SLC7A11 (xCT) is the light chain (catalytic subunit) of system xc-, a heterodimeric cystine/glutamate antiporter that forms a disulfide-linked heterodimer with SLC3A2 (4F2hc, the heavy chain). It mediates Na+-independent, electroneutral exchange of extracellular L-cystine for intracellular L-glutamate at ~1:1 stoichiometry (Km ~43-110 uM for cystine, ~48-224 uM for glutamate). The imported cystine is reduced intracellularly to cysteine, providing the rate-limiting substrate for glutathione (GSH) synthesis. This positions SLC7A11 as a critical regulator of cellular redox homeostasis and a suppressor of ferroptosis through the GSH/GPX4 axis. Recent studies have identified additional functions including L-kynurenine transport and a slow lysosomal H+ efflux pathway carried by the downward flux of cystine and glutamate rather than by a proton-conducting pore.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0015327 cystine:glutamate antiporter activity | IDA PMID:11417227 Identification and characterisation of human xCT that co-exp... | ACCEPT | Summary: This is the primary molecular function of SLC7A11. PMID:11417227 (Bassi et al., 2001) directly demonstrated that human xCT co-expressed with 4F2hc mediates Na+-independent cystine/glutamate antiport with Km values of 43 uM for cystine and 92 uM for glutamate. Reason: Core molecular function established by direct transport assays in reconstituted systems. Multiple studies confirm this antiporter activity with defined kinetics. Supporting Evidence: PMID:11417227 The amino acid transport activity induced by the co-expression of human 4F2hc and xCT in Xenopus oocytes was sodium independent and specific for L-cystine, L-glutamate and L-aspartate file:human/SLC7A11/SLC7A11-deep-research-falcon.md System xcβ exchanges extracellular L-cystine for intracellular L-glutamate at approximately 1:1 stoichiometry, enabling cystine import that is reduced intracellularly to cysteine for glutathione (GSH) synthesis; reported Km values are ~50 Β΅M (cystine) and ~200 Β΅M (glutamate) |
| GO:0015327 cystine:glutamate antiporter activity | IDA PMID:15151999 Membrane topology of system xc- light subunit reveals a re-e... | ACCEPT | Summary: PMID:15151999 (Gasol et al., 2004) characterized membrane topology and transport function, reporting Km of 110 uM for cystine and 224 uM for glutamate. Reason: Confirms core antiporter activity with detailed kinetic characterization and membrane topology analysis. Supporting Evidence: PMID:15151999 4F2hc/xCT elicits sodium-independent exchange of anionic L-cysteine and L-glutamate (system x(c)(-)) |
| GO:0015327 cystine:glutamate antiporter activity | IDA PMID:34120018 N-acetylcysteine, xCT and suppression of Maxi-chloride chann... | ACCEPT | Summary: PMID:34120018 (Lofthouse et al., 2021) demonstrated xCT-mediated cystine/glutamate antiport in human placenta, including N-acetylcysteine transport. Reason: Confirms antiporter activity in physiologically relevant tissue context (placenta). Supporting Evidence: PMID:34120018 Maternoplacental N-acetylcysteine administration stimulated intracellular glutamate efflux suggesting a role of the exchange transporter xCT |
| GO:0015327 cystine:glutamate antiporter activity | RCA PMID:34880232 Molecular basis for redox control by the human cystine/gluta... | ACCEPT | Summary: PMID:34880232 (Parker et al., 2021) provided cryo-EM structure of xCT-4F2hc complex with L-glutamate bound, revealing molecular basis of antiporter function. Reason: Structural evidence confirming antiporter mechanism with substrate-bound structure. Supporting Evidence: PMID:34880232 Here we present the cryo-EM structure of system xc- in both the apo and glutamate bound states |
| GO:0015327 cystine:glutamate antiporter activity | IDA PMID:35352032 The structure of erastin-bound xCT-4F2hc complex reveals mol... | ACCEPT | Summary: PMID:35352032 (Yan et al., 2022) provided erastin-bound xCT-4F2hc structure showing inhibitor binding site and transport mechanism. Reason: Structural and functional evidence for antiporter activity with inhibitor binding site. Supporting Evidence: PMID:35352032 The small-molecule compound erastin induces ferroptosis via inhibiting the cystine-glutamate antiporter system xcβ |
| GO:0015327 cystine:glutamate antiporter activity | IDA PMID:35245456 Kynurenine importation by SLC7A11 propagates anti-ferroptoti... | ACCEPT | Summary: PMID:35245456 (Fiore et al., 2022) confirmed cystine:glutamate antiport while also discovering kynurenine transport capability. Reason: Confirms core antiporter function in context of expanded substrate repertoire study. Supporting Evidence: PMID:35245456 We show that this effect requires KYN export from IDO1-expressing cells, which is then available for non-IDO1-expressing cells via SLC7A11, the central transporter involved in ferroptosis suppression |
| GO:0015327 cystine:glutamate antiporter activity | IDA PMID:40280132 SLC7A11 is an unconventional H(+) transporter in lysosomes. | ACCEPT | Summary: PMID:40280132 confirmed canonical cystine:glutamate antiporter function while discovering a slow lysosomal H+ efflux pathway carried by cystine/glutamate flux. Reason: Confirms core antiporter function in context of study expanding known functions. Supporting Evidence: PMID:40280132 SLC7A11, the protein target of the ferroptosis-inducing compound erastin, mediates a slow lysosomal H+ leak through downward flux of cystine and glutamate |
| GO:0015327 cystine:glutamate antiporter activity | TAS PMID:10206947 Cloning and expression of a plasma membrane cystine/glutamat... | ACCEPT | Summary: PMID:10206947 (Sato et al., 1999) was the original cloning paper identifying xCT as the light chain of system xc-. Reason: Foundational paper establishing identity and function of xCT. Supporting Evidence: PMID:10206947 The latter protein, named xCT, showed a significant homology with those recently reported to mediate cationic or zwitterionic amino acid transport when co-expressed with 4F2hc |
| GO:0015811 L-cystine transport | IEA GO_REF:0000120 | ACCEPT | Summary: Automated annotation based on ARBA rules and orthology. L-cystine transport is the primary biological process mediated by SLC7A11. Reason: Core biological process - IEA is redundant with multiple IDA annotations but correctly captures the function. |
| GO:0015811 L-cystine transport | IDA PMID:11417227 Identification and characterisation of human xCT that co-exp... | ACCEPT | Summary: Direct demonstration of L-cystine uptake via xCT/4F2hc complex with Km = 43 uM. Reason: Core biological process with direct kinetic evidence. Supporting Evidence: PMID:11417227 The amino acid transport activity induced by the co-expression of human 4F2hc and xCT in Xenopus oocytes was sodium independent and specific for L-cystine, L-glutamate and L-aspartate |
| GO:0015811 L-cystine transport | IDA PMID:15151999 Membrane topology of system xc- light subunit reveals a re-e... | ACCEPT | Summary: Confirmed cystine transport with Km = 110 uM in detailed topology study. Reason: Core biological process confirmed with kinetic parameters. Supporting Evidence: PMID:15151999 4F2hc/xCT elicits sodium-independent exchange of anionic L-cysteine and L-glutamate (system x(c)(-)) |
| GO:0015811 L-cystine transport | IDA PMID:34880232 Molecular basis for redox control by the human cystine/gluta... | ACCEPT | Summary: Structural study confirming cystine transport mechanism. Reason: Core biological process supported by structural evidence. Supporting Evidence: PMID:34880232 Under redox stress conditions mammalian cells use a specific system to increase cystine uptake to increase GSH synthesis, termed system xcβ a dedicated cystine-glutamate antiporter |
| GO:0015811 L-cystine transport | IDA PMID:35352032 The structure of erastin-bound xCT-4F2hc complex reveals mol... | ACCEPT | Summary: Confirmed cystine transport in context of erastin inhibition study. Reason: Core biological process with inhibitor sensitivity data. Supporting Evidence: PMID:35352032 inhibiting xCT impairs cystine uptake, causing an accumulation of ROS and suppressing tumor growth |
| GO:0015811 L-cystine transport | IDA PMID:11133847 Structure, function, and regulation of human cystine/glutama... | ACCEPT | Summary: PMID:11133847 (Bridges et al., 2001) characterized xCT function in retinal pigment epithelial cells. Reason: Core biological process demonstrated in RPE cells. Supporting Evidence: PMID:11133847 Coexpression of human xCT with 4F2hc in HeLa cells leads to the induction of cystine and glutamate uptake with characteristics similar to that of x(c)(-) |
| GO:0015811 L-cystine transport | IDA PMID:11213471 Molecular cloning and expression of human xCT, the light cha... | ACCEPT | Summary: PMID:11213471 (Sato et al., 2000) original molecular cloning paper confirming cystine transport function. Reason: Foundational paper establishing cystine transport function. Supporting Evidence: PMID:11213471 Transport of system xc- is an exchange agency with high specificity for anionic form of cystine and glutamate |
| GO:0015813 L-glutamate transmembrane transport | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA annotation capturing glutamate export function of the antiporter. Reason: Core biological process - glutamate efflux is integral to antiporter mechanism. |
| GO:0015813 L-glutamate transmembrane transport | IDA PMID:11417227 Identification and characterisation of human xCT that co-exp... | ACCEPT | Summary: Direct demonstration of glutamate efflux coupled to cystine import with Km = 92 uM. Reason: Core biological process with kinetic evidence. Supporting Evidence: PMID:11417227 This activity also functioned in an exchange mode (e.g. cystine/glutamate) with a substrate stoichiometry of 1:1 |
| GO:0015813 L-glutamate transmembrane transport | IDA PMID:15151999 Membrane topology of system xc- light subunit reveals a re-e... | ACCEPT | Summary: Glutamate transport confirmed with Km = 224 uM. Reason: Core biological process with kinetic parameters. Supporting Evidence: PMID:15151999 4F2hc/xCT elicits sodium-independent exchange of anionic L-cysteine and L-glutamate (system x(c)(-)) |
| GO:0015813 L-glutamate transmembrane transport | IDA PMID:34880232 Molecular basis for redox control by the human cystine/gluta... | ACCEPT | Summary: Structural study with glutamate-bound structure. Reason: Core biological process with structural evidence of glutamate binding. Supporting Evidence: PMID:34880232 Here we present the cryo-EM structure of system xc- in both the apo and glutamate bound states |
| GO:0015813 L-glutamate transmembrane transport | IDA PMID:35352032 The structure of erastin-bound xCT-4F2hc complex reveals mol... | ACCEPT | Summary: Glutamate transport in context of erastin inhibition. Reason: Core biological process confirmed. Supporting Evidence: PMID:35352032 The small-molecule compound erastin induces ferroptosis via inhibiting the cystine-glutamate antiporter system xcβ |
| GO:0015813 L-glutamate transmembrane transport | IDA PMID:11133847 Structure, function, and regulation of human cystine/glutama... | ACCEPT | Summary: Glutamate transport in RPE cells. Reason: Core biological process in physiological context. Supporting Evidence: PMID:11133847 the uptake of glutamate in the absence of Na(+) occurs exclusively via x(c)(-) |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Automated annotation for plasma membrane localization. Reason: Core localization - xCT functions primarily at the plasma membrane. |
| GO:0005886 plasma membrane | IDA PMID:11417227 Identification and characterisation of human xCT that co-exp... | ACCEPT | Summary: Direct demonstration of plasma membrane localization. Reason: Core localization established by immunofluorescence and functional studies. Supporting Evidence: PMID:11417227 The amino acid transport activity induced by the co-expression of human 4F2hc and xCT in Xenopus oocytes was sodium independent and specific for L-cystine, L-glutamate and L-aspartate |
| GO:0005886 plasma membrane | IDA PMID:15151999 Membrane topology of system xc- light subunit reveals a re-e... | ACCEPT | Summary: Membrane topology study confirming plasma membrane localization. Reason: Core localization with detailed topology mapping. Supporting Evidence: PMID:15151999 we propose a topological model for xCT of 12 transmembrane domains with the N and C termini located inside the cell |
| GO:0005886 plasma membrane | IDA PMID:40246981 Galectin-13 reduces membrane localization of SLC7A11 for fer... | ACCEPT | Summary: PMID:40246981 studied galectin-13-mediated regulation of SLC7A11 membrane localization. Reason: Confirms plasma membrane as functional location. Supporting Evidence: PMID:40246981 Galectin-13, which binds to CD44 and inhibits the plasma membrane localization of SLC7A11 in neighboring cells, thereby accelerating neighboring cell death and promoting ferroptosis propagation |
| GO:0005886 plasma membrane | IPI PMID:34880232 Molecular basis for redox control by the human cystine/gluta... | ACCEPT | Summary: Co-localization with SLC3A2 at plasma membrane in structural study. Reason: Core localization confirmed through complex formation. Supporting Evidence: PMID:34880232 The light subunit of human xc- transporter, xCT, (SLC7A11), consists of 12 transmembrane helices (TMs) |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-375131 | ACCEPT | Summary: Reactome pathway annotation for basigin interactions at plasma membrane. Reason: Core localization supported by pathway database. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-378513 | ACCEPT | Summary: Reactome pathway for SLC7A11-mediated cystine/glutamate exchange. Reason: Core localization in transport pathway context. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9761841 | ACCEPT | Summary: Reactome NFE2L2-dependent SLC7A11 expression pathway. Reason: Core localization in regulatory pathway context. |
| GO:0110076 negative regulation of ferroptosis | IDA PMID:40246981 Galectin-13 reduces membrane localization of SLC7A11 for fer... | ACCEPT | Summary: PMID:40246981 demonstrated that SLC7A11 suppresses ferroptosis; galectin-13 reduces membrane SLC7A11 to propagate ferroptosis. Reason: Core function - SLC7A11 is a central suppressor of ferroptosis through cystine import and GSH/GPX4 pathway. This is one of the most well-established physiological consequences of xCT function. Supporting Evidence: PMID:40246981 Galectin-13, which binds to CD44 and inhibits the plasma membrane localization of SLC7A11 in neighboring cells, thereby accelerating neighboring cell death and promoting ferroptosis propagation |
| GO:0110076 negative regulation of ferroptosis | IDA PMID:40280132 SLC7A11 is an unconventional H(+) transporter in lysosomes. | ACCEPT | Summary: PMID:40280132 confirmed anti-ferroptotic function while discovering lysosomal role. Reason: Core function confirmed in context of expanded functional characterization. Supporting Evidence: PMID:40280132 SLC7A11 deficiency or inhibition caused lysosomal over-acidification, reduced degradation, accumulation of storage materials, and ferroptosis |
| GO:0110076 negative regulation of ferroptosis | IDA PMID:35245456 Kynurenine importation by SLC7A11 propagates anti-ferroptoti... | ACCEPT | Summary: PMID:35245456 showed kynurenine import via SLC7A11 propagates anti-ferroptotic signaling. Reason: Core function demonstrated through novel kynurenine pathway. Supporting Evidence: PMID:35245456 We show that this effect requires KYN export from IDO1-expressing cells, which is then available for non-IDO1-expressing cells via SLC7A11, the central transporter involved in ferroptosis suppression |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location annotation based on lysosomal membrane localization. Reason: Recently validated secondary localization - IDA evidence in PMID:40280132 confirms lysosomal membrane localization. |
| GO:0005765 lysosomal membrane | IDA PMID:40280132 SLC7A11 is an unconventional H(+) transporter in lysosomes. | ACCEPT | Summary: PMID:40280132 directly demonstrated SLC7A11 localization and H+ transport activity at lysosomal membranes. Reason: Novel secondary localization with direct experimental evidence for functional role at lysosomes. Supporting Evidence: PMID:40280132 SLC7A11, the protein target of the ferroptosis-inducing compound erastin, mediates a slow lysosomal H+ leak through downward flux of cystine and glutamate |
