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Protein

Sodium-coupled neutral amino acid transporter 2

Gene

SLC38A2

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 neutral amino acids and sodium ions with a stoichiometry of 1:1. May function in the transport of amino acids at the blood-brain barrier and in the supply of maternal nutrients to the fetus through the placenta.2 Publications

Enzyme regulationi

Inhibited by N-methyl-D-glucamine and probably choline.1 Publication

Kineticsi

  1. KM=0.39 mM for 2-methylamino-isobutyric acid (MeAIB) (at pH 8.0)

    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-210500. Glutamate Neurotransmitter Release Cycle.
    R-HSA-352230. Amino acid transport across the plasma membrane.

    Protein family/group databases

    TCDBi2.A.18.6.5. the amino acid/auxin permease (aaap) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sodium-coupled neutral amino acid transporter 2
    Alternative name(s):
    Amino acid transporter A2
    Protein 40-9-1
    Solute carrier family 38 member 2
    System A amino acid transporter 2
    System A transporter 1
    System N amino acid transporter 2
    Gene namesi
    Name:SLC38A2
    Synonyms:ATA2, KIAA1382, SAT2, SNAT2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:13448. SLC38A2.

    Subcellular locationi

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 76CytoplasmicSequence analysisAdd BLAST76
    Transmembranei77 – 97HelicalSequence analysisAdd BLAST21
    Topological domaini98 – 102ExtracellularSequence analysis5
    Transmembranei103 – 123HelicalSequence analysisAdd BLAST21
    Topological domaini124 – 158CytoplasmicSequence analysisAdd BLAST35
    Transmembranei159 – 179HelicalSequence analysisAdd BLAST21
    Topological domaini180 – 188ExtracellularSequence analysis9
    Transmembranei189 – 209HelicalSequence analysisAdd BLAST21
    Topological domaini210 – 217CytoplasmicSequence analysis8
    Transmembranei218 – 238HelicalSequence analysisAdd BLAST21
    Topological domaini239 – 292ExtracellularSequence analysisAdd BLAST54
    Transmembranei293 – 313HelicalSequence analysisAdd BLAST21
    Topological domaini314 – 329CytoplasmicSequence analysisAdd BLAST16
    Transmembranei330 – 350HelicalSequence analysisAdd BLAST21
    Topological domaini351 – 371ExtracellularSequence analysisAdd BLAST21
    Transmembranei372 – 392HelicalSequence analysisAdd BLAST21
    Topological domaini393 – 413CytoplasmicSequence analysisAdd BLAST21
    Transmembranei414 – 434HelicalSequence analysisAdd BLAST21
    Topological domaini435 – 436ExtracellularSequence analysis2
    Transmembranei437 – 457HelicalSequence analysisAdd BLAST21
    Topological domaini458 – 474CytoplasmicSequence analysisAdd BLAST17
    Transmembranei475 – 495HelicalSequence analysisAdd BLAST21
    Topological domaini496 – 506ExtracellularSequence analysisAdd BLAST11

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi54407.
    OpenTargetsiENSG00000134294.
    PharmGKBiPA37773.

    Polymorphism and mutation databases

    BioMutai2/14/2002.
    DMDMi162416227.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00003113691 – 506Sodium-coupled neutral amino acid transporter 2Add BLAST506

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei10PhosphoserineCombined sources1
    Modified residuei12PhosphoserineCombined sources1
    Modified residuei21PhosphoserineBy similarity1
    Modified residuei22PhosphoserineCombined sources1
    Modified residuei55PhosphoserineCombined sources1
    Glycosylationi258N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi274N-linked (GlcNAc...)Sequence analysis1

    Post-translational modificationi

    Polyubiquitination by NEDD4L regulates the degradation and the activity of SLC38A2.By similarity

    Keywords - PTMi

    Glycoprotein, Phosphoprotein, Ubl conjugation

    Proteomic databases

    EPDiQ96QD8.
    MaxQBiQ96QD8.
    PaxDbiQ96QD8.
    PeptideAtlasiQ96QD8.
    PRIDEiQ96QD8.

    PTM databases

    iPTMnetiQ96QD8.
    PhosphoSitePlusiQ96QD8.
    SwissPalmiQ96QD8.

    Expressioni

    Tissue specificityi

    Ubiquitously expressed. Widely expressed in the central nervous system with higher concentrations in caudal regions. Expressed by glutamatergic and GABAergic neurons together with astrocytes and other non-neuronal cells in the cerebral cortex (at protein level).3 Publications

    Inductioni

    Up-regulated upon hypertonic conditions and amino acid deprivation.3 Publications

    Gene expression databases

    BgeeiENSG00000134294.
    CleanExiHS_SAT2.
    HS_SLC38A2.
    ExpressionAtlasiQ96QD8. baseline and differential.
    GenevisibleiQ96QD8. HS.

    Organism-specific databases

    HPAiHPA035180.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    RNF5Q999423EBI-723083,EBI-348482

    Protein-protein interaction databases

    BioGridi119943. 26 interactors.
    IntActiQ96QD8. 25 interactors.
    MINTiMINT-1398587.
    STRINGi9606.ENSP00000256689.

    Structurei

    3D structure databases

    ProteinModelPortaliQ96QD8.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni1 – 96Regulates protein turnover upon amino acid deprivationBy similarityAdd BLAST96

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG1305. Eukaryota.
    COG0814. LUCA.
    GeneTreeiENSGT00760000119147.
    HOGENOMiHOG000013088.
    HOVERGENiHBG059571.
    InParanoidiQ96QD8.
    KOiK14207.
    OMAiITHLLCA.
    OrthoDBiEOG091G0GP8.
    PhylomeDBiQ96QD8.
    TreeFamiTF328787.

    Family and domain databases

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

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q96QD8-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MKKAEMGRFS ISPDEDSSSY SSNSDFNYSY PTKQAALKSH YADVDPENQN
    60 70 80 90 100
    FLLESNLGKK KYETEFHPGT TSFGMSVFNL SNAIVGSGIL GLSYAMANTG
    110 120 130 140 150
    IALFIILLTF VSIFSLYSVH LLLKTANEGG SLLYEQLGYK AFGLVGKLAA
    160 170 180 190 200
    SGSITMQNIG AMSSYLFIVK YELPLVIQAL TNIEDKTGLW YLNGNYLVLL
    210 220 230 240 250
    VSLVVILPLS LFRNLGYLGY TSGLSLLCMV FFLIVVICKK FQVPCPVEAA
    260 270 280 290 300
    LIINETINTT LTQPTALVPA LSHNVTENDS CRPHYFIFNS QTVYAVPILI
    310 320 330 340 350
    FSFVCHPAVL PIYEELKDRS RRRMMNVSKI SFFAMFLMYL LAALFGYLTF
    360 370 380 390 400
    YEHVESELLH TYSSILGTDI LLLIVRLAVL MAVTLTVPVV IFPIRSSVTH
    410 420 430 440 450
    LLCASKDFSW WRHSLITVSI LAFTNLLVIF VPTIRDIFGF IGASAASMLI
    460 470 480 490 500
    FILPSAFYIK LVKKEPMKSV QKIGALFFLL SGVLVMTGSM ALIVLDWVHN

    APGGGH
    Length:506
    Mass (Da):56,026
    Last modified:December 4, 2007 - v2
    Checksum:i125C70875793D031
    GO
    Isoform 2 (identifier: Q96QD8-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-100: Missing.
         101-105: IALFI → MKQNL

    Show »
    Length:406
    Mass (Da):45,179
    Checksum:iC72772C3238776CE
    GO

    Sequence cautioni

    The sequence BAD18765 differs from that shown. Reason: Erroneous initiation.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti156M → V in CAC51434 (Ref. 3) Curated1
    Sequence conflicti273H → R in BAA91846 (PubMed:14702039).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_03723548N → K.Corresponds to variant rs11183450dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0295531 – 100Missing in isoform 2. 2 PublicationsAdd BLAST100
    Alternative sequenceiVSP_029554101 – 105IALFI → MKQNL in isoform 2. 2 Publications5

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF259799 mRNA. Translation: AAK38510.1.
    AF298897 mRNA. Translation: AAG24618.1.
    AJ344099 mRNA. Translation: CAC51434.1.
    AB037803 mRNA. Translation: BAA92620.2.
    AK001700 mRNA. Translation: BAA91846.1.
    AK172784 mRNA. Translation: BAD18765.1. Different initiation.
    CR457267 mRNA. Translation: CAG33548.1.
    CH471111 Genomic DNA. Translation: EAW57900.1.
    CH471111 Genomic DNA. Translation: EAW57901.1.
    BC040342 mRNA. Translation: AAH40342.1.
    CCDSiCCDS76551.1. [Q96QD8-2]
    CCDS8749.1. [Q96QD8-1]
    RefSeqiNP_001294865.1. NM_001307936.1. [Q96QD8-2]
    NP_061849.2. NM_018976.4. [Q96QD8-1]
    UniGeneiHs.221847.

