E2RFJ3 · S40A1_CANLF
- ProteinFerroportin
- GeneSLC40A1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids576 (go to sequence)
- Protein existenceInferred from homology
- Annotation score4/5
Function
function
Transports Fe2+ from the inside of a cell to the outside of the cell, playing a key role for maintaining systemic iron homeostasis (By similarity).
Transports iron from intestinal, splenic, hepatic cells, macrophages and erythrocytes into the blood to provide iron to other tissues. Controls therefore dietary iron uptake, iron recycling by macrophages and erythrocytes, and release of iron stores in hepatocytes (By similarity).
When iron is in excess in serum, circulating HAMP/hepcidin levels increase resulting in a degradation of SLC40A1, thus limiting the iron efflux to plasma (By similarity).
Transports iron from intestinal, splenic, hepatic cells, macrophages and erythrocytes into the blood to provide iron to other tissues. Controls therefore dietary iron uptake, iron recycling by macrophages and erythrocytes, and release of iron stores in hepatocytes (By similarity).
When iron is in excess in serum, circulating HAMP/hepcidin levels increase resulting in a degradation of SLC40A1, thus limiting the iron efflux to plasma (By similarity).
Catalytic activity
- Fe2+(in) = Fe2+(out)
Activity regulation
During elevated serum iron levels, liver-derived hepcidin/HAMP negatively regulates cell surface ferroportin/SLC40A1 by inducing its ubiquitination, internalization, and degradation. Indeed, hepcidin/HAMP affinity towards ferroportin/SLC40A1 increases by 80-fold in the presence of iron.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | basolateral plasma membrane | |
Molecular Function | iron ion transmembrane transporter activity | |
Molecular Function | metal ion binding | |
Molecular Function | peptide hormone binding | |
Biological Process | iron ion export across plasma membrane |
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameFerroportin
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Carnivora > Caniformia > Canidae > Canis
Accessions
- Primary accessionE2RFJ3
- Secondary accessions
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Basolateral cell membrane ; Multi-pass membrane protein
Note: Localized to the basolateral membrane of polarized epithelial cells.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-23 | Cytoplasmic | ||||
Sequence: MPKAGEQARQGGCCGSLANYLTS | ||||||
Transmembrane | 24-53 | Helical | ||||
Sequence: AKFLLYLGHSLSTWGDRMWHFAVSVFLVEL | ||||||
Topological domain | 54-57 | Extracellular | ||||
Sequence: YGNS | ||||||
Transmembrane | 58-84 | Helical | ||||
Sequence: LLLTAVYGLVVAGSVLVLGAIIGDWVD | ||||||
Topological domain | 85-87 | Cytoplasmic | ||||
Sequence: KNA | ||||||
Transmembrane | 88-118 | Helical | ||||
Sequence: RLKVAQTSLVVQNVSVILCGIILMMVFLHKN | ||||||
Topological domain | 119-126 | Extracellular | ||||
Sequence: ELLTMYHG | ||||||
Transmembrane | 127-162 | Helical | ||||
Sequence: WVLTFCYILIITIADVANLASTATAITIQRDWIVVV | ||||||
Topological domain | 163-164 | Cytoplasmic | ||||
Sequence: AG | ||||||
Transmembrane | 165-195 | Helical | ||||
Sequence: GDRSKLADMNATIRRIDQLTNILAPMAVGQI | ||||||
Topological domain | 196-202 | Extracellular | ||||
Sequence: MTFGSAV | ||||||
Transmembrane | 203-229 | Helical | ||||
Sequence: IGCGFISGWNLVSMCVEYFLLWKVYQK | ||||||
Topological domain | 230-306 | Cytoplasmic | ||||
