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2.A.23.2.7
Excitatory amino acid transporter 2, EAAT2 (Glutamate/aspartate transporter II) (Sodium-dependent glutamate/aspartate transporter 2) (Solute carrier family 1 member 2).  This system may be important for the pathophysiology of schizophrenia (Parkin et al. 2018). Amino acids in the TMS2 of EAAT2 are essential for membrane-bound localization, substrate binding, transporter function and anion currents (Mai et al. 2021). The distance between the TMS3-TMS4 loop and TMS7 changes when substrates are transported (Qu et al. 2021).  SLC1A2 and SLC1A3 encode the glial glutamate transporters EAAT2 and EAAT1, which are not only the predominant glutamate uptake carriers in the brain, but also function as anion channels. Two homologous mutations, which substitute prolines in the center of the fifth TMS by arginine (P289R EAAT2, P290R EAAT1) cause  epileptic encephalopathy (SLC1A2) or with episodic ataxia type 6 (SLC1A3). Both mutations impair glutamate uptake and increase anion conduction (Suslova et al. 2023). Additionally, the P312R mutation generates an anion conducting state that is accessible in the outward facing apo state that is the main determinant of the increased anion conduction of EAAT transporters carrying this mutation.

Accession Number:P43004
Protein Name:Excitatory amino acid transporter 2
Length:574
Molecular Weight:62104.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:9
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate sodium(1+), glutamate(2-), aspartate(2-)

Cross database links:

Entrez Gene ID: 6506   
Pfam: PF00375   
KEGG: hsa:6506   

Gene Ontology

GO:0030673 C:axolemma
GO:0043198 C:dendritic shaft
GO:0043197 C:dendritic spine
GO:0016021 C:integral to membrane
GO:0005624 C:membrane fraction
GO:0005886 C:plasma membrane
GO:0042734 C:presynaptic membrane
GO:0015501 F:glutamate:sodium symporter activity
GO:0005314 F:high-affinity glutamate transmembrane transporter activity
GO:0005313 F:L-glutamate transmembrane transporter activity
GO:0017153 F:sodium:dicarboxylate symporter activity
GO:0030534 P:adult behavior
GO:0031668 P:cellular response to extracellular stimulus
GO:0070779 P:D-aspartate import
GO:0051938 P:L-glutamate import
GO:0035264 P:multicellular organism growth
GO:0010259 P:multicellular organismal aging
GO:0046326 P:positive regulation of glucose import
GO:0043200 P:response to amino acid stimulus
GO:0042493 P:response to drug
GO:0009611 P:response to wounding
GO:0007268 P:synaptic transmission
GO:0021537 P:telencephalon development
GO:0007632 P:visual behavior

References (9)

[1] “Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex.”  Arriza J.L.et.al.   7521911
[2] “Molecular cloning of human brain glutamate/aspartate transporter II.”  Shashidharan P.et.al.   8172925
[3] “Cloning and characterization of a glutamate transporter cDNA from human brain and pancreas.”  Manfras B.J.et.al.   7522567
[4] “DL-threo-beta-benzyloxyaspartate, a potent blocker of excitatory amino acid transporters.”  Shimamoto K.et.al.   9463476
[5] “Cloning and characterization of the 3'-untranslated region of the human excitatory amino acid transporter 2 transcript.”  Kim S.Y.et.al.   12950454
[6] “Human chromosome 11 DNA sequence and analysis including novel gene identification.”  Taylor T.D.et.al.   16554811
[7] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[8] “A trimeric quaternary structure is conserved in bacterial and human glutamate transporters.”  Gendreau S.et.al.   15265858
[9] “Phosphoproteomic analysis of synaptosomes from human cerebral cortex.”  DeGiorgis J.A.et.al.   15822905

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FASTA formatted sequence
1:	MASTEGANNM PKQVEVRMHD SHLGSEEPKH RHLGLRLCDK LGKNLLLTLT VFGVILGAVC 
61:	GGLLRLASPI HPDVVMLIAF PGDILMRMLK MLILPLIISS LITGLSGLDA KASGRLGTRA 
121:	MVYYMSTTII AAVLGVILVL AIHPGNPKLK KQLGPGKKND EVSSLDAFLD LIRNLFPENL 
181:	VQACFQQIQT VTKKVLVAPP PDEEANATSA VVSLLNETVT EVPEETKMVI KKGLEFKDGM 
241:	NVLGLIGFFI AFGIAMGKMG DQAKLMVDFF NILNEIVMKL VIMIMWYSPL GIACLICGKI 
301:	IAIKDLEVVA RQLGMYMVTV IIGLIIHGGI FLPLIYFVVT RKNPFSFFAG IFQAWITALG 
361:	TASSAGTLPV TFRCLEENLG IDKRVTRFVL PVGATINMDG TALYEAVAAI FIAQMNGVVL 
421:	DGGQIVTVSL TATLASVGAA SIPSAGLVTM LLILTAVGLP TEDISLLVAV DWLLDRMRTS 
481:	VNVVGDSFGA GIVYHLSKSE LDTIDSQHRV HEDIEMTKTQ SIYDDMKNHR ESNSNQCVYA 
541:	AHNSVIVDEC KVTLAANGKS ADCSVEEEPW KREK