref> Ferroportin can also function as a manganese exporter.<ref>{{cite journal | vauthors = Madejczyk MS, Ballatori N | title = The iron transporter ferroportin can also function as a manganese exporter | journal = Biochimica et Biophysica Acta | volume = 1818 | issue = 3 | pages = 651–7 | date = March 2012 | pmid = 22178646 | pmc = 5695046 | doi = 10.1016/j.bbamem.2011.12.002 }}</ref> Because ferroportin extrudes Fe<sup>2+</sup> from the cell, ferroportin is presumed to function by cation (H<sup>+</sup> or Na<sup>+</sup>) [[Antiporter|antiport]].


==  Transport reaction ==
==  Transport reaction ==
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== Tissue distribution ==
== Tissue distribution ==


Ferroportin is found on the basolateral membranes of intestinal epithelia of mammals, including:<ref name="Donovan_2005">{{cite journal |vauthors=Donovan A, Lima CA, Pinkus JL, Pinkus GS, Zon LI, Robine S, Andrews NC | title = The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis | journal = Cell Metab. | volume = 1 | issue = 3 | pages = 191–200 |date=March 2005 | pmid = 16054062 | doi = 10.1016/j.cmet.2005.01.003 }}</ref><ref>{{Cite journal|last=Delaby|first=Constance|last2=Pilard|first2=Nathalie|last3=Puy|first3=Hervé|last4=Canonne-Hergaux|first4=François|date=2008-04-01|title=Sequential regulation of ferroportin expression after erythrophagocytosis in murine macrophages: early mRNA induction by haem, followed by iron-dependent protein expression|journal=The Biochemical Journal|volume=411|issue=1|pages=123–131|doi=10.1042/BJ20071474|issn=1470-8728|pmid=18072938}}</ref>
Ferroportin is found on the basolateral membranes of intestinal epithelia of mammals, including:<ref name="Donovan_2005">{{cite journal | vauthors = Donovan A, Lima CA, Pinkus JL, Pinkus GS, Zon LI, Robine S, Andrews NC | title = The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis | journal = Cell Metabolism | volume = 1 | issue = 3 | pages = 191–200 | date = March 2005 | pmid = 16054062 | doi = 10.1016/j.cmet.2005.01.003 }}</ref><ref>{{cite journal | vauthors = Delaby C, Pilard N, Puy H, Canonne-Hergaux F | title = Sequential regulation of ferroportin expression after erythrophagocytosis in murine macrophages: early mRNA induction by haem, followed by iron-dependent protein expression | journal = The Biochemical Journal | volume = 411 | issue = 1 | pages = 123–31 | date = April 2008 | pmid = 18072938 | doi = 10.1042/BJ20071474 }}</ref>
* [[Enterocytes]] in the [[duodenum]]
* [[Enterocytes]] in the [[duodenum]]
* [[Hepatocytes]]
* [[Hepatocytes]]
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== Role in development ==
== Role in development ==


Ferroportin-1 plays an important role in [[neural tube]] closure and [[forebrain]] patterning.<ref name="Mao_2010">{{cite journal |vauthors=Mao J, McKean DM, Warrier S, Corbin JG, Niswander L, Zohn IE | title = The iron exporter ferroportin 1 is essential for development of the mouse embryo, forebrain patterning and neural tube closure | journal = Development | volume = 137 | issue = 18 | pages = 3079–88 |date=September 2010 | pmid = 20702562 | pmc = 2926957 | doi = 10.1242/dev.048744 }}</ref> Mouse embyros lacking the ''Scl40a1'' gene are aborted before [[gastrulation]] occurs, suggesting that the Fpn1 protein encoded is necessary and essential for normal embryonic development.<ref name="Donovan_2005" /> Fpn1 is expressed in the [[syncytiotrophoblast]] cells in the placenta and visceral endoderm of mice at E7.5.<ref name="Donovan_2000" /><ref name="Donovan_2005" /> Further, several retrospective studies have noted an increased incidence of [[spina bifida]] occurring after low maternal intake of iron during embryonic and fetal development.<ref name="pmid16315101">{{cite journal |vauthors=Felkner MM, Suarez L, Brender J, Scaife B, Hendricks K | title = Iron status indicators in women with prior neural tube defect-affected pregnancies | journal = Matern Child Health J | volume = 9 | issue = 4 | pages = 421–8 |date=December 2005 | pmid = 16315101 | doi = 10.1007/s10995-005-0017-3 }}</ref><ref name="pmid15173422">{{cite journal |vauthors=Groenen PM, van Rooij IA, Peer PG, Ocké MC, Zielhuis GA, Steegers-Theunissen RP | title = Low maternal dietary intakes of iron, magnesium, and niacin are associated with spina bifida in the offspring | journal = J. Nutr. | volume = 134 | issue = 6 | pages = 1516–22 |date=June 2004 | pmid = 15173422 | doi = }}</ref>
Ferroportin-1 plays an important role in [[neural tube]] closure and [[forebrain]] patterning.<ref name="Mao_2010">{{cite journal | vauthors = Mao J, McKean DM, Warrier S, Corbin JG, Niswander L, Zohn IE | title = The iron exporter ferroportin 1 is essential for development of the mouse embryo, forebrain patterning and neural tube closure | journal = Development | volume = 137 | issue = 18 | pages = 3079–88 | date = September 2010 | pmid = 20702562 | pmc = 2926957 | doi = 10.1242/dev.048744 }}</ref> Mouse embyros lacking the ''Scl40a1'' gene are aborted before [[gastrulation]] occurs, suggesting that the Fpn1 protein encoded is necessary and essential for normal embryonic development.<ref name="Donovan_2005" /> Fpn1 is expressed in the [[syncytiotrophoblast]] cells in the placenta and visceral endoderm of mice at E7.5.<ref name="Donovan_2000" /><ref name="Donovan_2005" /> Further, several retrospective studies have noted an increased incidence of [[spina bifida]] occurring after low maternal intake of iron during embryonic and fetal development.<ref name="pmid16315101">{{cite journal | vauthors = Felkner MM, Suarez L, Brender J, Scaife B, Hendricks K | title = Iron status indicators in women with prior neural tube defect-affected pregnancies | journal = Maternal and Child Health Journal | volume = 9 | issue = 4 | pages = 421–8 | date = December 2005 | pmid = 16315101 | doi = 10.1007/s10995-005-0017-3 }}</ref><ref name="pmid15173422">{{cite journal | vauthors = Groenen PM, van Rooij IA, Peer PG, Ocké MC, Zielhuis GA, Steegers-Theunissen RP | title = Low maternal dietary intakes of iron, magnesium, and niacin are associated with spina bifida in the offspring | journal = The Journal of Nutrition | volume = 134 | issue = 6 | pages = 1516–22 | date = June 2004 | pmid = 15173422 | doi = 10.1093/jn/134.6.1516}}</ref>


