Q8WNR0 · COPT1_PIG

  • Protein
    High affinity copper uptake protein 1
  • Gene
    SLC31A1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at transcript level
  • Annotation score
    5/5

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).

Truncated CTR1 form

Mobilizes copper1+ out of the endosomal compartment, making copper1+ available for export out of the cells.

Catalytic activity

Features

Showing features for site.

TypeIDPosition(s)Description
Site41-42Cleavage

GO annotations

AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentbasolateral plasma membrane
Cellular Componentearly endosome membrane
Cellular Componentlate endosome membrane
Cellular Componentplasma membrane
Cellular Componentrecycling endosome membrane
Molecular Functioncopper ion binding
Molecular Functioncopper ion transmembrane transporter activity
Molecular Functionsilver ion transmembrane transporter activity
Molecular Functionxenobiotic transmembrane transporter activity
Biological Processangiogenesis
Biological Processcopper ion import
Biological Processcopper ion transport
Biological Processplasma membrane copper ion transport
Biological Processprotein complex oligomerization
Biological Processsilver ion transmembrane transport
Biological Processvascular endothelial growth factor receptor-2 signaling pathway
Biological Processxenobiotic transport

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    High affinity copper uptake protein 1
  • Alternative names
    • Copper transporter 1
      (CTR1
      )
    • Solute carrier family 31 member 1
  • Cleaved into 1 chains

Gene names

    • Name
      SLC31A1
    • Synonyms
      CTR1

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Suina > Suidae > Sus

Accessions

  • Primary accession
    Q8WNR0

Proteomes

Organism-specific databases

Subcellular Location

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).

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-67Extracellular
Transmembrane68-88Helical
Topological domain89-131Cytoplasmic
Transmembrane132-152Helical
Topological domain153-155Extracellular
Transmembrane156-176Helical
Topological domain177-189Cytoplasmic

Keywords

PTM/Processing

Features

Showing features for chain, modified residue, disulfide bond.

TypeIDPosition(s)Description
ChainPRO_00002901901-189High affinity copper uptake protein 1
ChainPRO_000045801042-189Truncated CTR1 form
Modified residue113Phosphothreonine
Modified residue188Cysteine sulfenic acid (-SOH)
Disulfide bond188Interchain (with C-1208 in KDR)

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

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

Family & Domains

Features

Showing features for motif, region.

TypeIDPosition(s)Description
Motif13-18Methionine segments (Mets) motif
Region15-36Disordered

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

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    189
  • Mass (Da)
    20,953
  • Last updated
    2002-03-01 v1
  • Checksum
    C0327F7C5AE919B4
MDHSAHMGMSTHMGMSDMNHSTTMPPSHHHPTSSGSHESMMMPMTFYFGFKKVEVLFAGLVINTAGEMAGAFVAVFLLAMFYEGLKIAREGLLRKSQVSIRYNSMPVPGPNGTILMETHKTVGQQMLSFPHLLQTVLHIIQVVISYFLMLIFMTYNGYLCIAVAAGAGTGYFLFSWKKAVVVDITEHCH

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

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