    Genome annotation databases

    EnsembliENST00000256689; ENSP00000256689; ENSG00000134294. [Q96QD8-1]
    ENST00000612232; ENSP00000482873; ENSG00000134294. [Q96QD8-2]
    GeneIDi54407.
    KEGGihsa:54407.
    UCSCiuc001rpg.4. human. [Q96QD8-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF259799 mRNA. Translation: AAK38510.1.
    AF298897 mRNA. Translation: AAG24618.1.
    AJ344099 mRNA. Translation: CAC51434.1.
    AB037803 mRNA. Translation: BAA92620.2.
    AK001700 mRNA. Translation: BAA91846.1.
    AK172784 mRNA. Translation: BAD18765.1. Different initiation.
    CR457267 mRNA. Translation: CAG33548.1.
    CH471111 Genomic DNA. Translation: EAW57900.1.
    CH471111 Genomic DNA. Translation: EAW57901.1.
    BC040342 mRNA. Translation: AAH40342.1.
    CCDSiCCDS76551.1. [Q96QD8-2]
    CCDS8749.1. [Q96QD8-1]
    RefSeqiNP_001294865.1. NM_001307936.1. [Q96QD8-2]
    NP_061849.2. NM_018976.4. [Q96QD8-1]
    UniGeneiHs.221847.

    3D structure databases

    ProteinModelPortaliQ96QD8.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi119943. 26 interactors.
    IntActiQ96QD8. 25 interactors.
    MINTiMINT-1398587.
    STRINGi9606.ENSP00000256689.

    Protein family/group databases

    TCDBi2.A.18.6.5. the amino acid/auxin permease (aaap) family.

    PTM databases

    iPTMnetiQ96QD8.
    PhosphoSitePlusiQ96QD8.
    SwissPalmiQ96QD8.

    Polymorphism and mutation databases

    BioMutai2/14/2002.
    DMDMi162416227.

    Proteomic databases

    EPDiQ96QD8.
    MaxQBiQ96QD8.
    PaxDbiQ96QD8.
    PeptideAtlasiQ96QD8.
    PRIDEiQ96QD8.

    Protocols and materials databases

    DNASUi54407.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000256689; ENSP00000256689; ENSG00000134294. [Q96QD8-1]
    ENST00000612232; ENSP00000482873; ENSG00000134294. [Q96QD8-2]
    GeneIDi54407.
    KEGGihsa:54407.
    UCSCiuc001rpg.4. human. [Q96QD8-1]

    Organism-specific databases

    CTDi54407.
    DisGeNETi54407.
    GeneCardsiSLC38A2.
    HGNCiHGNC:13448. SLC38A2.
    HPAiHPA035180.
    MIMi605180. gene.
    neXtProtiNX_Q96QD8.
    OpenTargetsiENSG00000134294.
    PharmGKBiPA37773.
    HUGEiSearch...
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1305. Eukaryota.
    COG0814. LUCA.
    GeneTreeiENSGT00760000119147.
    HOGENOMiHOG000013088.
    HOVERGENiHBG059571.
    InParanoidiQ96QD8.
    KOiK14207.
    OMAiITHLLCA.
    OrthoDBiEOG091G0GP8.
    PhylomeDBiQ96QD8.
    TreeFamiTF328787.

    Enzyme and pathway databases

    ReactomeiR-HSA-210500. Glutamate Neurotransmitter Release Cycle.
    R-HSA-352230. Amino acid transport across the plasma membrane.

    Miscellaneous databases

    ChiTaRSiSLC38A2. human.
    GeneWikiiSLC38A2.
    GenomeRNAii54407.
    PROiQ96QD8.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000134294.
    CleanExiHS_SAT2.
    HS_SLC38A2.
    ExpressionAtlasiQ96QD8. baseline and differential.
    GenevisibleiQ96QD8. HS.

    Family and domain databases

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

    Entry informationi

    Entry nameiS38A2_HUMAN
    AccessioniPrimary (citable) accession number: Q96QD8
    Secondary accession number(s): Q6IA88
    , Q6ZMG2, Q9HAV3, Q9NVA8, Q9P2G5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 4, 2007
    Last sequence update: December 4, 2007
    Last modified: November 30, 2016
    This is version 126 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

    Miscellaneous

    Depletion of SCL38A2 by siRNA prevents the recovery of cells from hypertonic stress.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: 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.