A study examining the consequences of several different mutations of the ''Slc40a1'' mouse gene suggested that several serious neural tube and patterning defects were produced as a result, including spina bifida, [[exencephaly]], and forebrain truncations, among others.<ref name="Mao_2010" /> Given the findings of studies to date, there appears to be significant evidence that intact iron transport mechanisms are critical to normal neural tube closure. Furthermore, other experiments have suggested that ''Fpn1'' product and activity is required along the entire anterior-posterior axis of the animal to ensure proper closure of the neural tube.<ref name="Mao_2010" />
A study examining the consequences of several different mutations of the ''Slc40a1'' mouse gene suggested that several serious neural tube and patterning defects were produced as a result, including spina bifida, [[exencephaly]], and forebrain truncations, among others.<ref name="Mao_2010" /> Given the findings of studies to date, there appears to be significant evidence that intact iron transport mechanisms are critical to normal neural tube closure. Furthermore, other experiments have suggested that ''Fpn1'' product and activity is required along the entire anterior-posterior axis of the animal to ensure proper closure of the neural tube.<ref name="Mao_2010" />
== Role in fertility ==
It is known that ferroportin (SLC40A1) gene is expressed at a low level in infertile women. Its mRNA levels were discovered to be down-regulated in these women, specifically in granulosa cells. What's more, low expression of ferroportin is also associated with infertily  when some features like age and smoking habits are considered.
It is also important to mention that, not only is ferroportin down-regulated in granulosa cells, but also in cervical cells of infertile women, and that the association between infertility and low ferroportin levels in these cells can be seen, again, when mRNA ferroportin levels was adjusted by age and smoking status.<ref>Moreno-Navarrete JM, López-Navarro E, Candenas L, Pinto F, Ortega FJ, Sabater-Masdeu M, et al.Ferroportin mRNA is down-regulated in granulosa and cervical cells from infertile women.Fertil Steril. 2017 Jan;107(1):236-242.  </ref>


== Role in iron metabolism ==
== Role in iron metabolism ==


Ferroportin is inhibited by [[hepcidin]], which binds to ferroportin and internalizes it within the cell.<ref name="pmid15514116">{{cite journal |vauthors=Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J | title = Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization | journal = Science | volume = 306 | issue = 5704 | pages = 2090–3 |date=December 2004 | pmid = 15514116 | doi = 10.1126/science.1104742 }}</ref> This results in the retention of iron within enterocytes, hepatocytes, and macrophages with a consequent reduction in iron levels within the blood serum. This is especially significant with enterocytes which, when shed at the end of their lifespan, results in significant iron loss. This is part of the mechanism that causes [[anaemia of chronic disease]]; hepcidin is released from the liver in response to inflammatory cytokines, namely [[interleukin-6]], which results in an increased hepcidin concentration and a consequent decrease in plasma iron levels.<ref name="pmid15124018">{{cite journal |vauthors=Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, Ganz T | title = IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin | journal = J. Clin. Invest. | volume = 113 | issue = 9 | pages = 1271–6 |date=May 2004 | pmid = 15124018 | pmc = 398432 | doi = 10.1172/JCI20945 }}</ref>
Ferroportin is inhibited by [[hepcidin]], which binds to ferroportin and internalizes it within the cell.<ref name="pmid15514116">{{cite journal | vauthors = Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J | title = Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization | journal = Science | volume = 306 | issue = 5704 | pages = 2090–3 | date = December 2004 | pmid = 15514116 | doi = 10.1126/science.1104742 | bibcode = 2004Sci...306.2090N }}</ref> This results in the retention of iron within enterocytes, hepatocytes, and macrophages with a consequent reduction in iron levels within the blood serum. This is especially significant with enterocytes which, when shed at the end of their lifespan, results in significant iron loss. This is part of the mechanism that causes [[anaemia of chronic disease]]; hepcidin is released from the liver in response to inflammatory cytokines, namely [[interleukin-6]], which results in an increased hepcidin concentration and a consequent decrease in plasma iron levels.<ref name="pmid15124018">{{cite journal | vauthors = Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, Ganz T | title = IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin | journal = The Journal of Clinical Investigation | volume = 113 | issue = 9 | pages = 1271–6 | date = May 2004 | pmid = 15124018 | pmc = 398432 | doi = 10.1172/JCI20945 }}</ref>


