SLC31A1
entrez
1317
canonical
uniprot
O15431
canonical
ensembl
ENSG00000136868
resolver
ensp
ENSP00000363329
resolver
ensp
ENSP00000572302
resolver
ensp
ENSP00000607609
resolver
ensp
ENSP00000607610
resolver
ensp
ENSP00000607611
resolver
enst
ENST00000374212
resolver
enst
ENST00000902243
resolver
enst
ENST00000937550
resolver
enst
ENST00000937551
resolver
enst
ENST00000937552
resolver
genesymbol
SLC31A1
resolver
genesymbol_syn
COPT1
resolver
genesymbol_syn
CTR1
resolver
hgnc
HGNC:11016
resolver
uniprot
A8K8Z6
resolver
uniprot
Q53GR5
resolver
uniprot
Q5T1M4
resolver
uniprot_entry
COPT1_HUMAN
resolver
uniprot_sec
A8K8Z6
resolver
uniprot_sec
Q53GR5
resolver
uniprot_sec
Q5T1M4
resolver
activity_regulation
ACTIVITY REGULATION: Copper(1+) transport is stimulated by extracellular acidic pH and high potassium ions concentrations (PubMed:11734551). Copper(1+) import is regulated by a copper(1+)-dependent recycling of SLC31A1 (PubMed:19740744). {ECO:0000269|PubMed:11734551, ECO:0000269|PubMed:19740744}.
uniprot
proteins
amino_acid_sequence
MDHSHHMGMSYMDSNSTMQPSHHHPTTSASHSHGGGDSSMMMMPMTFYFGFKNVELLFSGLVINTAGEMAGAFVAVFLLAMFYEGLKIARESLLRKSQVSIRYNSMPVPGPNGTILMETHKTVGQQMLSFPHLLQTVLHIIQVVISYFLMLIFMTYNGYLCIAVAAGAGTGYFLFSWKKAVVVDITEHCH
uniprot
proteins
disease_involvement
DISEASE: Neurodegeneration and seizures due to copper transport defect (NSCT) [MIM:620306]: An autosomal recessive disorder of copper metabolism characterized by global developmental delay, seizures, cortical and cerebellar atrophy, and axial hypotonia. Death in infancy may occur. {ECO:0000269|PubMed:35913762, ECO:0000269|PubMed:36562171}. Note=The disease may be caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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 (PubMed:11734551, PubMed:16135512, PubMed:17525160, PubMed:19740744, PubMed:20451502, PubMed:20569931, PubMed:23658018) 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 (PubMed:11734551, PubMed:16135512, PubMed:17525160, PubMed:19740744, PubMed:20451502, PubMed:20569931, PubMed:23658018, PubMed:26745413). 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 (PubMed:11734551). Also mediates the uptake of silver(1+) (PubMed:20569931). May function in the influx of the platinum-containing chemotherapeutic agents (PubMed:20451502, PubMed:20569931). The platinum-containing chemotherapeutic agents uptake is saturable (By similarity). In vitro, mediates the transport of cadmium(2+) into cells (PubMed:33294387). 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 (PubMed:30489586). 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 (PubMed:35027734). The SLC31A1-KDR complex is then co-internalized to early endosomes, driving a sustained VEGFR2 signaling (PubMed:35027734). {ECO:0000250|UniProtKB:Q8K211, ECO:0000250|UniProtKB:Q9JK41, ECO:0000269|PubMed:11734551, ECO:0000269|PubMed:16135512, ECO:0000269|PubMed:17525160, ECO:0000269|PubMed:19740744, ECO:0000269|PubMed:20451502, ECO:0000269|PubMed:20569931, ECO:0000269|PubMed:23658018, ECO:0000269|PubMed:26745413, ECO:0000269|PubMed:30489586, ECO:0000269|PubMed:33294387, ECO:0000269|PubMed:35027734}.; FUNCTION: [Truncated CTR1 form]: Mobilizes copper(1+) out of the endosomal compartment, making copper(1+) available for export out of the cells. {ECO:0000250|UniProtKB:Q8K211}.
uniprot
proteins
mass_dalton
21091
uniprot
proteins
mutagenesis
MUTAGEN 3; /note="H->A: Decreases affinity towards copper(1+)."; /evidence="ECO:0000269|Ref.24"; MUTAGEN 5; /note="H->A: Affects copper(2+) binding. Increases the efficiency of the reduction."; /evidence="ECO:0000269|Ref.24"; MUTAGEN 6; /note="H->A: Increases the efficiency of the reduction."; /evidence="ECO:0000269|Ref.24"; MUTAGEN 7..12; /note="MGMSYM->AGASYA: Affects homotrimer formation; when associated with 40-A--A-45. Does not affect localization at the plasma membrane; when associated with 40-A--A-45."; /evidence="ECO:0000269|PubMed:15326162"; MUTAGEN 40..45; /note="MMMMPM->AAAAPA: Affects homotrimer formation; when associated with 7-A--A-12. Does not affect localization at the plasma membrane; when associated with 7-A--A-12."; /evidence="ECO:0000269|PubMed:15326162"; MUTAGEN 139; /note="H->A: Decreases of about 40% the copper(1+) transport activity."; /evidence="ECO:0000269|PubMed:16135512"; MUTAGEN 139; /note="H->R: Dramatically decreases copper(1+) affinity. Reduces copper(1+) uptake; when associated with L-150 and L-154. Does not affect cell membrane expression."; /evidence="ECO:0000269|PubMed:16135512, ECO:0000269|PubMed:23658018"; MUTAGEN 150; /note="M->I: Reduces of about 30% the copper(1+) transport activity; when associated with I-154. Does not affect copper(1+) affinity; when associated with I-154. Abolishes silver(1+) transport activity; when associated with I-154."; /evidence="ECO:0000269|PubMed:16135512, ECO:0000269|PubMed:20569931"; MUTAGEN 150; /note="M->L: Reduces copper(1+) uptake; when associated with L-154. Reduces copper(1+) uptake; when associated with L-154 and R-139. Reduces copper(1+) uptake; when associated with L-154 and 188-A--A-190."; /evidence="ECO:0000269|PubMed:23658018"; MUTAGEN 154; /note="M->A: Inhibits copper(1+)-induced MAPK activation. Loss of copper(1+)-induced endothelil cell (EC) migration and capillary formation."; /evidence="ECO:0000269|PubMed:35027734"; MUTAGEN 154; /note="M->I: Reduces of about 30% the copper(1+) transport activity; when associated with I-150. Does not affect copper(1+) affinity; when associated with I-150. Abolishes silver(1+) transport activity when associated with I-150."; /evidence="ECO:0000269|PubMed:16135512, ECO:0000269|PubMed:20569931"; MUTAGEN 154; /note="M->L: Reduces copper(1+) uptake; when associated with L-150. Reduces copper(1+) uptake; when associated with L-150 and R-139. Reduces copper(1+) uptake; when associated with L-150 and 188-A--A-190."; /evidence="ECO:0000269|PubMed:23658018"; MUTAGEN 156; /note="Y->A: Dramatically affects copper(1+) transport activity."; /evidence="ECO:0000269|PubMed:16135512"; MUTAGEN 161; /note="C->S: Markedly decreases the copper(1+) transport activity; when associated with S-189."; /evidence="ECO:0000269|PubMed:16135512"; MUTAGEN 179..190; /note="Missing: Does not affect expression. Does not affect cell membrane localization. Significantly reduces copper(1+) transport activity."; /evidence="ECO:0000269|PubMed:16135512"; MUTAGEN 180..190; /note="Missing: Increases copper(1+) uptake. Reduces affinity for copper(1+)."; /evidence="ECO:0000269|PubMed:23658018"; MUTAGEN 184..190; /note="Missing: Increases copper(1+) uptake."; /evidence="ECO:0000269|PubMed:23658018"; MUTAGEN 185..190; /note="Missing: Does not affect expression. Does not affect cell membrane localization. Moderately affects copper(1+) transport activity."; /evidence="ECO:0000269|PubMed:16135512"; MUTAGEN 188..190; /note="HCH->AAA: Increases copper(1+) uptake. Reduces affinity for copper(1+). Reduces copper(1+) uptake; when associated with L-150 and L-154. Impairs endocytosis in response to higher extracellular copper(1+) concentration."; /evidence="ECO:0000269|PubMed:23658018, ECO:0000269|PubMed:26745413"; MUTAGEN 188..190; /note="HCH->ACA: Decreases of 45-fold copper(1+) affinity."; /evidence="ECO:0000269|PubMed:26745413"; MUTAGEN 189; /note="C->A: Does not affect copper(1+)-induced MAPK activation. Does not affect copper(1+)-induced endothelial cells migration and capillary formation. Almost completely loss of VEGFA-induced internalization of KDR and SLC31A1. Almost completely loss of VEGFA-induced interaction between KDR and SLC31A1. Decreases of 200-fold affinity for copper(1+) ion. Loss of ATOX1 interaction in the absence of copper(1+)."; /evidence="ECO:0000269|PubMed:26745413, ECO:0000269|PubMed:35027734"; MUTAGEN 189; /note="C->S: Markedly decreases the copper(1+) transport activity; when associated with S-161."; /evidence="ECO:0000269|PubMed:16135512
uniprot
proteins
post_translational_modification
PTM: O-Glycosylation at Thr-27 protects from proteolytic cleavage in the N-terminal extracellular domain. {ECO:0000269|PubMed:17525160}.; PTM: Proteolytic cleavage, leading to a truncated form, is facilitated by SLC31A2 (PubMed:24167251) and initiated preferentially by CTSL and to a minor extend by CTSB in endolysosomal compartments (PubMed:24167251, PubMed:27143361). In vitro, is cleaved by CTSL/cathepsin L between residues 8 and 9 from the amino terminus (PubMed:27143361). A post-CTSL/cathepsin L processing occurs to yield to the fully truncated form (PubMed:27143361). {ECO:0000269|PubMed:24167251, ECO:0000269|PubMed:27143361}.; PTM: Sulfenylated at Cys-189 after stimulation with VEGFA, which induces SLC31A1-KDR disulfide bond formation and their co-internalization to early endosomes, driving to a sustained VEGFR2 signaling. {ECO:0000269|PubMed:35027734}.
uniprot
proteins
protein_family
Copper transporter (Ctr) (TC 1.A.56) family
uniprot
proteins
protein_family
SLC31A subfamily
uniprot
proteins
pubmed
11734551
uniprot
proteins
pubmed
12023893
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15326162
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16135512
uniprot
proteins
pubmed
16501047
uniprot
proteins
pubmed
17525160
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
19740744
uniprot
proteins
pubmed
20451502
uniprot
proteins
pubmed
20569931
uniprot
proteins
pubmed
22615137
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23658018
uniprot
proteins
pubmed
24167251
uniprot
proteins
pubmed
24837030
uniprot
proteins
pubmed
26205368
uniprot
proteins
pubmed
26745413
uniprot
proteins
pubmed
26945057
uniprot
proteins
pubmed
27143361
uniprot
proteins
pubmed
30489586
uniprot
proteins
pubmed
31292775
uniprot
proteins
pubmed
32914794
uniprot
proteins
pubmed
33294387
uniprot
proteins
pubmed
35027734
uniprot
proteins
pubmed
35601835
uniprot
proteins
pubmed
35913762
uniprot
proteins
pubmed
36562171
uniprot
proteins
pubmed
9207117
uniprot
proteins
sequence_length
190
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11734551, ECO:0000269|PubMed:12023893, ECO:0000269|PubMed:15326162, ECO:0000269|PubMed:17525160, ECO:0000269|PubMed:20451502, ECO:0000269|PubMed:26205368, ECO:0000269|PubMed:26945057, ECO:0000269|PubMed:35913762}; Multi-pass membrane protein {ECO:0000255}. Early endosome membrane {ECO:0000269|PubMed:26945057}; Multi-pass membrane protein {ECO:0000255}. Recycling endosome membrane {ECO:0000269|PubMed:26945057}; Multi-pass membrane protein {ECO:0000255}. Apical cell membrane {ECO:0000250|UniProtKB:Q8K211}; Multi-pass membrane protein {ECO:0000255}. Late endosome membrane {ECO:0000250|UniProtKB:Q8K211}; Multi-pass membrane protein {ECO:0000255}. Basolateral cell membrane {ECO:0000250|UniProtKB:Q8K211}; Multi-pass membrane protein {ECO:0000255}. Note=The localization is controlled by the intra and extra-cellular copper concentration (PubMed:15326162, PubMed:19740744, PubMed:23658018, PubMed:26205368, PubMed:26945057). 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 (PubMed:15326162, PubMed:19740744, PubMed:23658018, PubMed:26205368, PubMed:26945057). 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 (PubMed:26945057). Localizes to the apical membrane in intestinal epithelial cells (By similarity). Mainly localized on the basolateral side of renal tubular cells (By similarity). Localizes to the neuronal cell body plasma membranes (By similarity). {ECO:0000250|UniProtKB:Q8K211, ECO:0000250|UniProtKB:Q9JK41, ECO:0000269|PubMed:15326162, ECO:0000269|PubMed:19740744, ECO:0000269|PubMed:23658018, ECO:0000269|PubMed:26205368, ECO:0000269|PubMed:26945057}.
uniprot
proteins
transmembrane_region
TRANSMEM 62..82; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 133..153; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 157..177; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins