P43003 (EAA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Excitatory amino acid transporter 1

Alternative name(s):
Sodium-dependent glutamate/aspartate transporter 1
Short name=GLAST-1
Solute carrier family 1 member 3

Gene names

Name:	SLC1A3
Synonyms:	EAAT1, GLAST, GLAST1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	542 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transports L-glutamate and also L- and D-aspartate. Essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. Acts as a symport by cotransporting sodium.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Highly expressed in cerebellum, but also found in frontal cortex, hippocampus and basal ganglia.
Post-translational modification	Glycosylated.
Involvement in disease	Episodic ataxia 6 (EA6) [MIM:612656]: A disorder characterized by episodic ataxia, seizures, migraine and alternating hemiplegia. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10
Sequence similarities	Belongs to the sodium:dicarboxylate (SDF) symporter (TC 2.A.23) family. SLC1A3 subfamily. [View classification]

Ontologies

Keywords
Biological process	Symport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	D-aspartate import Inferred from direct assay Ref.2. Source: UniProtKB L-glutamate import Inferred from direct assay Ref.2. Source: UniProtKB auditory behavior Inferred from electronic annotation. Source: Compara cell morphogenesis involved in neuron differentiation Inferred from electronic annotation. Source: Compara cranial nerve development Inferred from electronic annotation. Source: Compara gamma-aminobutyric acid biosynthetic process Inferred from electronic annotation. Source: Compara glutamate biosynthetic process Inferred from electronic annotation. Source: Compara neuromuscular process controlling balance Inferred from electronic annotation. Source: Compara neurotransmitter uptake Traceable author statement Ref.4. Source: ProtInc positive regulation of synaptic transmission Inferred from electronic annotation. Source: Compara response to antibiotic Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to light stimulus Inferred from electronic annotation. Source: Compara response to wounding Inferred from electronic annotation. Source: Compara sensory perception of sound Inferred from electronic annotation. Source: Compara
Cellular_component	cell projection Inferred from electronic annotation. Source: Compara cell surface Inferred from electronic annotation. Source: Compara fibril Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuronal cell body Inferred from electronic annotation. Source: Compara plasma membrane Traceable author statement. Source: Reactome
Molecular_function	L-glutamate transmembrane transporter activity Traceable author statement Ref.2. Source: ProtInc glutamate binding Inferred from electronic annotation. Source: Compara high-affinity glutamate transmembrane transporter activity Inferred from electronic annotation. Source: Compara sodium:dicarboxylate symporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P43003-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P43003-2)

Also known as: EAAT1ex9skip;

The sequence of this isoform differs from the canonical sequence as follows:
     430-475: SITATAASIGAAGIPQAGLVTMVIVLTSVGLPTDDITLIIAVDWFL → R

Note: Expressed throughout the CNS, both in gray matter and axonal tracts, at levels ranging between 10% and 20% of isoform 1. Localizes to ER, has no functional glutamate uptake activity, and exerts a dominant negative effect isoform 1.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 542	542	Excitatory amino acid transporter 1		PRO_0000202057
Regions
	Topological domain	1 – 47	47	Cytoplasmic Potential
	Transmembrane	48 – 68	21	Helical; Potential
	Transmembrane	91 – 111	21	Helical; Potential
	Transmembrane	123 – 145	23	Helical; Potential
	Topological domain	146 – 237	92	Extracellular Potential
	Transmembrane	238 – 260	23	Helical; Potential
	Transmembrane	281 – 302	22	Helical; Potential
	Transmembrane	319 – 340	22	Helical; Potential
Amino acid modifications
	Modified residue	512	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	430 – 475	46	SITAT…VDWFL → R in isoform 2.		VSP_043913
	Natural variant	219	1	E → D. Corresponds to variant rs2032892 [ dbSNP | Ensembl ].		VAR_011877
	Natural variant	290	1	P → R in EA6. Ref.10		VAR_031733
Experimental info
	Sequence conflict	366	1	S → CT Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 6E9F62D35A3A5A29	FASTA	542	59,572
	10 20 30 40 50 60 MTKSNGEEPK MGGRMERFQQ GVRKRTLLAK KKVQNITKED VKSYLFRNAF VLLTVTAVIV 70 80 90 100 110 120 GTILGFTLRP YRMSYREVKY FSFPGELLMR MLQMLVLPLI ISSLVTGMAA LDSKASGKMG 130 140 150 160 170 180 MRAVVYYMTT TIIAVVIGII IVIIIHPGKG TKENMHREGK IVRVTAADAF LDLIRNMFPP 190 200 210 220 230 240 NLVEACFKQF KTNYEKRSFK VPIQANETLV GAVINNVSEA METLTRITEE LVPVPGSVNG 250 260 270 280 290 300 VNALGLVVFS MCFGFVIGNM KEQGQALREF FDSLNEAIMR LVAVIMWYAP VGILFLIAGK 310 320 330 340 350 360 IVEMEDMGVI GGQLAMYTVT VIVGLLIHAV IVLPLLYFLV TRKNPWVFIG GLLQALITAL 370 380 390 400 410 420 GTSSSSATLP ITFKCLEENN GVDKRVTRFV LPVGATINMD GTALYEALAA IFIAQVNNFE 430 440 450 460 470 480 LNFGQIITIS ITATAASIGA AGIPQAGLVT MVIVLTSVGL PTDDITLIIA VDWFLDRLRT 490 500 510 520 530 540 TTNVLGDSLG AGIVEHLSRH ELKNRDVEMG NSVIEENEMK KPYQLIAQDN ETEKPIDSET KM
	Isoform 2 (EAAT1ex9skip) [UniParc]. Checksum: 7C21EC2B467E1C11	FASTA	497	55,149
	10 20 30 40 50 60 MTKSNGEEPK MGGRMERFQQ GVRKRTLLAK KKVQNITKED VKSYLFRNAF VLLTVTAVIV 70 80 90 100 110 120 GTILGFTLRP YRMSYREVKY FSFPGELLMR MLQMLVLPLI ISSLVTGMAA LDSKASGKMG 130 140 150 160 170 180 MRAVVYYMTT TIIAVVIGII IVIIIHPGKG TKENMHREGK IVRVTAADAF LDLIRNMFPP 190 200 210 220 230 240 NLVEACFKQF KTNYEKRSFK VPIQANETLV GAVINNVSEA METLTRITEE LVPVPGSVNG 250 260 270 280 290 300 VNALGLVVFS MCFGFVIGNM KEQGQALREF FDSLNEAIMR LVAVIMWYAP VGILFLIAGK 310 320 330 340 350 360 IVEMEDMGVI GGQLAMYTVT VIVGLLIHAV IVLPLLYFLV TRKNPWVFIG GLLQALITAL 370 380 390 400 410 420 GTSSSSATLP ITFKCLEENN GVDKRVTRFV LPVGATINMD GTALYEALAA IFIAQVNNFE 430 440 450 460 470 480 LNFGQIITIR DRLRTTTNVL GDSLGAGIVE HLSRHELKNR DVEMGNSVIE ENEMKKPYQL 490 IAQDNETEKP IDSETKM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of a glutamate transporter cDNA from human cerebellum." Shashidharan P., Plaitakis A. Biochim. Biophys. Acta 1216:161-164(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Cerebellum.
[2]	"Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex." Arriza J.L., Fairman W.A., Wendy A., Wadiche J.I., Murdoch G.H., Kavanaugh M.P., Amara S.G. J. Neurosci. 14:5559-5569(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain cortex.
[3]	"Cloning and expression of a human glutamate transporter." Kawakami H., Tanaka K., Nakayama T., Inoue K., Nakamura S. Biochem. Biophys. Res. Commun. 199:171-176(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[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., Sasse J., Dueker M., Mueller R., Hofmann K.O., Fink T., Lichter P. FEBS Lett. 386:189-193(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"A novel alternative splicing form of excitatory amino acid transporter 1 is a negative regulator of glutamate uptake." Vallejo-Illarramendi A., Domercq M., Matute C. J. Neurochem. 95:341-348(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Cerebellum.
[7]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[10]	"Mutation in the glutamate transporter EAAT1 causes episodic ataxia, hemiplegia, and seizures." Jen J.C., Wan J., Palos T.P., Howard B.D., Baloh R.W. Neurology 65:529-534(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT EA6 ARG-290.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	L19158 mRNA. No translation available. U03504 mRNA. Translation: AAA50428.1. D26443 mRNA. Translation: BAA05462.1. Z31713 , Z31703, Z31704, Z31705, Z31706, Z31707, Z31708, Z31709, Z31710 Genomic DNA. Translation: CAA83507.1. AY954110 mRNA. Translation: AAY28724.1. AK312304 mRNA. Translation: BAG35230.1. AC008957 Genomic DNA. No translation available. AC010631 Genomic DNA. No translation available. CH471119 Genomic DNA. Translation: EAW55945.1.
IPI	IPI00015473. IPI00642894.
PIR	S38353.
RefSeq	NP_001160167.1. NM_001166695.1. NP_004163.3. NM_004172.4.
UniGene	Hs.481918.
3D structure databases
ProteinModelPortal	P43003.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-5004226.
STRING	9606.ENSP00000265113.
PTM databases
PhosphoSite	P43003.
Polymorphism databases
DMDM	1169458.
Proteomic databases
PaxDb	P43003.
PRIDE	P43003.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000265113; ENSP00000265113; ENSG00000079215. ENST00000381918; ENSP00000371343; ENSG00000079215.
GeneID	6507.
KEGG	hsa:6507.
UCSC	uc003jkj.4. human.
Organism-specific databases
CTD	6507.
GeneCards	GC05P036606.
HGNC	HGNC:10941. SLC1A3.
HPA	CAB002573. HPA037467. HPA037468.
MIM	600111. gene. 612656. phenotype.
neXtProt	NX_P43003.
Orphanet	2131. Alternating hemiplegia of childhood. 209967. Episodic ataxia type 6.
PharmGKB	PA35828.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1301.
HOGENOM	HOG000208776.
HOVERGEN	HBG000080.
InParanoid	P43003.
KO	K05614.
OMA	TLRPYRM.
OrthoDB	EOG46HG9R.
PhylomeDB	P43003.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System. REACT_15518. Transmembrane transport of small molecules. REACT_19419. Amino acid and oligopeptide SLC transporters.
Gene expression databases
ArrayExpress	P43003.
Bgee	P43003.
CleanEx	HS_SLC1A3.
Genevestigator	P43003.
GermOnline	ENSG00000079215. Homo sapiens.
Family and domain databases
InterPro	IPR001991. Na-dicarboxylate_symporter. IPR018107. Na-dicarboxylate_symporter_CS. [Graphical view]
PANTHER	PTHR11958. PTHR11958. 1 hit.
Pfam	PF00375. SDF. 1 hit. [Graphical view]
PRINTS	PR00173. EDTRNSPORT.
PROSITE	PS00713. NA_DICARBOXYL_SYMP_1. 1 hit. PS00714. NA_DICARBOXYL_SYMP_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P43003.
ChEMBL	CHEMBL3085.
ChiTaRS	SLC1A3. human.
DrugBank	DB00142. L-Glutamic Acid.
GenomeRNAi	6507.
NextBio	25301.
SOURCE	Search...

Entry information

Entry name

EAA1_HUMAN

Accession

Primary (citable) accession number: P43003
Secondary accession number(s): B2R5T3, Q4JCQ8

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.