S40A1_MOUSE
ID S40A1_MOUSE Reviewed; 570 AA.
AC Q9JHI9; Q3UHZ9; Q8BME5; Q8BUM5; Q9JIM9; Q9JKP4;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Solute carrier family 40 member 1;
DE AltName: Full=Ferroportin-1;
DE AltName: Full=Iron-regulated transporter 1;
DE AltName: Full=Metal transporter protein 1;
DE Short=MTP1;
GN Name=Slc40a1; Synonyms=Fpn1, Ireg1, Slc11a3, Slc39a1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
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.
RC TISSUE=Liver;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, Liver, Lung, and Stomach;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary tumor;
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 [6]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TRANSPORTER ACTIVITY.
RX PubMed=16054062; DOI=10.1016/j.cmet.2005.01.003;
RA Donovan A., Lima C.A., Pinkus J.L., Pinkus G.S., Zon L.I., Robine S.,
RA Andrews N.C.;
RT "The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis.";
RL Cell Metab. 1:191-200(2005).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TRANSPORTER ACTIVITY.
RX PubMed=30213870; DOI=10.1182/blood-2018-04-842997;
RA Zhang D.L., Ghosh M.C., Ollivierre H., Li Y., Rouault T.A.;
RT "Ferroportin deficiency in erythroid cells causes serum iron deficiency and
RT promotes hemolysis due to oxidative stress.";
RL Blood 132:2078-2087(2018).
RN [8]
RP UBIQUITINATION BY RNF217.
RX PubMed=33895792; DOI=10.1182/blood.2020008986;
RA Jiang L., Wang J., Wang K., Wang H., Wu Q., Yang C., Yu Y., Ni P.,
RA Zhong Y., Song Z., Xie E., Hu R., Min J., Wang F.;
RT "RNF217 regulates iron homeostasis through its E3 ubiquitin ligase activity
RT by modulating ferroportin degradation.";
RL Blood 138:689-705(2021).
CC -!- FUNCTION: Major iron transporter that plays a key role in balancing
CC cellular and systemic iron levels. Transports iron from intestinal,
CC splenic, and hepatic cells into the blood to provide iron to other
CC tissues (PubMed:30213870). Controls therefore dietary iron uptake, iron
CC recycling by macrophages, and release of iron stores in hepatocytes
CC (PubMed:16054062). When iron is in excess hepcidin/HAMP levels
CC increase, resulting in a degradation of ferroportin/SLC40A1 limiting
CC the iron efflux to plasma (By similarity).
CC {ECO:0000250|UniProtKB:Q9NP59, ECO:0000269|PubMed:16054062,
CC ECO:0000269|PubMed:30213870}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Fe(2+)(in) = Fe(2+)(out); Xref=Rhea:RHEA:28486,
CC ChEBI:CHEBI:29033; Evidence={ECO:0000269|PubMed:16054062,
CC ECO:0000269|PubMed:30213870};
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:0000250|UniProtKB:Q9NP59}.
CC -!- SUBUNIT: Identified in a complex with STOM. Interacts with HAMP; this
CC interaction promotes SLC40A1 rapid ubiquitination.
CC {ECO:0000250|UniProtKB:Q9NP59}.
CC -!- INTERACTION:
CC Q9JHI9; P12023: App; NbExp=2; IntAct=EBI-2931424, EBI-78814;
CC Q9JHI9; Q9JHI9: Slc40a1; NbExp=2; IntAct=EBI-2931424, EBI-2931424;
CC Q9JHI9; O60674: JAK2; Xeno; NbExp=3; IntAct=EBI-2931424, EBI-518647;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9NP59};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q9NP59}.
CC Note=Localized to the basolateral membrane of polarized epithelial
CC cells. {ECO:0000250|UniProtKB:Q9NP59}.
CC -!- TISSUE SPECIFICITY: High expression in spleen, liver, kidney, heart and
CC duodenum.
CC -!- PTM: Polyubiquitinated by RNF217; leading to proteasomal degradation
CC (PubMed:33895792). Ubiquitination is necessary for its internalization
CC by hepcidin/HAMP (By similarity). {ECO:0000250|UniProtKB:Q9NP59,
CC ECO:0000269|PubMed:33895792}.
