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Reviewed, UniProtKB/Swiss-Prot P43005 (EAA3_HUMAN)

Last modified November 25, 2008. Version 73. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Excitatory amino acid transporter 3
Alternative name(s):
    Sodium-dependent glutamate/aspartate transporter 3
    Excitatory amino-acid carrier 1
    Neuronal and epithelial glutamate transporter
    Solute carrier family 1 member 1
Gene names
Name: SLC1A1
Synonyms: EAAC1, EAAT3
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length524 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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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.

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).

Post-translational modification

Glycosylated.

Involvement in disease

Defects in SLC1A1 may be a cause of dicarboxylicamino aciduria [MIM:222730]; also known as glutamate-aspartate transport defect. This is as defect in renal and probably intestinal transport of glutamic and aspartic acids and is associated with moderate hyperprolinemia.

Sequence similarities

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

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Ontologies

Keywords

   Biological processSymport
Transport
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DomainTransmembrane
   PTMGlycoprotein

Gene Ontology (GO)

   Biological processL-glutamate transport Ref.3

Traceable author statement. Source: ProtInc

dicarboxylic acid transport

Inferred from electronic annotation. Source: InterPro

synaptic transmission Ref.3

Traceable author statement. Source: ProtInc

   Cellular componentintegral to plasma membrane Ref.3

Traceable author statement. Source: ProtInc

membrane fraction Ref.3

Traceable author statement. Source: ProtInc

   Molecular functionsodium:dicarboxylate symporter activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

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

Amino acid modifications

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

Natural variations

Natural variant271A → G: dbSNP rs2229885.
VAR_023309
Natural variant501F → Y: dbSNP rs16921449.
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

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Sequences

Sequence LengthMass (Da)Tools
P43005-1 [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

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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: 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. 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: 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.

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Web resources

GeneReviews

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Cross-references

Sequence databases

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.
PIRA54856.
I38433.
I38560.
RefSeqNP_004161.4.
UniGeneHs.444915

3D structure databases

ModBaseSearch...

Protein-protein interaction databases

IntActP43005.

PTM databases

PhosphoSiteP43005.

Genome annotation databases

EnsemblENSG00000106688. Homo sapiens. [Contig view]
GeneID6505.
KEGGhsa:6505.

Organism-specific databases

H-InvDBHIX0007892.
HGNCHGNC:10939. SLC1A1.
HPACAB015466.
MIM133550. gene.
222730. phenotype.
PharmGKBPA35826.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMP43005.
HOVERGENP43005.

Gene expression databases

ArrayExpressP43005.
CleanExHS_SLC1A1.
GermOnlineENSG00000106688. Homo sapiens.

Family and domain databases

InterProIPR001991. Na/diCO_symport.
[Graphical view]
PANTHERPTHR11958. Na/diCO_symport. 1 hit.
PfamPF00375. SDF. 1 hit.
[Graphical view]
PRINTSPR00173. EDTRNSPORT.
PROSITEPS00713. NA_DICARBOXYL_SYMP_1. 1 hit.
PS00714. NA_DICARBOXYL_SYMP_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00128. L-Aspartic Acid.
DB00142. L-Glutamic Acid.
NextBio25293.
SOURCESearch...

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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: November 25, 2008
This is version 73 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 9

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

UniProtKB secondary accession numbers

Index of UniProtKB secondary accession numbers

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents