SLC1A1 (EAAT3/EAAC1) is a sodium-dependent, high-affinity transmembrane transporter of acidic amino acids that mediates concentrative uptake of L-glutamate, L-aspartate and D-aspartate and also transports L-cysteine. It is a secondary active transporter belonging to the dicarboxylate/amino acid:cation symporter (DAACS; SLC1) family and assembles as a homotrimer in which each protomer works independently by an elevator-type mechanism. Each transport cycle couples uptake of one amino acid to the symport of three Na+ and one H+ and the antiport of one K+, allowing it to build transmembrane substrate gradients exceeding a millionfold; it additionally carries a thermodynamically uncoupled chloride (anion) conductance. EAAT3 operates at the plasma membrane and, in polarized epithelia, at the apical membrane. Its dominant physiological role in humans is reabsorption of glutamate and aspartate from the glomerular filtrate in the renal proximal tubule (and uptake in intestine); loss of function causes dicarboxylic aminoaciduria. In neurons it is a somatodendritic/perisynaptic transporter that buffers extracellular glutamate and, uniquely among the EAATs, provides the major Na+-dependent cysteine-uptake route that supplies cysteine, the rate-limiting precursor for glutathione synthesis, thereby supporting antioxidant defense. Surface expression is set by regulated endosomal trafficking and by interactions with partners including ARL6IP5 (GTRAP3-18), caveolin-1, Numb and PDZ-domain scaffolds.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001975 response to amphetamine | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'response to amphetamine' is an organismal/behavioral phenotype electronically projected from mouse Slc1a1 knockout studies. Reason: Downstream, pleiotropic phenotype of altered neuronal glutamate/cysteine handling rather than a molecular function the transporter performs; an IEA ortholog projection of a KO phenotype. Over-annotation for a transporter. |
| GO:0002027 regulation of heart rate | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'regulation of heart rate' is an indirect/downstream role electronically projected from mouse Slc1a1 (GO_REF:0000107). Reason: Reflects the physiological consequences of EAAT3-mediated amino-acid transport (and its loss in KO mice) rather than a step the transporter itself carries out. Pleiotropic/indirect; over-annotation for the molecular transporter. |
| GO:0005253 monoatomic anion channel activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EAATs possess a substrate-gated uncoupled anion conductance; monoatomic anion channel activity reflects this genuine biophysical property. Reason: Real anion-channel behaviour of the EAAT family (uncoupled Cl- flux), but modulatory/non-core relative to the concentrative amino-acid transport function. Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport |
| GO:0005313 L-glutamate transmembrane transporter activity | IBA GO_REF:0000033 | TOO GENERAL | Summary: SLC1A1/EAAT3 is a Na+-dependent high-affinity L-glutamate transmembrane transporter; direct uptake assays in heterologous systems establish this as a primary molecular function. Reason: True of SLC1A1 but uninformative. The more specific high-affinity child term (GO:0005314) and the symporter term (GO:0015501) are accepted elsewhere in this review and entail this parent, so the general glutamate-transporter term adds no information beyond them. This judges the term, not the row's evidence; the electrogenic Na+-coupled L-glutamate uptake it describes (Km in the low-micromolar range) is genuine. Marked TOO_GENERAL for consistency with the sibling EAAT reviews (SLC1A2, SLC1A3), which make the identical parent/child call on this pair. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:12562531 GTRAP3-18 (JWA, Arl6ip5) is a novel protein that interacts with EAAT3 and negatively modulates EAAT3-mediated glutamate uptake file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0005313 L-glutamate transmembrane transporter activity | IDA PMID:12562531 Methyl-beta-cyclodextrin but not retinoic acid reduces EAAT3... | TOO GENERAL | Summary: SLC1A1/EAAT3 is a Na+-dependent high-affinity L-glutamate transmembrane transporter; direct uptake assays in heterologous systems establish this as a primary molecular function. Reason: True of SLC1A1 but uninformative. The more specific high-affinity child term (GO:0005314) and the symporter term (GO:0015501) are accepted elsewhere in this review and entail this parent, so the general glutamate-transporter term adds no information beyond them. This judges the term, not the row's evidence; the electrogenic Na+-coupled L-glutamate uptake it describes (Km in the low-micromolar range) is genuine. Marked TOO_GENERAL for consistency with the sibling EAAT reviews (SLC1A2, SLC1A3), which make the identical parent/child call on this pair. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:12562531 GTRAP3-18 (JWA, Arl6ip5) is a novel protein that interacts with EAAT3 and negatively modulates EAAT3-mediated glutamate uptake file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0005313 L-glutamate transmembrane transporter activity | IDA PMID:21123949 Loss-of-function mutations in the glutamate transporter SLC1... | TOO GENERAL | Summary: SLC1A1/EAAT3 is a Na+-dependent high-affinity L-glutamate transmembrane transporter; direct uptake assays in heterologous systems establish this as a primary molecular function. Reason: True of SLC1A1 but uninformative. The more specific high-affinity child term (GO:0005314) and the symporter term (GO:0015501) are accepted elsewhere in this review and entail this parent, so the general glutamate-transporter term adds no information beyond them. This judges the term, not the row's evidence; the electrogenic Na+-coupled L-glutamate uptake it describes (Km in the low-micromolar range) is genuine. Marked TOO_GENERAL for consistency with the sibling EAAT reviews (SLC1A2, SLC1A3), which make the identical parent/child call on this pair. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:12562531 GTRAP3-18 (JWA, Arl6ip5) is a novel protein that interacts with EAAT3 and negatively modulates EAAT3-mediated glutamate uptake file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0005313 L-glutamate transmembrane transporter activity | IDA PMID:7521911 Functional comparisons of three glutamate transporter subtyp... | TOO GENERAL | Summary: SLC1A1/EAAT3 is a Na+-dependent high-affinity L-glutamate transmembrane transporter; direct uptake assays in heterologous systems establish this as a primary molecular function. Reason: True of SLC1A1 but uninformative. The more specific high-affinity child term (GO:0005314) and the symporter term (GO:0015501) are accepted elsewhere in this review and entail this parent, so the general glutamate-transporter term adds no information beyond them. This judges the term, not the row's evidence; the electrogenic Na+-coupled L-glutamate uptake it describes (Km in the low-micromolar range) is genuine. Marked TOO_GENERAL for consistency with the sibling EAAT reviews (SLC1A2, SLC1A3), which make the identical parent/child call on this pair. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:12562531 GTRAP3-18 (JWA, Arl6ip5) is a novel protein that interacts with EAAT3 and negatively modulates EAAT3-mediated glutamate uptake file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0005313 L-glutamate transmembrane transporter activity | IDA PMID:7914198 The neuronal and epithelial human high affinity glutamate tr... | TOO GENERAL | Summary: SLC1A1/EAAT3 is a Na+-dependent high-affinity L-glutamate transmembrane transporter; direct uptake assays in heterologous systems establish this as a primary molecular function. Reason: True of SLC1A1 but uninformative. The more specific high-affinity child term (GO:0005314) and the symporter term (GO:0015501) are accepted elsewhere in this review and entail this parent, so the general glutamate-transporter term adds no information beyond them. This judges the term, not the row's evidence; the electrogenic Na+-coupled L-glutamate uptake it describes (Km in the low-micromolar range) is genuine. Marked TOO_GENERAL for consistency with the sibling EAAT reviews (SLC1A2, SLC1A3), which make the identical parent/child call on this pair. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:12562531 GTRAP3-18 (JWA, Arl6ip5) is a novel protein that interacts with EAAT3 and negatively modulates EAAT3-mediated glutamate uptake file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0005313 L-glutamate transmembrane transporter activity | IEA GO_REF:0000120 | TOO GENERAL | Summary: SLC1A1/EAAT3 is a Na+-dependent high-affinity L-glutamate transmembrane transporter; direct uptake assays in heterologous systems establish this as a primary molecular function. Reason: True of SLC1A1 but uninformative. The more specific high-affinity child term (GO:0005314) and the symporter term (GO:0015501) are accepted elsewhere in this review and entail this parent, so the general glutamate-transporter term adds no information beyond them. This judges the term, not the row's evidence; the electrogenic Na+-coupled L-glutamate uptake it describes (Km in the low-micromolar range) is genuine. Marked TOO_GENERAL for consistency with the sibling EAAT reviews (SLC1A2, SLC1A3), which make the identical parent/child call on this pair. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:12562531 GTRAP3-18 (JWA, Arl6ip5) is a novel protein that interacts with EAAT3 and negatively modulates EAAT3-mediated glutamate uptake file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0005314 high-affinity L-glutamate transmembrane transporter activity | IDA PMID:26690923 Caveolin-1 Sensitivity of Excitatory Amino Acid Transporters... | ACCEPT | Summary: High-affinity L-glutamate transmembrane transporter activity is the defining molecular function of EAAT3, with reported Km for L-glutamate in the ~24-97 uM range. Reason: Most specific supported glutamate-transporter MF: high affinity is directly measured (Kanai Km ~30 uM; Arriza 18-97 uM) and confirmed structurally. Treated as a core molecular function. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:26690923 was taken as a measure of glutamate transport file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0005314 high-affinity L-glutamate transmembrane transporter activity | IDA PMID:8857541 Flux coupling in a neuronal glutamate transporter. | ACCEPT | Summary: High-affinity L-glutamate transmembrane transporter activity is the defining molecular function of EAAT3, with reported Km for L-glutamate in the ~24-97 uM range. Reason: Most specific supported glutamate-transporter MF: high affinity is directly measured (Kanai Km ~30 uM; Arriza 18-97 uM) and confirmed structurally. Treated as a core molecular function. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:26690923 was taken as a measure of glutamate transport file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0005314 high-affinity L-glutamate transmembrane transporter activity | TAS Reactome:R-HSA-210404 | ACCEPT | Summary: High-affinity L-glutamate transmembrane transporter activity is the defining molecular function of EAAT3, with reported Km for L-glutamate in the ~24-97 uM range. Reason: Most specific supported glutamate-transporter MF: high affinity is directly measured (Kanai Km ~30 uM; Arriza 18-97 uM) and confirmed structurally. Treated as a core molecular function. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:26690923 was taken as a measure of glutamate transport file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0005314 high-affinity L-glutamate transmembrane transporter activity | TAS Reactome:R-HSA-428015 | ACCEPT | Summary: High-affinity L-glutamate transmembrane transporter activity is the defining molecular function of EAAT3, with reported Km for L-glutamate in the ~24-97 uM range. Reason: Most specific supported glutamate-transporter MF: high affinity is directly measured (Kanai Km ~30 uM; Arriza 18-97 uM) and confirmed structurally. Treated as a core molecular function. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:26690923 was taken as a measure of glutamate transport file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0005314 high-affinity L-glutamate transmembrane transporter activity | TAS Reactome:R-HSA-5625029 | ACCEPT | Summary: High-affinity L-glutamate transmembrane transporter activity is the defining molecular function of EAAT3, with reported Km for L-glutamate in the ~24-97 uM range. Reason: Most specific supported glutamate-transporter MF: high affinity is directly measured (Kanai Km ~30 uM; Arriza 18-97 uM) and confirmed structurally. Treated as a core molecular function. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:26690923 was taken as a measure of glutamate transport file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:27358480 Numb directs the subcellular localization of EAAT3 through b... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:30126976 Proteome-wide analysis of phospho-regulated PDZ domain inter... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: High-throughput or targeted interaction mapping reporting a physical interaction; the term itself conveys no functional information. Reason: Bare 'protein binding' (GO:0005515) is uninformative and is removed per the project protein-binding policy. SLC1A1 does have functionally meaningful partners (ARL6IP5/GTRAP3-18 and caveolin-1 as negative regulators, Numb for trafficking, the RNF5 ubiquitin ligase, and PDZ scaffolds such as PSD-95/DLG4, GRIP1/2, PDZK1 and NHERF2); these are summarized in the gene notes and description rather than captured as uninformative binding rows. |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'Active in cytoplasm' is misleading: EAAT3 performs transport at the plasma membrane; its intracellular pool resides in endosomal membranes, not free in cytoplasm. Reason: The transport activity is exerted at the plasma membrane; the cytoplasmic/endosomal pool is a trafficking reservoir. The is_active_in cytoplasm assertion over-states the site of activity. Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Cell membrane |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: EAAT3 is a plasma-membrane (cell-membrane) multi-pass transporter; this is its core site of action. Reason: Well established by functional and immunolocalization studies and UniProt; core location. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:21123949 In normal human kidney, SLC1A1 was distributed at the apical surface throughout the proximal tubule file:human/SLC1A1/SLC1A1-uniprot.txt Cell membrane |
| GO:0005886 plasma membrane | IDA PMID:21123949 Loss-of-function mutations in the glutamate transporter SLC1... | ACCEPT | Summary: EAAT3 is a plasma-membrane (cell-membrane) multi-pass transporter; this is its core site of action. Reason: Well established by functional and immunolocalization studies and UniProt; core location. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:21123949 In normal human kidney, SLC1A1 was distributed at the apical surface throughout the proximal tubule file:human/SLC1A1/SLC1A1-uniprot.txt Cell membrane |
| GO:0005886 plasma membrane | IDA PMID:7914198 The neuronal and epithelial human high affinity glutamate tr... | ACCEPT | Summary: EAAT3 is a plasma-membrane (cell-membrane) multi-pass transporter; this is its core site of action. Reason: Well established by functional and immunolocalization studies and UniProt; core location. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:21123949 In normal human kidney, SLC1A1 was distributed at the apical surface throughout the proximal tubule file:human/SLC1A1/SLC1A1-uniprot.txt Cell membrane |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: EAAT3 is a plasma-membrane (cell-membrane) multi-pass transporter; this is its core site of action. Reason: Well established by functional and immunolocalization studies and UniProt; core location. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:21123949 In normal human kidney, SLC1A1 was distributed at the apical surface throughout the proximal tubule file:human/SLC1A1/SLC1A1-uniprot.txt Cell membrane |
| GO:0005886 plasma membrane | IMP PMID:26690923 Caveolin-1 Sensitivity of Excitatory Amino Acid Transporters... | ACCEPT | Summary: EAAT3 is a plasma-membrane (cell-membrane) multi-pass transporter; this is its core site of action. Reason: Well established by functional and immunolocalization studies and UniProt; core location. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:21123949 In normal human kidney, SLC1A1 was distributed at the apical surface throughout the proximal tubule file:human/SLC1A1/SLC1A1-uniprot.txt Cell membrane |
| GO:0005886 plasma membrane | IMP PMID:8857541 Flux coupling in a neuronal glutamate transporter. | ACCEPT | Summary: EAAT3 is a plasma-membrane (cell-membrane) multi-pass transporter; this is its core site of action. Reason: Well established by functional and immunolocalization studies and UniProt; core location. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:21123949 In normal human kidney, SLC1A1 was distributed at the apical surface throughout the proximal tubule file:human/SLC1A1/SLC1A1-uniprot.txt Cell membrane |
