SLC1A2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005313 L-glutamate transmembrane transporter activity	IBA GO_REF:0000033	TOO GENERAL	Summary: Family-level IBA (node PTN000238242) asserting L-glutamate transporter activity. Correct for EAAT2, which is the defining glutamate transporter. The target appears in its own WITH/FROM because EAAT2 has direct experimental grounding for the term. Reason: True of the gene, but the more specific supported terms asserted elsewhere in this review — high-affinity L-glutamate transmembrane transporter activity (GO:0005314) and glutamate:sodium symporter activity (GO:0015501) — already entail it (GO:0005314 is a verified descendant of GO:0005313). Keep the specific terms as the core molecular function.
GO:0005313 L-glutamate transmembrane transporter activity	IDA PMID:7521911 Functional comparisons of three glutamate transporter subtyp...	TOO GENERAL	Summary: Original functional cloning of human EAAT2: radiolabel uptake and voltage-clamp measurements established high-affinity L-glutamate transport (KM 48-97 uM). Reason: The claim is correct and directly measured, but the term is entailed by the more specific high-affinity transporter and glutamate:sodium symporter terms accepted as the core function. Judges the term, not this IDA row. Supporting Evidence: PMID:7521911 The affinities of the EAAT subtypes for L-glutamate were similar, with Km determinations varying from 48 to 97 microM in the mammalian cell assay
GO:0005313 L-glutamate transmembrane transporter activity	IEA GO_REF:0000120	TOO GENERAL	Summary: Electronic assertion of L-glutamate transporter activity; correct. Reason: Entailed by the accepted, more specific high-affinity L-glutamate transporter (GO:0005314) and glutamate:sodium symporter (GO:0015501) terms.
GO:0005313 L-glutamate transmembrane transporter activity	TAS PMID:21757002 The nuclear receptor FXR regulates hepatic transport and met...	TOO GENERAL	Summary: BHF-UCL TAS from a hepatic study; EAAT2 mediates glutamate uptake in perivenous hepatocytes feeding glutamine synthesis. Reason: Correct activity but entailed by the accepted specific terms GO:0005314 and GO:0015501. Supporting Evidence: PMID:21757002 Glutamate is taken up by perivenous hepatocytes and is the main source for the synthesis of glutamine, catalyzed by glutamine synthase (GS)
GO:0005314 high-affinity L-glutamate transmembrane transporter activity	IDA PMID:26690923 Caveolin-1 Sensitivity of Excitatory Amino Acid Transporters...	ACCEPT	Summary: Direct electrophysiological measurement of glutamate-induced inward current in EAAT2-expressing oocytes; a core, high-affinity activity. Reason: Directly measured high-affinity L-glutamate transport is the central molecular function of EAAT2. Supporting Evidence: PMID:26690923 I Glu was observed in EAAT1-, EAAT2-, EAAT3-, or EAAT4-expressing oocytes but not in water-injected oocytes
GO:0005314 high-affinity L-glutamate transmembrane transporter activity	IEA GO_REF:0000107	ACCEPT	Summary: Electronic transfer from rat GLT-1; consistent with direct human data. Reason: High-affinity L-glutamate transport is the core function and is directly demonstrated for human EAAT2.
GO:0005314 high-affinity L-glutamate transmembrane transporter activity	TAS Reactome:R-HSA-210404	ACCEPT	Summary: Reactome reaction for the SLC1 high-affinity glutamate exchange; EAAT2 is a member of this high-affinity transporter set. Reason: Core high-affinity glutamate transporter activity. Supporting Evidence: Reactome:R-HSA-210404 Astrocytic SLC1As are responsible for majority of the glutamate uptake
GO:0005314 high-affinity L-glutamate transmembrane transporter activity	TAS Reactome:R-HSA-428015	ACCEPT	Summary: Reactome cotransport reaction; EAAT2 is a high-affinity glutamate transporter. Reason: Core high-affinity glutamate transporter activity. Supporting Evidence: Reactome:R-HSA-428015 GLT1 is expressed mainly in the brain and is essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft
GO:0005515 protein binding	IPI PMID:19527721 Excitatory amino acid transporter 2 associates with phosphor...	REMOVE	Summary: IntAct IPI recording an interaction with MAPT/tau (P10636); EAAT2 was found associated with phosphorylated tau in neurofibrillary tangles of tauopathic brains. Reason: Bare GO:0005515 protein binding is uninformative and is removed per the protein-binding policy. Removal does not dispute the reported tau association; it carries no molecular-function information for EAAT2. Supporting Evidence: PMID:19527721 excitatory amino acid transporter 2 (EAAT2) preferentially interacted with phosphorylated tau and was localized in neurofibrillary tangles
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: IntAct IPI recording a yeast-two-hybrid/interactome interaction with HTT (P42858, huntingtin) from a neurodegenerative-disease interactome map. Reason: Bare GO:0005515 protein binding is uninformative and is removed per the protein-binding policy. The reported HTT interaction is retained in the record but conveys no molecular-function information for EAAT2.
