S40A1_HUMAN
ID S40A1_HUMAN Reviewed; 571 AA.
AC Q9NP59; Q6FI62; Q7Z4F8; Q8IVB2; Q9NRL0;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Solute carrier family 40 member 1;
DE AltName: Full=Ferroportin-1;
DE AltName: Full=Iron-regulated transporter 1;
GN Name=SLC40A1; Synonyms=FPN1, IREG1, SLC11A3; ORFNames=MSTP079;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT HFE4 ASP-77.
RX PubMed=10747949; DOI=10.1074/jbc.m000713200;
RA Abboud S., Haile D.J.;
RT "A novel mammalian iron-regulated protein involved in intracellular iron
RT metabolism.";
RL J. Biol. Chem. 275:19906-19912(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
RX PubMed=10882071; DOI=10.1016/s1097-2765(00)80425-6;
RA McKie A.T., Marciani P., Rolfs A., Brennan K., Wehr K., Barrow D.,
RA Miret S., Bomford A., Peters T.J., Farzaneh F., Hediger M.A., Hentze M.W.,
RA Simpson R.J.;
RT "A novel duodenal iron-regulated transporter, IREG1, implicated in the
RT basolateral transfer of iron to the circulation.";
RL Mol. Cell 5:299-309(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=10693807; DOI=10.1038/35001596;
RA Donovan A., Brownlie A., Zhou Y., Shepard J., Pratt S.J., Moynihan J.,
RA Paw B.H., Drejer A., Barut B., Zapata A., Law T.C., Brugnara C.,
RA Lux S.E. IV, Pinkus G.S., Pinkus J.L., Kingsley P.D., Palis J.,
RA Fleming M.D., Andrews N.C., Zon L.I.;
RT "Positional cloning of zebrafish ferroportin1 identifies a conserved
RT vertebrate iron exporter.";
RL Nature 403:776-781(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Blood, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-133.
RC TISSUE=Aorta;
RA Hui R.T., Zhao B., Sheng H., Qin B.M., Liu Y.Q., Liu B., Wang X.Y.,
RA Xu H.S., Zhang Q., Tong Y.K., Song L., Ji X.J., Liu B.H., Lu H., Chen J.Z.,
RA Cai M.Q., Zheng W.Y., Teng C.Y., Liu Q., Yu L.T., Lin J., Gong Q.,
RA Zhang A.M., Gao R.L.;
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-6; 16-129 AND 255-316, AND VARIANT
RP HFE4 VAL-270.
RX PubMed=15338274; DOI=10.1007/s00439-004-1166-y;
RA Zaahl M.G., Merryweather-Clarke A.T., Kotze M.J., van der Merwe S.,
RA Warnich L., Robson K.J.H.;
RT "Analysis of genes implicated in iron regulation in individuals presenting
RT with primary iron overload.";
RL Hum. Genet. 115:409-417(2004).
RN [12]
RP FUNCTION, TRANSPORTER ACTIVITY, MUTAGENESIS OF ALA-77; LEU-170 AND GLY-490,
RP AND SUBCELLULAR LOCATION.
RX PubMed=15692071; DOI=10.1182/blood-2004-11-4502;
RA Schimanski L.M., Drakesmith H., Merryweather-Clarke A.T., Viprakasit V.,
RA Edwards J.P., Sweetland E., Bastin J.M., Cowley D., Chinthammitr Y.,
RA Robson K.J., Townsend A.R.;
RT "In vitro functional analysis of human ferroportin (FPN) and
RT hemochromatosis-associated FPN mutations.";
RL Blood 105:4096-4102(2005).
RN [13]
RP FUNCTION, INTERACTION WITH HAMP, UBIQUITINATION, AND MUTAGENESIS OF
RP LYS-236; LYS-240; LYS-253 AND CYS-326.
RX PubMed=22682227; DOI=10.1016/j.cmet.2012.03.018;
RA Qiao B., Sugianto P., Fung E., Del-Castillo-Rueda A., Moran-Jimenez M.J.,
RA Ganz T., Nemeth E.;
RT "Hepcidin-induced endocytosis of ferroportin is dependent on ferroportin
RT ubiquitination.";
RL Cell Metab. 15:918-924(2012).
RN [14]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, IDENTIFICATION IN A COMPLEX WITH
RP STOM, AND SUBUNIT.
RX PubMed=23219802; DOI=10.1016/j.bbamem.2012.11.030;
RA Rungaldier S., Oberwagner W., Salzer U., Csaszar E., Prohaska R.;
RT "Stomatin interacts with GLUT1/SLC2A1, band 3/SLC4A1, and aquaporin-1 in
RT human erythrocyte membrane domains.";
RL Biochim. Biophys. Acta 1828:956-966(2013).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH HAMP, AND MUTAGENESIS OF
RP ASN-144; LYS-240; CYS-326; TYR-501 AND ASP-504.
RX PubMed=29237594; DOI=10.1182/blood-2017-05-786590;
RA Aschemeyer S., Qiao B., Stefanova D., Valore E.V., Sek A.C., Ruwe T.A.,
RA Vieth K.R., Jung G., Casu C., Rivella S., Jormakka M., Mackenzie B.,
RA Ganz T., Nemeth E.;
RT "Structure-function analysis of ferroportin defines the binding site and an
RT alternative mechanism of action of hepcidin.";
RL Blood 131:899-910(2018).
RN [16] {ECO:0007744|PDB:6W4S, ECO:0007744|PDB:6WBV}
RP STRUCTURE BY ELECTRON MICROSCOPY (2.50 ANGSTROMS) IN COMPLEX WITH COBALT,
RP INTERACTION WITH HAMP, ACTIVITY REGULATION, AND FUNCTION.
RX PubMed=32814342; DOI=10.1038/s41586-020-2668-z;
RA Billesbolle C.B., Azumaya C.M., Kretsch R.C., Powers A.S., Gonen S.,
RA Schneider S., Arvedson T., Dror R.O., Cheng Y., Manglik A.;
RT "Structure of hepcidin-bound ferroportin reveals iron homeostatic
RT mechanisms.";
RL Nature 586:807-811(2020).
RN [17]
RP VARIANT HFE4 ASP-77.
RX PubMed=11518736; DOI=10.1172/jci200113468;
RA Montosi G., Donovan A., Totaro A., Garuti C., Pignatti E., Cassanelli S.,
RA Trenor C.C., Gasparini P., Andrews N.C., Pietrangelo A.;
RT "Autosomal-dominant hemochromatosis is associated with a mutation in the
RT ferroportin (SLC11A3) gene.";
RL J. Clin. Invest. 108:619-623(2001).
RN [18]
RP VARIANT HFE4 HIS-144.
RX PubMed=11431687; DOI=10.1038/90038;
RA Njajou O.T., Vaessen N., Joosse M., Berghuis B., van Dongen J.W.F.,
RA Breuning M.H., Snijders P.J.L.M., Rutten W.P.F., Sandkuijl L.A.,
RA Oostra B.A., van Duijn C.M., Heutink P.;
RT "A mutation in SLC11A3 is associated with autosomal dominant
RT hemochromatosis.";
RL Nat. Genet. 28:213-214(2001).
RN [19]
RP VARIANT HFE4 VAL-162 DEL.
RX PubMed=12091366; DOI=10.1182/blood.v100.2.692;
RA Wallace D.F., Pedersen P., Dixon J.L., Stephenson P., Searle J.W.,
RA Powell L.W., Subramaniam V.N.;
RT "Novel mutation in ferroportin1 is associated with autosomal dominant
RT hemochromatosis.";
RL Blood 100:692-694(2002).
RN [20]
RP VARIANT HFE4 VAL-162 DEL.
RX PubMed=12091367; DOI=10.1182/blood-2001-11-0132;
RA Devalia V., Carter K., Walker A.P., Perkins S.J., Worwood M., May A.,
RA Dooley J.S.;
RT "Autosomal dominant reticuloendothelial iron overload associated with a 3-
RT base pair deletion in the ferroportin 1 gene (SLC11A3).";
RL Blood 100:695-697(2002).
RN [21]
RP VARIANT HFE4 VAL-162 DEL.
RX PubMed=12123233; DOI=10.1182/blood-2002-03-0693;
RA Roetto A., Merryweather-Clarke A.T., Daraio F., Livesey K., Pointon J.J.,
RA Barbabietola G., Piga A., Mackie P.H., Robson K.J.H., Camaschella C.;
RT "A valine deletion of ferroportin 1: a common mutation in hemochromastosis
RT type 4.";
RL Blood 100:733-734(2002).
RN [22]
RP VARIANT HFE4 VAL-162 DEL.
RX PubMed=12406098; DOI=10.1046/j.1365-2141.2002.03946.x;
RA Cazzola M., Cremonesi L., Papaioannou M., Soriani N., Kioumi A.,
RA Charalambidou A., Paroni R., Romtsou K., Levi S., Ferrari M., Arosio P.,
RA Christakis J.;
RT "Genetic hyperferritinaemia and reticuloendothelial iron overload
RT associated with a three base pair deletion in the coding region of the
RT ferroportin gene (SLC11A3).";
RL Br. J. Haematol. 119:539-546(2002).
RN [23]
RP VARIANTS HFE4 GLY-157; HIS-182 AND VAL-323.
RX PubMed=12730114; DOI=10.1182/blood-2003-02-0439;
RA Hetet G., Devaux I., Soufir N., Grandchamp B., Beaumont C.;
RT "Molecular analyses of patients with hyperferritinemia and normal serum
RT iron values reveal both L ferritin IRE and 3 new ferroportin (SLC11A3)
RT mutations.";
RL Blood 102:1904-1910(2003).
RN [24]
RP VARIANT HIS-248.
RX PubMed=14636642; DOI=10.1016/s1079-9796(03)00164-5;
RA Gordeuk V.R., Caleffi A., Corradini E., Ferrara F., Jones R.A., Castro O.,
RA Onyekwere O., Kittles R., Pignatti E., Montosi G., Garuti C.,
RA Gangaidzo I.T., Gomo Z.A.R., Moyo V.M., Rouault T.A., MacPhail P.,
RA Pietrangelo A.;
RT "Iron overload in Africans and African-Americans and a common mutation in
RT the SCL40A1 (ferroportin 1) gene.";
RL Blood Cells Mol. Dis. 31:299-304(2003).
RN [25]
RP VARIANT HFE4 THR-144.
RX PubMed=12865285; DOI=10.1136/gut.52.8.1215;
RA Arden K.E., Wallace D.F., Dixon J.L., Summerville L., Searle J.W.,
RA Anderson G.J., Ramm G.A., Powell L.W., Subramaniam V.N.;
RT "A novel mutation in ferroportin1 is associated with haemochromatosis in a
RT Solomon Islands patient.";
RL Gut 52:1215-1217(2003).
RN [26]
RP VARIANT HFE4 ASN-64.
RX PubMed=12857562;
RA Rivard S.R., Lanzara C., Grimard D., Carella M., Simard H., Ficarella R.,
RA Simard R., D'Adamo A.P., De Braekeleer M., Gasparini P.;
RT "Autosomal dominant reticuloendothelial iron overload (HFE type 4) due to a
RT new missense mutation in the FERROPORTIN 1 gene (SLC11A3) in a large
RT French-Canadian family.";
RL Haematologica 88:824-826(2003).
RN [27]
RP VARIANT IRON OVERLOAD ASP-490.
RX PubMed=12873829; DOI=10.1016/s0168-8278(03)00148-x;
RA Jouanolle A.-M., Douabin-Gicquel V., Halimi C., Loreal O., Fergelot P.,
RA Delacour T., de Lajarte-Thirouard A.-S., Turlin B., Le Gall J.-Y.,
RA Cadet E., Rochette J., David V., Brissot P.;
RT "Novel mutation in ferroportin 1 gene is associated with autosomal dominant
RT iron overload.";
RL J. Hepatol. 39:286-289(2003).
RN [28]
RP VARIANTS IRON OVERLOAD SER-80 AND ILE-174.
RX PubMed=14757427; DOI=10.1016/j.bcmd.2003.08.003;
RA Pietrangelo A.;
RT "The ferroportin disease.";
RL Blood Cells Mol. Dis. 32:131-138(2004).
RN [29]
RP VARIANTS HFE4 ASP-144 AND VAL-270, AND VARIANT IRON OVERLOAD TYR-326.
RX PubMed=15466004; DOI=10.1136/jmg.2004.020644;
RA Robson K.J.H., Merryweather-Clarke A.T., Cadet E., Viprakasit V.,
RA Zaahl M.G., Pointon J.J., Weatherall D.J., Rochette J.;
RT "Recent advances in understanding haemochromatosis: a transition state.";
RL J. Med. Genet. 41:721-730(2004).
RN [30]
RP ERRATUM OF PUBMED:15466004.
RA Robson K.J.H., Merryweather-Clarke A.T., Cadet E., Viprakasit V.,
RA Zaahl M.G., Pointon J.J., Weatherall D.J., Rochette J.;
RL J. Med. Genet. 41:959-959(2004).
RN [31]
RP VARIANTS HFE4 VAL-80; VAL-181 AND ASP-267.
RX PubMed=16351644; DOI=10.1111/j.1365-2141.2005.05815.x;
RA Cremonesi L., Forni G.L., Soriani N., Lamagna M., Fermo I., Daraio F.,
RA Galli A., Pietra D., Malcovati L., Ferrari M., Camaschella C., Cazzola M.;
RT "Genetic and clinical heterogeneity of ferroportin disease.";
RL Br. J. Haematol. 131:663-670(2005).
RN [32]
RP ERRATUM OF PUBMED:16351644.
RA Cremonesi L., Forni G.L., Soriani N., Lamagna M., Fermo I., Daraio F.,
RA Galli A., Pietra D., Malcovati L., Ferrari M., Camaschella C., Cazzola M.;
RL Br. J. Haematol. 132:806-806(2006).
CC -!- FUNCTION: Major iron transporter that plays a key role in balancing
CC cellular and systemic iron levels (PubMed:29237594, PubMed:22682227,
CC PubMed:15692071). Transports iron from intestinal, splenic, and hepatic
CC cells into the blood to provide iron to other tissues (By similarity).
CC Controls therefore dietary iron uptake, iron recycling by macrophages,
CC and release of iron stores in hepatocytes (By similarity). When iron is
CC in excess, hepcidin/HAMP levels increase resulting in a degradation of
CC ferroportin/SLC40A1 limiting the iron efflux to plasma
CC (PubMed:22682227, PubMed:29237594, PubMed:32814342).
CC {ECO:0000250|UniProtKB:Q9JHI9, ECO:0000269|PubMed:15692071,
CC ECO:0000269|PubMed:22682227, ECO:0000269|PubMed:29237594,
CC ECO:0000269|PubMed:32814342}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Fe(2+)(in) = Fe(2+)(out); Xref=Rhea:RHEA:28486,
CC ChEBI:CHEBI:29033; Evidence={ECO:0000269|PubMed:15692071};
CC -!- ACTIVITY REGULATION: During elevated serum iron levels, liver-derived
CC hepcidin/HAMP negatively regulates cell surface ferroportin/SLC40A1 by
CC inducing its ubiquitination, internalization, and degradation. Indeed,
CC hepcidin/HAMP affinity towards ferroportin/SLC40A1 increases by 80-fold
CC in the presence of iron. {ECO:0000269|PubMed:32814342}.
CC -!- SUBUNIT: Identified in a complex with STOM (PubMed:23219802). Interacts
CC with HAMP; this interaction promotes SLC40A1 rapid ubiquitination
CC (PubMed:22682227, PubMed:29237594). {ECO:0000269|PubMed:22682227,
CC ECO:0000269|PubMed:23219802, ECO:0000269|PubMed:29237594}.
CC -!- INTERACTION:
CC Q9NP59; P05067: APP; NbExp=5; IntAct=EBI-725153, EBI-77613;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10882071,
CC ECO:0000269|PubMed:15692071, ECO:0000269|PubMed:23219802,
CC ECO:0000269|PubMed:29237594}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:10882071, ECO:0000269|PubMed:23219802}.
CC Note=Localized to the basolateral membrane of polarized epithelial
CC cells.
CC -!- TISSUE SPECIFICITY: Detected in erythrocytes (at protein level).
CC Expressed in placenta, intestine, muscle and spleen.
CC {ECO:0000269|PubMed:10747949, ECO:0000269|PubMed:23219802}.
CC -!- PTM: Polyubiquitinated by RNF217; leading to proteasomal degradation.
CC Ubiquitination is necessary for its internalization by hepcidin/HAMP
CC (PubMed:22682227). {ECO:0000250|UniProtKB:Q9JHI9,
CC ECO:0000269|PubMed:22682227}.
CC -!- DISEASE: Hemochromatosis 4 (HFE4) [MIM:606069]: A disorder of iron
CC metabolism characterized by iron overload. Excess iron is deposited in
CC a variety of organs leading to their failure, and resulting in serious
CC illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy,
CC arthritis, and hypogonadotropic hypogonadism. Severe effects of the
CC disease usually do not appear until after decades of progressive iron
CC loading. {ECO:0000269|PubMed:10747949, ECO:0000269|PubMed:11431687,
CC ECO:0000269|PubMed:11518736, ECO:0000269|PubMed:12091366,
CC ECO:0000269|PubMed:12091367, ECO:0000269|PubMed:12123233,
CC ECO:0000269|PubMed:12406098, ECO:0000269|PubMed:12730114,
CC ECO:0000269|PubMed:12857562, ECO:0000269|PubMed:12865285,
CC ECO:0000269|PubMed:15338274, ECO:0000269|PubMed:15466004,
CC ECO:0000269|PubMed:16351644}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ferroportin (FP) (TC 2.A.100) family. SLC40A
CC subfamily. {ECO:0000305}.
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DR EMBL; AF215636; AAF80986.1; -; mRNA.
DR EMBL; AF231121; AAF44330.1; -; mRNA.
DR EMBL; AF226614; AAF36697.1; -; mRNA.
DR EMBL; AL136944; CAB66878.1; -; mRNA.
DR EMBL; AK314827; BAG37348.1; -; mRNA.
DR EMBL; CR533564; CAG38595.1; -; mRNA.
DR EMBL; AC013439; AAX93082.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX10902.1; -; Genomic_DNA.
DR EMBL; BC035893; AAH35893.1; -; mRNA.
DR EMBL; BC037733; AAH37733.1; -; mRNA.
DR EMBL; AF171087; AAQ13603.1; -; mRNA.
DR EMBL; AJ604512; CAE53170.1; -; Genomic_DNA.
DR EMBL; AJ609539; CAE81347.1; -; Genomic_DNA.
DR EMBL; AJ609540; CAE81348.1; -; Genomic_DNA.
DR EMBL; AJ616848; CAE83578.1; -; Genomic_DNA.
DR EMBL; AJ616847; CAE83578.1; JOINED; Genomic_DNA.
DR CCDS; CCDS2299.1; -.
DR RefSeq; NP_055400.1; NM_014585.5.
DR PDB; 6W4S; EM; 3.20 A; F=1-571.
DR PDB; 6WBV; EM; 2.50 A; A=1-571.
DR PDBsum; 6W4S; -.
DR PDBsum; 6WBV; -.
DR AlphaFoldDB; Q9NP59; -.
DR SMR; Q9NP59; -.
DR BioGRID; 119033; 5.
DR IntAct; Q9NP59; 8.
DR MINT; Q9NP59; -.
DR STRING; 9606.ENSP00000261024; -.
DR BindingDB; Q9NP59; -.
DR ChEMBL; CHEMBL3392948; -.
DR DrugBank; DB13257; Ferrous sulfate anhydrous.
DR DrugBank; DB14520; Tetraferric tricitrate decahydrate.
DR TCDB; 2.A.100.1.4; the ferroportin (fpn) family.
DR GlyGen; Q9NP59; 3 sites.
DR iPTMnet; Q9NP59; -.
DR PhosphoSitePlus; Q9NP59; -.
DR BioMuta; SLC40A1; -.
DR DMDM; 48428687; -.
DR jPOST; Q9NP59; -.
DR MassIVE; Q9NP59; -.
DR PaxDb; Q9NP59; -.
DR PeptideAtlas; Q9NP59; -.
DR PRIDE; Q9NP59; -.
DR ProteomicsDB; 81890; -.
DR ABCD; Q9NP59; 9 sequenced antibodies.
DR Antibodypedia; 34022; 373 antibodies from 33 providers.
DR DNASU; 30061; -.
DR Ensembl; ENST00000261024.7; ENSP00000261024.3; ENSG00000138449.11.
DR GeneID; 30061; -.
DR KEGG; hsa:30061; -.
DR MANE-Select; ENST00000261024.7; ENSP00000261024.3; NM_014585.6; NP_055400.1.
DR UCSC; uc002uqp.5; human.
DR CTD; 30061; -.
DR DisGeNET; 30061; -.
DR GeneCards; SLC40A1; -.
DR HGNC; HGNC:10909; SLC40A1.
DR HPA; ENSG00000138449; Low tissue specificity.
DR MalaCards; SLC40A1; -.
DR MIM; 604653; gene.
DR MIM; 606069; phenotype.
DR neXtProt; NX_Q9NP59; -.
DR OpenTargets; ENSG00000138449; -.
DR Orphanet; 139491; Hemochromatosis type 4.
DR PharmGKB; PA35805; -.
DR VEuPathDB; HostDB:ENSG00000138449; -.
DR eggNOG; KOG2601; Eukaryota.
DR GeneTree; ENSGT00390000015143; -.
DR HOGENOM; CLU_020370_1_1_1; -.
DR InParanoid; Q9NP59; -.
DR OMA; NVHELEH; -.
DR OrthoDB; 334057at2759; -.
DR PhylomeDB; Q9NP59; -.
DR TreeFam; TF313463; -.
DR PathwayCommons; Q9NP59; -.
DR Reactome; R-HSA-425410; Metal ion SLC transporters.
DR Reactome; R-HSA-5619049; Defective SLC40A1 causes hemochromatosis 4 (HFE4) (macrophages).
DR Reactome; R-HSA-5619060; Defective CP causes aceruloplasminemia (ACERULOP).
DR Reactome; R-HSA-5655799; Defective SLC40A1 causes hemochromatosis 4 (HFE4) (duodenum).
DR Reactome; R-HSA-917937; Iron uptake and transport.
DR SignaLink; Q9NP59; -.
DR BioGRID-ORCS; 30061; 15 hits in 1081 CRISPR screens.
DR ChiTaRS; SLC40A1; human.
DR GeneWiki; Ferroportin; -.
DR GenomeRNAi; 30061; -.
DR Pharos; Q9NP59; Tchem.
DR PRO; PR:Q9NP59; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9NP59; protein.
DR Bgee; ENSG00000138449; Expressed in pancreatic ductal cell and 186 other tissues.
DR ExpressionAtlas; Q9NP59; baseline and differential.
DR Genevisible; Q9NP59; HS.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0005887; C:integral component of plasma membrane; IC:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0008021; C:synaptic vesicle; IEA:Ensembl.
DR GO; GO:0015093; F:ferrous iron transmembrane transporter activity; ISS:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0005381; F:iron ion transmembrane transporter activity; IMP:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017046; F:peptide hormone binding; IPI:BHF-UCL.
DR GO; GO:0006915; P:apoptotic process; IEA:Ensembl.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IMP:BHF-UCL.
DR GO; GO:0003158; P:endothelium development; IEA:Ensembl.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:1903988; P:iron ion export across plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0055072; P:iron ion homeostasis; IBA:GO_Central.
DR GO; GO:0034755; P:iron ion transmembrane transport; IMP:BHF-UCL.
DR GO; GO:0002260; P:lymphocyte homeostasis; IEA:Ensembl.
DR GO; GO:0060586; P:multicellular organismal iron ion homeostasis; ISS:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0034395; P:regulation of transcription from RNA polymerase II promoter in response to iron; IEA:Ensembl.
DR GO; GO:0060345; P:spleen trabecula formation; IEA:Ensembl.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR CDD; cd17480; MFS_SLC40A1_like; 1.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR009716; Ferroportin-1.
DR InterPro; IPR036259; MFS_trans_sf.
DR PANTHER; PTHR11660; PTHR11660; 1.
DR Pfam; PF06963; FPN1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disease variant; Glycoprotein; Ion transport;
KW Iron; Iron transport; Membrane; Metal-binding; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport; Ubl conjugation.
FT CHAIN 1..571
FT /note="Solute carrier family 40 member 1"
FT /id="PRO_0000191310"
FT TOPO_DOM 1..23
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:32814342"
FT TRANSMEM 24..53
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:32814342,
FT ECO:0007744|PDB:6W4S"
FT TOPO_DOM 54..57
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:32814342"
FT TRANSMEM 58..84
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:32814342,
FT ECO:0007744|PDB:6W4S"
FT TOPO_DOM 85..87
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:32814342"
FT TRANSMEM 88..118
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:32814342,
FT ECO:0007744|PDB:6W4S"
FT TOPO_DOM 119..126
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:32814342"
FT TRANSMEM 127..162
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:32814342,
FT ECO:0007744|PDB:6W4S"
FT TOPO_DOM 163..164
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:32814342"
FT TRANSMEM 165..195
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:32814342,
FT ECO:0007744|PDB:6W4S"
FT TOPO_DOM 196..202
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:32814342"
FT TRANSMEM 203..229
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:32814342,
FT ECO:0007744|PDB:6W4S"
FT TOPO_DOM 230..306
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:32814342"
FT TRANSMEM 307..333
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:32814342,
FT ECO:0007744|PDB:6W4S"
FT TOPO_DOM 334..338
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:32814342"
FT TRANSMEM 339..366
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:32814342,
FT ECO:0007744|PDB:6W4S"
FT TOPO_DOM 367..368
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:32814342"
FT TRANSMEM 369..391
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:32814342,
FT ECO:0007744|PDB:6W4S"
FT TOPO_DOM 392..453
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:32814342"
FT TRANSMEM 454..483
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:32814342,
FT ECO:0007744|PDB:6W4S"
FT TOPO_DOM 484..488
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:32814342"
FT TRANSMEM 489..513
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:32814342,
FT ECO:0007744|PDB:6W4S"
FT TOPO_DOM 514..516
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:32814342"
FT TRANSMEM 517..542
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:32814342,
FT ECO:0007744|PDB:6W4S"
FT TOPO_DOM 543..571
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:32814342"
FT BINDING 39
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:32814342"
FT BINDING 43
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:32814342"
FT BINDING 326
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:32814342"
FT BINDING 507
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:32814342"
FT CARBOHYD 434
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 64
FT /note="Y -> N (in HFE4; dbSNP:rs1285653301)"
FT /evidence="ECO:0000269|PubMed:12857562"
FT /id="VAR_030057"
FT VARIANT 77
FT /note="A -> D (in HFE4; dbSNP:rs28939076)"
FT /evidence="ECO:0000269|PubMed:10747949,
FT ECO:0000269|PubMed:11518736"
FT /id="VAR_022594"
FT VARIANT 80
FT /note="G -> S (in iron overload; dbSNP:rs978427853)"
FT /evidence="ECO:0000269|PubMed:14757427"
FT /id="VAR_030058"
FT VARIANT 80
FT /note="G -> V (in HFE4; dbSNP:rs104893673)"
FT /evidence="ECO:0000269|PubMed:16351644"
FT /id="VAR_030059"
FT VARIANT 144
FT /note="N -> D (in HFE4; dbSNP:rs104893662)"
FT /evidence="ECO:0000269|PubMed:15466004"
FT /id="VAR_030060"
FT VARIANT 144
FT /note="N -> H (in HFE4; dbSNP:rs104893662)"
FT /evidence="ECO:0000269|PubMed:11431687"
FT /id="VAR_022595"
FT VARIANT 144
FT /note="N -> T (in HFE4; dbSNP:rs1434101655)"
FT /evidence="ECO:0000269|PubMed:12865285"
FT /id="VAR_030061"
FT VARIANT 157
FT /note="D -> G (in HFE4; dbSNP:rs104893663)"
FT /evidence="ECO:0000269|PubMed:12730114"
FT /id="VAR_022596"
FT VARIANT 162
FT /note="Missing (in HFE4)"
FT /evidence="ECO:0000269|PubMed:12091366,
FT ECO:0000269|PubMed:12091367, ECO:0000269|PubMed:12123233,
FT ECO:0000269|PubMed:12406098"
FT /id="VAR_022597"
FT VARIANT 174
FT /note="N -> I (in iron overload; dbSNP:rs1397119020)"
FT /evidence="ECO:0000269|PubMed:14757427"
FT /id="VAR_030062"
FT VARIANT 181
FT /note="D -> V (in HFE4; dbSNP:rs104893672)"
FT /evidence="ECO:0000269|PubMed:16351644"
FT /id="VAR_030063"
FT VARIANT 182
FT /note="Q -> H (in HFE4; dbSNP:rs104893670)"
FT /evidence="ECO:0000269|PubMed:12730114"
FT /id="VAR_022598"
FT VARIANT 248
FT /note="Q -> H (associated with mild anemia and a tendency
FT to iron loading; dbSNP:rs11568350)"
FT /evidence="ECO:0000269|PubMed:14636642"
FT /id="VAR_020295"
FT VARIANT 267
FT /note="G -> D (in HFE4; dbSNP:rs104893664)"
FT /evidence="ECO:0000269|PubMed:16351644"
FT /id="VAR_030064"
FT VARIANT 270
FT /note="D -> V (in HFE4; dbSNP:rs368420430)"
FT /evidence="ECO:0000269|PubMed:15338274,
FT ECO:0000269|PubMed:15466004"
FT /id="VAR_030065"
FT VARIANT 323
FT /note="G -> V (in HFE4; dbSNP:rs104893671)"
FT /evidence="ECO:0000269|PubMed:12730114"
FT /id="VAR_022599"
FT VARIANT 326
FT /note="C -> Y (in iron overload)"
FT /evidence="ECO:0000269|PubMed:15466004"
FT /id="VAR_030066"
FT VARIANT 432
FT /note="M -> V (in dbSNP:rs11568355)"
FT /id="VAR_020296"
FT VARIANT 443
FT /note="P -> L (in dbSNP:rs45606432)"
FT /id="VAR_029299"
FT VARIANT 490
FT /note="G -> D (in iron overload; dbSNP:rs1060501102)"
FT /evidence="ECO:0000269|PubMed:12873829"
FT /id="VAR_030067"
FT VARIANT 561
FT /note="R -> G (in dbSNP:rs11568346)"
FT /id="VAR_018980"
FT MUTAGEN 77
FT /note="A->D: Loss of iron export function."
FT /evidence="ECO:0000269|PubMed:15692071"
FT MUTAGEN 144
FT /note="N->D: Complete loss of HAMP-binding."
FT /evidence="ECO:0000269|PubMed:29237594"
FT MUTAGEN 170
FT /note="L->F: Loss of iron export function."
FT /evidence="ECO:0000269|PubMed:15692071"
FT MUTAGEN 236
FT /note="K->R: No loss of ubiquitination; when associated
FT with R-253."
FT /evidence="ECO:0000269|PubMed:22682227"
FT MUTAGEN 240
FT /note="K->E: Loss of HAMP-induced endocytosis."
FT /evidence="ECO:0000269|PubMed:22682227,
FT ECO:0000269|PubMed:29237594"
FT MUTAGEN 253
FT /note="K->R: No loss of ubiquitination; when associated
FT with R-236."
FT /evidence="ECO:0000269|PubMed:22682227"
FT MUTAGEN 326
FT /note="C->S: Complete loss of HAMP-dependent
FT ubiquitination."
FT /evidence="ECO:0000269|PubMed:22682227"
FT MUTAGEN 490
FT /note="G->D: Loss of iron export function."
FT /evidence="ECO:0000269|PubMed:15692071"
FT MUTAGEN 501
FT /note="Y->C: About 90% loss of HAMP binding."
FT /evidence="ECO:0000269|PubMed:29237594"
FT MUTAGEN 504
FT /note="D->N: About 95% loss of HAMP binding."
FT /evidence="ECO:0000269|PubMed:29237594"
FT CONFLICT 130..133
FT /note="TSCY -> VSSQ (in Ref. 10; AAQ13603)"
FT /evidence="ECO:0000305"
FT CONFLICT 324
FT /note="F -> S (in Ref. 9; AAH35893)"
FT /evidence="ECO:0000305"
FT CONFLICT 430..431
FT /note="IY -> RD (in Ref. 1; AAF80986)"
FT /evidence="ECO:0000305"
FT HELIX 17..20
FT /evidence="ECO:0007829|PDB:6WBV"
FT HELIX 24..53
FT /evidence="ECO:0007829|PDB:6WBV"
FT TURN 54..56
FT /evidence="ECO:0007829|PDB:6WBV"
FT HELIX 59..85
FT /evidence="ECO:0007829|PDB:6WBV"
FT HELIX 88..115
FT /evidence="ECO:0007829|PDB:6WBV"
FT HELIX 117..122
FT /evidence="ECO:0007829|PDB:6WBV"
FT HELIX 126..155
FT /evidence="ECO:0007829|PDB:6WBV"
FT HELIX 158..162
FT /evidence="ECO:0007829|PDB:6WBV"
FT HELIX 167..198
FT /evidence="ECO:0007829|PDB:6WBV"
FT HELIX 201..229
FT /evidence="ECO:0007829|PDB:6WBV"
FT HELIX 231..234
FT /evidence="ECO:0007829|PDB:6WBV"
FT HELIX 290..303
FT /evidence="ECO:0007829|PDB:6WBV"
FT HELIX 308..316
FT /evidence="ECO:0007829|PDB:6WBV"
FT TURN 324..327
FT /evidence="ECO:0007829|PDB:6WBV"
FT HELIX 328..334
FT /evidence="ECO:0007829|PDB:6WBV"
FT HELIX 339..366
FT /evidence="ECO:0007829|PDB:6WBV"
FT HELIX 369..390
FT /evidence="ECO:0007829|PDB:6WBV"
FT HELIX 453..483
FT /evidence="ECO:0007829|PDB:6WBV"
FT HELIX 486..488
FT /evidence="ECO:0007829|PDB:6WBV"
FT HELIX 489..513
FT /evidence="ECO:0007829|PDB:6WBV"
FT HELIX 517..545
FT /evidence="ECO:0007829|PDB:6WBV"
SQ SEQUENCE 571 AA; 62542 MW; E4D6B5594C904959 CRC64;
MTRAGDHNRQ RGCCGSLADY LTSAKFLLYL GHSLSTWGDR MWHFAVSVFL VELYGNSLLL
TAVYGLVVAG SVLVLGAIIG DWVDKNARLK VAQTSLVVQN VSVILCGIIL MMVFLHKHEL
LTMYHGWVLT SCYILIITIA NIANLASTAT AITIQRDWIV VVAGEDRSKL ANMNATIRRI
DQLTNILAPM AVGQIMTFGS PVIGCGFISG WNLVSMCVEY VLLWKVYQKT PALAVKAGLK
EEETELKQLN LHKDTEPKPL EGTHLMGVKD SNIHELEHEQ EPTCASQMAE PFRTFRDGWV
SYYNQPVFLA GMGLAFLYMT VLGFDCITTG YAYTQGLSGS ILSILMGASA ITGIMGTVAF
TWLRRKCGLV RTGLISGLAQ LSCLILCVIS VFMPGSPLDL SVSPFEDIRS RFIQGESITP
TKIPEITTEI YMSNGSNSAN IVPETSPESV PIISVSLLFA GVIAARIGLW SFDLTVTQLL
QENVIESERG IINGVQNSMN YLLDLLHFIM VILAPNPEAF GLLVLISVSF VAMGHIMYFR
FAQNTLGNKL FACGPDAKEV RKENQANTSV V