Sequence: TPALAVKAALKVEEAELKQLNLHKETEPKPLEGTHLMGEKDPNVHELEHEQEPSCASQMAEPFRTFRDGWVSYYNQS | ||||||
Transmembrane | 307-333 | Helical | ||||
Sequence: VFLAGMGLAFLYMTVLGFDCITTGYAY | ||||||
Topological domain | 334-338 | Extracellular | ||||
Sequence: TQGLS | ||||||
Transmembrane | 339-366 | Helical | ||||
Sequence: GSILSILMGASAITGIMGTVAFTWLRRK | ||||||
Topological domain | 367-368 | Cytoplasmic | ||||
Sequence: CG | ||||||
Transmembrane | 369-391 | Helical | ||||
Sequence: LVRTGLISGFAQLSCLILCVISV | ||||||
Topological domain | 392-458 | Extracellular | ||||
Sequence: FMPGSPLDLSVSPFEDIRSRFIQAEPLSTMTPTKVPEIIFTTEMHMSNGSDPAGIFPETTPKSVPII | ||||||
Transmembrane | 459-488 | Helical | ||||
Sequence: SVSLLFAGVIAARIGLWSFDLTVTQLLQEN | ||||||
Topological domain | 489-493 | Cytoplasmic | ||||
Sequence: VIESE | ||||||
Transmembrane | 494-518 | Helical | ||||
Sequence: RGIINGVQNSMNYLLDLLHFIMVIL | ||||||
Topological domain | 519-521 | Extracellular | ||||
Sequence: APN | ||||||
Transmembrane | 522-547 | Helical | ||||
Sequence: PEAFGLLVLISVSFVAMGHIMYFRFA | ||||||
Topological domain | 548-576 | Cytoplasmic | ||||
Sequence: QKTLGSKLFACGADDEEVTNENQANTSVV |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000454470 | 1-576 | Ferroportin | |||
Sequence: MPKAGEQARQGGCCGSLANYLTSAKFLLYLGHSLSTWGDRMWHFAVSVFLVELYGNSLLLTAVYGLVVAGSVLVLGAIIGDWVDKNARLKVAQTSLVVQNVSVILCGIILMMVFLHKNELLTMYHGWVLTFCYILIITIADVANLASTATAITIQRDWIVVVAGGDRSKLADMNATIRRIDQLTNILAPMAVGQIMTFGSAVIGCGFISGWNLVSMCVEYFLLWKVYQKTPALAVKAALKVEEAELKQLNLHKETEPKPLEGTHLMGEKDPNVHELEHEQEPSCASQMAEPFRTFRDGWVSYYNQSVFLAGMGLAFLYMTVLGFDCITTGYAYTQGLSGSILSILMGASAITGIMGTVAFTWLRRKCGLVRTGLISGFAQLSCLILCVISVFMPGSPLDLSVSPFEDIRSRFIQAEPLSTMTPTKVPEIIFTTEMHMSNGSDPAGIFPETTPKSVPIISVSLLFAGVIAARIGLWSFDLTVTQLLQENVIESERGIINGVQNSMNYLLDLLHFIMVILAPNPEAFGLLVLISVSFVAMGHIMYFRFAQKTLGSKLFACGADDEEVTNENQANTSVV | ||||||
Glycosylation | 439 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
Polyubiquitinated by RNF217; leading to proteasomal degradation (By similarity).
Under conditions of high systemic iron levels, both the hormone peptide hepcidin/HAMP and holo(iron bound)-transferrin/TF induce the ubiquitination, internalization and proteasomal degradation of SLC40A1 to control iron release from cells (By similarity).
Under conditions of high systemic iron levels, both the hormone peptide hepcidin/HAMP and holo(iron bound)-transferrin/TF induce the ubiquitination, internalization and proteasomal degradation of SLC40A1 to control iron release from cells (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Identified in a complex with STOM. Interacts with HAMP; affinity of the peptide hormone HAMP for SLC40A1 increases by 80-fold in the presence of iron and the interaction promotes SLC40A1 ubiquitination and degradation. Part of a complex composed of SLC40A1/ferroportin, TF/transferrin and HEPH/hephaestin that transfers iron from cells to transferrin.
Protein-protein interaction databases
Structure
Family & Domains
Sequence similarities
Belongs to the ferroportin (FP) (TC 2.A.100) family. SLC40A subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
E2RFJ3-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length576
- Mass (Da)62,885
- Last updated2022-02-23 v3
- ChecksumD4254FEFAF398D62
E2RFJ3-2
- Name2
Features
Showing features for alternative sequence.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AAEX03017890 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AAEX03017891 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |