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P43005 (EAA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length524 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Involvement in disease

Schizophrenia 18 (SCZD18) [MIM:615232]: A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. A deletion at the chromosome 9p24.2 locus, including SLC1A1, has been identified in patients with psychotic disorders (Ref.9). This 84 kb deletion is immediately upstream of the SLC1A1 gene in a regulatory region that contains the full native promoter sequence, extends through exon 1 of the SLC1A1 mRNA, co-segregates with disease in an extended 5-generation pedigree and increases disease risk more than 18-fold for family members (Ref.10). Ref.9 Ref.10

Sequence similarities

Belongs to the sodium:dicarboxylate (SDF) symporter (TC 2.A.23) family. SLC1A1 subfamily. [View classification]

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 524524Excitatory amino acid transporter 3
PRO_0000202065

Regions

Topological domain1 – 1818Cytoplasmic Potential
Transmembrane19 – 3820Helical; Potential
Transmembrane62 – 8221Helical; Potential
Transmembrane94 – 11421Helical; Potential
Topological domain115 – 20995Extracellular Potential
Transmembrane210 – 22920Helical; Potential
Transmembrane254 – 27320Helical; Potential
Transmembrane290 – 30920Helical; Potential
Transmembrane316 – 33520Helical; Potential
Transmembrane362 – 38120Helical; Potential
Transmembrane392 – 41120Helical; Potential
Transmembrane420 – 43920Helical; Potential

Amino acid modifications

Glycosylation431N-linked (GlcNAc...) Potential
Glycosylation1781N-linked (GlcNAc...) Potential
Glycosylation1951N-linked (GlcNAc...) Potential

Natural variations

Natural variant271A → G.
Corresponds to variant rs2229885 [ dbSNP | Ensembl ].
VAR_023309
Natural variant501F → Y.
Corresponds to variant rs16921449 [ dbSNP | Ensembl ].
VAR_023308

Experimental info

Sequence conflict101E → PS in AAA50430. Ref.3
Sequence conflict921L → V in AAH33040. Ref.7
Sequence conflict941A → V in AAA68628. Ref.1
Sequence conflict941A → V in AAC27511. Ref.4
Sequence conflict961V → L in AAA53215. Ref.2
Sequence conflict1701K → N in AAA53215. Ref.2
Sequence conflict1721P → A in AAA53215. Ref.2
Sequence conflict2601L → H in AAA53215. Ref.2
Sequence conflict2801R → A in AAA68628. Ref.1
Sequence conflict3761V → G in AAC25029. Ref.8

Sequences

Sequence LengthMass (Da)Tools
P43005 [UniParc].

Last modified February 1, 1996. Version 2.
Checksum: FC6244ADC9EA228F

FASTA52457,100
        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 

« Hide

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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.
[9]"Copy number variants for schizophrenia and related psychotic disorders in Oceanic Palau: risk and transmission in extended pedigrees."
Melhem N., Middleton F., McFadden K., Klei L., Faraone S.V., Vinogradov S., Tiobech J., Yano V., Kuartei S., Roeder K., Byerley W., Devlin B., Myles-Worsley M.
Biol. Psychiatry 70:1115-1121(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SCZD18.
[10]"Deletion at the SLC1A1 glutamate transporter gene co-segregates with schizophrenia and bipolar schizoaffective disorder in a 5-generation family."
Myles-Worsley M., Tiobech J., Browning S.R., Korn J., Goodman S., Gentile K., Melhem N., Byerley W., Faraone S.V., Middleton F.A.
Am. J. Med. Genet. B Neuropsychiatr. Genet. 162B:87-95(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SCZD18.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U08989 mRNA. Translation: AAA68628.1.
U06469 mRNA. Translation: AAA53215.1.
U03506 mRNA. Translation: AAA50430.1.
AF074911 expand/collapse EMBL AC list , 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.
CCDSCCDS6452.1.
PIRA54856.
I38433.
I38560.
RefSeqNP_004161.4. NM_004170.5.
UniGeneHs.444915.

3D structure databases

ProteinModelPortalP43005.
SMRP43005. Positions 20-464.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112396. 4 interactions.
IntActP43005. 1 interaction.
STRING9606.ENSP00000262352.

Chemistry

BindingDBP43005.
ChEMBLCHEMBL2721.
DrugBankDB00128. L-Aspartic Acid.
DB00142. L-Glutamic Acid.
GuidetoPHARMACOLOGY870.

Protein family/group databases

TCDB2.A.23.2.3. the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family.

PTM databases

PhosphoSiteP43005.

Polymorphism databases

DMDM1352332.

Proteomic databases

MaxQBP43005.
PaxDbP43005.
PRIDEP43005.

Protocols and materials databases

DNASU6505.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262352; ENSP00000262352; ENSG00000106688.
GeneID6505.
KEGGhsa:6505.
UCSCuc003zij.2. human.

Organism-specific databases

CTD6505.
GeneCardsGC09P004480.
HGNCHGNC:10939. SLC1A1.
HPACAB015466.
HPA020086.
MIM133550. gene.
615232. phenotype.
neXtProtNX_P43005.
Orphanet3140. Schizophrenia.
PharmGKBPA35826.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1301.
HOGENOMHOG000208776.
HOVERGENHBG000080.
InParanoidP43005.
KOK05612.
OMARFLKNNW.
OrthoDBEOG7RV9G2.
PhylomeDBP43005.
TreeFamTF315206.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.
REACT_15518. Transmembrane transport of small molecules.
REACT_19419. Amino acid and oligopeptide SLC transporters.

Gene expression databases

BgeeP43005.
CleanExHS_SLC1A1.
GenevestigatorP43005.

Family and domain databases

Gene3D1.10.3860.10. 2 hits.
InterProIPR001991. Na-dicarboxylate_symporter.
IPR018107. Na-dicarboxylate_symporter_CS.
[Graphical view]
PANTHERPTHR11958. PTHR11958. 1 hit.
PfamPF00375. SDF. 1 hit.
[Graphical view]
PRINTSPR00173. EDTRNSPORT.
SUPFAMSSF118215. SSF118215. 2 hits.
PROSITEPS00713. NA_DICARBOXYL_SYMP_1. 1 hit.
PS00714. NA_DICARBOXYL_SYMP_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSLC1A1.
GenomeRNAi6505.
NextBio25293.
PROP43005.
SOURCESearch...

Entry information

Entry nameEAA3_HUMAN
AccessionPrimary (citable) accession number: P43005
Secondary accession number(s): O75587 expand/collapse secondary AC list , Q5VZ24, Q8N199, Q9UEW2
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: February 1, 1996
Last modified: July 9, 2014
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM