Q9UPY5 · XCT_HUMAN
- ProteinCystine/glutamate transporter
- GeneSLC7A11
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids501 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
In addition, mediates the import of L-kynurenine leading to anti-ferroptotic signaling propagation required to maintain L-cystine and glutathione homeostasis (PubMed:35245456).
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).
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).
In addition, mediates the import of L-kynurenine leading to anti-ferroptotic signaling propagation required to maintain L-cystine and glutathione homeostasis (PubMed:35245456).
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).
Catalytic activity
- L-cystine(out) + L-glutamate(in) = L-cystine(in) + L-glutamate(out)L-cystine (out)CHEBI:35491
+ L-glutamate (in)CHEBI:29985= L-cystine (in)CHEBI:35491+ L-glutamate (out)CHEBI:29985 - an L-alpha-amino acid(in) + L-kynurenine(out) = an L-alpha-amino acid(out) + L-kynurenine(in)
- L-glutamate(in) + N-acetyl-L-cysteine(out) = L-glutamate(out) + N-acetyl-L-cysteine(in)
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).
Inhibited by (S)-lactate (PubMed:11417227).
Inactivated by p-chloromercuribenzoic acid and p-chloromercuribenzenesulfonic acid (PubMed:14722095).
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
48 μM | L-glutamate | |||||
224 μM | L-glutamate | |||||
110 μM | L-cystine | |||||
92 μM | L-glutamate | |||||
43 μM | L-cystine | |||||
173 μM | L-glutamate |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
6087 pmol/min/mg | toward L-glutamate | ||||
9597 pmol/min/mg | toward L-cystine |
Features
Showing features for binding site.
GO annotations
Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameCystine/glutamate transporter
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9UPY5
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Cell projection, microvillus membrane ; Multi-pass membrane protein
Note: Localized to the microvillous membrane of the placental syncytiotrophoblast.
Features
Showing features for topological domain, transmembrane, intramembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-43 | Cytoplasmic | ||||
Sequence: MVRKPVVSTISKGGYLQGNVNGRLPSLGNKEPPGQEKVQLKRK | ||||||
Transmembrane | 44-64 | Helical | ||||
Sequence: VTLLRGVSIIIGTIIGAGIFI | ||||||
Topological domain | 65-74 | Extracellular | ||||
Sequence: SPKGVLQNTG | ||||||
Transmembrane | 75-95 | Helical | ||||
Sequence: SVGMSLTIWTVCGVLSLFGAL | ||||||
Topological domain | 96-101 | Cytoplasmic | ||||
Sequence: SYAELG | ||||||
Intramembrane | 102-116 | |||||
Sequence: TTIKKSGGHYTYILE | ||||||
Topological domain | 117-130 | Cytoplasmic | ||||
Sequence: VFGPLPAFVRVWVE | ||||||
Transmembrane | 131-150 | Helical | ||||
Sequence: LLIIRPAATAVISLAFGRYI | ||||||
Topological domain | 151-163 | Extracellular | ||||
Sequence: LEPFFIQCEIPEL | ||||||
Transmembrane | 164-179 | Helical | ||||
Sequence: AIKLITAVGITVVMVL | ||||||
Topological domain | 180-193 | Cytoplasmic | ||||
Sequence: NSMSVSWSARIQIF | ||||||
Transmembrane | 194-210 | Helical | ||||
Sequence: LTFCKLTAILIIIVPGV | ||||||
Topological domain | 211-234 | Extracellular | ||||
Sequence: MQLIKGQTQNFKDAFSGRDSSITR | ||||||
Transmembrane | 235-255 | Helical | ||||
Sequence: LPLAFYYGMYAYAGWFYLNFV | ||||||
Topological domain | 256-265 | Cytoplasmic | ||||
Sequence: TEEVENPEKT | ||||||
Transmembrane | 266-286 | Helical | ||||