| GO:0005886 plasma membrane | TAS PMID:7521911 Functional comparisons of three glutamate transporter subtyp... | ACCEPT | Summary: EAAT3 is a plasma-membrane (cell-membrane) multi-pass transporter; this is its core site of action. Reason: Well established by functional and immunolocalization studies and UniProt; core location. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:21123949 In normal human kidney, SLC1A1 was distributed at the apical surface throughout the proximal tubule file:human/SLC1A1/SLC1A1-uniprot.txt Cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-210404 | ACCEPT | Summary: EAAT3 is a plasma-membrane (cell-membrane) multi-pass transporter; this is its core site of action. Reason: Well established by functional and immunolocalization studies and UniProt; core location. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:21123949 In normal human kidney, SLC1A1 was distributed at the apical surface throughout the proximal tubule file:human/SLC1A1/SLC1A1-uniprot.txt Cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-428015 | ACCEPT | Summary: EAAT3 is a plasma-membrane (cell-membrane) multi-pass transporter; this is its core site of action. Reason: Well established by functional and immunolocalization studies and UniProt; core location. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:21123949 In normal human kidney, SLC1A1 was distributed at the apical surface throughout the proximal tubule file:human/SLC1A1/SLC1A1-uniprot.txt Cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5625029 | ACCEPT | Summary: EAAT3 is a plasma-membrane (cell-membrane) multi-pass transporter; this is its core site of action. Reason: Well established by functional and immunolocalization studies and UniProt; core location. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons PMID:21123949 In normal human kidney, SLC1A1 was distributed at the apical surface throughout the proximal tubule file:human/SLC1A1/SLC1A1-uniprot.txt Cell membrane |
| GO:0006750 glutathione biosynthetic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Glutathione biosynthetic process: EAAT3 supplies the rate-limiting precursor cysteine but does not catalyse any glutathione-biosynthesis step. Reason: Participation test fails: the biosynthetic steps are carried out by glutamate-cysteine ligase and glutathione synthetase; EAAT3 only imports the substrate (cysteine). UniProt frames this as a contributory role ('Contributes to glutathione biosynthesis ... via its role in ... transport'). Over-annotation; the correct machine-readable role is cysteine transport (retained). Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Contributes to glutathione biosynthesis and protection against oxidative stress via its role in L-glutamate and L-cysteine transport PMID:33658209 transport cysteine, which is a rate-limiting intermediate in the biosynthesis of the antioxidant glutathione |
| GO:0006801 superoxide metabolic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Superoxide metabolic process: an indirect antioxidant consequence of cysteine/glutathione supply, not an activity of EAAT3. Reason: EAAT3 does not metabolize superoxide; any effect is downstream of glutathione-dependent defense enabled by cysteine import. Over-annotation. Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Contributes to glutathione biosynthesis and protection against oxidative stress via its role in L-glutamate and L-cysteine transport |
| GO:0006836 neurotransmitter transport | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Glutamate is an excitatory neurotransmitter and EAAT3 contributes to its clearance/buffering in the CNS; neurotransmitter transport is an accurate contextual process. Reason: Real in the neuronal context, but EAAT3 is a minor synaptic clearer (EAAT2 dominates) and its dominant physiological role is epithelial reabsorption; kept as non-core. The specific glutamate transport terms are the core. Supporting Evidence: PMID:7521911 Reuptake plays an important role in regulating synaptic and extracellular concentrations of glutamate |
| GO:0006836 neurotransmitter transport | TAS Reactome:R-HSA-210500 | KEEP AS NON CORE | Summary: Glutamate is an excitatory neurotransmitter and EAAT3 contributes to its clearance/buffering in the CNS; neurotransmitter transport is an accurate contextual process. Reason: Real in the neuronal context, but EAAT3 is a minor synaptic clearer (EAAT2 dominates) and its dominant physiological role is epithelial reabsorption; kept as non-core. The specific glutamate transport terms are the core. Supporting Evidence: PMID:7521911 Reuptake plays an important role in regulating synaptic and extracellular concentrations of glutamate |
| GO:0006865 amino acid transport | TAS Reactome:R-HSA-9958863 | TOO GENERAL | Summary: Generic amino acid transport (Reactome grouping). Reason: True but uninformative: the specific glutamate/aspartate/cysteine transmembrane-transport terms are asserted and accepted here and entail amino acid transport. Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0006882 intracellular zinc ion homeostasis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Intracellular zinc ion homeostasis: not an established EAAT3 function. Reason: EAAT3 is an acidic-amino-acid transporter; zinc modulates it but EAAT3 is not a zinc-homeostasis effector. IEA ortholog projection; over-annotation. |
| GO:0007212 G protein-coupled dopamine receptor signaling pathway | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'G protein-coupled dopamine receptor signaling pathway' is an indirect/downstream role electronically projected from mouse Slc1a1 (GO_REF:0000107). Reason: Reflects the physiological consequences of EAAT3-mediated amino-acid transport (and its loss in KO mice) rather than a step the transporter itself carries out. Pleiotropic/indirect; over-annotation for the molecular transporter. |
| GO:0007215 glutamate receptor signaling pathway | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'glutamate receptor signaling pathway' is an indirect/downstream role electronically projected from mouse Slc1a1 (GO_REF:0000107). Reason: Reflects the physiological consequences of EAAT3-mediated amino-acid transport (and its loss in KO mice) rather than a step the transporter itself carries out. Pleiotropic/indirect; over-annotation for the molecular transporter. |
| GO:0007268 chemical synaptic transmission | TAS PMID:7521911 Functional comparisons of three glutamate transporter subtyp... | KEEP AS NON CORE | Summary: By buffering synaptic/perisynaptic glutamate, EAAT3 modulates chemical synaptic transmission. Reason: Accurate but peripheral/modulatory: EAAT3 contributes to, rather than being a core effector of, synaptic transmission (predominantly somatodendritic; EAAT2 handles bulk synaptic clearance). Non-core. Supporting Evidence: PMID:7521911 Reuptake plays an important role in regulating synaptic and extracellular concentrations of glutamate |
| GO:0007420 brain development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'brain development' is an indirect/downstream role electronically projected from mouse Slc1a1 (GO_REF:0000107). Reason: Reflects the physiological consequences of EAAT3-mediated amino-acid transport (and its loss in KO mice) rather than a step the transporter itself carries out. Pleiotropic/indirect; over-annotation for the molecular transporter. |
| GO:0007613 memory | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'memory' is an organismal/behavioral phenotype electronically projected from mouse Slc1a1 knockout studies. Reason: Downstream, pleiotropic phenotype of altered neuronal glutamate/cysteine handling rather than a molecular function the transporter performs; an IEA ortholog projection of a KO phenotype. Over-annotation for a transporter. |
| GO:0007625 grooming behavior | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'grooming behavior' is an organismal/behavioral phenotype electronically projected from mouse Slc1a1 knockout studies. Reason: Downstream, pleiotropic phenotype of altered neuronal glutamate/cysteine handling rather than a molecular function the transporter performs; an IEA ortholog projection of a KO phenotype. Over-annotation for a transporter. |
| GO:0007626 locomotory behavior | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'locomotory behavior' is an organismal/behavioral phenotype electronically projected from mouse Slc1a1 knockout studies. Reason: Downstream, pleiotropic phenotype of altered neuronal glutamate/cysteine handling rather than a molecular function the transporter performs; an IEA ortholog projection of a KO phenotype. Over-annotation for a transporter. |
| GO:0009986 cell surface | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EAAT3 is present at the cell surface (its functional PM pool is surface-exposed). Reason: Consistent with the accepted plasma-membrane location; retained as a non-core, coarser surface term. Supporting Evidence: PMID:21123949 In normal human kidney, SLC1A1 was distributed at the apical surface throughout the proximal tubule |
| GO:0010460 positive regulation of heart rate | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'positive regulation of heart rate' is an indirect/downstream role electronically projected from mouse Slc1a1 (GO_REF:0000107). Reason: Reflects the physiological consequences of EAAT3-mediated amino-acid transport (and its loss in KO mice) rather than a step the transporter itself carries out. Pleiotropic/indirect; over-annotation for the molecular transporter. |
| GO:0010467 gene expression | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'gene expression' is an indirect/downstream role electronically projected from mouse Slc1a1 (GO_REF:0000107). Reason: Reflects the physiological consequences of EAAT3-mediated amino-acid transport (and its loss in KO mice) rather than a step the transporter itself carries out. Pleiotropic/indirect; over-annotation for the molecular transporter. |
| GO:0015108 chloride transmembrane transporter activity | IMP PMID:8857541 Flux coupling in a neuronal glutamate transporter. | KEEP AS NON CORE | Summary: EAAT3 carries a thermodynamically uncoupled anion (Cl-) flux in addition to the coupled amino-acid symport; this substrate-gated anion conductance is a genuine but non-core property. Reason: The uncoupled Cl- flux is experimentally established and is a real activity, but it is a channel-like leak unrelated to the gene's core concentrative amino-acid transport role; retained as non-core. Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport |
| GO:0015183 L-aspartate transmembrane transporter activity | IDA PMID:7914198 The neuronal and epithelial human high affinity glutamate tr... | ACCEPT | Summary: EAAT3 transports L-aspartate with high affinity; L-aspartate is a bona fide physiological substrate of the acidic-amino-acid carrier. Reason: L-aspartate transport is directly characterized (UniProt curated catalytic activity with Rhea reaction; Km ~24-39 uM) and is central to the renal/intestinal reabsorption role. Core MF. Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate PMID:21123949 SLC1A1 is the major renal transporter of glutamate and aspartate in humans |
| GO:0015293 symporter activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: Generic symporter activity from an InterPro2GO mapping. Reason: True but uninformative: the specific glutamate:sodium symporter activity (GO:0015501) is asserted and accepted in this review and entails symporter activity. Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion |
| GO:0015501 glutamate:sodium symporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: EAAT3 couples amino acid uptake to Na+ symport (and H+ symport with K+ antiport); glutamate:sodium symporter activity captures the coupled secondary-active-transport mechanism. Reason: Flux-coupling measurements show 3 Na+ and 1 H+ are cotransported with each glutamate and 1 K+ counter-transported. Core mechanistic MF. Supporting Evidence: PMID:8857541 three sodium ions and one proton are cotransported with each glutamate ion into the cell, while one potassium ion is transported out of the cell file:human/SLC1A1/SLC1A1-uniprot.txt Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion |
| GO:0015501 glutamate:sodium symporter activity | IDA PMID:8857541 Flux coupling in a neuronal glutamate transporter. | ACCEPT | Summary: EAAT3 couples amino acid uptake to Na+ symport (and H+ symport with K+ antiport); glutamate:sodium symporter activity captures the coupled secondary-active-transport mechanism. Reason: Flux-coupling measurements show 3 Na+ and 1 H+ are cotransported with each glutamate and 1 K+ counter-transported. Core mechanistic MF. Supporting Evidence: PMID:8857541 three sodium ions and one proton are cotransported with each glutamate ion into the cell, while one potassium ion is transported out of the cell file:human/SLC1A1/SLC1A1-uniprot.txt Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion |
| GO:0015501 glutamate:sodium symporter activity | IEA GO_REF:0000120 | ACCEPT | Summary: EAAT3 couples amino acid uptake to Na+ symport (and H+ symport with K+ antiport); glutamate:sodium symporter activity captures the coupled secondary-active-transport mechanism. Reason: Flux-coupling measurements show 3 Na+ and 1 H+ are cotransported with each glutamate and 1 K+ counter-transported. Core mechanistic MF. Supporting Evidence: PMID:8857541 three sodium ions and one proton are cotransported with each glutamate ion into the cell, while one potassium ion is transported out of the cell file:human/SLC1A1/SLC1A1-uniprot.txt Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion |
| GO:0015813 L-glutamate transmembrane transport | IBA GO_REF:0000033 | ACCEPT | Summary: EAAT3 mediates L-glutamate transmembrane transport; this is the central biological process the transporter executes. Reason: Directly supported process matching the glutamate-transporter molecular function. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0015813 L-glutamate transmembrane transport | IDA PMID:21123949 Loss-of-function mutations in the glutamate transporter SLC1... | ACCEPT | Summary: EAAT3 mediates L-glutamate transmembrane transport; this is the central biological process the transporter executes. Reason: Directly supported process matching the glutamate-transporter molecular function. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0015813 L-glutamate transmembrane transport | IDA PMID:26690923 Caveolin-1 Sensitivity of Excitatory Amino Acid Transporters... | ACCEPT | Summary: EAAT3 mediates L-glutamate transmembrane transport; this is the central biological process the transporter executes. Reason: Directly supported process matching the glutamate-transporter molecular function. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0015813 L-glutamate transmembrane transport | IDA PMID:7914198 The neuronal and epithelial human high affinity glutamate tr... | ACCEPT | Summary: EAAT3 mediates L-glutamate transmembrane transport; this is the central biological process the transporter executes. Reason: Directly supported process matching the glutamate-transporter molecular function. Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0016020 membrane | IDA PMID:7914198 The neuronal and epithelial human high affinity glutamate tr... | MODIFY | Summary: Generic membrane localization; EAAT3 is specifically a plasma-membrane (and apical PM) protein. Reason: Per transporter curation convention, the generic 'membrane' term is refined to the supported specific compartment, plasma membrane, which EAAT3 already carries by direct evidence. Proposed replacements: plasma membrane Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons file:human/SLC1A1/SLC1A1-uniprot.txt Cell membrane |
| GO:0016020 membrane | IEA GO_REF:0000120 | MODIFY | Summary: Generic membrane localization; EAAT3 is specifically a plasma-membrane (and apical PM) protein. Reason: Per transporter curation convention, the generic 'membrane' term is refined to the supported specific compartment, plasma membrane, which EAAT3 already carries by direct evidence. Proposed replacements: plasma membrane Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons file:human/SLC1A1/SLC1A1-uniprot.txt Cell membrane |
| GO:0016020 membrane | ISS GO_REF:0000024 | MODIFY | Summary: Generic membrane localization; EAAT3 is specifically a plasma-membrane (and apical PM) protein. Reason: Per transporter curation convention, the generic 'membrane' term is refined to the supported specific compartment, plasma membrane, which EAAT3 already carries by direct evidence. Proposed replacements: plasma membrane Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons file:human/SLC1A1/SLC1A1-uniprot.txt Cell membrane |
| GO:0016020 membrane | TAS PMID:7521911 Functional comparisons of three glutamate transporter subtyp... | MODIFY | Summary: Generic membrane localization; EAAT3 is specifically a plasma-membrane (and apical PM) protein. Reason: Per transporter curation convention, the generic 'membrane' term is refined to the supported specific compartment, plasma membrane, which EAAT3 already carries by direct evidence. Proposed replacements: plasma membrane Supporting Evidence: PMID:7914198 High affinity transport of glutamate across plasma membranes of brain neurons file:human/SLC1A1/SLC1A1-uniprot.txt Cell membrane |
| GO:0016324 apical plasma membrane | IDA PMID:21123949 Loss-of-function mutations in the glutamate transporter SLC1... | ACCEPT | Summary: In polarized epithelia (renal proximal tubule, intestine) EAAT3 localizes to the apical plasma membrane. Reason: Directly shown in human kidney (apical proximal tubule) and in MDCK cells; core location for the epithelial reabsorption role. Supporting Evidence: PMID:21123949 In normal human kidney, SLC1A1 was distributed at the apical surface throughout the proximal tubule file:human/SLC1A1/SLC1A1-uniprot.txt Apical cell membrane |
| GO:0016324 apical plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: In polarized epithelia (renal proximal tubule, intestine) EAAT3 localizes to the apical plasma membrane. Reason: Directly shown in human kidney (apical proximal tubule) and in MDCK cells; core location for the epithelial reabsorption role. Supporting Evidence: PMID:21123949 In normal human kidney, SLC1A1 was distributed at the apical surface throughout the proximal tubule file:human/SLC1A1/SLC1A1-uniprot.txt Apical cell membrane |
| GO:0019221 cytokine-mediated signaling pathway | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'cytokine-mediated signaling pathway' is an indirect/downstream role electronically projected from mouse Slc1a1 (GO_REF:0000107). Reason: Reflects the physiological consequences of EAAT3-mediated amino-acid transport (and its loss in KO mice) rather than a step the transporter itself carries out. Pleiotropic/indirect; over-annotation for the molecular transporter. |
