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Protein

Sodium-coupled neutral amino acid transporter 1

Gene

SLC38A1

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

Functioni

Functions as a sodium-dependent amino acid transporter. Mediates the saturable, pH-sensitive and electrogenic cotransport of glutamine and sodium ions with a stoichiometry of 1:1. May also transport small zwitterionic and aliphatic amino acids with a lower affinity. May supply glutamatergic and GABAergic neurons with glutamine which is required for the synthesis of the neurotransmitters glutamate and GABA.1 Publication

Enzyme regulationi

Inhibited by potassium, choline ions and 2-methylamino-isobutyric acid (MeAIB) (By similarity). Inhibited by lithium and N-methyl-D-glucamine.By similarity1 Publication

Kineticsi

  1. KM=890 µM for 2-methylamino-isobutyric acid (MeAIB) (at pH 8.5)1 Publication

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Biological processi

    Amino-acid transport, Ion transport, Sodium transport, Symport, Transport

    Keywords - Ligandi

    Sodium

    Enzyme and pathway databases

    ReactomeiR-HSA-210455. Astrocytic Glutamate-Glutamine Uptake And Metabolism.
    R-HSA-352230. Amino acid transport across the plasma membrane.

    Protein family/group databases

    TCDBi2.A.18.6.14. the amino acid/auxin permease (aaap) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sodium-coupled neutral amino acid transporter 1
    Alternative name(s):
    Amino acid transporter A1
    N-system amino acid transporter 2
    Solute carrier family 38 member 1
    System A amino acid transporter 1
    System N amino acid transporter 1
    Gene namesi
    Name:SLC38A1
    Synonyms:ATA1, NAT2, SAT1, SNAT1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:13447. SLC38A1.

    Subcellular locationi

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 74CytoplasmicSequence analysisAdd BLAST74
    Transmembranei75 – 97HelicalSequence analysisAdd BLAST23
    Topological domaini98 – 112ExtracellularSequence analysisAdd BLAST15
    Transmembranei113 – 133HelicalSequence analysisAdd BLAST21
    Topological domaini134 – 147CytoplasmicSequence analysisAdd BLAST14
    Transmembranei148 – 168HelicalSequence analysisAdd BLAST21
    Topological domaini169 – 188ExtracellularSequence analysisAdd BLAST20
    Transmembranei189 – 211HelicalSequence analysisAdd BLAST23
    Topological domaini212 – 216CytoplasmicSequence analysis5
    Transmembranei217 – 237HelicalSequence analysisAdd BLAST21
    Topological domaini238 – 275ExtracellularSequence analysisAdd BLAST38
    Transmembranei276 – 296HelicalSequence analysisAdd BLAST21
    Topological domaini297 – 312CytoplasmicSequence analysisAdd BLAST16
    Transmembranei313 – 333HelicalSequence analysisAdd BLAST21
    Topological domaini334 – 350ExtracellularSequence analysisAdd BLAST17
    Transmembranei351 – 371HelicalSequence analysisAdd BLAST21
    Topological domaini372 – 393CytoplasmicSequence analysisAdd BLAST22
    Transmembranei394 – 414HelicalSequence analysisAdd BLAST21
    Topological domaini415 – 416ExtracellularSequence analysis2
    Transmembranei417 – 437HelicalSequence analysisAdd BLAST21
    Topological domaini438 – 452CytoplasmicSequence analysisAdd BLAST15
    Transmembranei453 – 473HelicalSequence analysisAdd BLAST21
    Topological domaini474 – 487ExtracellularSequence analysisAdd BLAST14

    GO - Cellular componenti

    • extracellular exosome Source: UniProtKB
    • integral component of membrane Source: UniProtKB
    • integral component of plasma membrane Source: GO_Central
    • plasma membrane Source: Reactome
    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi81539.
    OpenTargetsiENSG00000111371.
    PharmGKBiPA37772.

    Polymorphism and mutation databases

    BioMutaiSLC38A1.
    DMDMi74733561.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00003104751 – 487Sodium-coupled neutral amino acid transporter 1Add BLAST487

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei6PhosphoserineBy similarity1
    Modified residuei11PhosphothreonineBy similarity1
    Modified residuei25PhosphoserineCombined sources1
    Modified residuei28PhosphoserineCombined sources1
    Modified residuei49PhosphoserineCombined sources1
    Modified residuei52PhosphoserineCombined sources1
    Modified residuei54PhosphothreonineCombined sources1
    Modified residuei56PhosphoserineCombined sources1
    Glycosylationi251N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi257N-linked (GlcNAc...)Sequence analysis1

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    EPDiQ9H2H9.
    MaxQBiQ9H2H9.
    PaxDbiQ9H2H9.
    PeptideAtlasiQ9H2H9.
    PRIDEiQ9H2H9.

    PTM databases

    iPTMnetiQ9H2H9.
    PhosphoSitePlusiQ9H2H9.
    SwissPalmiQ9H2H9.

    Expressioni

    Tissue specificityi

    Expressed in the cerebral cortex by pyramidal and GABAergic neurons, astrocytes and other non-neuronal cells (at protein level). Expressed in placenta, heart, lung, skeletal muscle, spleen, stomach and testis.4 Publications

    Inductioni

    Down-regulated by bacterial lipopolysaccharides (LPS) in glial cells. Down-regulated upon hypoxia.2 Publications

    Gene expression databases

    BgeeiENSG00000111371.
    CleanExiHS_NAT2.
    HS_SAT1.
    HS_SLC38A1.
    ExpressionAtlasiQ9H2H9. baseline and differential.
    GenevisibleiQ9H2H9. HS.

    Organism-specific databases

    HPAiHPA052272.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    FATE1Q969F05EBI-9978441,EBI-743099

    Protein-protein interaction databases

    BioGridi123509. 6 interactors.
    IntActiQ9H2H9. 55 interactors.
    STRINGi9606.ENSP00000381634.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9H2H9.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG1305. Eukaryota.
    COG0814. LUCA.
    GeneTreeiENSGT00760000119147.
    HOGENOMiHOG000013088.
    HOVERGENiHBG059571.
    InParanoidiQ9H2H9.
    KOiK14990.
    PhylomeDBiQ9H2H9.
    TreeFamiTF328787.

    Family and domain databases

    InterProiIPR013057. AA_transpt_TM.
    [Graphical view]
    PfamiPF01490. Aa_trans. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9H2H9-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MMHFKSGLEL TELQNMTVPE DDNISNDSND FTEVENGQIN SKFISDRESR
    60 70 80 90 100
    RSLTNSHLEK KKCDEYIPGT TSLGMSVFNL SNAIMGSGIL GLAFALANTG
    110 120 130 140 150
    ILLFLVLLTS VTLLSIYSIN LLLICSKETG CMVYEKLGEQ VFGTTGKFVI
    160 170 180 190 200
    FGATSLQNTG AMLSYLFIVK NELPSAIKFL MGKEETFSAW YVDGRVLVVI
    210 220 230 240 250
    VTFGIILPLC LLKNLGYLGY TSGFSLSCMV FFLIVVIYKK FQIPCIVPEL
    260 270 280 290 300
    NSTISANSTN ADTCTPKYVT FNSKTVYALP TIAFAFVCHP SVLPIYSELK
    310 320 330 340 350
    DRSQKKMQMV SNISFFAMFV MYFLTAIFGY LTFYDNVQSD LLHKYQSKDD
    360 370 380 390 400
    ILILTVRLAV IVAVILTVPV LFFTVRSSLF ELAKKTKFNL CRHTVVTCIL
    410 420 430 440 450
    LVVINLLVIF IPSMKDIFGV VGVTSANMLI FILPSSLYLK ITDQDGDKGT
    460 470 480
    QRIWAALFLG LGVLFSLVSI PLVIYDWACS SSSDEGH
    Length:487
    Mass (Da):54,048
    Last modified:March 1, 2001 - v1
    Checksum:i5CBC96880D7BDE03
    GO

    Sequence cautioni

    The sequence AAG44546 differs from that shown. Reason: Frameshift at position 443.Curated
    The sequence BAC11186 differs from that shown. Reason: Erroneous initiation.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti107L → P in BAB55394 (PubMed:14702039).Curated1
    Sequence conflicti203F → V in BAC11310 (PubMed:16303743).Curated1
    Sequence conflicti375V → D in AAG44546 (Ref. 2) Curated1
    Sequence conflicti483 – 484SD → NG in AAG44546 (Ref. 2) Curated2

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF271070 mRNA. Translation: AAG39354.1.
    AF247166 mRNA. Translation: AAG44546.1. Frameshift.
    AK027825 mRNA. Translation: BAB55394.1.
    AK074758 mRNA. Translation: BAC11186.1. Different initiation.
    AK074949 mRNA. Translation: BAC11310.1.
    CH471111 Genomic DNA. Translation: EAW57895.1.
    BC010620 mRNA. Translation: AAH10620.1.
    CCDSiCCDS41774.1.
    PIRiJC7328.
    RefSeqiNP_001070952.1. NM_001077484.1.
    NP_001265316.1. NM_001278387.1.
    NP_001265317.1. NM_001278388.1.
    NP_001265318.1. NM_001278389.1.
    NP_109599.3. NM_030674.3.
    UniGeneiHs.533770.