| GO:0015252 proton channel activity | IDA PMID:40280132 SLC7A11 is an unconventional H(+) transporter in lysosomes. | MODIFY | Summary: PMID:40280132 showed SLC7A11 mediates a slow lysosomal H+ leak, but via downward flux of cystine and glutamate rather than through a proton-conducting pore. Reason: The H+ transport itself is experimentally supported and is retained, but 'channel' is the wrong mechanism class. GO:0015252 is defined as facilitated diffusion 'through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism', and the source reports the opposite: the H+ flux is carried by the downward movement of cystine and glutamate, i.e. by the antiporter's own protonatable substrates. The source calls SLC7A11 an 'unconventional H+ transporter'/'transport conduit' and explicitly contrasts it with the fast H+ leak through TMEM175 channels. Modified to the mechanism-neutral transporter term. Proposed replacements: proton transmembrane transporter activity Supporting Evidence: PMID:40280132 SLC7A11, the protein target of the ferroptosis-inducing compound erastin, mediates a slow lysosomal H+ leak through downward flux of cystine and glutamate PMID:40280132 These studies have revealed an unconventional H+ transport conduit |
| GO:0022840 leak channel activity | IDA PMID:40280132 SLC7A11 is an unconventional H(+) transporter in lysosomes. | MODIFY | Summary: PMID:40280132 showed SLC7A11 mediates a slow lysosomal H+ leak, but via downward flux of cystine and glutamate rather than through a proton-conducting pore. Reason: The H+ transport itself is experimentally supported and is retained, but 'channel' is the wrong mechanism class. GO:0022840 (leak channel activity) likewise implies a channel; GO:0015252 is defined as facilitated diffusion 'through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism', and the source reports the opposite: the H+ flux is carried by the downward movement of cystine and glutamate, i.e. by the antiporter's own protonatable substrates. The source calls SLC7A11 an 'unconventional H+ transporter'/'transport conduit' and explicitly contrasts it with the fast H+ leak through TMEM175 channels. Modified to the mechanism-neutral transporter term. Proposed replacements: proton transmembrane transporter activity Supporting Evidence: PMID:40280132 SLC7A11, the protein target of the ferroptosis-inducing compound erastin, mediates a slow lysosomal H+ leak through downward flux of cystine and glutamate PMID:40280132 These studies have revealed an unconventional H+ transport conduit |
| GO:0022840 leak channel activity | IDA PMID:40280132 SLC7A11 is an unconventional H(+) transporter in lysosomes. | MODIFY | Summary: PMID:40280132 showed SLC7A11 mediates a slow lysosomal H+ leak, but via downward flux of cystine and glutamate rather than through a proton-conducting pore. Reason: The H+ transport itself is experimentally supported and is retained, but 'channel' is the wrong mechanism class. GO:0022840 (leak channel activity) likewise implies a channel; GO:0015252 is defined as facilitated diffusion 'through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism', and the source reports the opposite: the H+ flux is carried by the downward movement of cystine and glutamate, i.e. by the antiporter's own protonatable substrates. The source calls SLC7A11 an 'unconventional H+ transporter'/'transport conduit' and explicitly contrasts it with the fast H+ leak through TMEM175 channels. Modified to the mechanism-neutral transporter term. Proposed replacements: proton transmembrane transporter activity Supporting Evidence: PMID:40280132 SLC7A11, the protein target of the ferroptosis-inducing compound erastin, mediates a slow lysosomal H+ leak through downward flux of cystine and glutamate PMID:40280132 These studies have revealed an unconventional H+ transport conduit |
| GO:0035752 lysosomal lumen pH elevation | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer from mouse ortholog. Reason: Supported by direct experimental evidence in PMID:40280132 demonstrating lysosomal pH elevation via SLC7A11-mediated H+ efflux. |
| GO:0035752 lysosomal lumen pH elevation | IDA PMID:40280132 SLC7A11 is an unconventional H(+) transporter in lysosomes. | ACCEPT | Summary: PMID:40280132 demonstrated that SLC7A11-mediated H+ efflux elevates lysosomal lumen pH. Reason: Novel biological process with direct experimental evidence. Supporting Evidence: PMID:40280132 SLC7A11 deficiency or inhibition caused lysosomal over-acidification, reduced degradation, accumulation of storage materials, and ferroptosis |
| GO:1902600 proton transmembrane transport | IDA PMID:40280132 SLC7A11 is an unconventional H(+) transporter in lysosomes. | ACCEPT | Summary: PMID:40280132 demonstrated proton transport activity at lysosomal membranes. Reason: Biological process supported by the H+ transport activity reported in the source. Supporting Evidence: PMID:40280132 SLC7A11, the protein target of the ferroptosis-inducing compound erastin, mediates a slow lysosomal H+ leak through downward flux of cystine and glutamate |
| GO:1902600 proton transmembrane transport | IDA PMID:40280132 SLC7A11 is an unconventional H(+) transporter in lysosomes. | ACCEPT | Summary: Duplicate annotation in GOA - same evidence as above. Reason: Same evidence supports proton transmembrane transport. Supporting Evidence: PMID:40280132 SLC7A11 deficiency or inhibition caused lysosomal over-acidification, reduced degradation, accumulation of storage materials, and ferroptosis |
| GO:0140924 L-kynurenine transmembrane transport | IDA PMID:35245456 Kynurenine importation by SLC7A11 propagates anti-ferroptoti... | ACCEPT | Summary: PMID:35245456 (Fiore et al., 2022) discovered that SLC7A11 imports L-kynurenine, a tryptophan metabolite, which propagates anti-ferroptotic signaling. Reason: Novel expanded substrate specificity with direct experimental evidence. Kynurenine import contributes to anti-ferroptotic function. Supporting Evidence: PMID:35245456 We show that this effect requires KYN export from IDO1-expressing cells, which is then available for non-IDO1-expressing cells via SLC7A11, the central transporter involved in ferroptosis suppression |
| GO:0140926 L-kynurenine transmembrane transporter activity | IDA PMID:35245456 Kynurenine importation by SLC7A11 propagates anti-ferroptoti... | ACCEPT | Summary: PMID:35245456 demonstrated L-kynurenine transporter activity for SLC7A11. Reason: Novel molecular function - expanded substrate specificity beyond cystine/glutamate. Supporting Evidence: PMID:35245456 We show that this effect requires KYN export from IDO1-expressing cells, which is then available for non-IDO1-expressing cells via SLC7A11, the central transporter involved in ferroptosis suppression |
| GO:0003333 amino acid transmembrane transport | IBA GO_REF:0000033 | MODIFY | Summary: IBA annotation from phylogenetic inference. While technically correct, this term is too general for a transporter with well-characterized substrate specificity. Reason: Too general. SLC7A11 specifically transports L-cystine and L-glutamate as an antiporter, plus recently discovered L-kynurenine. The more specific terms GO:0015811 (L-cystine transport) and GO:0015813 (L-glutamate transmembrane transport) are more appropriate. Proposed replacements: L-cystine transport L-glutamate transmembrane transport |
| GO:0015179 L-amino acid transmembrane transporter activity | IBA GO_REF:0000033 | MODIFY | Summary: IBA annotation from phylogenetic inference. Too general for a transporter with well-characterized antiporter mechanism. Reason: Too general. SLC7A11 has cystine:glutamate antiporter activity (GO:0015327), which is the appropriate specific term. Proposed replacements: cystine:glutamate antiporter activity |
| GO:0006865 amino acid transport | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: IEA from InterPro domain. Too general for well-characterized transporter. Reason: Too general. The specific transport processes (L-cystine, L-glutamate) are better captured by more specific annotations already present. |
| GO:0022857 transmembrane transporter activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: IEA from InterPro annotation. Too general for well-characterized antiporter. Reason: Too general. GO:0015327 (cystine:glutamate antiporter activity) is the appropriate specific molecular function. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: IEA from InterPro. Very general biological process. Reason: Too general. Specific transport processes are well-annotated. |
| GO:0016020 membrane | IEA GO_REF:0000120 | MODIFY | Summary: IEA annotation - too general for well-characterized membrane protein. Reason: Too general. SLC7A11 is specifically localized to plasma membrane (primary) and lysosomal membrane (secondary), both of which are already annotated. Proposed replacements: plasma membrane |
| GO:0016020 membrane | TAS PMID:10206947 Cloning and expression of a plasma membrane cystine/glutamat... | MODIFY | Summary: TAS annotation from original cloning paper. Too general. Reason: Too general. Original paper demonstrated plasma membrane localization. Proposed replacements: plasma membrane Supporting Evidence: PMID:10206947 The latter protein, named xCT, showed a significant homology with those recently reported to mediate cationic or zwitterionic amino acid transport when co-expressed with 4F2hc |
| GO:0089718 amino acid import across plasma membrane | IDA PMID:11417227 Identification and characterisation of human xCT that co-exp... | MODIFY | Summary: IDA from functional characterization study. While correct, this is less specific than the available terms. Reason: Partially accurate but less specific. SLC7A11 imports L-cystine (not general amino acids) in exchange for glutamate export. GO:0015811 (L-cystine transport) is more specific and accurate. Proposed replacements: L-cystine transport Supporting Evidence: PMID:11417227 The amino acid transport activity induced by the co-expression of human 4F2hc and xCT in Xenopus oocytes was sodium independent and specific for L-cystine, L-glutamate and L-aspartate |
| GO:0043067 regulation of programmed cell death | IEA GO_REF:0000117 | MODIFY | Summary: ARBA annotation linking xCT to cell death regulation. Too vague. Reason: Too general. SLC7A11 specifically negatively regulates ferroptosis (GO:0110076), a specific form of regulated cell death, through its role in GSH synthesis. Proposed replacements: negative regulation of ferroptosis |
| GO:0005515 protein binding | IPI PMID:21397861 CD44 variant regulates redox status in cancer cells by stabi... | REMOVE | Summary: PMID:21397861 (Ishimoto et al., 2011) showed CD44 variant interaction stabilizes xCT to regulate redox status in cancer cells. Reason: "Protein binding" is uninformative per GO curation guidelines. The specific interaction with CD44 variant (CD44v) that stabilizes xCT would be better captured by a more specific term if available. Supporting Evidence: PMID:21397861 CD44 variant (CD44v) interacts with xCT, a glutamate-cystine transporter, and controls the intracellular level of reduced glutathione (GSH) |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | REMOVE | Summary: High-throughput protein interaction study. Reason: "Protein binding" is uninformative. HT-PPI studies often capture non-specific or context-dependent interactions. Supporting Evidence: PMID:27173435 Here we use affinity proteomics, genetics and cell biology to interrogate cilia |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary protein interactome mapping study. Detected interactions with SLC3A2-4 isoform and keratin-associated proteins. Reason: "Protein binding" is uninformative. The SLC3A2 interaction is essential for function and better captured by complex formation annotations; keratin interactions may be non-specific. Supporting Evidence: PMID:32296183 Here we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI' |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary protein interactome mapping study - additional interaction. Reason: "Protein binding" is uninformative per GO guidelines. Supporting Evidence: PMID:32296183 Here we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI' |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary protein interactome mapping study - third interaction. Reason: "Protein binding" is uninformative per GO guidelines. Supporting Evidence: PMID:32296183 Here we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI' |
| GO:0005515 protein binding | IPI PMID:34880232 Molecular basis for redox control by the human cystine/gluta... | REMOVE | Summary: Structural study showing xCT-SLC3A2 complex. The interaction with SLC3A2 is essential for function. Reason: "Protein binding" is uninformative. The xCT-SLC3A2 heterodimer formation is a functional requirement, not just protein binding. This is better represented by the complex formation in ComplexPortal (CPX-8190). Supporting Evidence: PMID:34880232 Here we present the cryo-EM structure of system xc- in both the apo and glutamate bound states |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Multimodal cell maps study - high-throughput protein interaction data. Reason: "Protein binding" is uninformative per GO guidelines. Supporting Evidence: PMID:40205054 Here we construct a global map of human subcellular architecture through joint measurement of biophysical interactions and immunofluorescence images for over 5,100 proteins |
| GO:0005515 protein binding | IPI PMID:40355756 The solute carrier superfamily interactome. | REMOVE | Summary: Solute carrier superfamily interactome study detecting SLC7A11-SLC3A2 interaction. Reason: "Protein binding" is uninformative. The SLC3A2 interaction is essential for heterodimer function and better captured by functional annotations. Supporting Evidence: PMID:40355756 Here, we used a systematic AP-MS approach to determine the protein interaction network of human solute carriers |
| GO:0009986 cell surface | IDA PMID:25063885 KSHV attachment and entry are dependent on Ξ±VΞ²3 integrin loc... | ACCEPT | Summary: PMID:25063885 detected SLC7A11 at cell surface in context of KSHV entry study. Reason: Acceptable localization annotation - cell surface is parent of plasma membrane and represents the functionally relevant location for the transporter. Supporting Evidence: PMID:25063885 the presence of CD98 and heparan sulfate (HS), the putative attachment receptor, was more variable |
| GO:0031528 microvillus membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular location annotation based on placental syncytiotrophoblast microvillus membrane localization. Reason: Cell type-specific localization in placenta. This is a specialized localization, not universally applicable. Supporting Evidence: PMID:34120018 xCT, which was localised to the microvillous membrane of the placental syncytiotrophoblast |
| GO:0031526 brush border membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer from mouse ortholog - intestinal/renal brush border. Reason: Cell type-specific localization in polarized epithelia. Not the primary localization but relevant in specific tissue contexts. |
| GO:0045177 apical part of cell | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer from mouse ortholog. Reason: Cell type-specific localization in polarized cells. Consistent with brush border and microvillus membrane annotations. |
| GO:0097449 astrocyte projection | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer - astrocyte-specific localization. Reason: Cell type-specific localization in astrocytes. xCT is highly expressed in brain and plays important role in astrocyte glutamate release, but this is not the universal localization. |
| GO:0009636 response to toxic substance | IDA PMID:17575980 Differential expression of intestinal membrane transporters ... | KEEP AS NON CORE | Summary: PMID:17575980 examined differential expression of intestinal transporters in cholera patients, showing xCT involvement in response. Reason: Context-specific response - xCT expression changes in response to toxic insults/disease states as part of oxidative stress response, but this is not the core function. Supporting Evidence: PMID:17575980 Two amino acid transporters, SLC7A11 and SLC6A14, were upregulated in acute cholera patients compared to convalescence |
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Download this section (compressed HTML)Q: Is the slow lysosomal H+ efflux attributed to SLC7A11 fully accounted for by cystine/glutamate antiport, or is there an additional, substrate-independent H+ conductance? The distinction determines whether any channel-type molecular function is warranted.
Q: Does SLC7A11-mediated kynurenine transport (PMID:35245456) represent a major physiological substrate or is it primarily relevant in specific disease contexts?
Experiment: Comparative analysis of SLC7A11 H+ efflux vs cystine/glutamate antiport under different cellular conditions (normal vs stress, plasma membrane vs lysosome) to understand the relative contributions of the two distinct activities.
Experiment: Structure-function studies to identify residues that separate H+ efflux from antiporter activity, which could enable selective modulation of one activity without affecting the other.
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