SLC7A11
entrez
23657
canonical
uniprot
Q9UPY5
canonical
ensembl
ENSG00000151012
resolver
ensp
ENSP00000280612
resolver
enst
ENST00000280612
resolver
genesymbol
SLC7A11
resolver
hgnc
HGNC:11059
resolver
uniprot
A8K2U4
resolver
uniprot_entry
XCT_HUMAN
resolver
uniprot_sec
A8K2U4
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by erastin and sulfasalazine (PubMed:35352032). Inhibited by (S)-lactate (PubMed:11417227). Inactivated by p-chloromercuribenzoic acid and p-chloromercuribenzenesulfonic acid (PubMed:14722095). {ECO:0000269|PubMed:11417227, ECO:0000269|PubMed:14722095, ECO:0000269|PubMed:35352032}.
uniprot
proteins
amino_acid_sequence
MVRKPVVSTISKGGYLQGNVNGRLPSLGNKEPPGQEKVQLKRKVTLLRGVSIIIGTIIGAGIFISPKGVLQNTGSVGMSLTIWTVCGVLSLFGALSYAELGTTIKKSGGHYTYILEVFGPLPAFVRVWVELLIIRPAATAVISLAFGRYILEPFFIQCEIPELAIKLITAVGITVVMVLNSMSVSWSARIQIFLTFCKLTAILIIIVPGVMQLIKGQTQNFKDAFSGRDSSITRLPLAFYYGMYAYAGWFYLNFVTEEVENPEKTIPLAICISMAIVTIGYVLTNVAYFTTINAEELLLSNAVAVTFSERLLGNFSLAVPIFVALSCFGSMNGGVFAVSRLFYVASREGHLPEILSMIHVRKHTPLPAVIVLHPLTMIMLFSGDLDSLLNFLSFARWLFIGLAVAGLIYLRYKCPDMHRPFKVPLFIPALFSFTCLFMVALSLYSDPFSTGIGFVITLTGVPAYYLFIIWDKKPRWFRIMSEKITRTLQIILEVVPEEDKL
uniprot
proteins
function
FUNCTION: Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:11133847, PubMed:11417227, PubMed:14722095, PubMed:15151999, PubMed:34880232, PubMed:35245456, PubMed:35352032). Provides L-cystine for the maintenance of the redox balance between extracellular L-cystine and L-cysteine and for the maintenance of the intracellular levels of glutathione that is essential for cells protection from oxidative stress (By similarity). The transport is sodium-independent, electroneutral with a stoichiometry of 1:1, and is drove by the high intracellular concentration of L-glutamate and the intracellular reduction of L-cystine (PubMed:11133847, PubMed:11417227). Acts as an inhibitor of ferroptosis by mediating the import of L-kynurenine leading to anti-ferroptotic signaling propagation required to maintain L-cystine and glutathione homeostasis (PubMed:35245456, PubMed:40246981). Also inhibits ferroptosis by acting as an atypical proton transporter that mediates a slow proton efflux from lysosomes via cystine and glutamate flux (PubMed:40280132). Glutamate and cystine contain side-chain groups that are protonatable in the physiological range of lysosomal pH and cytosolic pH, respectively, enabling a slow lysosomal proton leak through a substrate-as-proton mechanism (PubMed:40280132). Moreover, mediates N-acetyl-L-cysteine uptake into the placenta leading to subsequently down-regulation of pathways associated with oxidative stress, inflammation and apoptosis (PubMed:34120018). In vitro can also transport L-aspartate (PubMed:11417227). May participate in astrocyte and meningeal cell proliferation during development and can provide neuroprotection by promoting glutathione synthesis and delivery from non-neuronal cells such as astrocytes and meningeal cells to immature neurons (By similarity). Controls the production of pheomelanin pigment directly (By similarity). {ECO:0000250|UniProtKB:Q9WTR6, ECO:0000269|PubMed:11133847, ECO:0000269|PubMed:11417227, ECO:0000269|PubMed:14722095, ECO:0000269|PubMed:15151999, ECO:0000269|PubMed:34120018, ECO:0000269|PubMed:34880232, ECO:0000269|PubMed:35245456, ECO:0000269|PubMed:35352032, ECO:0000269|PubMed:40246981, ECO:0000269|PubMed:40280132}.
uniprot
proteins
mass_dalton
55423
uniprot
proteins
mutagenesis
MUTAGEN 86; /note="C->S: Does not affect L-cystine transport activity; when associated with S-158; S-197; S-271; S-327; S-414 and S-435. Does not affect affinity for L-cystine; when associated with S-158; S-197; S-271; S-327; S-414 and S-435. Significantly increases L-glutamate affinity; when associated with S-158; S-197; S-271; S-327; S-414 and S-435. Does not affect inhibition of L-glutamate transport activity by p-chloromercuribenzoic acid and p-chloromercuribenzenesulfonic acid."; /evidence="ECO:0000269|PubMed:14722095, ECO:0000269|PubMed:15151999"; MUTAGEN 135; /note="R->A: Loss of L-cystine transport activity."; /evidence="ECO:0000269|PubMed:34880232"; MUTAGEN 135; /note="R->K: Loss of L-cystine transport activity."; /evidence="ECO:0000269|PubMed:34880232"; MUTAGEN 158; /note="C->S: Does not affect L-cystine transport activity; when associated with S-86; S-197; S-271; S-327; S-414 and S-435. Does not affect affinity for L-cystine; when associated with S-86; S-197; S-271; S-327; S-414 and S-435. Does not affect affinity for L-cystine; when associated with S-86; S-197; S-271; S-327; S-414 and S-435. Significantly increases L-glutamate affinity; when associated with S-86; S-197; S-271; S-327; S-414 and S-435. Does not affect inhibition of L-glutamate transport activity by p-chloromercuribenzoic acid and p-chloromercuribenzenesulfonic acid."; /evidence="ECO:0000269|PubMed:14722095, ECO:0000269|PubMed:15151999"; MUTAGEN 191; /note="Q->A: Increases sensitivity to erastin-induced ferroptosis."; /evidence="ECO:0000269|PubMed:35352032"; MUTAGEN 197; /note="C->S: Does not affect L-cystine transport activity; when associated with S-86; S-158; S-271; S-327; S-414 and S-435. Does not affect affinity for L-cystine; when associated with S-86; S-158; S-271; S-327; S-414 and S-435. Significantly increases L-glutamate affinity; when associated with S-86; S-158; S-271; S-327; S-414 and S-435."; /evidence="ECO:0000269|PubMed:15151999"; MUTAGEN 198; /note="K->A: Loss of L-cystine transport activity. Does not affect location at the celle membrane. Does not affect expression level."; /evidence="ECO:0000269|PubMed:34880232"; MUTAGEN 254; /note="F->A: Increases resistance to erastin-induced ferroptosis. Decreases sensitivity to erastin-induced inhibition of L-cystine transport activity."; /evidence="ECO:0000269|PubMed:35352032"; MUTAGEN 271; /note="C->S: Does not affect L-cystine transport activity; when associated with S-86; S-158; S-197; S-327; S-414 and S-435. Does not affect affinity for L-cystine; when associated with S-86; S-158; S-197; S-327; S-414 and S-435. Significantly increases L-glutamate affinity; when associated with S-86; S-158; S-197; S-327; S-414 and S-435. Does not affect inhibition of L-glutamate transport activity by p-chloromercuribenzoic acid and p-chloromercuribenzenesulfonic acid."; /evidence="ECO:0000269|PubMed:14722095, ECO:0000269|PubMed:15151999"; MUTAGEN 327; /note="C->A: Does not affect L-glutamate transport activity. Does not affect location at cell membrane Does not affect expression level."; /evidence="ECO:0000269|PubMed:14722095"; MUTAGEN 327; /note="C->L: Loss of L-glutamate transport activity. Does not affect location at cell membrane. Does not affect expression level."; /evidence="ECO:0000269|PubMed:14722095"; MUTAGEN 327; /note="C->S: Does not affect L-cystine transport activity; when associated with S-86; S-158; S-197; S-271; S-414 and S-435. Does not affect affinity for L-cystine; when associated with S-86; S-158; S-197; S-271; S-414 and S-435. Significantly increases L-glutamate affinity; when associated with S-86; S-158; S-197; S-271; S-414 and S-435. Loss of inhibitio nof L-glutamate transport activity by p-chloromercuribenzoic acid and p-chloromercuribenzenesulfonic acid. Decrease L-glutamate transport activity. Does not affect location at cell membrane. Does not affect expression level."; /evidence="ECO:0000269|PubMed:14722095, ECO:0000269|PubMed:15151999"; MUTAGEN 327; /note="C->T: Does not affect L-glutamate transport activity. Does not affect location at cell membrane. Does not affect expression level."; /evidence="ECO:0000269|PubMed:14722095"; MUTAGEN 336; /note="F->A: Decreases L-cystine transport activity about 50%. Increases sensitivity to erastin-induced