| GO:0022008 neurogenesis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'neurogenesis' is an indirect/downstream role electronically projected from mouse Slc1a1 (GO_REF:0000107). Reason: Reflects the physiological consequences of EAAT3-mediated amino-acid transport (and its loss in KO mice) rather than a step the transporter itself carries out. Pleiotropic/indirect; over-annotation for the molecular transporter. |
| GO:0030424 axon | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Fine-grained neuronal subcellular localization transferred by curator (ISS) from experimentally characterized rodent EAAT3 orthologs. Reason: Consistent with EAAT3 being a somatodendritic/perisynaptic neuronal transporter; curated ortholog transfers of real localization data. Peripheral to the core function, kept as non-core. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:0030425 dendrite | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EAAT3 localizes to dendrites. Reason: Supported neuronal location (somatodendritic transporter); non-core. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:0030425 dendrite | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: EAAT3 localizes to dendrites. Reason: Supported neuronal location (somatodendritic transporter); non-core. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:0030534 adult behavior | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'adult behavior' is an organismal/behavioral phenotype electronically projected from mouse Slc1a1 knockout studies. Reason: Downstream, pleiotropic phenotype of altered neuronal glutamate/cysteine handling rather than a molecular function the transporter performs; an IEA ortholog projection of a KO phenotype. Over-annotation for a transporter. |
| GO:0031901 early endosome membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: EAAT3 cycles through an intracellular endosomal/vesicular pool; surface levels are set by regulated trafficking/recycling. Reason: Supported by trafficking studies (Numb-directed localization; intracellular reservoir) and UniProt endosome locations; a genuine but non-core regulatory pool, not the site of transport activity. Supporting Evidence: PMID:27358480 localizes primarily within the cell and at the apical plasma membrane |
| GO:0031901 early endosome membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: EAAT3 cycles through an intracellular endosomal/vesicular pool; surface levels are set by regulated trafficking/recycling. Reason: Supported by trafficking studies (Numb-directed localization; intracellular reservoir) and UniProt endosome locations; a genuine but non-core regulatory pool, not the site of transport activity. Supporting Evidence: PMID:27358480 localizes primarily within the cell and at the apical plasma membrane |
| GO:0031902 late endosome membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: EAAT3 cycles through an intracellular endosomal/vesicular pool; surface levels are set by regulated trafficking/recycling. Reason: Supported by trafficking studies (Numb-directed localization; intracellular reservoir) and UniProt endosome locations; a genuine but non-core regulatory pool, not the site of transport activity. Supporting Evidence: PMID:27358480 localizes primarily within the cell and at the apical plasma membrane |
| GO:0031902 late endosome membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: EAAT3 cycles through an intracellular endosomal/vesicular pool; surface levels are set by regulated trafficking/recycling. Reason: Supported by trafficking studies (Numb-directed localization; intracellular reservoir) and UniProt endosome locations; a genuine but non-core regulatory pool, not the site of transport activity. Supporting Evidence: PMID:27358480 localizes primarily within the cell and at the apical plasma membrane |
| GO:0031982 vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EAAT3 cycles through an intracellular endosomal/vesicular pool; surface levels are set by regulated trafficking/recycling. Reason: Supported by trafficking studies (Numb-directed localization; intracellular reservoir) and UniProt endosome locations; a genuine but non-core regulatory pool, not the site of transport activity. Supporting Evidence: PMID:27358480 localizes primarily within the cell and at the apical plasma membrane |
| GO:0032279 asymmetric synapse | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Fine-grained neuronal subcellular localization transferred by curator (ISS) from experimentally characterized rodent EAAT3 orthologs. Reason: Consistent with EAAT3 being a somatodendritic/perisynaptic neuronal transporter; curated ortholog transfers of real localization data. Peripheral to the core function, kept as non-core. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:0033229 L-cysteine transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: EAAT3 transports L-cysteine; among the EAATs this cysteine-transport capacity is physiologically important as the major neuronal Na+-dependent cysteine route supplying glutathione synthesis. Reason: Cysteine transport is directly demonstrated (Bailey oocyte uptake; UniProt catalytic activity) and is a distinctive, physiologically relevant EAAT3 function. Core MF. Supporting Evidence: PMID:21123949 Neurons use sodium-dependent cysteine uptake as the major route for cysteine uptake (80%-90% of total uptake), most of which is handled by SLC1A1 PMID:33658209 transport cysteine, which is a rate-limiting intermediate in the biosynthesis of the antioxidant glutathione file:human/SLC1A1/SLC1A1-uniprot.txt Can also transport L-cysteine |
| GO:0033229 L-cysteine transmembrane transporter activity | IDA PMID:21123949 Loss-of-function mutations in the glutamate transporter SLC1... | ACCEPT | Summary: EAAT3 transports L-cysteine; among the EAATs this cysteine-transport capacity is physiologically important as the major neuronal Na+-dependent cysteine route supplying glutathione synthesis. Reason: Cysteine transport is directly demonstrated (Bailey oocyte uptake; UniProt catalytic activity) and is a distinctive, physiologically relevant EAAT3 function. Core MF. Supporting Evidence: PMID:21123949 Neurons use sodium-dependent cysteine uptake as the major route for cysteine uptake (80%-90% of total uptake), most of which is handled by SLC1A1 PMID:33658209 transport cysteine, which is a rate-limiting intermediate in the biosynthesis of the antioxidant glutathione file:human/SLC1A1/SLC1A1-uniprot.txt Can also transport L-cysteine |
| GO:0033229 L-cysteine transmembrane transporter activity | IEA GO_REF:0000107 | ACCEPT | Summary: EAAT3 transports L-cysteine; among the EAATs this cysteine-transport capacity is physiologically important as the major neuronal Na+-dependent cysteine route supplying glutathione synthesis. Reason: Cysteine transport is directly demonstrated (Bailey oocyte uptake; UniProt catalytic activity) and is a distinctive, physiologically relevant EAAT3 function. Core MF. Supporting Evidence: PMID:21123949 Neurons use sodium-dependent cysteine uptake as the major route for cysteine uptake (80%-90% of total uptake), most of which is handled by SLC1A1 PMID:33658209 transport cysteine, which is a rate-limiting intermediate in the biosynthesis of the antioxidant glutathione file:human/SLC1A1/SLC1A1-uniprot.txt Can also transport L-cysteine |
| GO:0035633 maintenance of blood-brain barrier | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: 'maintenance of blood-brain barrier': EAAT3 is a neuronal/epithelial acidic-amino-acid transporter; a direct blood-brain-barrier/vascular role is not established. Reason: Supported only by NAS statements in BBB review articles and ISS ortholog transfer (acts_upstream_of_or_within). EAAT3 is not a recognized BBB-endothelial transporter; its established sites are neurons and renal/intestinal epithelia. Over-annotation. |
| GO:0035640 exploration behavior | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'exploration behavior' is an organismal/behavioral phenotype electronically projected from mouse Slc1a1 knockout studies. Reason: Downstream, pleiotropic phenotype of altered neuronal glutamate/cysteine handling rather than a molecular function the transporter performs; an IEA ortholog projection of a KO phenotype. Over-annotation for a transporter. |
| GO:0042417 dopamine metabolic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'dopamine metabolic process' is an indirect/downstream role electronically projected from mouse Slc1a1 (GO_REF:0000107). Reason: Reflects the physiological consequences of EAAT3-mediated amino-acid transport (and its loss in KO mice) rather than a step the transporter itself carries out. Pleiotropic/indirect; over-annotation for the molecular transporter. |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EAAT3 assembles as a homotrimer; identical protein binding reflects subunit self-association, the functional transport unit. Reason: Supported by cryo-EM and UniProt (homotrimer). Informative self-association (unlike bare protein binding), but structural rather than the core catalytic transport function. Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Homotrimer PMID:33658209 It is the major glutamate and aspartate transporter outside of the central nervous system, including kidneys and intestines |
| GO:0042883 L-cysteine transport | IDA PMID:21123949 Loss-of-function mutations in the glutamate transporter SLC1... | ACCEPT | Summary: EAAT3 transports L-cysteine; the major neuronal Na+-dependent cysteine-uptake route supplying glutathione synthesis. Reason: Directly demonstrated (Bailey). Physiologically important process; retained as a core transport role. Supporting Evidence: PMID:21123949 Neurons use sodium-dependent cysteine uptake as the major route for cysteine uptake (80%-90% of total uptake), most of which is handled by SLC1A1 file:human/SLC1A1/SLC1A1-uniprot.txt Can also transport L-cysteine |
| GO:0043025 neuronal cell body | IDA PMID:9409715 Immunohistochemical localization of the neuron-specific glut... | KEEP AS NON CORE | Summary: EAAT3 is strongly expressed in neuronal cell bodies (somata). Reason: Directly shown by immunolabeling of neuronal somata; genuine neuronal location, non-core. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EAAT3 is strongly expressed in neuronal cell bodies (somata). Reason: Directly shown by immunolabeling of neuronal somata; genuine neuronal location, non-core. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:0043025 neuronal cell body | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: EAAT3 is strongly expressed in neuronal cell bodies (somata). Reason: Directly shown by immunolabeling of neuronal somata; genuine neuronal location, non-core. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:0043083 synaptic cleft | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Fine-grained neuronal subcellular localization transferred by curator (ISS) from experimentally characterized rodent EAAT3 orthologs. Reason: Consistent with EAAT3 being a somatodendritic/perisynaptic neuronal transporter; curated ortholog transfers of real localization data. Peripheral to the core function, kept as non-core. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:0043197 dendritic spine | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Fine-grained neuronal subcellular localization transferred by curator (ISS) from experimentally characterized rodent EAAT3 orthologs. Reason: Consistent with EAAT3 being a somatodendritic/perisynaptic neuronal transporter; curated ortholog transfers of real localization data. Peripheral to the core function, kept as non-core. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:0043198 dendritic shaft | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Fine-grained neuronal subcellular localization transferred by curator (ISS) from experimentally characterized rodent EAAT3 orthologs. Reason: Consistent with EAAT3 being a somatodendritic/perisynaptic neuronal transporter; curated ortholog transfers of real localization data. Peripheral to the core function, kept as non-core. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:0043204 perikaryon | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Fine-grained neuronal subcellular localization transferred by curator (ISS) from experimentally characterized rodent EAAT3 orthologs. Reason: Consistent with EAAT3 being a somatodendritic/perisynaptic neuronal transporter; curated ortholog transfers of real localization data. Peripheral to the core function, kept as non-core. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:0043278 response to morphine | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'response to morphine' is an organismal/behavioral phenotype electronically projected from mouse Slc1a1 knockout studies. Reason: Downstream, pleiotropic phenotype of altered neuronal glutamate/cysteine handling rather than a molecular function the transporter performs; an IEA ortholog projection of a KO phenotype. Over-annotation for a transporter. |
| GO:0043524 negative regulation of neuron apoptotic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'negative regulation of neuron apoptotic process' is an indirect/downstream role electronically projected from mouse Slc1a1 (GO_REF:0000107). Reason: Reflects the physiological consequences of EAAT3-mediated amino-acid transport (and its loss in KO mice) rather than a step the transporter itself carries out. Pleiotropic/indirect; over-annotation for the molecular transporter. |
| GO:0043679 axon terminus | IDA PMID:9409715 Immunohistochemical localization of the neuron-specific glut... | KEEP AS NON CORE | Summary: EAAT3 immunoreactivity is reported in axonal/terminal structures (fibers and puncta). Reason: Supported by immunolocalization (fine-caliber fibers and puncta); deferring to the experimental/ortholog curation, though EAAT3 is predominantly somatodendritic. Non-core. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:0043679 axon terminus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: EAAT3 immunoreactivity is reported in axonal/terminal structures (fibers and puncta). Reason: Supported by immunolocalization (fine-caliber fibers and puncta); deferring to the experimental/ortholog curation, though EAAT3 is predominantly somatodendritic. Non-core. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:0045121 membrane raft | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EAAT3 associates with caveolin-1/lipid-raft microdomains of the plasma membrane. Reason: Supported by caveolin-1 interaction/regulation studies; a membrane sub-domain localization, non-core. Supporting Evidence: PMID:26690923 caveolin-1 is a powerful negative regulator of the excitatory glutamate transporters EAAT1, EAAT2, EAAT3, and EAAT4 |
| GO:0045177 apical part of cell | IDA PMID:27358480 Numb directs the subcellular localization of EAAT3 through b... | KEEP AS NON CORE | Summary: EAAT3 is enriched in the apical part of the cell in polarized cells. Reason: Consistent with apical plasma-membrane localization; a coarser location term kept as non-core. Supporting Evidence: PMID:27358480 localizes primarily within the cell and at the apical plasma membrane |
| GO:0045202 synapse | IDA PMID:9409715 Immunohistochemical localization of the neuron-specific glut... | KEEP AS NON CORE | Summary: EAAT3 is present at synapses (peri/postsynaptic and somatodendritic), where it buffers glutamate. Reason: Supported neuronal location; non-core relative to the transporter activity and dominant epithelial role. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:0045202 synapse | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: EAAT3 is present at synapses (peri/postsynaptic and somatodendritic), where it buffers glutamate. Reason: Supported neuronal location; non-core relative to the transporter activity and dominant epithelial role. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:0048514 blood vessel morphogenesis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: 'blood vessel morphogenesis': EAAT3 is a neuronal/epithelial acidic-amino-acid transporter; a direct blood-brain-barrier/vascular role is not established. Reason: Supported only by NAS statements in BBB review articles and ISS ortholog transfer (acts_upstream_of_or_within). EAAT3 is not a recognized BBB-endothelial transporter; its established sites are neurons and renal/intestinal epithelia. Over-annotation. |
| GO:0050808 synapse organization | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'synapse organization' is an indirect/downstream role electronically projected from mouse Slc1a1 (GO_REF:0000107). Reason: Reflects the physiological consequences of EAAT3-mediated amino-acid transport (and its loss in KO mice) rather than a step the transporter itself carries out. Pleiotropic/indirect; over-annotation for the molecular transporter. |
| GO:0051402 neuron apoptotic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'neuron apoptotic process' is an indirect/downstream role electronically projected from mouse Slc1a1 (GO_REF:0000107). Reason: Reflects the physiological consequences of EAAT3-mediated amino-acid transport (and its loss in KO mice) rather than a step the transporter itself carries out. Pleiotropic/indirect; over-annotation for the molecular transporter. |
| GO:0051938 L-glutamate import | IDA PMID:7521911 Functional comparisons of three glutamate transporter subtyp... | ACCEPT | Summary: EAAT3 imports L-glutamate into cells; reinforces the glutamate-uptake process. Reason: True process; essentially the same concentrative glutamate import as GO:0098712 (also accepted). Retained as an accurate statement of the core uptake role. Supporting Evidence: PMID:12562531 GTRAP3-18 (JWA, Arl6ip5) is a novel protein that interacts with EAAT3 and negatively modulates EAAT3-mediated glutamate uptake |
| GO:0055037 recycling endosome | IDA PMID:27358480 Numb directs the subcellular localization of EAAT3 through b... | KEEP AS NON CORE | Summary: EAAT3 cycles through an intracellular endosomal/vesicular pool; surface levels are set by regulated trafficking/recycling. Reason: Supported by trafficking studies (Numb-directed localization; intracellular reservoir) and UniProt endosome locations; a genuine but non-core regulatory pool, not the site of transport activity. Supporting Evidence: PMID:27358480 localizes primarily within the cell and at the apical plasma membrane |
| GO:0055037 recycling endosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EAAT3 cycles through an intracellular endosomal/vesicular pool; surface levels are set by regulated trafficking/recycling. Reason: Supported by trafficking studies (Numb-directed localization; intracellular reservoir) and UniProt endosome locations; a genuine but non-core regulatory pool, not the site of transport activity. Supporting Evidence: PMID:27358480 localizes primarily within the cell and at the apical plasma membrane |
| GO:0055038 recycling endosome membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: EAAT3 cycles through an intracellular endosomal/vesicular pool; surface levels are set by regulated trafficking/recycling. Reason: Supported by trafficking studies (Numb-directed localization; intracellular reservoir) and UniProt endosome locations; a genuine but non-core regulatory pool, not the site of transport activity. Supporting Evidence: PMID:27358480 localizes primarily within the cell and at the apical plasma membrane |
| GO:0055038 recycling endosome membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: EAAT3 cycles through an intracellular endosomal/vesicular pool; surface levels are set by regulated trafficking/recycling. Reason: Supported by trafficking studies (Numb-directed localization; intracellular reservoir) and UniProt endosome locations; a genuine but non-core regulatory pool, not the site of transport activity. Supporting Evidence: PMID:27358480 localizes primarily within the cell and at the apical plasma membrane |
| GO:0060041 retina development in camera-type eye | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'retina development in camera-type eye' is an indirect/downstream role electronically projected from mouse Slc1a1 (GO_REF:0000107). Reason: Reflects the physiological consequences of EAAT3-mediated amino-acid transport (and its loss in KO mice) rather than a step the transporter itself carries out. Pleiotropic/indirect; over-annotation for the molecular transporter. |
| GO:0061744 motor behavior | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'motor behavior' is an organismal/behavioral phenotype electronically projected from mouse Slc1a1 knockout studies. Reason: Downstream, pleiotropic phenotype of altered neuronal glutamate/cysteine handling rather than a molecular function the transporter performs; an IEA ortholog projection of a KO phenotype. Over-annotation for a transporter. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: EAAT3 is detected in urinary exosomes by large-scale proteomics (consistent with its apical renal expression). Reason: High-throughput HDA proteomic detection in urinary exosomes; a genuine detection site but not a functional location. Non-core. Supporting Evidence: PMID:19056867 Normal human urine contains large numbers of exosomes |
| GO:0070633 transepithelial transport | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: In renal and intestinal epithelia EAAT3 operates at the apical membrane to reabsorb glutamate/aspartate, contributing to transepithelial handling of these amino acids. Reason: Supported by the epithelial apical localization and the DCBXA reabsorption phenotype; a real but contextual process (non-core relative to the transporter MF itself). Supporting Evidence: PMID:21123949 SLC1A1 is the major renal transporter of glutamate and aspartate in humans |
| GO:0070777 D-aspartate transmembrane transport | IDA PMID:7914198 The neuronal and epithelial human high affinity glutamate tr... | ACCEPT | Summary: EAAT3 mediates D-aspartate transmembrane transport. Reason: Accurate process matching the D-aspartate transporter activity; retained. Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0070778 L-aspartate transmembrane transport | IDA PMID:7914198 The neuronal and epithelial human high affinity glutamate tr... | ACCEPT | Summary: EAAT3 mediates L-aspartate transmembrane transport. Reason: Accurate process for the aspartate-transporter activity; retained. Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0070778 L-aspartate transmembrane transport | ISS GO_REF:0000024 | ACCEPT | Summary: EAAT3 mediates L-aspartate transmembrane transport. Reason: Accurate process for the aspartate-transporter activity; retained. Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0070779 D-aspartate import across plasma membrane | IDA PMID:7521911 Functional comparisons of three glutamate transporter subtyp... | ACCEPT | Summary: EAAT3 imports D-aspartate across the plasma membrane. Reason: Genuine, directly measured process (D-aspartate is a characterized EAAT3 substrate). Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0070779 D-aspartate import across plasma membrane | IMP PMID:8857541 Flux coupling in a neuronal glutamate transporter. | ACCEPT | Summary: EAAT3 imports D-aspartate across the plasma membrane. Reason: Genuine, directly measured process (D-aspartate is a characterized EAAT3 substrate). Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0071314 cellular response to cocaine | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'cellular response to cocaine' is an organismal/behavioral phenotype electronically projected from mouse Slc1a1 knockout studies. Reason: Downstream, pleiotropic phenotype of altered neuronal glutamate/cysteine handling rather than a molecular function the transporter performs; an IEA ortholog projection of a KO phenotype. Over-annotation for a transporter. |
| GO:0071577 zinc ion transmembrane transport | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Zinc ion transmembrane transport: EAAT3 is not a zinc transporter. Reason: No evidence that EAAT3 transports zinc; its characterized substrates are acidic amino acids and cysteine (plus an uncoupled anion flux). IEA ortholog projection; over-annotation. |
| GO:0071944 cell periphery | IEA GO_REF:0000117 | TOO GENERAL | Summary: Cell periphery is a generic parent of plasma membrane. Reason: True but uninformative: plasma membrane (GO:0005886) is asserted and accepted here and entails cell periphery. Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Cell membrane |
| GO:0071944 cell periphery | ISS GO_REF:0000024 | TOO GENERAL | Summary: Cell periphery is a generic parent of plasma membrane. Reason: True but uninformative: plasma membrane (GO:0005886) is asserted and accepted here and entails cell periphery. Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Cell membrane |
| GO:0071944 cell periphery | ISS GO_REF:0000024 | TOO GENERAL | Summary: Cell periphery is a generic parent of plasma membrane. Reason: True but uninformative: plasma membrane (GO:0005886) is asserted and accepted here and entails cell periphery. Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Cell membrane |
| GO:0097386 glial cell projection | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Glial cell projection; EAAT3/EAAC1 is a neuronal/epithelial transporter and is not expressed in astrocytes. Reason: Contradicted by immunolocalization showing EAAC1 is neuronal and that astrocytes are not labeled; an ISS ortholog transfer that over-reaches for EAAT3. (EAAT1/EAAT2 are the glial glutamate transporters.) Supporting Evidence: PMID:9409715 astrocytes were not co-labeled for EAAC1 |
| GO:0097440 apical dendrite | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Fine-grained neuronal subcellular localization transferred by curator (ISS) from experimentally characterized rodent EAAT3 orthologs. Reason: Consistent with EAAT3 being a somatodendritic/perisynaptic neuronal transporter; curated ortholog transfers of real localization data. Peripheral to the core function, kept as non-core. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:0098657 import into cell | IEA GO_REF:0000117 | TOO GENERAL | Summary: Generic import into cell (ARBA mapping). Reason: True but uninformative: the specific 'import across plasma membrane' terms for glutamate/aspartate/cysteine are asserted and accepted and entail import into cell. Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0098685 Schaffer collateral - CA1 synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EAAT3 is present at hippocampal (Schaffer collateral-CA1) synapses. Reason: Supported neuronal synaptic location (ortholog projection); non-core. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:0098712 L-glutamate import across plasma membrane | IDA PMID:26690923 Caveolin-1 Sensitivity of Excitatory Amino Acid Transporters... | ACCEPT | Summary: EAAT3 imports L-glutamate across the plasma membrane (concentrative, inward); the directional, PM-specific process term. Reason: Accurate specific process: concentrative inward glutamate transport at the plasma membrane. Core. Supporting Evidence: PMID:8857541 three sodium ions and one proton are cotransported with each glutamate ion into the cell, while one potassium ion is transported out of the cell file:human/SLC1A1/SLC1A1-uniprot.txt Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion |
| GO:0098712 L-glutamate import across plasma membrane | IMP PMID:8857541 Flux coupling in a neuronal glutamate transporter. | ACCEPT | Summary: EAAT3 imports L-glutamate across the plasma membrane (concentrative, inward); the directional, PM-specific process term. Reason: Accurate specific process: concentrative inward glutamate transport at the plasma membrane. Core. Supporting Evidence: PMID:8857541 three sodium ions and one proton are cotransported with each glutamate ion into the cell, while one potassium ion is transported out of the cell file:human/SLC1A1/SLC1A1-uniprot.txt Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion |
| GO:0098793 presynapse | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Presynaptic localization; EAAT3 is predominantly somatodendritic and is reported to be excluded from presynaptic membranes. Reason: An ISS ortholog transfer that conflicts with the established somatodendritic distribution of EAAT3 and its exclusion from presynaptic membranes; likely over-annotation. Supporting Evidence: PMID:33658209 excluded from presynaptic membranes |
| GO:0099170 postsynaptic modulation of chemical synaptic transmission | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'postsynaptic modulation of chemical synaptic transmission' is an indirect/downstream role electronically projected from mouse Slc1a1 (GO_REF:0000107). Reason: Reflects the physiological consequences of EAAT3-mediated amino-acid transport (and its loss in KO mice) rather than a step the transporter itself carries out. Pleiotropic/indirect; over-annotation for the molecular transporter. |
| GO:0099544 perisynaptic space | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Fine-grained neuronal subcellular localization transferred by curator (ISS) from experimentally characterized rodent EAAT3 orthologs. Reason: Consistent with EAAT3 being a somatodendritic/perisynaptic neuronal transporter; curated ortholog transfers of real localization data. Peripheral to the core function, kept as non-core. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:0140009 L-aspartate import across plasma membrane | IDA PMID:7521911 Functional comparisons of three glutamate transporter subtyp... | ACCEPT | Summary: EAAT3 imports L-aspartate across the plasma membrane. Reason: L-aspartate is a core physiological substrate; PM import is directly supported and underlies renal/intestinal reabsorption. Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate PMID:21123949 SLC1A1 is the major renal transporter of glutamate and aspartate in humans |
| GO:0140009 L-aspartate import across plasma membrane | IMP PMID:8857541 Flux coupling in a neuronal glutamate transporter. | ACCEPT | Summary: EAAT3 imports L-aspartate across the plasma membrane. Reason: L-aspartate is a core physiological substrate; PM import is directly supported and underlies renal/intestinal reabsorption. Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate PMID:21123949 SLC1A1 is the major renal transporter of glutamate and aspartate in humans |
| GO:0140010 D-aspartate transmembrane transporter activity | IDA PMID:7914198 The neuronal and epithelial human high affinity glutamate tr... | ACCEPT | Summary: EAAT3 transports D-aspartate (non-stereoselective for aspartate), a well-characterized substrate used to probe the transport cycle. Reason: D-aspartate transport is a genuine, curated transporter activity of EAAT3 (UniProt catalytic activity, Rhea RHEA:71379; Km ~47 uM). Retained as a real molecular function. Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate |
| GO:0150002 distal dendrite | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Fine-grained neuronal subcellular localization transferred by curator (ISS) from experimentally characterized rodent EAAT3 orthologs. Reason: Consistent with EAAT3 being a somatodendritic/perisynaptic neuronal transporter; curated ortholog transfers of real localization data. Peripheral to the core function, kept as non-core. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:0150104 transport across blood-brain barrier | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: 'transport across blood-brain barrier': EAAT3 is a neuronal/epithelial acidic-amino-acid transporter; a direct blood-brain-barrier/vascular role is not established. Reason: Supported only by NAS statements in BBB review articles and ISS ortholog transfer (acts_upstream_of_or_within). EAAT3 is not a recognized BBB-endothelial transporter; its established sites are neurons and renal/intestinal epithelia. Over-annotation. |
| GO:0150104 transport across blood-brain barrier | NAS PMID:26590417 Establishment and Dysfunction of the Blood-Brain Barrier. | MARK AS OVER ANNOTATED | Summary: 'transport across blood-brain barrier': EAAT3 is a neuronal/epithelial acidic-amino-acid transporter; a direct blood-brain-barrier/vascular role is not established. Reason: Supported only by NAS statements in BBB review articles and ISS ortholog transfer (acts_upstream_of_or_within). EAAT3 is not a recognized BBB-endothelial transporter; its established sites are neurons and renal/intestinal epithelia. Over-annotation. |
| GO:0150104 transport across blood-brain barrier | NAS PMID:30280653 Blood-Brain Barrier: From Physiology to Disease and Back. | MARK AS OVER ANNOTATED | Summary: 'transport across blood-brain barrier': EAAT3 is a neuronal/epithelial acidic-amino-acid transporter; a direct blood-brain-barrier/vascular role is not established. Reason: Supported only by NAS statements in BBB review articles and ISS ortholog transfer (acts_upstream_of_or_within). EAAT3 is not a recognized BBB-endothelial transporter; its established sites are neurons and renal/intestinal epithelia. Over-annotation. |
| GO:1902476 chloride transmembrane transport | IMP PMID:8857541 Flux coupling in a neuronal glutamate transporter. | KEEP AS NON CORE | Summary: EAAT3 carries an uncoupled chloride flux associated with the transport cycle. Reason: Genuine uncoupled anion conductance (consistent with GO:0015108), but a channel-like leak that is non-core relative to concentrative amino-acid transport. Supporting Evidence: file:human/SLC1A1/SLC1A1-uniprot.txt Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport |
| GO:1903712 L-cysteine transmembrane transport | IEA GO_REF:0000107 | ACCEPT | Summary: EAAT3 mediates L-cysteine transmembrane transport. Reason: Accurate specific process matching the L-cysteine transporter activity; consistent with GO:0042883. Supporting Evidence: PMID:33658209 transport cysteine, which is a rate-limiting intermediate in the biosynthesis of the antioxidant glutathione file:human/SLC1A1/SLC1A1-uniprot.txt Can also transport L-cysteine |
| GO:1990635 proximal dendrite | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Fine-grained neuronal subcellular localization transferred by curator (ISS) from experimentally characterized rodent EAAT3 orthologs. Reason: Consistent with EAAT3 being a somatodendritic/perisynaptic neuronal transporter; curated ortholog transfers of real localization data. Peripheral to the core function, kept as non-core. Supporting Evidence: PMID:9409715 intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta |
| GO:1990708 conditioned place preference | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: 'conditioned place preference' is an organismal/behavioral phenotype electronically projected from mouse Slc1a1 knockout studies. Reason: Downstream, pleiotropic phenotype of altered neuronal glutamate/cysteine handling rather than a molecular function the transporter performs; an IEA ortholog projection of a KO phenotype. Over-annotation for a transporter. |
Loading supporting content…
Download this section (compressed HTML)Q: What is the physiological role, if any, of the EAAT3 uncoupled chloride (anion) conductance in neuronal excitability and epithelial function, as distinct from its concentrative amino-acid transport?
Q: To what extent does EAAT3-mediated neuronal cysteine uptake (vs system xc- and other routes) determine neuronal glutathione levels and vulnerability to oxidative stress in humans?
Experiment: Cell-type-specific conditional Slc1a1 knockout combined with glutathione and oxidative-stress readouts in neurons vs renal epithelium to dissect the cysteine/glutathione-supply role from the glutamate/aspartate reabsorption role.
Experiment: Structure-guided mutations that selectively abolish the uncoupled anion conductance while preserving coupled amino-acid transport, assayed in neurons for effects on excitability, to test whether the anion channel has an independent physiological function.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)