    Genome annotation databases

    EnsembliENST00000398637; ENSP00000381634; ENSG00000111371.
    ENST00000439706; ENSP00000398142; ENSG00000111371.
    ENST00000546893; ENSP00000447853; ENSG00000111371.
    ENST00000549049; ENSP00000449607; ENSG00000111371.
    GeneIDi81539.
    KEGGihsa:81539.
    UCSCiuc001rpb.5. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF271070 mRNA. Translation: AAG39354.1.
    AF247166 mRNA. Translation: AAG44546.1. Frameshift.
    AK027825 mRNA. Translation: BAB55394.1.
    AK074758 mRNA. Translation: BAC11186.1. Different initiation.
    AK074949 mRNA. Translation: BAC11310.1.
    CH471111 Genomic DNA. Translation: EAW57895.1.
    BC010620 mRNA. Translation: AAH10620.1.
    CCDSiCCDS41774.1.
    PIRiJC7328.
    RefSeqiNP_001070952.1. NM_001077484.1.
    NP_001265316.1. NM_001278387.1.
    NP_001265317.1. NM_001278388.1.
    NP_001265318.1. NM_001278389.1.
    NP_109599.3. NM_030674.3.
    UniGeneiHs.533770.

    3D structure databases

    ProteinModelPortaliQ9H2H9.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi123509. 6 interactors.
    IntActiQ9H2H9. 55 interactors.
    STRINGi9606.ENSP00000381634.

    Protein family/group databases

    TCDBi2.A.18.6.14. the amino acid/auxin permease (aaap) family.

    PTM databases

    iPTMnetiQ9H2H9.
    PhosphoSitePlusiQ9H2H9.
    SwissPalmiQ9H2H9.

    Polymorphism and mutation databases

    BioMutaiSLC38A1.
    DMDMi74733561.

    Proteomic databases

    EPDiQ9H2H9.
    MaxQBiQ9H2H9.
    PaxDbiQ9H2H9.
    PeptideAtlasiQ9H2H9.
    PRIDEiQ9H2H9.

    Protocols and materials databases

    DNASUi81539.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000398637; ENSP00000381634; ENSG00000111371.
    ENST00000439706; ENSP00000398142; ENSG00000111371.
    ENST00000546893; ENSP00000447853; ENSG00000111371.
    ENST00000549049; ENSP00000449607; ENSG00000111371.
    GeneIDi81539.
    KEGGihsa:81539.
    UCSCiuc001rpb.5. human.

    Organism-specific databases

    CTDi81539.
    DisGeNETi81539.
    GeneCardsiSLC38A1.
    HGNCiHGNC:13447. SLC38A1.
    HPAiHPA052272.
    MIMi608490. gene.
    neXtProtiNX_Q9H2H9.
    OpenTargetsiENSG00000111371.
    PharmGKBiPA37772.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1305. Eukaryota.
    COG0814. LUCA.
    GeneTreeiENSGT00760000119147.
    HOGENOMiHOG000013088.
    HOVERGENiHBG059571.
    InParanoidiQ9H2H9.
    KOiK14990.
    PhylomeDBiQ9H2H9.
    TreeFamiTF328787.

    Enzyme and pathway databases

    ReactomeiR-HSA-210455. Astrocytic Glutamate-Glutamine Uptake And Metabolism.
    R-HSA-352230. Amino acid transport across the plasma membrane.

    Miscellaneous databases

    ChiTaRSiSLC38A1. human.
    GeneWikiiSLC38A1.
    GenomeRNAii81539.
    PROiQ9H2H9.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000111371.
    CleanExiHS_NAT2.
    HS_SAT1.
    HS_SLC38A1.
    ExpressionAtlasiQ9H2H9. baseline and differential.
    GenevisibleiQ9H2H9. HS.

    Family and domain databases

    InterProiIPR013057. AA_transpt_TM.
    [Graphical view]
    PfamiPF01490. Aa_trans. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiS38A1_HUMAN
    AccessioniPrimary (citable) accession number: Q9H2H9
    Secondary accession number(s): Q8NC61
    , Q8NCF8, Q96JX2, Q9H2Q2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 13, 2007
    Last sequence update: March 1, 2001
    Last modified: November 30, 2016
    This is version 122 of the entry and version 1 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 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. 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.