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2.A.23.2.3
Glutamate/aspartate/cysteine:Na+ symporter, EAAC1; EAAT3 (Li+ can replace Na+; EAAC1 also mediates glutamate-independent anion conductance.) Cotransports glutamic acid with three Na+ followed by countertransport of K+(Teichman et al., 2009). The 50 residue 4B-4C loop (following TMS4) binds Na+ (Koch et al., 2007). (The dicarboxylic aminoaciduria protein in humans; NP_004161; Bröer, 2008a; 2008b). Neutralizing aspartate 83 modifies substrate translocation (Hotzy et al., 2012).  An SLC1A1 deletion segregates with schizophrenia and bipolar schizoaffective disorder in a 5-generation family (Myles-Worsley et al. 2013).  Thr101 in TMS3 is essential for Na+ binding (Tao et al. 2010).  Klotho, a 1012 aa protein with N- and C-terminal TMSs, is a regulator of the excitatory amino acid transporters EAAT3 and EAAT4 (Almilaji et al. 2013).

Accession Number:P43005
Protein Name:EAA3 aka SLC1A1 aka EAAT3 aka EAAC1
Length:524
Molecular Weight:57100.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:9
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate glutamate, aspartate, Cysteine, Na+, Li+, K+

Cross database links:

Genevestigator: P43005 P43005
eggNOG: prNOG17150 COG1301
HEGENOM: HBG739804 HOG000208776
RefSeq: NP_004161.4   
Entrez Gene ID: 6505   
Pfam: PF00375   
Drugbank: Drugbank Link   
OMIM: 133550  gene
222730  phenotype
KEGG: hsa:6505    hsa:6505   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0005624 C:membrane fraction
GO:0017153 F:sodium:dicarboxylate symporter activity
GO:0070779 P:D-aspartate import
GO:0006835 P:dicarboxylic acid transport
GO:0051938 P:L-glutamate import
GO:0007268 P:synaptic transmission
GO:0016595 F:glutamate binding
GO:0015501 F:glutamate:sodium symporter activity
GO:0005313 F:L-glutamate transmembrane transporter activity
GO:0051260 P:protein homooligomerization

References (12)

[1] “Neuron-specific human glutamate transporter: molecular cloning, characterization and expression in human brain.”  Shashidharan P.et.al.   7859077
[2] “The neuronal and epithelial human high affinity glutamate transporter. Insights into structure and mechanism of transport.”  Kanai Y.et.al.   7914198
[3] “Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex.”  Arriza J.L.et.al.   7521911
[4] “Genomic organization of the SLC1A1/EAAC1 gene and mutation screening in early-onset obsessive-compulsive disorder.”  Veenstra-VanderWeele J.et.al.   11317217
[5] “DNA sequence and analysis of human chromosome 9.”  Humphray S.J.et.al.   15164053
[6] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[7] “Neuron-specific human glutamate transporter: molecular cloning, characterization and expression in human brain.”  Shashidharan P.et.al.   7859077
[8] “The neuronal and epithelial human high affinity glutamate transporter. Insights into structure and mechanism of transport.”  Kanai Y.et.al.   7914198
[9] “Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex.”  Arriza J.L.et.al.   7521911
[10] “Genomic organization of the SLC1A1/EAAC1 gene and mutation screening in early-onset obsessive-compulsive disorder.”  Veenstra-VanderWeele J.et.al.   11317217
[11] “DNA sequence and analysis of human chromosome 9.”  Humphray S.J.et.al.   15164053
[12] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334

External Searches:

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  • 2° Structure (Network Protein Sequence Analysis)

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MGKPARKGCE WKRFLKNNWV LLSTVAAVVL GITTGVLVRE HSNLSTLEKF YFAFPGEILM 
61:	RMLKLIILPL IISSMITGVA ALDSNVSGKI GLRAVVYYFC TTLIAVILGI VLVVSIKPGV 
121:	TQKVGEIART GSTPEVSTVD AMLDLIRNMF PENLVQACFQ QYKTKREEVK PPSDPEMNMT 
181:	EESFTAVMTT AISKNKTKEY KIVGMYSDGI NVLGLIVFCL VFGLVIGKMG EKGQILVDFF 
241:	NALSDATMKI VQIIMCYMPL GILFLIAGKI IEVEDWEIFR KLGLYMATVL TGLAIHSIVI 
301:	LPLIYFIVVR KNPFRFAMGM AQALLTALMI SSSSATLPVT FRCAEENNQV DKRITRFVLP 
361:	VGATINMDGT ALYEAVAAVF IAQLNDLDLG IGQIITISIT ATSASIGAAG VPQAGLVTMV 
421:	IVLSAVGLPA EDVTLIIAVD WLLDRFRTMV NVLGDAFGTG IVEKLSKKEL EQMDVSSEVN 
481:	IVNPFALEST ILDNEDSDTK KSYVNGGFAV DKSDTISFTQ TSQF