Q8WNR0 · COPT1_PIG
- ProteinHigh affinity copper uptake protein 1
- GeneSLC31A1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids189 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
Function
function
High affinity copper uptake protein 1
Uniporter that mediates the transport of copper1+ from the extracellular space to the cytoplasm, across the plasma membrane and delivers directly copper1+ to specific chaperone such as ATOX1, via a copper1+- mediated transient interaction between the C-terminal domain and a copper1+ chaperone, thus controlling intracellular copper1+ levels (By similarity).
May function in copper1+ import from the apical membrane thus may drive intestinal copper absorption (By similarity).
The copper1+ transport mechanism is sodium-independent, saturable and of high-affinity. Also mediates the uptake of silver1+. May function in the influx of the platinum-containing chemotherapeutic agents (By similarity).
The platinum-containing chemotherapeutic agents uptake is saturable (By similarity).
In vitro, mediates the transport of cadmium2+ into cells. Also participates in the first step of copper2+ acquisition by cells through a direct transfer of copper2+ from copper2+ carriers in blood, such as ALB to the N-terminal domain of SLC31A1, leading to copper2+ reduction and probably followed by copper1+ stabilization. In addition, functions as a redox sensor to promote angiogenesis in endothelial cells, in a copper1+ transport independent manner, by transmitting the VEGF-induced ROS signal through a sulfenylation at Cys-189 leadin g to a subsequent disulfide bond formation between SLC31A1 and KDR. The SLC31A1-KDR complex is then co-internalized to early endosomes, driving a sustained VEGFR2 signaling (By similarity).
May function in copper1+ import from the apical membrane thus may drive intestinal copper absorption (By similarity).
The copper1+ transport mechanism is sodium-independent, saturable and of high-affinity. Also mediates the uptake of silver1+. May function in the influx of the platinum-containing chemotherapeutic agents (By similarity).
The platinum-containing chemotherapeutic agents uptake is saturable (By similarity).
In vitro, mediates the transport of cadmium2+ into cells. Also participates in the first step of copper2+ acquisition by cells through a direct transfer of copper2+ from copper2+ carriers in blood, such as ALB to the N-terminal domain of SLC31A1, leading to copper2+ reduction and probably followed by copper1+ stabilization. In addition, functions as a redox sensor to promote angiogenesis in endothelial cells, in a copper1+ transport independent manner, by transmitting the VEGF-induced ROS signal through a sulfenylation at Cys-189 leadin g to a subsequent disulfide bond formation between SLC31A1 and KDR. The SLC31A1-KDR complex is then co-internalized to early endosomes, driving a sustained VEGFR2 signaling (By similarity).
Truncated CTR1 form
Mobilizes copper1+ out of the endosomal compartment, making copper1+ available for export out of the cells.
Catalytic activity
- Ag+(out) = Ag+(in)
- Cu+(out) = Cu+(in)
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 41-42 | Cleavage | ||||
Sequence: MM |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | apical plasma membrane | |
Cellular Component | basolateral plasma membrane | |
Cellular Component | early endosome membrane | |
Cellular Component | late endosome membrane | |
Cellular Component | plasma membrane | |
Cellular Component | recycling endosome membrane | |
Molecular Function | copper ion binding | |
Molecular Function | copper ion transmembrane transporter activity | |
Molecular Function | silver ion transmembrane transporter activity | |
Molecular Function | xenobiotic transmembrane transporter activity | |
Biological Process | angiogenesis | |
Biological Process | copper ion import | |
Biological Process | copper ion transport | |
Biological Process | plasma membrane copper ion transport | |
Biological Process | protein complex oligomerization | |
Biological Process | silver ion transmembrane transport | |
Biological Process | vascular endothelial growth factor receptor-2 signaling pathway | |
Biological Process | xenobiotic transport |
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameHigh affinity copper uptake protein 1
- Alternative names
- Cleaved into 1 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Suina > Suidae > Sus
Accessions
- Primary accessionQ8WNR0
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Early endosome membrane ; Multi-pass membrane protein
Recycling endosome membrane ; Multi-pass membrane protein
Apical cell membrane ; Multi-pass membrane protein
Late endosome membrane ; Multi-pass membrane protein
Basolateral cell membrane ; Multi-pass membrane protein
Note: The localization is controlled by the intra and extra-cellular copper concentration. Under conditions of elevated extracellular copper concentrations, it is rapidly internalized by endocytosis from the plasma membrane by a clathrin- and dynamin-mediated process and degradated in order to prevent intracellular copper accumulation and to reduce the transport of the copper across the membrane. The internalized SLC31A1 is then localized in early endosomes, and, upon a low extracellular copper concentrations, it is transported back to the plasma membrane in a RAB11A-dependent recycling pathway (By similarity).
Localizes to the apical membrane in intestinal epithelial cells (PubMed:20699218).
Localizes to the neuronal cell body plasma membranes (By similarity).
Mainly localized on the basolateral side of renal tubular cells (By similarity).
Localizes to the apical membrane in intestinal epithelial cells (PubMed:20699218).
Localizes to the neuronal cell body plasma membranes (By similarity).
Mainly localized on the basolateral side of renal tubular cells (By similarity).
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-67 | Extracellular | ||||
Sequence: MDHSAHMGMSTHMGMSDMNHSTTMPPSHHHPTSSGSHESMMMPMTFYFGFKKVEVLFAGLVINTAGE | ||||||
Transmembrane | 68-88 | Helical | ||||
Sequence: MAGAFVAVFLLAMFYEGLKIA | ||||||
Topological domain | 89-131 | Cytoplasmic | ||||
Sequence: REGLLRKSQVSIRYNSMPVPGPNGTILMETHKTVGQQMLSFPH | ||||||
Transmembrane | 132-152 | Helical | ||||
Sequence: LLQTVLHIIQVVISYFLMLIF | ||||||
Topological domain | 153-155 | Extracellular | ||||
Sequence: MTY | ||||||
Transmembrane | 156-176 | Helical | ||||
Sequence: NGYLCIAVAAGAGTGYFLFSW | ||||||
Topological domain | 177-189 | Cytoplasmic | ||||
Sequence: KKAVVVDITEHCH |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, modified residue, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000290190 | 1-189 | High affinity copper uptake protein 1 | |||
Sequence: MDHSAHMGMSTHMGMSDMNHSTTMPPSHHHPTSSGSHESMMMPMTFYFGFKKVEVLFAGLVINTAGEMAGAFVAVFLLAMFYEGLKIAREGLLRKSQVSIRYNSMPVPGPNGTILMETHKTVGQQMLSFPHLLQTVLHIIQVVISYFLMLIFMTYNGYLCIAVAAGAGTGYFLFSWKKAVVVDITEHCH | ||||||
Chain | PRO_0000458010 | 42-189 | Truncated CTR1 form | |||
Sequence: MPMTFYFGFKKVEVLFAGLVINTAGEMAGAFVAVFLLAMFYEGLKIAREGLLRKSQVSIRYNSMPVPGPNGTILMETHKTVGQQMLSFPHLLQTVLHIIQVVISYFLMLIFMTYNGYLCIAVAAGAGTGYFLFSWKKAVVVDITEHCH | ||||||
Modified residue | 113 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 188 | Cysteine sulfenic acid (-SOH) | ||||
Sequence: C | ||||||
Disulfide bond | 188 | Interchain (with C-1208 in KDR) | ||||
Sequence: C |
Post-translational modification
Proteolytic cleavage, leading to a truncated form, is facilitated by SLC31A2 and initiated preferentially by CTSL and to a minor extend by CTSB in endolysosomal compartments. A post-CTSL/cathepsin L processing occurs to yield to the fully truncated form.
Sulfenylated at Cys-188 after stimulation with VEGFA, which induces SLC31A1-KDR disulfide bond formation and their co-internalization to early endosomes, driving to a sustained VEGFR2 signaling.
Keywords
- PTM
Proteomic databases
Expression
Gene expression databases
Interaction
Subunit
Homotrimer; is stabilized by cisplatin via interactions between cisplatin and the methionine-rich clusters, and could be crucial for the copper2+ reduction process and copper1+ stabilization. Heterotrimer between SLC31A1, CCS and SOD1; this heterotrimer is copper1+-mediated and its maintenance is regulated through SOD1 activation. Interacts with KDR; this interaction is induced upon VEGFA stimulation leading to SLC31A1 and KDR subsequent co-internalization to early endosomes, thereby activating KDR downstream signaling in endothelial cells. Interacts (via C-terminal domain) with ATOX1 (via dimer form); this interaction improves ATOX1 stability and controls intracellular copper1+ levels. Interacts with SLC31A2; this interaction stabilizes SLC31A2 and protects its from ubiquitination and degradation. Interacts (via C-terminal domain) with CCS; this interaction is copper1+-mediated.
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for motif, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 13-18 | Methionine segments (Mets) motif | ||||
Sequence: MGMSDM | ||||||
Region | 15-36 | Disordered | ||||
Sequence: MSDMNHSTTMPPSHHHPTSSGS |
Domain
The C-terminal domain mediates copper1+ binding and is involved in the copper1+-dependent-ATOX1 interaction. The C-terminal domain appears to act to limit transport through the pore by regulating the rate of exit of copper ions at the intracellular side. The N-terminal domain can collect copper2+ from copper2+ carriers in blood. The N-terminal domain, in the trimeric arrangement, tunes its reactivity with copper, promoting copper2+ reduction and copper1+ stabilization. The Mets motif is involved in copper1+ binding.
Sequence similarities
Belongs to the copper transporter (Ctr) (TC 1.A.56) family. SLC31A subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length189
- Mass (Da)20,953
- Last updated2002-03-01 v1
- ChecksumC0327F7C5AE919B4
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF320815 EMBL· GenBank· DDBJ | AAL49494.1 EMBL· GenBank· DDBJ | mRNA | ||
AY141204 EMBL· GenBank· DDBJ | AAN46363.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AY141203 EMBL· GenBank· DDBJ | AAN46363.1 EMBL· GenBank· DDBJ | Genomic DNA |