CC -!- DISRUPTION PHENOTYPE: Deletion mice die prenatallys. These mice cannot
CC transfer iron from the extraembryonic visceral endoderm into the embryo
CC proper, leading to a defect in embryonic growth and consequent death
CC (PubMed:16054062). Erythroid-specific deletion reduces serum iron but
CC increased tissue iron contents (PubMed:30213870).
CC {ECO:0000269|PubMed:16054062, ECO:0000269|PubMed:30213870}.
CC -!- SIMILARITY: Belongs to the ferroportin (FP) (TC 2.A.100) family. SLC40A
CC subfamily. {ECO:0000305}.
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DR EMBL; AF215637; AAF80987.1; -; mRNA.
DR EMBL; AF216834; AAF82036.1; -; Genomic_DNA.
DR EMBL; AF226613; AAF36696.1; -; mRNA.
DR EMBL; AF231120; AAF44329.1; -; mRNA.
DR EMBL; AK008700; BAB25840.1; -; mRNA.
DR EMBL; AK032732; BAC28001.1; -; mRNA.
DR EMBL; AK083288; BAC38844.1; -; mRNA.
DR EMBL; AK144780; BAE26063.1; -; mRNA.
DR EMBL; AK147137; BAE27707.1; -; mRNA.
DR EMBL; AK159294; BAE34969.1; -; mRNA.
DR EMBL; AK159855; BAE35431.1; -; mRNA.
DR EMBL; BC003438; AAH03438.1; -; mRNA.
DR CCDS; CCDS14933.1; -.
DR RefSeq; NP_058613.2; NM_016917.2.
DR RefSeq; XP_006496200.1; XM_006496137.2.
DR RefSeq; XP_017177198.1; XM_017321709.1.
DR AlphaFoldDB; Q9JHI9; -.
DR SMR; Q9JHI9; -.
DR DIP; DIP-58649N; -.
DR IntAct; Q9JHI9; 4.
DR STRING; 10090.ENSMUSP00000027137; -.
DR ChEMBL; CHEMBL4523462; -.
DR GuidetoPHARMACOLOGY; 1194; -.
DR TCDB; 2.A.100.1.1; the ferroportin (fpn) family.
DR GlyGen; Q9JHI9; 4 sites.
DR iPTMnet; Q9JHI9; -.
DR PhosphoSitePlus; Q9JHI9; -.
DR SwissPalm; Q9JHI9; -.
DR MaxQB; Q9JHI9; -.
DR PaxDb; Q9JHI9; -.
DR PRIDE; Q9JHI9; -.
DR ProteomicsDB; 256902; -.
DR Antibodypedia; 34022; 373 antibodies from 33 providers.
DR DNASU; 53945; -.
DR Ensembl; ENSMUST00000027137; ENSMUSP00000027137; ENSMUSG00000025993.
DR GeneID; 53945; -.
DR KEGG; mmu:53945; -.
DR UCSC; uc007awu.1; mouse.
DR CTD; 30061; -.
DR MGI; MGI:1315204; Slc40a1.
DR VEuPathDB; HostDB:ENSMUSG00000025993; -.
DR eggNOG; KOG2601; Eukaryota.
DR GeneTree; ENSGT00390000015143; -.
DR HOGENOM; CLU_020370_1_1_1; -.
DR InParanoid; Q9JHI9; -.
DR OMA; NVHELEH; -.
DR OrthoDB; 334057at2759; -.
DR PhylomeDB; Q9JHI9; -.
DR TreeFam; TF313463; -.
DR Reactome; R-MMU-425410; Metal ion SLC transporters.
DR Reactome; R-MMU-917937; Iron uptake and transport.
DR BioGRID-ORCS; 53945; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Slc40a1; mouse.
DR PRO; PR:Q9JHI9; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9JHI9; protein.
DR Bgee; ENSMUSG00000025993; Expressed in epithelium of small intestine and 237 other tissues.
DR ExpressionAtlas; Q9JHI9; baseline and differential.
DR Genevisible; Q9JHI9; MM.
DR GO; GO:0016323; C:basolateral plasma membrane; IGI:BHF-UCL.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0008021; C:synaptic vesicle; IDA:MGI.
DR GO; GO:0015093; F:ferrous iron transmembrane transporter activity; IDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005381; F:iron ion transmembrane transporter activity; IDA: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; IMP:MGI.
DR GO; GO:0006879; P:cellular iron ion homeostasis; ISO:MGI.
DR GO; GO:0003158; P:endothelium development; IMP:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IGI:MGI.
DR GO; GO:1903988; P:iron ion export across plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0055072; P:iron ion homeostasis; IMP:MGI.
DR GO; GO:0034755; P:iron ion transmembrane transport; IGI:MGI.
DR GO; GO:0006826; P:iron ion transport; IDA:MGI.
DR GO; GO:0002260; P:lymphocyte homeostasis; IMP:MGI.
DR GO; GO:0060586; P:multicellular organismal iron ion homeostasis; IMP:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0034395; P:regulation of transcription from RNA polymerase II promoter in response to iron; IDA:MGI.
DR GO; GO:0048536; P:spleen development; IMP:MGI.
DR GO; GO:0060345; P:spleen trabecula formation; IMP:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IGI:MGI.
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 Cell membrane; Glycoprotein; Ion transport; Iron; Iron transport; Membrane;
KW Metal-binding; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport; Ubl conjugation.
FT CHAIN 1..570
FT /note="Solute carrier family 40 member 1"
FT /id="PRO_0000191311"
FT TOPO_DOM 1..23
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TRANSMEM 24..53
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TOPO_DOM 54..57
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TRANSMEM 58..84
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TOPO_DOM 85..87
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TRANSMEM 88..118
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TOPO_DOM 119..126
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TRANSMEM 127..162
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TOPO_DOM 163..164
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TRANSMEM 165..195
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TOPO_DOM 196..202
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TRANSMEM 203..229
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TOPO_DOM 230..306
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TRANSMEM 307..333
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TOPO_DOM 334..338
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TRANSMEM 339..366
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TOPO_DOM 367..368
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TRANSMEM 369..391
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TOPO_DOM 392..452
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TRANSMEM 453..482
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TOPO_DOM 483..487
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TRANSMEM 488..512
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TOPO_DOM 513..515
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TRANSMEM 516..541
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TOPO_DOM 542..570
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT BINDING 39
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT BINDING 43
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT BINDING 326
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT BINDING 506
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT CARBOHYD 437
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 570 AA; 62702 MW; 7125CC6171394A0A CRC64;
MTKARDQTHQ EGCCGSLANY LTSAKFLLYL GHSLSTWGDR MWHFAVSVFL VELYGNSLLL
TAVYGLVVAG SVLVLGAIIG DWVDKNARLK VAQTSLVVQN VSVILCGIIL MMVFLHKNEL
LTMYHGWVLT VCYILIITIA NIANLASTAT AITIQRDWIV VVAGENRSRL ADMNATIRRI
DQLTNILAPM AVGQIMTFGS PVIGCGFISG WNLVSMCVEY FLLWKVYQKT PALAVKAALK
VEESELKQLT SPKDTEPKPL EGTHLMGEKD SNIRELECEQ EPTCASQMAE PFRTFRDGWV
SYYNQPVFLA GMGLAFLYMT VLGFDCITTG YAYTQGLSGS ILSILMGASA ITGIMGTVAF
TWLRRKCGLV RTGLFSGLAQ LSCLILCVIS VFMPGSPLDL SVSPFEDIRS RFVNVEPVSP
TTKIPETVFT TEMHMSNMSN VHEMSTKPIP IVSVSLLFAG VIAARIGLWS FDLTVTQLLQ
ENVIESERGI INGVQNSMNY LLDLLHFIMV ILAPNPEAFG LLVLISVSFV AMGHLMYFRF
AQKTLGNQIF VCGPDEKEVT DENQPNTSVV