ferroptosis. Significantly decreases the L-cystine transport activity."; /evidence="ECO:0000269|PubMed:34880232, ECO:0000269|PubMed:35352032"; MUTAGEN 336; /note="F->Y: Does not affect L-cystine transport activity."; /evidence="ECO:0000269|PubMed:34880232"; MUTAGEN 388..389; /note="LL->AA: Decreased localization to lysosomes; when associated with S-409."; /evidence="ECO:0000269|PubMed:40280132"; MUTAGEN 396; /note="R->A: Loss of L-cystine transport activity."; /evidence="ECO:0000269|PubMed:34880232"; MUTAGEN 396; /note="R->K: Loss of L-cystine transport activity."; /evidence="ECO:0000269|PubMed:34880232"; MUTAGEN 396; /note="R->N: Loss of L-cystine transport activity."; /evidence="ECO:0000269|PubMed:34880232"; MUTAGEN 409; /note="Y->S: Decreased localization to lysosomes; when associated with 388-A-A-389."; /evidence="ECO:0000269|PubMed:40280132"; MUTAGEN 414; /note="C->S: Does not affect L-cystine transport activity; when associated with S-86; S-158; S-197; S-271; S-327 and S-435. Does not affect affinity for L-cystine; when associated with S-86; S-158; S-197; S-271; S-327 and S-435. Significantly increases L-glutamate affinity; when associated with S-86; S-158; S-197; S-271; S-327 and S-435. Does not affect inhibition of L-glutamate transport activity by p-chloromercuribenzoic acid and p-chloromercuribenzenesulfonic acid."; /evidence="ECO:0000269|PubMed:14722095, ECO:0000269|PubMed:15151999"; MUTAGEN 435; /note="C->S: Does not affect L-cystine transport activity; when associated with S-86; S-158; S-197; S-271; S-327 and S-414. Does not affect affinity for L-cystine; when associated with S-86; S-158; S-197; S-271; S-327 and S-414. Significantly increases L-glutamate affinity; when associated with S-86; S-158; S-197; S-271; S-327 and S-414. Does not affect inhibition of L-glutamate transport activity by p-chloromercuribenzoic acid and p-chloromercuribenzenesulfonic acid."; /evidence="ECO:0000269|PubMed:14722095, ECO:0000269|PubMed:15151999
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated by TRIM26; leading to proteasomal degradation. {ECO:0000250|UniProtKB:Q9WTR6}.
uniprot
proteins
protein_family
Amino acid-polyamine-organocation (APC) superfamily
uniprot
proteins
protein_family
L-type amino acid transporter (LAT) (TC 2.A.3.8) family
uniprot
proteins
pubmed
11133847
uniprot
proteins
pubmed
11213471
uniprot
proteins
pubmed
11417227
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14722095
uniprot
proteins
pubmed
15151999
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
34120018
uniprot
proteins
pubmed
34880232
uniprot
proteins
pubmed
35245456
uniprot
proteins
pubmed
35352032
uniprot
proteins
pubmed
40246981
uniprot
proteins
pubmed
40280132
uniprot
proteins
sequence_length
501
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11417227, ECO:0000269|PubMed:15151999, ECO:0000269|PubMed:34880232, ECO:0000269|PubMed:40246981}; Multi-pass membrane protein {ECO:0000269|PubMed:15151999}. Lysosome membrane {ECO:0000269|PubMed:40280132}; Multi-pass membrane protein {ECO:0000255}. Cell projection, microvillus membrane {ECO:0000269|PubMed:34120018}; Multi-pass membrane protein {ECO:0000255}. Note=Localized to the microvillous membrane of the placental syncytiotrophoblast (PubMed:34120018). Plasma membrane localization is impaired by LGALS13 (PubMed:40246981). {ECO:0000269|PubMed:34120018, ECO:0000269|PubMed:40246981}.
uniprot
proteins
transmembrane_region
TRANSMEM 44..64; /note="Helical"; /evidence="ECO:0000305|PubMed:15151999"; TRANSMEM 75..95; /note="Helical"; /evidence="ECO:0000305|PubMed:15151999"; TRANSMEM 131..150; /note="Helical"; /evidence="ECO:0000305|PubMed:15151999"; TRANSMEM 164..179; /note="Helical"; /evidence="ECO:0000305|PubMed:15151999"; TRANSMEM 194..210; /note="Helical"; /evidence="ECO:0000305|PubMed:15151999"; TRANSMEM 235..255; /note="Helical"; /evidence="ECO:0000305|PubMed:15151999"; TRANSMEM 266..286; /note="Helical"; /evidence="ECO:0000305|PubMed:15151999"; TRANSMEM 318..338; /note="Helical"; /evidence="ECO:0000305|PubMed:15151999"; TRANSMEM 365..385; /note="Helical"; /evidence="ECO:0000305|PubMed:15151999"; TRANSMEM 388..408; /note="Helical"; /evidence="ECO:0000305|PubMed:15151999"; TRANSMEM 423..443; /note="Helical"; /evidence="ECO:0000305|PubMed:15151999"; TRANSMEM 450..470; /note="Helical"; /evidence="ECO:0000305|PubMed:15151999
uniprot
proteins