Ferroportin expression is also regulated by the [[Iron-responsive element-binding protein|IRP]] regulatory mechanism. If the iron concentration is too low, the IRP concentration increases, thus inhibiting the ferroportin translation. The ferroportin translation is also regulated by the micro RNA miR-485-3p.
Ferroportin expression is also regulated by the [[Iron-responsive element-binding protein|IRP]] regulatory mechanism. If the iron concentration is too low, the IRP concentration increases, thus inhibiting the ferroportin translation. The ferroportin translation is also regulated by the micro RNA miR-485-3p.<ref name="pmid23593016">{{cite journal | vauthors = Sangokoya C, Doss JF, Chi JT | title = Iron-responsive miR-485-3p regulates cellular iron homeostasis by targeting ferroportin | journal = PLoS Genetics | volume = 9 | issue = 4 | pages = e1003408 | date = April 2013 | pmid = 23593016 | pmc = 3616902 | doi = 10.1371/journal.pgen.1003408 }}</ref>


== Clinical significance ==
== Clinical significance ==


Mutations in the ferroportin gene are known to cause an autosomal dominant form of iron overload known as type IV [[Iron overload#Haemochromatosis or haemosiderosis|haemochromatosis]] or Ferroportin Disease. The effects of the mutations are generally not severe but a spectrum of clinical outcomes are seen with different mutations. Ferroportin is also associated with [[African iron overload]]. Ferroportin and [[hepcidin]] are critical proteins for the regulation of systemic [[iron homeostasis]]. Both ferroportin and hepcidin are expressed in cultured human breast epithelial cells, and hepcidin regulates ferroportin in these cells. Transfection of breast cancer cells with ferroportin significantly reduces their growth after orthotopic implantation in the mouse mammary fat pad. Therefore, ferroportin is a pivotal protein in breast biology and a strong and independent predictor of prognosis in breast cancer.<ref>{{Cite journal |vauthors=Pinnix ZK, Miller LD, Wang W, ((D'Agostino R Jr)), Kute T, Willingham MC, Hatcher H, Tesfay L, Sui G, Di X, Torti SV, Torti FM | doi = 10.1126/scitranslmed.3001127 | title = Ferroportin and Iron Regulation in Breast Cancer Progression and Prognosis | journal = Science Translational Medicine | volume = 2 | issue = 43 | pages = 43ra56 | year = 2010 | pmid =  20686179| pmc = }}</ref>
Mutations in the ferroportin gene are known to cause an autosomal dominant form of iron overload known as type IV [[Iron overload#Haemochromatosis or haemosiderosis|haemochromatosis]] or Ferroportin Disease. The effects of the mutations are generally not severe but a spectrum of clinical outcomes are seen with different mutations. Ferroportin is also associated with [[African iron overload]]. Ferroportin and [[hepcidin]] are critical proteins for the regulation of systemic [[iron homeostasis]].


==References==
== References ==
{{reflist|colwidth=35em}}
{{reflist|colwidth=35em}}


==Further reading==
== Further reading ==
{{refbegin|colwidth=35em}}
{{refbegin|colwidth=35em}}
* {{cite journal | vauthors = Schimanski LM, Drakesmith H, Merryweather-Clarke AT, Viprakasit V, Edwards JP, Sweetland E, Bastin JM, Cowley D, Chinthammitr Y, Robson KJ, Townsend AR | title = ''In vitro'' functional analysis of human ferroportin (FPN) and hemochromatosis-associated FPN mutations | journal = Blood | volume = 105 | issue = 10 | pages = 4096–102 |date=May 2005 | pmid = 15692071 | doi = 10.1182/blood-2004-11-4502 }}
* {{cite journal | vauthors = Schimanski LM, Drakesmith H, Merryweather-Clarke AT, Viprakasit V, Edwards JP, Sweetland E, Bastin JM, Cowley D, Chinthammitr Y, Robson KJ, Townsend AR | title = In vitro functional analysis of human ferroportin (FPN) and hemochromatosis-associated FPN mutations | journal = Blood | volume = 105 | issue = 10 | pages = 4096–102 | date = May 2005 | pmid = 15692071 | doi = 10.1182/blood-2004-11-4502 }}
* {{cite journal | author = Pietrangelo A | title = The ferroportin disease | journal = Blood Cells Mol. Dis. | volume = 32 | issue = 1 | pages = 131–8 | year = 2004 | pmid = 14757427 | doi = 10.1016/j.bcmd.2003.08.003 }}
* {{cite journal | vauthors = Pietrangelo A | title = The ferroportin disease | journal = Blood Cells, Molecules & Diseases | volume = 32 | issue = 1 | pages = 131–8 | year = 2004 | pmid = 14757427 | doi = 10.1016/j.bcmd.2003.08.003 }}
* {{cite journal | vauthors = Robson KJ, Merryweather-Clarke AT, Cadet E, Viprakasit V, Zaahl MG, Pointon JJ, Weatherall DJ, Rochette J | title = Recent advances in understanding haemochromatosis: a transition state | journal = J. Med. Genet. | volume = 41 | issue = 10 | pages = 721–30 |date=October 2004 | pmid = 15466004 | pmc = 1735598 | doi = 10.1136/jmg.2004.020644 }}
* {{cite journal | vauthors = Robson KJ, Merryweather-Clarke AT, Cadet E, Viprakasit V, Zaahl MG, Pointon JJ, Weatherall DJ, Rochette J | title = Recent advances in understanding haemochromatosis: a transition state | journal = Journal of Medical Genetics | volume = 41 | issue = 10 | pages = 721–30 | date = October 2004 | pmid = 15466004 | pmc = 1735598 | doi = 10.1136/jmg.2004.020644 }}
* {{cite journal |vauthors=Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1-2 | pages = 171–4 |date=January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
* {{cite journal |vauthors=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1-2 | pages = 149–56 |date=October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
* {{cite journal |vauthors=Abboud S, Haile DJ | title = A novel mammalian iron-regulated protein involved in intracellular iron metabolism | journal = J. Biol. Chem. | volume = 275 | issue = 26 | pages = 19906–12 |date=June 2000 | pmid = 10747949 | doi = 10.1074/jbc.M000713200 }}
* {{cite journal | vauthors = Abboud S, Haile DJ | title = A novel mammalian iron-regulated protein involved in intracellular iron metabolism | journal = The Journal of Biological Chemistry | volume = 275 | issue = 26 | pages = 19906–12 | date = June 2000 | pmid = 10747949 | doi = 10.1074/jbc.M000713200 }}
* {{cite journal | author = Haile DJ | title = Assignment of Slc11a3 to mouse chromosome 1 band 1B and SLC11A3 to human chromosome 2q32 by in situ hybridization | journal = Cytogenet. Cell Genet. | volume = 88 | issue = 3-4 | pages = 328–9 | year = 2000 | pmid = 10828623 | doi = 10.1159/000015522 }}
* {{cite journal | vauthors = Haile DJ | title = Assignment of Slc11a3 to mouse chromosome 1 band 1B and SLC11A3 to human chromosome 2q32 by in situ hybridization | journal = Cytogenetics and Cell Genetics | volume = 88 | issue = 3–4 | pages = 328–9 | year = 2000 | pmid = 10828623 | doi = 10.1159/000015522 }}
* {{cite journal |vauthors=McKie AT, Marciani P, Rolfs A, Brennan K, Wehr K, Barrow D, Miret S, Bomford A, Peters TJ, Farzaneh F, Hediger MA, Hentze MW, Simpson RJ | title = A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation | journal = Mol. Cell | volume = 5 | issue = 2 | pages = 299–309 |date=February 2000 | pmid = 10882071 | doi = 10.1016/S1097-2765(00)80425-6 }}
* {{cite journal | vauthors = McKie AT, Marciani P, Rolfs A, Brennan K, Wehr K, Barrow D, Miret S, Bomford A, Peters TJ, Farzaneh F, Hediger MA, Hentze MW, Simpson RJ | title = A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation | journal = Molecular Cell | volume = 5 | issue = 2 | pages = 299–309 | date = February 2000 | pmid = 10882071 | doi = 10.1016/S1097-2765(00)80425-6 }}
* {{cite journal |vauthors=Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Res. | volume = 10 | issue = 11 | pages = 1788–95 |date=November 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
* {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–95 | date = November 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
* {{cite journal |vauthors=Njajou OT, Vaessen N, Joosse M, Berghuis B, van Dongen JW, Breuning MH, Snijders PJ, Rutten WP, Sandkuijl LA, Oostra BA, van Duijn CM, Heutink P | title = A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis | journal = Nat. Genet. | volume = 28 | issue = 3 | pages = 213–4 |date=July 2001 | pmid = 11431687 | doi = 10.1038/90038 | url = }}
* {{cite journal | vauthors = Njajou OT, Vaessen N, Joosse M, Berghuis B, van Dongen JW, Breuning MH, Snijders PJ, Rutten WP, Sandkuijl LA, Oostra BA, van Duijn CM, Heutink P | title = A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis | journal = Nature Genetics | volume = 28 | issue = 3 | pages = 213–4 | date = July 2001 | pmid = 11431687 | doi = 10.1038/90038 }}
* {{cite journal |vauthors=Montosi G, Donovan A, Totaro A, Garuti C, Pignatti E, Cassanelli S, Trenor CC, Gasparini P, Andrews NC, Pietrangelo A | title = Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene | journal = J. Clin. Invest. | volume = 108 | issue = 4 | pages = 619–23 |date=August 2001 | pmid = 11518736 | pmc = 209405 | doi = 10.1172/JCI13468 }}
* {{cite journal | vauthors = Montosi G, Donovan A, Totaro A, Garuti C, Pignatti E, Cassanelli S, Trenor CC, Gasparini P, Andrews NC, Pietrangelo A | title = Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene | journal = The Journal of Clinical Investigation | volume = 108 | issue = 4 | pages = 619–23 | date = August 2001 | pmid = 11518736 | pmc = 209405 | doi = 10.1172/JCI13468 }}
* {{cite journal | author = Press RD | title = Hemochromatosis caused by mutations in the iron-regulatory proteins ferroportin and H ferritin | journal = Mol. Diagn. | volume = 6 | issue = 4 | pages = 347 |date=December 2001 | pmid = 11774199 | doi = 10.1054/modi.2001.0060347 }}
* {{cite journal | vauthors = Press RD | title = Hemochromatosis caused by mutations in the iron-regulatory proteins ferroportin and H ferritin | journal = Molecular Diagnosis | volume = 6 | issue = 4 | pages = 347–349 | date = December 2001 | pmid = 11774199 | doi = 10.1054/modi.2001.0060347 }}
* {{cite journal |vauthors=Lee PL, Gelbart T, West C, Halloran C, Felitti V, Beutler E | title = A study of genes that may modulate the expression of hereditary hemochromatosis: transferrin receptor-1, ferroportin, ceruloplasmin, ferritin light and heavy chains, iron regulatory proteins (IRP)-1 and -2, and hepcidin | journal = Blood Cells Mol. Dis. | volume = 27 | issue = 5 | pages = 783–802 | year = 2001 | pmid = 11783942 | doi = 10.1006/bcmd.2001.0445 }}
* {{cite journal | vauthors = Lee PL, Gelbart T, West C, Halloran C, Felitti V, Beutler E | title = A study of genes that may modulate the expression of hereditary hemochromatosis: transferrin receptor-1, ferroportin, ceruloplasmin, ferritin light and heavy chains, iron regulatory proteins (IRP)-1 and -2, and hepcidin | journal = Blood Cells, Molecules & Diseases | volume = 27 | issue = 5 | pages = 783–802 | year = 2001 | pmid = 11783942 | doi = 10.1006/bcmd.2001.0445 }}
* {{cite journal |vauthors=Rolfs A, Bonkovsky HL, Kohlroser JG, McNeal K, Sharma A, Berger UV, Hediger MA | title = Intestinal expression of genes involved in iron absorption in humans | journal = Am. J. Physiol. Gastrointest. Liver Physiol. | volume = 282 | issue = 4 | pages = G598–607 |date=April 2002 | pmid = 11897618 | doi = 10.1152/ajpgi.00371.2001 | url = }}
* {{cite journal | vauthors = Rolfs A, Bonkovsky HL, Kohlroser JG, McNeal K, Sharma A, Berger UV, Hediger MA | title = Intestinal expression of genes involved in iron absorption in humans | journal = American Journal of Physiology. Gastrointestinal and Liver Physiology | volume = 282 | issue = 4 | pages = G598–607 | date = April 2002 | pmid = 11897618 | doi = 10.1152/ajpgi.00371.2001 }}
*{{cite journal |vauthors=Thomas C, Oates PS | title = IEC-6 cells are an appropriate model of intestinal iron absorption in rats | journal = J. Nutr. | volume = 132 | issue = 4 | pages = 680–7 |date=April 2002 | pmid = 11925460 | doi =  }}
* {{cite journal | vauthors = Thomas C, Oates PS | title = IEC-6 cells are an appropriate model of intestinal iron absorption in rats | journal = The Journal of Nutrition | volume = 132 | issue = 4 | pages = 680–7 | date = April 2002 | pmid = 11925460 | doi =  10.1093/jn/132.4.680}}
* {{cite journal |vauthors=Wallace DF, Pedersen P, Dixon JL, Stephenson P, Searle JW, Powell LW, Subramaniam VN | title = Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis | journal = Blood | volume = 100 | issue = 2 | pages = 692–4 |date=July 2002 | pmid = 12091366 | doi = 10.1182/blood.v100.2.692}}
* {{cite journal | vauthors = Wallace DF, Pedersen P, Dixon JL, Stephenson P, Searle JW, Powell LW, Subramaniam VN | title = Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis | journal = Blood | volume = 100 | issue = 2 | pages = 692–4 | date = July 2002 | pmid = 12091366 | doi = 10.1182/blood.v100.2.692 }}
* {{cite journal |vauthors=Devalia V, Carter K, Walker AP, Perkins SJ, Worwood M, May A, Dooley JS | title = Autosomal dominant reticuloendothelial iron overload associated with a 3-base pair deletion in the ferroportin 1 gene (SLC11A3) | journal = Blood | volume = 100 | issue = 2 | pages = 695–7 |date=July 2002 | pmid = 12091367 | doi = 10.1182/blood-2001-11-0132 }}
* {{cite journal | vauthors = Devalia V, Carter K, Walker AP, Perkins SJ, Worwood M, May A, Dooley JS | title = Autosomal dominant reticuloendothelial iron overload associated with a 3-base pair deletion in the ferroportin 1 gene (SLC11A3) | journal = Blood | volume = 100 | issue = 2 | pages = 695–7 | date = July 2002 | pmid = 12091367 | doi = 10.1182/blood-2001-11-0132 }}
* {{cite journal | vauthors = Roetto A, Merryweather-Clarke AT, Daraio F, Livesey K, Pointon JJ, Barbabietola G, Piga A, Mackie PH, Robson KJ, Camaschella C | title = A valine deletion of ferroportin 1: a common mutation in hemochromastosis type 4 | journal = Blood | volume = 100 | issue = 2 | pages = 733–4 |date=July 2002 | pmid = 12123233 | doi = 10.1182/blood-2002-03-0693 }}
* {{cite journal | vauthors = Roetto A, Merryweather-Clarke AT, Daraio F, Livesey K, Pointon JJ, Barbabietola G, Piga A, Mackie PH, Robson KJ, Camaschella C | title = A valine deletion of ferroportin 1: a common mutation in hemochromastosis type 4 | journal = Blood | volume = 100 | issue = 2 | pages = 733–4 | date = July 2002 | pmid = 12123233 | doi = 10.1182/blood-2002-03-0693 }}
{{refend}}
{{refend}}


==External links==
== External links ==
* {{MeshName|ferroportin1+protein}}
* {{MeshName|ferroportin1+protein}}


Latest revision as of 22:54, 25 December 2018

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Ferroportin-1, also known as solute carrier family 40 member 1 (SLC40A1) or iron-regulated transporter 1 (IREG1), is a protein that in humans is encoded by the SLC40A1 gene, and is part of the Ferroportin (Fpn) Family (TC# 2.A.100).[1] Ferroportin is a transmembrane protein that transports iron from the inside of a cell to the outside of the cell. After iron is absorbed into the cells of the intestine, ferroportin allows that iron to be transported out of those cells and into the bloodstream. Ferroportin is the only known iron exporter.[2]

Structure

Members of the FPN family consist of 400-800 amino acid residues,[3] with a highly conserved histidine at residue position 32 (H32), and exhibit 8-11 putative transmembrane segments (TMSs). When H32 is mutated, lower activity in its iron transport role is observed.[4] Ferroportin can also function as a manganese exporter.[5] Because ferroportin extrudes Fe2+ from the cell, ferroportin is presumed to function by cation (H+ or Na+) antiport.

Transport reaction

The transport reaction catalyzed by ferroportin is:

Fe2+/Mn2+ (in) + nH+ (out) ⇌ Fe2+/Mn2+ (out) + nH+ (in)

Tissue distribution

Ferroportin is found on the basolateral membranes of intestinal epithelia of mammals, including:[6][7]

Role in development

Ferroportin-1 plays an important role in neural tube closure and forebrain patterning.[8] Mouse embyros lacking the Scl40a1 gene are aborted before gastrulation occurs, suggesting that the Fpn1 protein encoded is necessary and essential for normal embryonic development.[6] Fpn1 is expressed in the syncytiotrophoblast cells in the placenta and visceral endoderm of mice at E7.5.[1][6] Further, several retrospective studies have noted an increased incidence of spina bifida occurring after low maternal intake of iron during embryonic and fetal development.[9][10]

A study examining the consequences of several different mutations of the Slc40a1 mouse gene suggested that several serious neural tube and patterning defects were produced as a result, including spina bifida, exencephaly, and forebrain truncations, among others.[8] Given the findings of studies to date, there appears to be significant evidence that intact iron transport mechanisms are critical to normal neural tube closure. Furthermore, other experiments have suggested that Fpn1 product and activity is required along the entire anterior-posterior axis of the animal to ensure proper closure of the neural tube.[8]

Role in fertility

It is known that ferroportin (SLC40A1) gene is expressed at a low level in infertile women. Its mRNA levels were discovered to be down-regulated in these women, specifically in granulosa cells. What's more, low expression of ferroportin is also associated with infertily when some features like age and smoking habits are considered. It is also important to mention that, not only is ferroportin down-regulated in granulosa cells, but also in cervical cells of infertile women, and that the association between infertility and low ferroportin levels in these cells can be seen, again, when mRNA ferroportin levels was adjusted by age and smoking status.[11]

Role in iron metabolism

Ferroportin is inhibited by hepcidin, which binds to ferroportin and internalizes it within the cell.[12] This results in the retention of iron within enterocytes, hepatocytes, and macrophages with a consequent reduction in iron levels within the blood serum. This is especially significant with enterocytes which, when shed at the end of their lifespan, results in significant iron loss. This is part of the mechanism that causes anaemia of chronic disease; hepcidin is released from the liver in response to inflammatory cytokines, namely interleukin-6, which results in an increased hepcidin concentration and a consequent decrease in plasma iron levels.[13]

Ferroportin expression is also regulated by the IRP regulatory mechanism. If the iron concentration is too low, the IRP concentration increases, thus inhibiting the ferroportin translation. The ferroportin translation is also regulated by the micro RNA miR-485-3p.[14]

Clinical significance

Mutations in the ferroportin gene are known to cause an autosomal dominant form of iron overload known as type IV haemochromatosis or Ferroportin Disease. The effects of the mutations are generally not severe but a spectrum of clinical outcomes are seen with different mutations. Ferroportin is also associated with African iron overload. Ferroportin and hepcidin are critical proteins for the regulation of systemic iron homeostasis.

References

  1. ↑ 1.0 1.1 Donovan A, Brownlie A, Zhou Y, Shepard J, Pratt SJ, Moynihan J, Paw BH, Drejer A, Barut B, Zapata A, Law TC, Brugnara C, Lux SE, Pinkus GS, Pinkus JL, Kingsley PD, Palis J, Fleming MD, Andrews NC, Zon LI (February 2000). "Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter". Nature. 403 (6771): 776–81. Bibcode:2000Natur.403..776D. doi:10.1038/35001596. PMID 10693807.
  2. ↑ Ward, DM; Kaplan, J (September 2012). "Ferroportin-mediated iron transport: expression and regulation". Biochimica et Biophysica Acta. 1823 (9): 1426–33. doi:10.1016/j.bbamcr.2012.03.004. PMC 3718258. PMID 22440327.
  3. ↑ "SLC11A3 iron transporter [Homo sapiens]". Protein - NCBI.
  4. ↑ Zohn IE, De Domenico I, Pollock A, Ward DM, Goodman JF, Liang X, Sanchez AJ, Niswander L, Kaplan J (May 2007). "The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease". Blood. 109 (10): 4174–80. doi:10.1182/blood-2007-01-066068. PMC 1885502. PMID 17289807.
  5. ↑ Madejczyk MS, Ballatori N (March 2012). "The iron transporter ferroportin can also function as a manganese exporter". Biochimica et Biophysica Acta. 1818 (3): 651–7. doi:10.1016/j.bbamem.2011.12.002. PMC 5695046. PMID 22178646.
  6. ↑ 6.0 6.1 6.2 Donovan A, Lima CA, Pinkus JL, Pinkus GS, Zon LI, Robine S, Andrews NC (March 2005). "The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis". Cell Metabolism. 1 (3): 191–200. doi:10.1016/j.cmet.2005.01.003. PMID 16054062.
  7. ↑ Delaby C, Pilard N, Puy H, Canonne-Hergaux F (April 2008). "Sequential regulation of ferroportin expression after erythrophagocytosis in murine macrophages: early mRNA induction by haem, followed by iron-dependent protein expression". The Biochemical Journal. 411 (1): 123–31. doi:10.1042/BJ20071474. PMID 18072938.
  8. ↑ 8.0 8.1 8.2 Mao J, McKean DM, Warrier S, Corbin JG, Niswander L, Zohn IE (September 2010). "The iron exporter ferroportin 1 is essential for development of the mouse embryo, forebrain patterning and neural tube closure". Development. 137 (18): 3079–88. doi:10.1242/dev.048744. PMC 2926957. PMID 20702562.
  9. ↑ Felkner MM, Suarez L, Brender J, Scaife B, Hendricks K (December 2005). "Iron status indicators in women with prior neural tube defect-affected pregnancies". Maternal and Child Health Journal. 9 (4): 421–8. doi:10.1007/s10995-005-0017-3. PMID 16315101.
  10. ↑ Groenen PM, van Rooij IA, Peer PG, Ocké MC, Zielhuis GA, Steegers-Theunissen RP (June 2004). "Low maternal dietary intakes of iron, magnesium, and niacin are associated with spina bifida in the offspring". The Journal of Nutrition. 134 (6): 1516–22. doi:10.1093/jn/134.6.1516. PMID 15173422.
  11. ↑ Moreno-Navarrete JM, López-Navarro E, Candenas L, Pinto F, Ortega FJ, Sabater-Masdeu M, et al.Ferroportin mRNA is down-regulated in granulosa and cervical cells from infertile women.Fertil Steril. 2017 Jan;107(1):236-242.
  12. ↑ Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J (December 2004). "Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization". Science. 306 (5704): 2090–3. Bibcode:2004Sci...306.2090N. doi:10.1126/science.1104742. PMID 15514116.
  13. ↑ Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, Ganz T (May 2004). "IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin". The Journal of Clinical Investigation. 113 (9): 1271–6. doi:10.1172/JCI20945. PMC 398432. PMID 15124018.
  14. ↑ Sangokoya C, Doss JF, Chi JT (April 2013). "Iron-responsive miR-485-3p regulates cellular iron homeostasis by targeting ferroportin". PLoS Genetics. 9 (4): e1003408. doi:10.1371/journal.pgen.1003408. PMC 3616902. PMID 23593016.

Further reading

  • Schimanski LM, Drakesmith H, Merryweather-Clarke AT, Viprakasit V, Edwards JP, Sweetland E, Bastin JM, Cowley D, Chinthammitr Y, Robson KJ, Townsend AR (May 2005). "In vitro functional analysis of human ferroportin (FPN) and hemochromatosis-associated FPN mutations". Blood. 105 (10): 4096–102. doi:10.1182/blood-2004-11-4502. PMID 15692071.
  • Pietrangelo A (2004). "The ferroportin disease". Blood Cells, Molecules & Diseases. 32 (1): 131–8. doi:10.1016/j.bcmd.2003.08.003. PMID 14757427.
  • Robson KJ, Merryweather-Clarke AT, Cadet E, Viprakasit V, Zaahl MG, Pointon JJ, Weatherall DJ, Rochette J (October 2004). "Recent advances in understanding haemochromatosis: a transition state". Journal of Medical Genetics. 41 (10): 721–30. doi:10.1136/jmg.2004.020644. PMC 1735598. PMID 15466004.
  • Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
  • Abboud S, Haile DJ (June 2000). "A novel mammalian iron-regulated protein involved in intracellular iron metabolism". The Journal of Biological Chemistry. 275 (26): 19906–12. doi:10.1074/jbc.M000713200. PMID 10747949.
  • Haile DJ (2000). "Assignment of Slc11a3 to mouse chromosome 1 band 1B and SLC11A3 to human chromosome 2q32 by in situ hybridization". Cytogenetics and Cell Genetics. 88 (3–4): 328–9. doi:10.1159/000015522. PMID 10828623.
  • McKie AT, Marciani P, Rolfs A, Brennan K, Wehr K, Barrow D, Miret S, Bomford A, Peters TJ, Farzaneh F, Hediger MA, Hentze MW, Simpson RJ (February 2000). "A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation". Molecular Cell. 5 (2): 299–309. doi:10.1016/S1097-2765(00)80425-6. PMID 10882071.
  • Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
  • Njajou OT, Vaessen N, Joosse M, Berghuis B, van Dongen JW, Breuning MH, Snijders PJ, Rutten WP, Sandkuijl LA, Oostra BA, van Duijn CM, Heutink P (July 2001). "A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis". Nature Genetics. 28 (3): 213–4. doi:10.1038/90038. PMID 11431687.
  • Montosi G, Donovan A, Totaro A, Garuti C, Pignatti E, Cassanelli S, Trenor CC, Gasparini P, Andrews NC, Pietrangelo A (August 2001). "Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene". The Journal of Clinical Investigation. 108 (4): 619–23. doi:10.1172/JCI13468. PMC 209405. PMID 11518736.
  • Press RD (December 2001). "Hemochromatosis caused by mutations in the iron-regulatory proteins ferroportin and H ferritin". Molecular Diagnosis. 6 (4): 347–349. doi:10.1054/modi.2001.0060347. PMID 11774199.
  • Lee PL, Gelbart T, West C, Halloran C, Felitti V, Beutler E (2001). "A study of genes that may modulate the expression of hereditary hemochromatosis: transferrin receptor-1, ferroportin, ceruloplasmin, ferritin light and heavy chains, iron regulatory proteins (IRP)-1 and -2, and hepcidin". Blood Cells, Molecules & Diseases. 27 (5): 783–802. doi:10.1006/bcmd.2001.0445. PMID 11783942.
  • Rolfs A, Bonkovsky HL, Kohlroser JG, McNeal K, Sharma A, Berger UV, Hediger MA (April 2002). "Intestinal expression of genes involved in iron absorption in humans". American Journal of Physiology. Gastrointestinal and Liver Physiology. 282 (4): G598–607. doi:10.1152/ajpgi.00371.2001. PMID 11897618.
  • Thomas C, Oates PS (April 2002). "IEC-6 cells are an appropriate model of intestinal iron absorption in rats". The Journal of Nutrition. 132 (4): 680–7. doi:10.1093/jn/132.4.680. PMID 11925460.
  • Wallace DF, Pedersen P, Dixon JL, Stephenson P, Searle JW, Powell LW, Subramaniam VN (July 2002). "Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis". Blood. 100 (2): 692–4. doi:10.1182/blood.v100.2.692. PMID 12091366.
  • Devalia V, Carter K, Walker AP, Perkins SJ, Worwood M, May A, Dooley JS (July 2002). "Autosomal dominant reticuloendothelial iron overload associated with a 3-base pair deletion in the ferroportin 1 gene (SLC11A3)". Blood. 100 (2): 695–7. doi:10.1182/blood-2001-11-0132. PMID 12091367.
  • Roetto A, Merryweather-Clarke AT, Daraio F, Livesey K, Pointon JJ, Barbabietola G, Piga A, Mackie PH, Robson KJ, Camaschella C (July 2002). "A valine deletion of ferroportin 1: a common mutation in hemochromastosis type 4". Blood. 100 (2): 733–4. doi:10.1182/blood-2002-03-0693. PMID 12123233.

External links

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