Protein: High affinity copper uptake protein 1 (Q8WNR0)
Organism: Sus scrofa (Pig)
Function: [High affinity copper uptake protein 1]: Uniporter that mediates the transport of copper(1+) from the extracellular space to the cytoplasm, across the plasma membrane and delivers directly copper(1+) to specific chaperone such as ATOX1, via a copper(1+)- mediated transient interaction between the C-terminal domain and a copper(1+) chaperone, thus controlling intracellular copper(1+) levels (By similarity). May function in copper(1+) import from the apical membrane thus may drive intestinal copper absorption (By similarity). The copper(1+) transport mechanism is sodium- independent, saturable and of high-affinity. Also mediates the uptake of silver(1+). 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 cadmium(2+) into cells. Also participates in the first step of copper(2+) acquisition by cells through a direct transfer of copper(2+) from copper(2+) carriers in blood, such as ALB to the N-terminal domain of SLC31A1, leading to copper(2+) reduction and probably followed by copper(1+) stabilization. In addition, functions as a redox sensor to promote angiogenesis in endothelial cells, in a copper(1+) 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)
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. Localizes to the neuronal cell body plasma membranes (By similarity). Mainly localized on the basolateral side of renal tubular cells (By similarity)
Sequence: MDHSAHMGMSTHMGMSDMNHSTTMPPSHHHPTSSGSHESMMMPMTFYFGFKKVEVLFAGLVINTAGEMAGAFVAVFLLAMFYEGLKIAREGLLRKSQVSIRYNSMPVPGPNGTILMETHKTVGQQMLSFPHLLQTVLHIIQVVISYFLMLIFMTYNGYLCIAVAAGAGTGYFLFSWKKAVVVDITEHCH
InterPro domains: - IPR007274: Ctr copper transporter (family) [33-187]
Interaction partners: - P-type Cu(+) transporter
- Copper transport protein ATOX1
- Copper-transporting ATPase 1
- Cytochrome c oxidase copper chaperone
- Transmembrane ascorbate-dependent reductase CYB561
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005215 (transporter activity), GO:0022857 (transmembrane transporter activity), GO:0005515 (protein binding), GO:0015075 (monoatomic ion transmembrane transporter activity), GO:0015318 (inorganic molecular entity transmembrane transporter activity), GO:0022890 (inorganic cation transmembrane transporter activity), GO:0008324 (monoatomic cation transmembrane transporter activity), GO:0046873 (metal ion transmembrane transporter activity), GO:0046915 (transition metal ion transmembrane transporter activity), GO:0005375 (copper ion transmembrane transporter activity)
Biological Process (BP): GO:0008150 (biological process), GO:0009987 (cellular process), GO:0050896 (response to stimulus), GO:0051716 (cellular response to stimulus), GO:0009628 (response to abiotic stimulus), GO:0006950 (response to stress), GO:0042221 (response to chemical), GO:0009719 (response to endogenous stimulus), GO:0006970 (response to osmotic stress), GO:0071495 (cellular response to endogenous stimulus), GO:0010035 (response to inorganic substance), GO:0010033 (response to organic substance), GO:0009725 (response to hormone), GO:0070887 (cellular response to chemical stimulus), GO:0010038 (response to metal ion), GO:0009651 (response to salt stress), GO:0032870 (cellular response to hormone stimulus), GO:0043627 (response to estrogen), GO:0071310 (cellular response to organic substance), GO:0006971 (hypotonic response), GO:0046688 (response to copper ion), GO:0071391 (cellular response to estrogen stimulus)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0005768 (endosome), GO:0043227 (membrane-bounded organelle), GO:0055037 (recycling endosome), GO:0043231 (intracellular membrane-bounded organelle), GO:0031982 (vesicle), GO:0097708 (intracellular vesicle)