GO:0005886 plasma membrane	EXP PMID:14506254 Glutamate modifies ion conduction and voltage-dependent gati...	ACCEPT	Summary: Whole-cell patch clamp of EAAT2 at the surface of transfected mammalian cells; the transporter functions at the plasma membrane. Reason: Plasma membrane is the core functional location of EAAT2. Supporting Evidence: PMID:14506254 a stoichiometrically coupled transport of glutamate, Na+, K+, and H+, and a pore-mediated anion conductance
GO:0005886 plasma membrane	EXP PMID:7521911 Functional comparisons of three glutamate transporter subtyp...	ACCEPT	Summary: EAAT2 assayed as a surface transporter in transfected cells and oocytes. Reason: Core plasma-membrane location.
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: Family IBA placing transporter activity at the plasma membrane; agrees with direct human data. Reason: Core plasma-membrane location where EAAT2 is active.
GO:0005886 plasma membrane	IEA GO_REF:0000120	ACCEPT	Summary: Electronic plasma-membrane assignment; correct. Reason: Core plasma-membrane location.
GO:0005886 plasma membrane	IMP PMID:15265858 A trimeric quaternary structure is conserved in bacterial an...	ACCEPT	Summary: Functional/biochemical study of surface-expressed hEAAT2 trimers. Reason: Core plasma-membrane location.
GO:0005886 plasma membrane	IMP PMID:26690923 Caveolin-1 Sensitivity of Excitatory Amino Acid Transporters...	ACCEPT	Summary: Surface transport current measured at the plasma membrane of EAAT2-expressing oocytes. Reason: Core plasma-membrane location.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-210404	ACCEPT	Summary: Reactome places the SLC1 glutamate-exchange reaction at the plasma membrane. Reason: Core plasma-membrane location.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-428015	ACCEPT	Summary: Reactome cotransport reaction located at the plasma membrane. Reason: Core plasma-membrane location.
GO:0006750 glutathione biosynthetic process	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic transfer from rat GLT-1, presumably via cysteine uptake providing a glutathione precursor. Reason: EAAT2 performs no enzymatic step of glutathione biosynthesis; at most it supplies a precursor (cysteine), and cysteine transport is a minor, promiscuous activity of EAAT2 (EAAT3/EAAC1 is the dedicated neuronal cysteine/glutathione-linked transporter). Supplying a substrate is not participation in the biosynthetic process.
GO:0006836 neurotransmitter transport	IEA GO_REF:0000117	TOO GENERAL	Summary: ARBA electronic assertion that EAAT2 transports a neurotransmitter (glutamate). Reason: Correct but entailed by the accepted, more specific neurotransmitter reuptake (GO:0098810) and L-glutamate import across plasma membrane (GO:0098712).
GO:0006836 neurotransmitter transport	TAS Reactome:R-HSA-210500	TOO GENERAL	Summary: Reactome glutamate neurotransmitter release cycle; EAAT2 provides the uptake step. Reason: Entailed by the accepted neurotransmitter reuptake (GO:0098810) term, which captures the specific role.
GO:0006865 amino acid transport	TAS Reactome:R-HSA-9958863	TOO GENERAL	Summary: Reactome SLC-mediated amino acid transport; EAAT2 is an amino-acid transporter. Reason: Broad parent entailed by the accepted specific processes L-glutamate import across plasma membrane (GO:0098712) and L-aspartate import (GO:0140009).
GO:0007268 chemical synaptic transmission	TAS PMID:7521911 Functional comparisons of three glutamate transporter subtyp...	KEEP AS NON CORE	Summary: EAAT2-mediated glutamate reuptake terminates the postsynaptic action of glutamate and shapes glutamatergic transmission. Reason: EAAT2 participates in the synaptic-transmission cycle through the reuptake/clearance step rather than performing transmission itself. The role is real but peripheral to the core transport activity; the specific capture is neurotransmitter reuptake at the glutamatergic synapse. Supporting Evidence: PMID:7521911 Reuptake plays an important role in regulating synaptic and extracellular concentrations of glutamate.
GO:0008509 monoatomic anion transmembrane transporter activity	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Captures the thermodynamically uncoupled chloride conductance intrinsic to the EAAT transport pore. Reason: EAAT2 genuinely conducts a Cl- current not coupled to amino-acid transport, a real biophysical property but secondary to its glutamate-transport function. Supporting Evidence: file:human/SLC1A2/SLC1A2-uniprot.txt flux that is not coupled to amino acid transport
GO:0009986 cell surface	IDA PMID:21399631 Flotillin-1 is essential for PKC-triggered endocytosis and m...	KEEP AS NON CORE	Summary: EAAT2 detected at the cell surface and shown to undergo PKC-triggered, flotillin-1-dependent internalization. Reason: Cell surface is a coarser, correct localization; the precise core location is plasma membrane (GO:0005886). Supporting Evidence: PMID:21399631 required for PKC-regulated internalization of members of two different NTT families, the DA transporter (DAT) and the glial glutamate transporter EAAT2
GO:0015175 neutral L-amino acid transmembrane transporter activity	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Family IBA; the node spans both the acidic-amino-acid EAATs and the neutral-amino-acid ASCT members (e.g. Q15758/ASCT2). Reason: EAAT2 is a high-affinity acidic (glutamate/aspartate) amino-acid transporter; neutral L-amino acid transport is the characterized function of the ASCT paralogs on this shared node, not of EAAT2. The term reflects family-level inclusion rather than EAAT2's own activity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN000238242 SUPPORTS SOURCE BUT NOT TARGET Node spans both the acidic-amino-acid EAATs and the neutral-amino-acid ASCT transporters (e.g. SLC1A5/ASCT2, Q15758). Neutral L-amino acid transporter activity is characterized for the ASCT members, not for the EAAT2 subfamily, whose substrates are glutamate/aspartate.
GO:0015293 symporter activity	IEA GO_REF:0000002	TOO GENERAL	Summary: InterPro2GO electronic assertion of symporter activity. Reason: Correct mechanism, but entailed by the accepted, more specific glutamate:sodium symporter activity (GO:0015501), a verified descendant.
GO:0015501 glutamate:sodium symporter activity	IBA GO_REF:0000033	ACCEPT	Summary: Family IBA asserting Na+-coupled glutamate symport; the mechanistically precise core activity, grounded in direct human data (target in WITH/FROM). Reason: Na+-coupled glutamate symport is the defining molecular function of EAAT2 and the right level of specificity. Supporting Evidence: file:human/SLC1A2/SLC1A2-uniprot.txt Functions as a symporter that transports one amino acid molecule
GO:0015501 glutamate:sodium symporter activity	IDA PMID:15265858 A trimeric quaternary structure is conserved in bacterial an...	ACCEPT	Summary: Glutamate uptake currents of the inducibly expressed hEAAT2 correlate with the amount of trimeric transporter. Reason: Direct evidence for the core Na+-coupled glutamate transport activity. Supporting Evidence: PMID:15265858 the glutamate uptake currents correlate to the amount of trimeric transporters
GO:0015501 glutamate:sodium symporter activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assertion of glutamate:sodium symport; correct. Reason: Core Na+-coupled glutamate symport activity.
GO:0015804 neutral amino acid transport	IEA GO_REF:0000108	MARK AS OVER ANNOTATED	Summary: Inter-ontology inference from the neutral L-amino acid transporter activity. Reason: Inherits the over-annotation of GO:0015175: EAAT2 is an acidic-amino-acid transporter, and neutral amino acid transport belongs to the ASCT paralogs.
