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Protein

Excitatory amino acid transporter 3

Gene

SLC1A1

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

Functioni

Transports L-glutamate, L- and D-aspartate and L-cystein (PubMed:21123949). 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 similarity1 Publication

GO - Molecular functioni

GO - Biological processi

  • chemical synaptic transmission Source: ProtInc
  • cysteine transport Source: UniProtKB
  • D-aspartate import Source: UniProtKB
  • glutamate secretion Source: Reactome
  • ion transport Source: Reactome
  • L-glutamate import Source: UniProtKB
  • L-glutamate transmembrane transport Source: UniProtKB
  • positive regulation of heart rate Source: Ensembl
  • protein homooligomerization Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Symport, Transport

Enzyme and pathway databases

BioCyciZFISH:ENSG00000106688-MONOMER.
ReactomeiR-HSA-210500. Glutamate Neurotransmitter Release Cycle.
R-HSA-425393. 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
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:10939. SLC1A1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 18CytoplasmicSequence analysisAdd BLAST18
Transmembranei19 – 38HelicalSequence analysisAdd BLAST20
Transmembranei62 – 82HelicalSequence analysisAdd BLAST21
Transmembranei94 – 114HelicalSequence analysisAdd BLAST21
Topological domaini115 – 209ExtracellularSequence analysisAdd BLAST95
Transmembranei210 – 229HelicalSequence analysisAdd BLAST20
Transmembranei254 – 273HelicalSequence analysisAdd BLAST20
Transmembranei290 – 309HelicalSequence analysisAdd BLAST20
Transmembranei316 – 335HelicalSequence analysisAdd BLAST20
Transmembranei362 – 381HelicalSequence analysisAdd BLAST20
Transmembranei392 – 411HelicalSequence analysisAdd BLAST20
Transmembranei420 – 439HelicalSequence analysisAdd BLAST20

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • integral component of plasma membrane Source: ProtInc
  • membrane Source: ProtInc
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Dicarboxylic aminoaciduria (DCBXA)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disorder characterized by abnormal excretion of urinary glutamate and aspartate, resulting from the incomplete reabsorption of anionic amino acids from the glomerular filtrate in the kidney. It can be associated with mental retardation.
See also OMIM:222730
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071953395Missing in DCBXA; inhibits L-glutamate and L-cysteine transport activities. 1 Publication1
Natural variantiVAR_071954445R → W in DCBXA; reduces L-glutamate and L-cysteine transport activities; reduces cell membrane expression. 1 PublicationCorresponds to variant rs587777696dbSNPEnsembl.1
Schizophrenia 18 (SCZD18)2 Publications
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
Disease descriptionA 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.
See also OMIM:615232

Keywords - Diseasei

Disease mutation, Schizophrenia

Organism-specific databases

DisGeNETi6505.
MalaCardsiSLC1A1.
MIMi222730. phenotype.
615232. phenotype.
OpenTargetsiENSG00000106688.
Orphaneti2195. Dicarboxylic aminoaciduria.
3140. Schizophrenia.
PharmGKBiPA35826.

Chemistry databases

ChEMBLiCHEMBL2721.
DrugBankiDB00128. L-Aspartic Acid.
DB00230. Pregabalin.
GuidetoPHARMACOLOGYi870.

Polymorphism and mutation databases

BioMutaiSLC1A1.
DMDMi1352332.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002020651 – 524Excitatory amino acid transporter 3Add BLAST524

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi43N-linked (GlcNAc...)Sequence analysis1
Glycosylationi178N-linked (GlcNAc...)Sequence analysis1
Glycosylationi195N-linked (GlcNAc...)Sequence analysis1
Modified residuei517PhosphoserineBy similarity1
Modified residuei522PhosphoserineBy similarity1

Post-translational modificationi

Glycosylated.

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP43005.
MaxQBiP43005.
PaxDbiP43005.
PeptideAtlasiP43005.
PRIDEiP43005.

PTM databases

iPTMnetiP43005.
PhosphoSitePlusiP43005.

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

BgeeiENSG00000106688.
CleanExiHS_SLC1A1.
ExpressionAtlasiP43005. baseline and differential.
GenevisibleiP43005. HS.

Organism-specific databases

HPAiCAB015466.
HPA020086.

