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P43005

- EAA3_HUMAN

UniProt

P43005 - EAA3_HUMAN

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Protein

Excitatory amino acid transporter 3

Gene

SLC1A1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).By similarity

GO - Molecular functioni

  1. glutamate:sodium symporter activity Source: Ensembl
  2. glutamate binding Source: Ensembl
  3. L-glutamate transmembrane transporter activity Source: BHF-UCL
  4. sodium:dicarboxylate symporter activity Source: InterPro

GO - Biological processi

  1. D-aspartate import Source: UniProtKB
  2. ion transport Source: Reactome
  3. L-glutamate import Source: UniProtKB
  4. protein homooligomerization Source: Ensembl
  5. synaptic transmission Source: ProtInc
  6. transmembrane transport Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Symport, Transport

Enzyme and pathway databases

ReactomeiREACT_12591. Glutamate Neurotransmitter Release Cycle.
REACT_19397. Transport of inorganic cations/anions and amino acids/oligopeptides.

Protein family/group databases

TCDBi2.A.23.2.3. the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family.

Names & Taxonomyi

Protein namesi
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 namesi
Name:SLC1A1
Synonyms:EAAC1, EAAT3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 9

Organism-specific databases

HGNCiHGNC:10939. SLC1A1.

Subcellular locationi

GO - Cellular componenti

  1. extracellular vesicular exosome Source: UniProt
  2. integral component of plasma membrane Source: ProtInc
  3. membrane Source: ProtInc
  4. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

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.2 Publications
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 (PubMed:21982423). 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 (PubMed:23341099).2 Publications

Keywords - Diseasei

Schizophrenia

Organism-specific databases

MIMi615232. phenotype.
Orphaneti3140. Schizophrenia.
PharmGKBiPA35826.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 524524Excitatory amino acid transporter 3PRO_0000202065Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi43 – 431N-linked (GlcNAc...)Sequence Analysis
Glycosylationi178 – 1781N-linked (GlcNAc...)Sequence Analysis
Glycosylationi195 – 1951N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

Glycosylated.

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiP43005.
PaxDbiP43005.
PRIDEiP43005.

PTM databases

PhosphoSiteiP43005.

Expressioni

Tissue specificityi

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).3 Publications

Gene expression databases

BgeeiP43005.
CleanExiHS_SLC1A1.
GenevestigatoriP43005.

Organism-specific databases

HPAiCAB015466.
HPA020086.

Interactioni

Subunit structurei

Interacts with ARL6IP5/PRAF3.By similarity

Protein-protein interaction databases

BioGridi112396. 6 interactions.
IntActiP43005. 1 interaction.
STRINGi9606.ENSP00000262352.

Structurei

3D structure databases

ProteinModelPortaliP43005.
SMRiP43005. Positions 20-464.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1818CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini115 – 20995ExtracellularSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei19 – 3820HelicalSequence AnalysisAdd
BLAST
Transmembranei62 – 8221HelicalSequence AnalysisAdd
BLAST
Transmembranei94 – 11421HelicalSequence AnalysisAdd
BLAST
Transmembranei210 – 22920HelicalSequence AnalysisAdd
BLAST
Transmembranei254 – 27320HelicalSequence AnalysisAdd
BLAST
Transmembranei290 – 30920HelicalSequence AnalysisAdd
BLAST
Transmembranei316 – 33520HelicalSequence AnalysisAdd
BLAST
Transmembranei362 – 38120HelicalSequence AnalysisAdd
BLAST
Transmembranei392 – 41120HelicalSequence AnalysisAdd
BLAST
Transmembranei420 – 43920HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1301.
GeneTreeiENSGT00760000119117.
HOGENOMiHOG000208776.
HOVERGENiHBG000080.
InParanoidiP43005.
KOiK05612.
OMAiRFLKNNW.
OrthoDBiEOG7RV9G2.
PhylomeDBiP43005.
TreeFamiTF315206.

Family and domain databases

Gene3Di1.10.3860.10. 2 hits.
InterProiIPR001991. Na-dicarboxylate_symporter.
IPR018107. Na-dicarboxylate_symporter_CS.
[Graphical view]
PANTHERiPTHR11958. PTHR11958. 1 hit.
PfamiPF00375. SDF. 1 hit.
[Graphical view]
PRINTSiPR00173. EDTRNSPORT.
SUPFAMiSSF118215. SSF118215. 2 hits.
PROSITEiPS00713. NA_DICARBOXYL_SYMP_1. 1 hit.
PS00714. NA_DICARBOXYL_SYMP_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P43005-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MGKPARKGCE WKRFLKNNWV LLSTVAAVVL GITTGVLVRE HSNLSTLEKF
60 70 80 90 100
YFAFPGEILM RMLKLIILPL IISSMITGVA ALDSNVSGKI GLRAVVYYFC
110 120 130 140 150
TTLIAVILGI VLVVSIKPGV TQKVGEIART GSTPEVSTVD AMLDLIRNMF
160 170 180 190 200
PENLVQACFQ QYKTKREEVK PPSDPEMNMT EESFTAVMTT AISKNKTKEY
210 220 230 240 250
KIVGMYSDGI NVLGLIVFCL VFGLVIGKMG EKGQILVDFF NALSDATMKI
260 270 280 290 300
VQIIMCYMPL GILFLIAGKI IEVEDWEIFR KLGLYMATVL TGLAIHSIVI
310 320 330 340 350
LPLIYFIVVR KNPFRFAMGM AQALLTALMI SSSSATLPVT FRCAEENNQV
360 370 380 390 400
DKRITRFVLP VGATINMDGT ALYEAVAAVF IAQLNDLDLG IGQIITISIT
410 420 430 440 450
ATSASIGAAG VPQAGLVTMV IVLSAVGLPA EDVTLIIAVD WLLDRFRTMV
460 470 480 490 500
NVLGDAFGTG IVEKLSKKEL EQMDVSSEVN IVNPFALEST ILDNEDSDTK
510 520
KSYVNGGFAV DKSDTISFTQ TSQF
Length:524
Mass (Da):57,100
Last modified:February 1, 1996 - v2
Checksum:iFC6244ADC9EA228F
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti10 – 101E → PS in AAA50430. (PubMed:7521911)Curated
Sequence conflicti92 – 921L → V in AAH33040. (PubMed:15489334)Curated
Sequence conflicti94 – 941A → V in AAA68628. (PubMed:7859077)Curated
Sequence conflicti94 – 941A → V in AAC27511. (PubMed:11317217)Curated
Sequence conflicti96 – 961V → L in AAA53215. (PubMed:7914198)Curated
Sequence conflicti170 – 1701K → N in AAA53215. (PubMed:7914198)Curated
Sequence conflicti172 – 1721P → A in AAA53215. (PubMed:7914198)Curated
Sequence conflicti260 – 2601L → H in AAA53215. (PubMed:7914198)Curated
Sequence conflicti280 – 2801R → A in AAA68628. (PubMed:7859077)Curated
Sequence conflicti376 – 3761V → G in AAC25029. 1 PublicationCurated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti27 – 271A → G.
Corresponds to variant rs2229885 [ dbSNP | Ensembl ].
VAR_023309
Natural varianti50 – 501F → Y.
Corresponds to variant rs16921449 [ dbSNP | Ensembl ].
VAR_023308

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS6452.1.
PIRiA54856.
I38433.
I38560.
RefSeqiNP_004161.4. NM_004170.5.
UniGeneiHs.444915.

Genome annotation databases

EnsembliENST00000262352; ENSP00000262352; ENSG00000106688.
GeneIDi6505.
KEGGihsa:6505.
UCSCiuc003zij.2. human.

Polymorphism databases

DMDMi1352332.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS6452.1.
PIRi A54856.
I38433.
I38560.
RefSeqi NP_004161.4. NM_004170.5.
UniGenei Hs.444915.

3D structure databases

ProteinModelPortali P43005.
SMRi P43005. Positions 20-464.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112396. 6 interactions.
IntActi P43005. 1 interaction.
STRINGi 9606.ENSP00000262352.

Chemistry

BindingDBi P43005.
ChEMBLi CHEMBL2721.
DrugBanki DB00128. L-Aspartic Acid.
DB00230. Pregabalin.
GuidetoPHARMACOLOGYi 870.

Protein family/group databases

TCDBi 2.A.23.2.3. the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family.

PTM databases

PhosphoSitei P43005.

Polymorphism databases

DMDMi 1352332.

Proteomic databases

MaxQBi P43005.
PaxDbi P43005.
PRIDEi P43005.

Protocols and materials databases

DNASUi 6505.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000262352 ; ENSP00000262352 ; ENSG00000106688 .
GeneIDi 6505.
KEGGi hsa:6505.
UCSCi uc003zij.2. human.

Organism-specific databases

CTDi 6505.
GeneCardsi GC09P004490.
HGNCi HGNC:10939. SLC1A1.
HPAi CAB015466.
HPA020086.
MIMi 133550. gene.
615232. phenotype.
neXtProti NX_P43005.
Orphaneti 3140. Schizophrenia.
PharmGKBi PA35826.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1301.
GeneTreei ENSGT00760000119117.
HOGENOMi HOG000208776.
HOVERGENi HBG000080.
InParanoidi P43005.
KOi K05612.
OMAi RFLKNNW.
OrthoDBi EOG7RV9G2.
PhylomeDBi P43005.
TreeFami TF315206.

Enzyme and pathway databases

Reactomei REACT_12591. Glutamate Neurotransmitter Release Cycle.
REACT_19397. Transport of inorganic cations/anions and amino acids/oligopeptides.

Miscellaneous databases

GeneWikii SLC1A1.
GenomeRNAii 6505.
NextBioi 25293.
PROi P43005.
SOURCEi Search...

Gene expression databases

Bgeei P43005.
CleanExi HS_SLC1A1.
Genevestigatori P43005.

Family and domain databases

Gene3Di 1.10.3860.10. 2 hits.
InterProi IPR001991. Na-dicarboxylate_symporter.
IPR018107. Na-dicarboxylate_symporter_CS.
[Graphical view ]
PANTHERi PTHR11958. PTHR11958. 1 hit.
Pfami PF00375. SDF. 1 hit.
[Graphical view ]
PRINTSi PR00173. EDTRNSPORT.
SUPFAMi SSF118215. SSF118215. 2 hits.
PROSITEi PS00713. NA_DICARBOXYL_SYMP_1. 1 hit.
PS00714. NA_DICARBOXYL_SYMP_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

Entry informationi

Entry nameiEAA3_HUMAN
AccessioniPrimary (citable) accession number: P43005
Secondary accession number(s): O75587
, Q5VZ24, Q8N199, Q9UEW2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: February 1, 1996
Last modified: October 29, 2014
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3