GO:0015813 L-glutamate transmembrane transport	IDA PMID:26690923 Caveolin-1 Sensitivity of Excitatory Amino Acid Transporters...	TOO GENERAL	Summary: Direct measurement of L-glutamate transport by EAAT2. Reason: Correct and directly shown, but entailed by the accepted, more specific L-glutamate import across plasma membrane (GO:0098712), a verified descendant.
GO:0016020 membrane	IEA GO_REF:0000120	MODIFY	Summary: Generic membrane localization from electronic methods. Reason: EAAT2 is a plasma-membrane transporter; the generic membrane term should be refined to plasma membrane (GO:0005886), which the gene already carries with direct evidence. Proposed replacements: plasma membrane
GO:0016020 membrane	TAS PMID:7521911 Functional comparisons of three glutamate transporter subtyp...	MODIFY	Summary: Early traceable membrane assignment from the cloning paper. Reason: Refine the generic membrane term to the supported, more specific plasma membrane (GO:0005886). Proposed replacements: plasma membrane
GO:0030424 axon	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Reflects the minority neuronal EAAT2 pool localized to axons/axon terminals. Reason: Axonal localization is real but a minority pool; the dominant, core localization is astrocytic perisynaptic plasma membrane. Supporting Evidence: PMID:21258616 In both astrocytic processes and axon terminals, most EAAT2a is perisynaptic
GO:0030673 axolemma	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Axonal plasma membrane (axolemma) localization of the neuronal EAAT2 pool. Reason: Consistent with the minority axonal pool; peripheral to the core astrocytic localization.
GO:0031982 vesicle	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Generic vesicle localization, consistent with trafficking/endocytosis of EAAT2. Reason: Compatible with the transporter's trafficking (surface delivery and PKC-/flotillin-regulated endocytosis) but uninformative about its core function.
GO:0033229 L-cysteine transmembrane transporter activity	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic transfer from rat GLT-1 asserting cysteine transport. Reason: EAAT2 can transport cysteine only weakly/promiscuously; the dedicated cysteine transporter in the family is EAAT3/EAAC1. This is not an evolved function of EAAT2.
GO:0042734 presynaptic membrane	IDA PMID:21258616 Cellular and Synaptic Localization of EAAT2a in Human Cerebr...	KEEP AS NON CORE	Summary: SynGO immunogold EM in human neocortex: a fraction (~14-17%) of EAAT2 is in axon terminals, perisynaptic to the active zone. Reason: The presynaptic (neuronal axon-terminal) pool is real but minority; EAAT2's core activity is in astrocytic perisynaptic processes. Supporting Evidence: PMID:21258616 In both astrocytic processes and axon terminals, most EAAT2a is perisynaptic
GO:0044297 cell body	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Cell-body (soma) localization transferred electronically from the rat ortholog. Reason: Somatic localization is peripheral to the core perisynaptic function.
GO:0044297 cell body	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS cell-body localization from a mammalian SLC1 ortholog (P31596). Reason: Peripheral localization; consistent with but not central to function.
GO:0044297 cell body	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS cell-body localization from rat GLT-1. Reason: Peripheral localization.
GO:0044306 neuron projection terminus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Neuron-projection terminus (axon terminal) localization of the neuronal EAAT2 pool. Reason: Consistent with the minority axon-terminal pool; peripheral to the core astrocytic localization. Supporting Evidence: PMID:21258616 In both astrocytic processes and axon terminals, most EAAT2a is perisynaptic
GO:0045121 membrane raft	IDA PMID:20193040 Increased expression of cholesterol 24S-hydroxylase results ...	KEEP AS NON CORE	Summary: EAAT2 is directly shown to reside in cholesterol-rich lipid raft microdomains of the plasma membrane; raft association is disrupted in Alzheimer brain. Reason: A real plasma-membrane subdomain localization relevant to regulation, but peripheral to the core transport function. Supporting Evidence: PMID:20193040 EAAT2 is associated with lipid raft microdomains of the plasma membrane
GO:0045121 membrane raft	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic transfer of raft localization from rat GLT-1. Reason: Consistent with direct human raft-localization data; peripheral to core function.
GO:0045121 membrane raft	ISS PMID:20193040 Increased expression of cholesterol 24S-hydroxylase results ...	KEEP AS NON CORE	Summary: ISS raft localization based on the rat ortholog from the same study. Reason: Peripheral plasma-membrane subdomain localization. Supporting Evidence: PMID:20193040 EAAT2 is associated with lipid raft microdomains of the plasma membrane
GO:0045202 synapse	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Generic synapse localization; EAAT2 concentrates perisynaptically. Reason: Correct but broad; the informative capture is glutamatergic synapse (GO:0098978) and astrocyte perisynaptic processes.
GO:0070207 protein homotrimerization	IDA PMID:15265858 A trimeric quaternary structure is conserved in bacterial an...	ACCEPT	Summary: Blue-native PAGE, concatemer analysis and cross-linking show hEAAT2 assembles as a homotrimer of three identical subunits. Reason: Homotrimerization is the directly demonstrated, functionally required quaternary assembly of EAAT2. Supporting Evidence: PMID:15265858 assembled as trimers composed of three identical subunits
GO:0070207 protein homotrimerization	IDA PMID:15483603 Structure of a glutamate transporter homologue from Pyrococc...	ACCEPT	Summary: Crystal structure of the archaeal homolog GltPh shows a bowl-shaped trimer; cited by UniProt for the conserved trimeric assembly of EAAT2. Reason: Supports the homotrimeric assembly conserved across the family and directly demonstrated for human EAAT2. Supporting Evidence: PMID:15483603 The transporter is a bowl-shaped trimer
GO:0070633 transepithelial transport	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: ISS from the bovine ortholog (F1MUJ6) asserting transepithelial transport. Reason: EAAT2 is a glial/neuronal glutamate uptake transporter; it is not an epithelial transcellular carrier. The claim does not hold for the characterized human brain function and rests on an ortholog transfer.
GO:0070778 L-aspartate transmembrane transport	IBA GO_REF:0000033	TOO GENERAL	Summary: Family IBA for L-aspartate transport; EAAT2 does transport L-aspartate. Reason: Correct, but entailed by the accepted, more specific L-aspartate import across plasma membrane (GO:0140009), a verified descendant.
GO:0070778 L-aspartate transmembrane transport	ISS GO_REF:0000024	TOO GENERAL	Summary: ISS L-aspartate transport from the bovine ortholog. Reason: Entailed by the accepted L-aspartate import across plasma membrane (GO:0140009).
GO:0070779 D-aspartate import across plasma membrane	IDA PMID:7521911 Functional comparisons of three glutamate transporter subtyp...	KEEP AS NON CORE	Summary: EAAT2 directly transports D-aspartate (KM 13-54 uM), a stereoisomer substrate often used as a transport tracer. Reason: D-aspartate is a genuine but non-canonical substrate; the physiologically central cargo is L-glutamate (and L-aspartate). Supporting Evidence: file:human/SLC1A2/SLC1A2-uniprot.txt D-aspartate(out) + K(+)(in) + 3 Na(+)(out) + H(+)(out)
GO:0071314 cellular response to cocaine	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic transfer from rat GLT-1, reflecting regulation of EAAT2 expression/activity in cocaine/addiction models. Reason: This captures a stimulus regulating EAAT2 rather than a function EAAT2 executes; it is not a core activity of the human protein.
GO:0090461 intracellular glutamate homeostasis	TAS PMID:21757002 The nuclear receptor FXR regulates hepatic transport and met...	KEEP AS NON CORE	Summary: Hepatic uptake of glutamate by EAAT2 contributes to intracellular glutamate levels feeding glutamine synthesis in perivenous hepatocytes. Reason: A downstream consequence of the import activity; the core capture is L-glutamate import across the plasma membrane. Supporting Evidence: PMID:21757002 Glutamate is taken up by perivenous hepatocytes and is the main source for the synthesis of glutamine, catalyzed by glutamine synthase (GS)
GO:0097449 astrocyte projection	IEA GO_REF:0000107	ACCEPT	Summary: Astrocyte-process localization; EAAT2 is the dominant astrocytic glutamate transporter concentrated in fine perisynaptic astrocytic processes. Reason: Astrocytic perisynaptic processes are the principal site of EAAT2 function; this is a core location. Supporting Evidence: PMID:21258616 In both astrocytic processes and axon terminals, most EAAT2a is perisynaptic
GO:0097449 astrocyte projection	ISS GO_REF:0000024	ACCEPT	Summary: ISS astrocyte-process localization from a mammalian ortholog. Reason: Core astrocytic perisynaptic localization, agreeing with direct human data.
GO:0097449 astrocyte projection	ISS GO_REF:0000024	ACCEPT	Summary: ISS astrocyte-process localization from rat GLT-1. Reason: Core astrocytic perisynaptic localization.
GO:0098656 monoatomic anion transmembrane transport	IEA GO_REF:0000108	KEEP AS NON CORE	Summary: Process counterpart of the uncoupled chloride conductance. Reason: The uncoupled Cl- flux is a genuine secondary biophysical property of the EAAT pore, peripheral to glutamate transport. Supporting Evidence: file:human/SLC1A2/SLC1A2-uniprot.txt flux that is not coupled to amino acid transport
GO:0098657 import into cell	IEA GO_REF:0000117	TOO GENERAL	Summary: Broad ARBA assertion that EAAT2 imports its substrate into the cell. Reason: Entailed by the accepted, specific L-glutamate import across plasma membrane (GO:0098712), a verified descendant.
GO:0098712 L-glutamate import across plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: Family IBA (node PTN004328784) for glutamate import across the plasma membrane; the core biological process of EAAT2, with the target itself among the experimental sources. Reason: Clearance of extracellular glutamate by import across the plasma membrane is EAAT2's central physiological role.
GO:0098712 L-glutamate import across plasma membrane	IDA PMID:15265858 A trimeric quaternary structure is conserved in bacterial an...	ACCEPT	Summary: Direct glutamate-uptake currents measured for surface-expressed hEAAT2. Reason: Core glutamate import process, directly demonstrated. Supporting Evidence: PMID:15265858 the glutamate uptake currents correlate to the amount of trimeric transporters
GO:0098712 L-glutamate import across plasma membrane	IDA PMID:26690923 Caveolin-1 Sensitivity of Excitatory Amino Acid Transporters...	ACCEPT	Summary: Glutamate-induced inward transport current directly measured for EAAT2. Reason: Core glutamate import process. Supporting Evidence: PMID:26690923 I Glu was observed in EAAT1-, EAAT2-, EAAT3-, or EAAT4-expressing oocytes but not in water-injected oocytes
GO:0098712 L-glutamate import across plasma membrane	IDA PMID:7521911 Functional comparisons of three glutamate transporter subtyp...	ACCEPT	Summary: Radiolabel glutamate uptake directly measured for cloned human EAAT2. Reason: Core glutamate import process, established at cloning. Supporting Evidence: PMID:7521911 Reuptake plays an important role in regulating synaptic and extracellular concentrations of glutamate.
GO:0098712 L-glutamate import across plasma membrane	IEA GO_REF:0000107	ACCEPT	Summary: Electronic transfer of the glutamate-import process from rat GLT-1. Reason: Core glutamate import process.
GO:0098712 L-glutamate import across plasma membrane	IGI PMID:20193040 Increased expression of cholesterol 24S-hydroxylase results ...	ACCEPT	Summary: Genetic interaction with CYP46A1 (Q9WVK8): increasing cholesterol 24S-hydroxylase lowers membrane cholesterol, dissociates EAAT2 from rafts and reduces glutamate uptake. Reason: Supports that EAAT2-mediated glutamate import depends on its raft localization; reinforces the core import process. Supporting Evidence: PMID:20193040 the dissociation of EAAT2 from lipid rafts and the loss of EAAT2 and associated glutamate uptake function
GO:0098712 L-glutamate import across plasma membrane	TAS PMID:21757002 The nuclear receptor FXR regulates hepatic transport and met...	ACCEPT	Summary: Hepatic glutamate uptake across the plasma membrane via EAAT2. Reason: Core glutamate import process, in a non-neural tissue context. Supporting Evidence: PMID:21757002 Glutamate is taken up by perivenous hepatocytes and is the main source for the synthesis of glutamine, catalyzed by glutamine synthase (GS)
GO:0098796 membrane protein complex	IDA PMID:20193040 Increased expression of cholesterol 24S-hydroxylase results ...	KEEP AS NON CORE	Summary: EAAT2 detected as part of a membrane protein complex (consistent with its homotrimeric, raft-associated assembly). Reason: Generic complex membership; the specific, informative assembly is the EAAT2 homotrimer (captured by GO:0070207 protein homotrimerization).
GO:0098796 membrane protein complex	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS membrane-protein-complex membership from a mammalian ortholog. Reason: Generic complex membership; informative capture is the homotrimer (GO:0070207).
GO:0098810 neurotransmitter reuptake	IEA GO_REF:0000107	ACCEPT	Summary: EAAT2 performs reuptake of released glutamate, the specific process role underlying its contribution to synaptic transmission. Reason: Glutamate reuptake/clearance is a core biological-process role of EAAT2. Supporting Evidence: Reactome:R-HSA-428015 GLT1 is expressed mainly in the brain and is essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft
GO:0098978 glutamatergic synapse	IEA GO_REF:0000107	ACCEPT	Summary: EAAT2 is active at glutamatergic synapses, clearing released glutamate from the cleft; it concentrates in perisynaptic astrocytic (and some axonal) membrane. Reason: The glutamatergic synapse is the principal site where EAAT2 acts; a core functional location. Supporting Evidence: PMID:21258616 In both astrocytic processes and axon terminals, most EAAT2a is perisynaptic
GO:0140009 L-aspartate import across plasma membrane	IDA PMID:7521911 Functional comparisons of three glutamate transporter subtyp...	ACCEPT	Summary: EAAT2 directly imports L-aspartate (KM ~7 uM in oocytes), a physiological co-substrate transported by the same Na+-coupled mechanism. Reason: L-aspartate is a genuine physiological substrate of EAAT2 (the glutamate/aspartate transporter), imported across the plasma membrane. Supporting Evidence: file:human/SLC1A2/SLC1A2-uniprot.txt mediates the uptake of L-glutamate and also L-aspartate and D-aspartate
GO:0150104 transport across blood-brain barrier	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: ISS from the bovine ortholog asserting transport across the blood-brain barrier. Reason: EAAT2 is an astrocytic/neuronal glutamate uptake transporter, not an endothelial carrier that moves solutes transcellularly across the blood-brain barrier. The claim rests on an ortholog transfer and is not supported for the characterized human function.
GO:0150104 transport across blood-brain barrier	NAS PMID:26590417 Establishment and Dysfunction of the Blood-Brain Barrier.	MARK AS OVER ANNOTATED	Summary: NAS citing a general blood-brain-barrier review; the cited paper does not mention EAAT2/SLC1A2 or glutamate transport. Reason: The cited review contains no EAAT2/glutamate-transporter content, and EAAT2 is not a transcellular blood-brain-barrier transporter. 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: NAS citing a general blood-brain-barrier review; the cited paper does not mention EAAT2/SLC1A2 or glutamate transport. Reason: No EAAT2/glutamate-transporter content in the cited review; EAAT2 is a glial uptake transporter, not a transcellular BBB carrier. Over-annotation.
GO:1903712 L-cysteine transmembrane transport	IEA GO_REF:0000108	MARK AS OVER ANNOTATED	Summary: Inter-ontology inference from the L-cysteine transporter activity. Reason: Inherits the over-annotation of GO:0033229: cysteine transport is a minor, promiscuous activity of EAAT2, not an evolved function (EAAT3/EAAC1 is the dedicated cysteine transporter).

Gene Description

Existing Annotations Review

Core Functions

High-affinity L-glutamate transmembrane transporter activity; EAAT2 provides the bulk of CNS glutamate uptake and is the dominant glutamate transporter by expression level. The same transport pathway also imports L-aspartate and D-aspartate.

Assembly into a functional homotrimer of three identical subunits, the native and functional quaternary state conserved across the glutamate-transporter family; each protomer carries its own transport pathway.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

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