S40A1_CANLF
ID S40A1_CANLF Reviewed; 576 AA.
AC E2RFJ3; A0A5F4D1S7;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 3.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=Solute carrier family 40 protein member 1 {ECO:0000305};
DE AltName: Full=Ferroportin-1 {ECO:0000305};
DE AltName: Full=Iron-regulated transporter 1 {ECO:0000305};
GN Name=SLC40A1;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615 {ECO:0000312|Proteomes:UP000002254};
RN [1] {ECO:0000312|Proteomes:UP000002254}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Boxer {ECO:0000312|Proteomes:UP000002254};
RX PubMed=16341006; DOI=10.1038/nature04338;
RA Lindblad-Toh K., Wade C.M., Mikkelsen T.S., Karlsson E.K., Jaffe D.B.,
RA Kamal M., Clamp M., Chang J.L., Kulbokas E.J. III, Zody M.C., Mauceli E.,
RA Xie X., Breen M., Wayne R.K., Ostrander E.A., Ponting C.P., Galibert F.,
RA Smith D.R., deJong P.J., Kirkness E.F., Alvarez P., Biagi T., Brockman W.,
RA Butler J., Chin C.-W., Cook A., Cuff J., Daly M.J., DeCaprio D., Gnerre S.,
RA Grabherr M., Kellis M., Kleber M., Bardeleben C., Goodstadt L., Heger A.,
RA Hitte C., Kim L., Koepfli K.-P., Parker H.G., Pollinger J.P.,
RA Searle S.M.J., Sutter N.B., Thomas R., Webber C., Baldwin J., Abebe A.,
RA Abouelleil A., Aftuck L., Ait-Zahra M., Aldredge T., Allen N., An P.,
RA Anderson S., Antoine C., Arachchi H., Aslam A., Ayotte L., Bachantsang P.,
RA Barry A., Bayul T., Benamara M., Berlin A., Bessette D., Blitshteyn B.,
RA Bloom T., Blye J., Boguslavskiy L., Bonnet C., Boukhgalter B., Brown A.,
RA Cahill P., Calixte N., Camarata J., Cheshatsang Y., Chu J., Citroen M.,
RA Collymore A., Cooke P., Dawoe T., Daza R., Decktor K., DeGray S.,
RA Dhargay N., Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L.,
RA Duffey N., Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S.,
RA Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K., Foley C.,
RA Franke A., Friedrich D., Gage D., Garber M., Gearin G., Giannoukos G.,
RA Goode T., Goyette A., Graham J., Grandbois E., Gyaltsen K., Hafez N.,
RA Hagopian D., Hagos B., Hall J., Healy C., Hegarty R., Honan T., Horn A.,
RA Houde N., Hughes L., Hunnicutt L., Husby M., Jester B., Jones C., Kamat A.,
RA Kanga B., Kells C., Khazanovich D., Kieu A.C., Kisner P., Kumar M.,
RA Lance K., Landers T., Lara M., Lee W., Leger J.-P., Lennon N., Leuper L.,
RA LeVine S., Liu J., Liu X., Lokyitsang Y., Lokyitsang T., Lui A.,
RA Macdonald J., Major J., Marabella R., Maru K., Matthews C., McDonough S.,
RA Mehta T., Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T.,
RA Miller K., Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A.,
RA Naylor J., Nguyen T., Nguyen N., Nguyen C., Nguyen T., Nicol R., Norbu N.,
RA Norbu C., Novod N., Nyima T., Olandt P., O'Neill B., O'Neill K., Osman S.,
RA Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F., Priest M.,
RA Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C., Rege F.,
RA Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S., Sharpe T.,
RA Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J., Smith C.,
RA Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S., Stone C.,
RA Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S., Thoulutsang D.,
RA Thoulutsang Y., Topham K., Topping I., Tsamla T., Vassiliev H.,
RA Venkataraman V., Vo A., Wangchuk T., Wangdi T., Weiand M., Wilkinson J.,
RA Wilson A., Yadav S., Yang S., Yang X., Young G., Yu Q., Zainoun J.,
RA Zembek L., Zimmer A., Lander E.S.;
RT "Genome sequence, comparative analysis and haplotype structure of the
RT domestic dog.";
RL Nature 438:803-819(2005).
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 (By similarity). Controls therefore dietary iron
CC uptake, iron recycling by macrophages, and release of iron stores in
CC hepatocytes (By similarity). When iron is in excess, hepcidin/HAMP
CC levels increase resulting in a degradation of ferroportin/SLC40A1
CC limiting the iron efflux to plasma (By similarity).
CC {ECO:0000250|UniProtKB:Q9JHI9, 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: Membrane {ECO:0000250|UniProtKB:Q9NP59}; Multi-
CC pass membrane protein {ECO:0000250|UniProtKB:Q9NP59}. Note=Localized to
CC the basolateral membrane of polarized epithelial cells.
CC {ECO:0000250|UniProtKB:Q9NP59}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=E2RFJ3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=E2RFJ3-2; Sequence=VSP_061344, VSP_061345;
CC -!- SIMILARITY: Belongs to the ferroportin (FP) (TC 2.A.100) family. SLC40A
CC subfamily. {ECO:0000255|RuleBase:RU365065}.
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DR EMBL; AAEX03017890; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAEX03017891; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR STRING; 9615.ENSCAFP00000013769; -.
DR PaxDb; E2RFJ3; -.
DR Ensembl; ENSCAFT00030026901; ENSCAFP00030023473; ENSCAFG00030014579. [E2RFJ3-2]
DR Ensembl; ENSCAFT00030027048; ENSCAFP00030023609; ENSCAFG00030014579. [E2RFJ3-1]
DR Ensembl; ENSCAFT00040022271; ENSCAFP00040019318; ENSCAFG00040012065. [E2RFJ3-2]
DR Ensembl; ENSCAFT00040022421; ENSCAFP00040019440; ENSCAFG00040012065. [E2RFJ3-1]
DR eggNOG; KOG2601; Eukaryota.
DR HOGENOM; CLU_020370_1_1_1; -.
DR InParanoid; E2RFJ3; -.
DR OMA; NVHELEH; -.
DR OrthoDB; 334057at2759; -.
DR TreeFam; TF313463; -.
DR Reactome; R-CFA-425410; Metal ion SLC transporters.
DR Reactome; R-CFA-917937; Iron uptake and transport.
DR Proteomes; UP000002254; Chromosome 37.
DR Bgee; ENSCAFG00000009343; Expressed in hair follicle and 45 other tissues.
DR GO; GO:0016323; C:basolateral plasma membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005381; F:iron ion transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017046; F:peptide hormone binding; IBA:GO_Central.
DR GO; GO:0055072; P:iron ion homeostasis; IBA:GO_Central.
DR GO; GO:0034755; P:iron ion transmembrane transport; IBA:GO_Central.
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 3: Inferred from homology;
KW Alternative splicing; Glycoprotein; Ion transport; Iron; Membrane;
KW Metal-binding; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..576
FT /note="Solute carrier family 40 protein member 1"
FT /id="PRO_0000454470"
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..458
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TRANSMEM 459..488
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TOPO_DOM 489..493
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TRANSMEM 494..518
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TOPO_DOM 519..521
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TRANSMEM 522..547
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT TOPO_DOM 548..576
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 512
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NP59"
FT CARBOHYD 439
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT VAR_SEQ 473..536
FT /note="GLWSFDLTVTQLLQENVIESERGIINGVQNSMNYLLDLLHFIMVILAPNPEA
FT FGLLVLISVSFV -> ASRHFSVNEKERAAEDRGDEEKTGERRQVRHWGMGGEFTCPPL
FT FGQGSHGAPVFIQSPPQVSLG (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_061344"
FT VAR_SEQ 537..576
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_061345"
SQ SEQUENCE 576 AA; 62885 MW; D4254FEFAF398D62 CRC64;
MPKAGEQARQ GGCCGSLANY LTSAKFLLYL GHSLSTWGDR MWHFAVSVFL VELYGNSLLL
TAVYGLVVAG SVLVLGAIIG DWVDKNARLK VAQTSLVVQN VSVILCGIIL MMVFLHKNEL
LTMYHGWVLT FCYILIITIA DVANLASTAT AITIQRDWIV VVAGGDRSKL ADMNATIRRI
DQLTNILAPM AVGQIMTFGS AVIGCGFISG WNLVSMCVEY FLLWKVYQKT PALAVKAALK
VEEAELKQLN LHKETEPKPL EGTHLMGEKD PNVHELEHEQ EPSCASQMAE PFRTFRDGWV
SYYNQSVFLA GMGLAFLYMT VLGFDCITTG YAYTQGLSGS ILSILMGASA ITGIMGTVAF
TWLRRKCGLV RTGLISGFAQ LSCLILCVIS VFMPGSPLDL SVSPFEDIRS RFIQAEPLST
MTPTKVPEII FTTEMHMSNG SDPAGIFPET TPKSVPIISV SLLFAGVIAA RIGLWSFDLT
VTQLLQENVI ESERGIINGV QNSMNYLLDL LHFIMVILAP NPEAFGLLVL ISVSFVAMGH
IMYFRFAQKT LGSKLFACGA DDEEVTNENQ ANTSVV
