S40A1_RAT
ID S40A1_RAT Reviewed; 570 AA.
AC Q923U9; Q9Z1C9;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 2.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Solute carrier family 40 member 1;
DE AltName: Full=CAR1;
DE AltName: Full=Cell adhesion regulator;
DE AltName: Full=Ferroportin-1;
GN Name=Slc40a1; Synonyms=Fpn1, Fpt1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RA Yeh K.-Y., Yeh M., Glass J.;
RT "Iron induces ferroportin 1 (FPT1) clustering and redistribution in rat
RT intestinal epithelial cells.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Yang X.Z.;
RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Major iron transporter that plays a key role in balancing
CC cellular and systemic iron levels (By similarity). Transports iron from
CC intestinal, splenic, and hepatic cells into the blood to provide iron
CC to other tissues. Controls therefore dietary iron uptake, iron
CC recycling by macrophages, and release of iron stores in hepatocytes (By
CC similarity). When iron is in excess, hepcidin/HAMP levels increase
CC resulting in a degradation of ferroportin/SLC40A1 limiting the iron
CC efflux to plasma (By similarity). {ECO:0000250|UniProtKB:Q9JHI9,
CC ECO:0000250|UniProtKB:Q9NP59}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Fe(2+)(in) = Fe(2+)(out); Xref=Rhea:RHEA:28486,
CC ChEBI:CHEBI:29033; Evidence={ECO:0000250|UniProtKB:Q9NP59};
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 -!- 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 -!- PTM: Polyubiquitinated by RNF217; leading to proteasomal degradation
CC (By similarity). Ubiquitination is necessary for its internalization by
CC hepcidin/HAMP (By similarity). {ECO:0000250|UniProtKB:Q9NP59}.
CC -!- SIMILARITY: Belongs to the ferroportin (FP) (TC 2.A.100) family. SLC40A
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD00260.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF394785; AAK77858.2; -; mRNA.
DR EMBL; U76714; AAD00260.1; ALT_FRAME; mRNA.
DR RefSeq; NP_579849.2; NM_133315.2.
DR AlphaFoldDB; Q923U9; -.
DR SMR; Q923U9; -.
DR BioGRID; 250996; 5.
DR STRING; 10116.ENSRNOP00000005228; -.
DR PaxDb; Q923U9; -.
DR GeneID; 170840; -.
DR KEGG; rno:170840; -.
DR UCSC; RGD:620180; rat.
DR CTD; 30061; -.
DR RGD; 620180; Slc40a1.
DR eggNOG; KOG2601; Eukaryota.
DR InParanoid; Q923U9; -.
DR OrthoDB; 334057at2759; -.
DR PhylomeDB; Q923U9; -.
DR Reactome; R-RNO-425410; Metal ion SLC transporters.
DR Reactome; R-RNO-917937; Iron uptake and transport.
DR PRO; PR:Q923U9; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0008021; C:synaptic vesicle; ISO:RGD.
DR GO; GO:0015093; F:ferrous iron transmembrane transporter activity; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0005381; F:iron ion transmembrane transporter activity; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017046; F:peptide hormone binding; ISO:RGD.
DR GO; GO:0006879; P:cellular iron ion homeostasis; ISO:RGD.
DR GO; GO:0003158; P:endothelium development; ISO:RGD.
DR GO; GO:1903988; P:iron ion export across plasma membrane; ISO:RGD.
DR GO; GO:0055072; P:iron ion homeostasis; ISO:RGD.
DR GO; GO:0034755; P:iron ion transmembrane transport; ISO:RGD.
DR GO; GO:0006826; P:iron ion transport; ISO:RGD.
DR GO; GO:0002260; P:lymphocyte homeostasis; ISO:RGD.
DR GO; GO:0060586; P:multicellular organismal iron ion homeostasis; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0034395; P:regulation of transcription from RNA polymerase II promoter in response to iron; ISO:RGD.
DR GO; GO:0048536; P:spleen development; ISO:RGD.
DR GO; GO:0060345; P:spleen trabecula formation; ISO:RGD.
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 2: Evidence at transcript level;
KW Cell membrane; 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_0000191312"
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 CONFLICT 57
FT /note="G -> S (in Ref. 2; AAD00260)"
FT /evidence="ECO:0000305"
FT CONFLICT 328..330
FT /note="TTG -> ATV (in Ref. 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 570 AA; 62586 MW; 766786F22F054E94 CRC64;
MTKSRDQTHQ EGCCGSLANY LTSAKFLLYL GHSLSTWGDR MWHFAVSVFL VELYGNGLLL
TAVYGLVVAG SVLVLGAIIG DWVDKNARLK VAQTSLVVQN VSVILCGIIL MMVFLHKNEL
LNMYHGWVLT VCYILIITIA NIANLASTAT AITIQRDWIV VVAGENRSRL ADMNATIRRI
DQLTNILAPM AVGQIMTFGS PVIGCGFISG WNLVSMCVEY FLLWKVYQKT PALAVKAALK
VEESELKQLT SPKDTEPKPL EGTHLMGEKD SNIRELECEQ EPTCASQIAE PFRTFRDGWV
SYYNQPVFLA GMGLAFLYMT VLGFDCITTG YAYTQGLSGS ILSVLMGASA ITGIMGTVAF
TWLRRKCGLV RTGLFSGLAQ LSCLILCVIS VFMPGSPLDL SVSPFEDIRS RFIHEEAVSS
TTKIPETEML MSNVSNVVNT VHEMSTKSVP IISVSLLFAG VIAARIGLWS FDLTVTQLLQ
ENVIESERGI INGVQNSMNY LLDLLHFIMV ILAPNPEAFG LLVLISVSFV AMGHLMYFRF
AQKTLGNQIF VCAPDEKEVT DESQPNTSVV
