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2.A.23.2.6
Excitatory amino acid transporter 1 (EAAT1) (Sodium-dependent glutamate/aspartate transporter 1) (GLAST-1) (Solute carrier family 1 member 3).  Mutations cause episodic ataxia type 6 (EA6) (Choi et al. 2016; Iwama et al. 2017). EAAT1 regulates the extent and duration of glutamate-mediated signals by the clearance of glutamate after synaptic release. It also has an anion channel activity that prevents additional glutamate release. This system may be important for the pathophysiology of schizophrenia (Parkin et al. 2018). Substrate-induced structural rearrangements occur between the TMS4b-4c loop and TMS7 during the transport cycle (Zhang et al. 2019). GLAST serves as a cell surface biomarker for astrocytes (Kumar et al. 2021). It interacts with NHERF1 and NHERF2 (see TC# 8.A.24.1.1) which modify its cell surface expression (Sato et al. 2013). The inhibitor, UCPH-101 slows substrate translocation rather than substrate or Na+ binding, confirming a non-competitive inhibitory mechanism. However, it only partially inhibits wild-type ASCT2 with relatively low affinity (Dong et al. 2023).  Perivascular fibroblasts expressing SLC1A3 are essential for penile erection in mice because they reduce norepinephrine availability, thereby promoting dilation of the corpora cavernosa. The number of SLC1A3+ perivascular fibroblasts decreased in aged mice, which reduced penile blood flow (Guimaraes et al. 2024).

Accession Number:P43003
Protein Name:Excitatory amino acid transporter 1
Length:542
Molecular Weight:59572.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:10
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate sodium(1+), glutamate(2-), aspartate(2-)

Cross database links:

Entrez Gene ID: 6507   
Pfam: PF00375   
KEGG: hsa:6507   

Gene Ontology

GO:0016323 C:basolateral plasma membrane
GO:0009986 C:cell surface
GO:0043197 C:dendritic spine
GO:0043205 C:fibril
GO:0016021 C:integral to membrane
GO:0005624 C:membrane fraction
GO:0005743 C:mitochondrial inner membrane
GO:0043025 C:neuronal cell body
GO:0005886 C:plasma membrane
GO:0045202 C:synapse
GO:0016595 F:glutamate binding
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:0031223 P:auditory behavior
GO:0048667 P:cell morphogenesis involved in neuron differentiation
GO:0021545 P:cranial nerve development
GO:0070779 P:D-aspartate import
GO:0009449 P:gamma-aminobutyric acid biosynthetic process
GO:0006537 P:glutamate biosynthetic process
GO:0051938 P:L-glutamate import
GO:0043490 P:malate-aspartate shuttle
GO:0050885 P:neuromuscular process controlling balance
GO:0001504 P:neurotransmitter uptake
GO:0050806 P:positive regulation of synaptic transmission
GO:0046677 P:response to antibiotic
GO:0042493 P:response to drug
GO:0010035 P:response to inorganic substance
GO:0009416 P:response to light stimulus
GO:0009611 P:response to wounding
GO:0007605 P:sensory perception of sound

References (9)

[1] “Cloning and characterization of a glutamate transporter cDNA from human cerebellum.”  Shashidharan P.et.al.   8218410
[2] “Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex.”  Arriza J.L.et.al.   7521911
[3] “Cloning and expression of a human glutamate transporter.”  Kawakami H.et.al.   8123008
[4] “Human high affinity, Na(+)-dependent L-glutamate/L-aspartate transporter GLAST-1 (EAAT-1): gene structure and localization to chromosome 5p11-p12.”  Stoffel W.et.al.   8647279
[5] “A novel alternative splicing form of excitatory amino acid transporter 1 is a negative regulator of glutamate uptake.”  Vallejo-Illarramendi A.et.al.   16042756
[6] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[7] “The DNA sequence and comparative analysis of human chromosome 5.”  Schmutz J.et.al.   15372022
[8] “A quantitative atlas of mitotic phosphorylation.”  Dephoure N.et.al.   18669648
[9] “Mutation in the glutamate transporter EAAT1 causes episodic ataxia, hemiplegia, and seizures.”  Jen J.C.et.al.   16116111
Structure:
5LLM   5LLU   5LM4   5MJU     

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MTKSNGEEPK MGGRMERFQQ GVRKRTLLAK KKVQNITKED VKSYLFRNAF VLLTVTAVIV 
61:	GTILGFTLRP YRMSYREVKY FSFPGELLMR MLQMLVLPLI ISSLVTGMAA LDSKASGKMG 
121:	MRAVVYYMTT TIIAVVIGII IVIIIHPGKG TKENMHREGK IVRVTAADAF LDLIRNMFPP 
181:	NLVEACFKQF KTNYEKRSFK VPIQANETLV GAVINNVSEA METLTRITEE LVPVPGSVNG 
241:	VNALGLVVFS MCFGFVIGNM KEQGQALREF FDSLNEAIMR LVAVIMWYAP VGILFLIAGK 
301:	IVEMEDMGVI GGQLAMYTVT VIVGLLIHAV IVLPLLYFLV TRKNPWVFIG GLLQALITAL 
361:	GTSSSSATLP ITFKCLEENN GVDKRVTRFV LPVGATINMD GTALYEALAA IFIAQVNNFE 
421:	LNFGQIITIS ITATAASIGA AGIPQAGLVT MVIVLTSVGL PTDDITLIIA VDWFLDRLRT 
481:	TTNVLGDSLG AGIVEHLSRH ELKNRDVEMG NSVIEENEMK KPYQLIAQDN ETEKPIDSET 
541:	KM