Interactioni

Subunit structurei

Interacts with ARL6IP5.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
LDLRAD1Q5T7003EBI-745376,EBI-10173166
RNF5Q999423EBI-745376,EBI-348482

Protein-protein interaction databases

BioGridi112396. 33 interactors.
IntActiP43005. 3 interactors.
STRINGi9606.ENSP00000262352.

Chemistry databases

BindingDBiP43005.

Structurei

3D structure databases

ProteinModelPortaliP43005.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3787. Eukaryota.
COG1301. LUCA.
GeneTreeiENSGT00760000119117.
HOGENOMiHOG000208776.
HOVERGENiHBG000080.
InParanoidiP43005.
KOiK05612.
OMAiCEKKSYV.
OrthoDBiEOG091G0UCE.
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)DescriptionActionsGraphical viewLength
Sequence conflicti10E → PS in AAA50430 (PubMed:7521911).Curated1
Sequence conflicti92L → V in AAH33040 (PubMed:15489334).Curated1
Sequence conflicti94A → V in AAA68628 (PubMed:7859077).Curated1
Sequence conflicti94A → V in AAC27511 (PubMed:11317217).Curated1
Sequence conflicti96V → L in AAA53215 (PubMed:7914198).Curated1
Sequence conflicti170K → N in AAA53215 (PubMed:7914198).Curated1
Sequence conflicti172P → A in AAA53215 (PubMed:7914198).Curated1
Sequence conflicti260L → H in AAA53215 (PubMed:7914198).Curated1
Sequence conflicti280R → A in AAA68628 (PubMed:7859077).Curated1
Sequence conflicti376V → G in AAC25029 (Ref. 8) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02330927A → G.Corresponds to variant rs2229885dbSNPEnsembl.1
Natural variantiVAR_02330850F → Y.Corresponds to variant rs2228621dbSNPEnsembl.1
Natural variantiVAR_071953395Missing in DCBXA; inhibits L-glutamate and L-cysteine transport activities. 1 Publication1
Natural variantiVAR_071954445R → W in DCBXA; reduces L-glutamate and L-cysteine transport activities; reduces cell membrane expression. 1 PublicationCorresponds to variant rs587777696dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliP43005.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112396. 33 interactors.
IntActiP43005. 3 interactors.
STRINGi9606.ENSP00000262352.

Chemistry databases

BindingDBiP43005.
ChEMBLiCHEMBL2721.
DrugBankiDB00128. L-Aspartic Acid.
DB00230. Pregabalin.
GuidetoPHARMACOLOGYi870.

Protein family/group databases

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

PTM databases

iPTMnetiP43005.
PhosphoSitePlusiP43005.

Polymorphism and mutation databases

BioMutaiSLC1A1.
DMDMi1352332.

Proteomic databases

EPDiP43005.
MaxQBiP43005.
PaxDbiP43005.
PeptideAtlasiP43005.
PRIDEiP43005.

Protocols and materials databases

DNASUi6505.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262352; ENSP00000262352; ENSG00000106688.
GeneIDi6505.
KEGGihsa:6505.
UCSCiuc003zij.3. human.

Organism-specific databases

CTDi6505.
DisGeNETi6505.
GeneCardsiSLC1A1.
HGNCiHGNC:10939. SLC1A1.
HPAiCAB015466.
HPA020086.
MalaCardsiSLC1A1.
MIMi133550. gene.
222730. phenotype.
615232. phenotype.
neXtProtiNX_P43005.
OpenTargetsiENSG00000106688.
Orphaneti2195. Dicarboxylic aminoaciduria.
3140. Schizophrenia.
PharmGKBiPA35826.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3787. Eukaryota.
COG1301. LUCA.
GeneTreeiENSGT00760000119117.
HOGENOMiHOG000208776.
HOVERGENiHBG000080.
InParanoidiP43005.
KOiK05612.
OMAiCEKKSYV.
OrthoDBiEOG091G0UCE.
PhylomeDBiP43005.
TreeFamiTF315206.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000106688-MONOMER.
ReactomeiR-HSA-210500. Glutamate Neurotransmitter Release Cycle.
R-HSA-425393. Transport of inorganic cations/anions and amino acids/oligopeptides.

Miscellaneous databases

ChiTaRSiSLC1A1. human.
GeneWikiiSLC1A1.
GenomeRNAii6505.
PROiP43005.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000106688.
CleanExiHS_SLC1A1.
ExpressionAtlasiP43005. baseline and differential.
GenevisibleiP43005. HS.

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]
ProtoNetiSearch...

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: November 30, 2016
This is version 150 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.