P43005 (EAA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Excitatory amino acid transporter 3

Alternative name(s):
Excitatory amino-acid carrier 1
Neuronal and epithelial glutamate transporter
Sodium-dependent glutamate/aspartate transporter 3
Solute carrier family 1 member 1

Gene names

Name:	SLC1A1
Synonyms:	EAAC1, EAAT3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	524 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. Negatively regulated by ARL6IP5 By similarity. Ref.2 Ref.3
Subunit structure	Interacts with ARL6IP5/PRAF3 By similarity.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Expressed in all tissues tested including liver, muscle, testis, ovary, retinoblastoma cell line, neurons and brain (in which there was dense expression in substantia nigra, red nucleus, hippocampus and in cerebral cortical layers). Ref.1 Ref.2 Ref.3
Post-translational modification	Glycosylated.
Sequence similarities	Belongs to the sodium:dicarboxylate (SDF) symporter (TC 2.A.23) family. SLC1A1 subfamily. [View classification]

Ontologies

Keywords
Biological process	Symport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	D-aspartate import Inferred from direct assay Ref.3. Source: UniProtKB L-glutamate import Inferred from direct assay Ref.3. Source: UniProtKB synaptic transmission Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc membrane fraction Traceable author statement. Source: ProtInc
Molecular function	sodium:dicarboxylate symporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 524	524	Excitatory amino acid transporter 3		PRO_0000202065
Regions
	Topological domain	1 – 18	18	Cytoplasmic Potential
	Transmembrane	19 – 38	20	Helical; Potential
	Transmembrane	62 – 82	21	Helical; Potential
	Transmembrane	94 – 114	21	Helical; Potential
	Topological domain	115 – 209	95	Extracellular Potential
	Transmembrane	210 – 229	20	Helical; Potential
	Transmembrane	254 – 273	20	Helical; Potential
	Transmembrane	290 – 309	20	Helical; Potential
	Transmembrane	316 – 335	20	Helical; Potential
	Transmembrane	362 – 381	20	Helical; Potential
	Transmembrane	392 – 411	20	Helical; Potential
	Transmembrane	420 – 439	20	Helical; Potential
Amino acid modifications
	Glycosylation	43	1	N-linked (GlcNAc...) Potential
	Glycosylation	178	1	N-linked (GlcNAc...) Potential
	Glycosylation	195	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	27	1	A → G. Corresponds to variant rs2229885 [ dbSNP | Ensembl ].		VAR_023309
	Natural variant	50	1	F → Y. Corresponds to variant rs16921449 [ dbSNP | Ensembl ].		VAR_023308
Experimental info
	Sequence conflict	10	1	E → PS in AAA50430. Ref.3
	Sequence conflict	92	1	L → V in AAH33040. Ref.7
	Sequence conflict	94	1	A → V in AAA68628. Ref.1
	Sequence conflict	94	1	A → V in AAC27511. Ref.4
	Sequence conflict	96	1	V → L in AAA53215. Ref.2
	Sequence conflict	170	1	K → N in AAA53215. Ref.2
	Sequence conflict	172	1	P → A in AAA53215. Ref.2
	Sequence conflict	260	1	L → H in AAA53215. Ref.2
	Sequence conflict	280	1	R → A in AAA68628. Ref.1
	Sequence conflict	376	1	V → G in AAC25029. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	P43005 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: FC6244ADC9EA228F	FASTA	524	57,100
	10 20 30 40 50 60 MGKPARKGCE WKRFLKNNWV LLSTVAAVVL GITTGVLVRE HSNLSTLEKF YFAFPGEILM 70 80 90 100 110 120 RMLKLIILPL IISSMITGVA ALDSNVSGKI GLRAVVYYFC TTLIAVILGI VLVVSIKPGV 130 140 150 160 170 180 TQKVGEIART GSTPEVSTVD AMLDLIRNMF PENLVQACFQ QYKTKREEVK PPSDPEMNMT 190 200 210 220 230 240 EESFTAVMTT AISKNKTKEY KIVGMYSDGI NVLGLIVFCL VFGLVIGKMG EKGQILVDFF 250 260 270 280 290 300 NALSDATMKI VQIIMCYMPL GILFLIAGKI IEVEDWEIFR KLGLYMATVL TGLAIHSIVI 310 320 330 340 350 360 LPLIYFIVVR KNPFRFAMGM AQALLTALMI SSSSATLPVT FRCAEENNQV DKRITRFVLP 370 380 390 400 410 420 VGATINMDGT ALYEAVAAVF IAQLNDLDLG IGQIITISIT ATSASIGAAG VPQAGLVTMV 430 440 450 460 470 480 IVLSAVGLPA EDVTLIIAVD WLLDRFRTMV NVLGDAFGTG IVEKLSKKEL EQMDVSSEVN 490 500 510 520 IVNPFALEST ILDNEDSDTK KSYVNGGFAV DKSDTISFTQ TSQF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Neuron-specific human glutamate transporter: molecular cloning, characterization and expression in human brain." Shashidharan P., Huntley G.W., Meyer T., Morrison J.H., Plaitakis A. Brain Res. 662:245-250(1994) [PubMed: 7859077] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Brain.
[2]	"The neuronal and epithelial human high affinity glutamate transporter. Insights into structure and mechanism of transport." Kanai Y., Stelzner M., Nussberger S., Khawaja S., Hebert S.C., Smith C.P., Hediger M.A. J. Biol. Chem. 269:20599-20606(1994) [PubMed: 7914198] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
[3]	"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: 7521911] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY. Tissue: Brain cortex.
[4]	"Genomic organization of the SLC1A1/EAAC1 gene and mutation screening in early-onset obsessive-compulsive disorder." Veenstra-VanderWeele J., Kim S.J., Gonen D., Hanna G.L., Leventhal B.L., Cook E.H. Jr. Mol. Psychiatry 6:160-167(2001) [PubMed: 11317217] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"A glutamate transporter related to EAAT3 from human brain." Yasuda-Kamatani Y. Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Brain.
[6]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[8]	Rome S., Mertani H.C., Lee K.O., Lobie P.E., Tome D. Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 268-446. Tissue: Placenta.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	U08989 mRNA. Translation: AAA68628.1. U06469 mRNA. Translation: AAA53215.1. U03506 mRNA. Translation: AAA50430.1. AF074911 , AF143773, AF074903, AF074904, AF074905, AF074906, AF074907, AF074908, AF074909, AF074910 Genomic DNA. Translation: AAC27511.3. AB008536 mRNA. Translation: BAB83767.1. AL162587, AL136231 Genomic DNA. Translation: CAH71965.1. AL136231, AL162587 Genomic DNA. Translation: CAI41264.1. BC033040 mRNA. Translation: AAH33040.1. AF037982 mRNA. Translation: AAC25029.1.
IPI	IPI00015475.
PIR	A54856. I38433. I38560.
RefSeq	NP_004161.4. NM_004170.5.
UniGene	Hs.444915.
3D structure databases
ProteinModelPortal	P43005.
ModBase	Search...
Protein-protein interaction databases
IntAct	P43005. 1 interaction.
STRING	P43005.
Protein family/group databases
TCDB	2.A.23.2.3. dicarboxylate/amino acid:cation (Na+ or H+) symporter (DAACS) family.
PTM databases
PhosphoSite	P43005.
Polymorphism databases
DMDM	1352332.
Proteomic databases
PRIDE	P43005.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262352; ENSP00000262352; ENSG00000106688.
GeneID	6505.
KEGG	hsa:6505.
UCSC	uc003zij.1. human.
Organism-specific databases
CTD	6505.
GeneCards	GC09P004480.
H-InvDB	HIX0007892.
HGNC	HGNC:10939. SLC1A1.
HPA	CAB015466. HPA020086.
MIM	133550. gene.
neXtProt	NX_P43005.
PharmGKB	PA35826.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17150.
GeneTree	ENSGT00550000074215.
HOGENOM	HBG739804.
HOVERGEN	HBG000080.
InParanoid	P43005.
OMA	MTEESFT.
OrthoDB	EOG4CVG6W.
PhylomeDB	P43005.
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	P43005.
Bgee	P43005.
CleanEx	HS_SLC1A1.
Genevestigator	P43005.
GermOnline	ENSG00000106688. Homo sapiens.
Family and domain databases
InterPro	IPR001991. Na-dicarboxylate_symporter. IPR018107. Na-dicarboxylate_symporter_CS. [Graphical view]
KO	K05612.
PANTHER	PTHR11958. Na/diCO_symport. 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
DrugBank	DB00128. L-Aspartic Acid. DB00142. L-Glutamic Acid.
NextBio	25293.
SOURCE	Search...

Entry information

Entry name

EAA3_HUMAN

Accession

Primary (citable) accession number: P43005
Secondary accession number(s): O75587 , Q5VZ24, Q8N199, Q9UEW2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	February 1, 1996
Last modified:	December 14, 2011
This is version 101 of the entry and version 2 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.