Sequence: IPLAICISMAIVTIGYVLTNV | ||||||
Topological domain | 287-317 | Extracellular | ||||
Sequence: AYFTTINAEELLLSNAVAVTFSERLLGNFSL | ||||||
Transmembrane | 318-338 | Helical | ||||
Sequence: AVPIFVALSCFGSMNGGVFAV | ||||||
Topological domain | 339-364 | Cytoplasmic | ||||
Sequence: SRLFYVASREGHLPEILSMIHVRKHT | ||||||
Transmembrane | 365-385 | Helical | ||||
Sequence: PLPAVIVLHPLTMIMLFSGDL | ||||||
Topological domain | 386-387 | Extracellular | ||||
Sequence: DS | ||||||
Transmembrane | 388-408 | Helical | ||||
Sequence: LLNFLSFARWLFIGLAVAGLI | ||||||
Topological domain | 409-422 | Cytoplasmic | ||||
Sequence: YLRYKCPDMHRPFK | ||||||
Transmembrane | 423-443 | Helical | ||||
Sequence: VPLFIPALFSFTCLFMVALSL | ||||||
Topological domain | 444-449 | Extracellular | ||||
Sequence: YSDPFS | ||||||
Transmembrane | 450-470 | Helical | ||||
Sequence: TGIGFVITLTGVPAYYLFIIW | ||||||
Topological domain | 471-501 | Cytoplasmic | ||||
Sequence: DKKPRWFRIMSEKITRTLQIILEVVPEEDKL |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 86 | 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. | ||||
Sequence: C → S | ||||||
Mutagenesis | 135 | Loss of L-cystine transport activity. | ||||
Sequence: R → A | ||||||
Mutagenesis | 135 | Loss of L-cystine transport activity. | ||||
Sequence: R → K | ||||||
Mutagenesis | 158 | 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. | ||||
Sequence: C → S | ||||||
Mutagenesis | 191 | Increases sensitivity to erastin-induced ferroptosis. | ||||
Sequence: Q → A | ||||||
Mutagenesis | 197 | 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. | ||||
Sequence: C → S | ||||||
Mutagenesis | 198 | Loss of L-cystine transport activity. Does not affect location at the celle membrane. Does not affect expression level. | ||||
Sequence: K → A | ||||||
Mutagenesis | 254 | Increases resistance to erastin-induced ferroptosis. Decreases sensitivity to erastin-induced inhibition of L-cystine transport activity. | ||||
Sequence: F → A | ||||||
Mutagenesis | 271 | 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. | ||||
Sequence: C → S | ||||||
Mutagenesis | 327 | Does not affect L-glutamate transport activity. Does not affect location at cell membrane Does not affect expression level. | ||||
Sequence: C → A | ||||||
Mutagenesis | 327 | Loss of L-glutamate transport activity. Does not affect location at cell membrane. Does not affect expression level. | ||||
Sequence: C → L | ||||||
Mutagenesis | 327 | 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. | ||||
Sequence: C → S | ||||||
Mutagenesis | 327 | Does not affect L-glutamate transport activity. Does not affect location at cell membrane. Does not affect expression level. | ||||
Sequence: C → T | ||||||
Mutagenesis | 336 | Decreases L-cystine transport activity about 50%. Increases sensitivity to erastin-induced ferroptosis. Significantly decreases the L-cystine transport activity. | ||||
Sequence: F → A | ||||||
Mutagenesis | 336 | Does not affect L-cystine transport activity. | ||||
Sequence: F → Y | ||||||
Mutagenesis | 396 | Loss of L-cystine transport activity. | ||||
Sequence: R → A | ||||||
Mutagenesis | 396 | Loss of L-cystine transport activity. | ||||
Sequence: R → K | ||||||
Mutagenesis | 396 | Loss of L-cystine transport activity. | ||||
Sequence: R → N | ||||||
Mutagenesis | 414 | 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. | ||||
Sequence: C → S | ||||||
Mutagenesis | 435 | 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. | ||||
Sequence: C → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 535 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue, disulfide bond, glycosylation.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000054279 | 1-501 | UniProt | Cystine/glutamate transporter | |||
Sequence: MVRKPVVSTISKGGYLQGNVNGRLPSLGNKEPPGQEKVQLKRKVTLLRGVSIIIGTIIGAGIFISPKGVLQNTGSVGMSLTIWTVCGVLSLFGALSYAELGTTIKKSGGHYTYILEVFGPLPAFVRVWVELLIIRPAATAVISLAFGRYILEPFFIQCEIPELAIKLITAVGITVVMVLNSMSVSWSARIQIFLTFCKLTAILIIIVPGVMQLIKGQTQNFKDAFSGRDSSITRLPLAFYYGMYAYAGWFYLNFVTEEVENPEKTIPLAICISMAIVTIGYVLTNVAYFTTINAEELLLSNAVAVTFSERLLGNFSLAVPIFVALSCFGSMNGGVFAVSRLFYVASREGHLPEILSMIHVRKHTPLPAVIVLHPLTMIMLFSGDLDSLLNFLSFARWLFIGLAVAGLIYLRYKCPDMHRPFKVPLFIPALFSFTCLFMVALSLYSDPFSTGIGFVITLTGVPAYYLFIIWDKKPRWFRIMSEKITRTLQIILEVVPEEDKL | |||||||
Modified residue (large scale data) | 9 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 15 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 26 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 26 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Disulfide bond | 158 | UniProt | Interchain (with C-210 in SLC3A2) | ||||
Sequence: C | |||||||
Glycosylation | 314 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
Ubiquitinated by TRIM26; leading to proteasomal degradation.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in term placenta and primary term cytotrophoblast (PubMed:34120018).
Expressed mainly in the brain, but also in pancreas (PubMed:11417227).
Expressed mainly in the brain, but also in pancreas (PubMed:11417227).
Induction
By oxygen in a concentration-dependent manner (PubMed:11213471).
Up-regulated by S-nitroso-N-acetyl-D-penicillamine (PubMed:11133847).
Up-regulated by S-nitroso-N-acetyl-D-penicillamine (PubMed:11133847).
Gene expression databases
Organism-specific databases
Interaction
Subunit
Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc; this interaction mediates cell membrane localization.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9UPY5 | CD44 P16070 | 4 | EBI-3843348, EBI-490245 | |
BINARY | Q9UPY5 | KRTAP1-1 Q07627 | 3 | EBI-3843348, EBI-11959885 | |
BINARY | Q9UPY5 | KRTAP1-3 Q8IUG1 | 3 | EBI-3843348, EBI-11749135 | |
BINARY | Q9UPY5 | SLC3A2 P08195 | 2 | EBI-3843348, EBI-702356 | |
BINARY | Q9UPY5 | SLC3A2 P08195-4 | 3 | EBI-3843348, EBI-12832276 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Sequence similarities
Belongs to the amino acid-polyamine-organocation (APC) superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length501
- Mass (Da)55,423
- Last updated2000-05-01 v1
- Checksum3EF2648B94A9F59E
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
H0Y9F9 | H0Y9F9_HUMAN | SLC7A11 | 75 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB026891 EMBL· GenBank· DDBJ | BAA82628.1 EMBL· GenBank· DDBJ | mRNA | ||
AF200708 EMBL· GenBank· DDBJ | AAG35592.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ277882 EMBL· GenBank· DDBJ | CAC81905.1 EMBL· GenBank· DDBJ | mRNA | ||
AF252872 EMBL· GenBank· DDBJ | AAK49111.1 EMBL· GenBank· DDBJ | mRNA | ||
AK290359 EMBL· GenBank· DDBJ | BAF83048.1 EMBL· GenBank· DDBJ | mRNA | ||
AK314855 EMBL· GenBank· DDBJ | BAG37372.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471056 EMBL· GenBank· DDBJ | EAX05135.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC012087 EMBL· GenBank· DDBJ | AAH12087.1 EMBL· GenBank· DDBJ | mRNA |