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P43005

- EAA3_HUMAN

UniProt

P43005 - EAA3_HUMAN

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
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    • History
      Entry version 128 (01 Oct 2014)
      Sequence version 2 (01 Feb 1996)
      Previous versions | rss
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    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

    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

    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. 4 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.
    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

    MGKPARKGCE WKRFLKNNWV LLSTVAAVVL GITTGVLVRE HSNLSTLEKF    50
    YFAFPGEILM RMLKLIILPL IISSMITGVA ALDSNVSGKI GLRAVVYYFC 100
    TTLIAVILGI VLVVSIKPGV TQKVGEIART GSTPEVSTVD AMLDLIRNMF 150
    PENLVQACFQ QYKTKREEVK PPSDPEMNMT EESFTAVMTT AISKNKTKEY 200
    KIVGMYSDGI NVLGLIVFCL VFGLVIGKMG EKGQILVDFF NALSDATMKI 250
    VQIIMCYMPL GILFLIAGKI IEVEDWEIFR KLGLYMATVL TGLAIHSIVI 300
    LPLIYFIVVR KNPFRFAMGM AQALLTALMI SSSSATLPVT FRCAEENNQV 350
    DKRITRFVLP VGATINMDGT ALYEAVAAVF IAQLNDLDLG IGQIITISIT 400
    ATSASIGAAG VPQAGLVTMV IVLSAVGLPA EDVTLIIAVD WLLDRFRTMV 450
    NVLGDAFGTG IVEKLSKKEL EQMDVSSEVN IVNPFALEST ILDNEDSDTK 500
    KSYVNGGFAV DKSDTISFTQ TSQF 524
    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. 4 interactions.
    IntActi P43005. 1 interaction.
    STRINGi 9606.ENSP00000262352.

    Chemistry

    BindingDBi P43005.
    ChEMBLi CHEMBL2721.
    DrugBanki DB00128. L-Aspartic Acid.
    DB00142. L-Glutamic Acid.
    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 GC09P004480.
    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.
    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

    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 1, 2014
    This is version 128 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