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Protein

Large neutral amino acids transporter small subunit 1

Gene

SLC7A5

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

Functioni

Sodium-independent, high-affinity transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan, when associated with SLC3A2/4F2hc. Involved in cellular amino acid uptake. Acts as an amino acid exchanger. Involved in the transport of L-DOPA across the blood-brain barrier, and that of thyroid hormones triiodothyronine (T3) and thyroxine (T4) across the cell membrane in tissues such as placenta. Plays a role in neuronal cell proliferation (neurogenesis) in brain. Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity. Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane. May play an important role in high-grade gliomas. Mediates blood-to-retina L-leucine transport across the inner blood-retinal barrier which in turn may play a key role in maintaining large neutral amino acids as well as neurotransmitters in the neural retina. Acts as the major transporter of tyrosine in fibroblasts. When associated with LAPTM4B, recruits SLC3A2 and SLC7A5 to lysosomes to promote leucine uptake into these organelles and is required for mTORC1 activation (PubMed:25998567).15 Publications

Miscellaneous

The uptake of leucine, tyrosine and tryptophan is inhibited by the different iodothyronines, in particular T3. Leucine transport is also inhibited by small zwitterionic amino acids (i.e. glycine, alanine, serine, threonine and cysteine) and by glutamine and asparagine. The uptake of T3 is almost completely blocked by coincubation with leucine, tryptophan, tyrosine, and phenylalanine, or 2-amino-bicyclo-(2,2,1)-heptane-2-carboxylate (BCH). Methionine uptake was inhibited by the L-system substrates L-leucine, BCH, L-cysteine and by the MeHg-L-cysteine complex and structurally related S-ethyl-L-cysteine. MeHg-L-cysteine uptake is inhibited by L-methionine, L-leucine, BCH and S-ethyl-L-cysteine. L-leucine uptake was inhibited by L-CNSO. Tyrosine uptake in fibroblasts was inhibited by D-methionine, and methyl-aminoisobutyric acid (MeAIB).

Kineticsi

  1. KM=7.9 µM for T4 (in the presence of choline chloride)5 Publications
  2. KM=0.8 µM for T3 (in the presence of choline chloride)5 Publications
  3. KM=12.5 µM for reverse triiodothyronine (rT3) (in the presence of choline chloride)5 Publications
  4. KM=7.9 µM for 3,3'-diiodothyronine (in the presence of choline chloride)5 Publications
  5. KM=46 µM for leucine (in the presence of choline chloride)5 Publications
  6. KM=19 µM for tryptophan (in the presence of choline chloride)5 Publications
  7. KM=32 µM for L-leucine5 Publications
  8. KM=10 mM for L-alanine5 Publications
  9. KM=2.2 mM for L-glutamine5 Publications
  10. KM=35 µM for L-histidine5 Publications
  11. KM=740 µM for L-phenylalanine5 Publications
  12. KM=98 µM for MeHg-L-cysteine5 Publications
  13. KM=99 µM for methionine5 Publications
  14. KM=55.2 µM for phenylalanine (in T24 human bladder carcinoma cells)5 Publications
  15. KM=60.4 µM for tyrosine (in T24 human bladder carcinoma cells)5 Publications
  16. KM=16.4 µM for tyrosine (in human fibroblasts)5 Publications
  17. KM=138 µM for Dopa (in T24 human bladder carcinoma cells)5 Publications
  18. KM=96.5 µM for 3-O-methyldopa (in T24 human bladder carcinoma cells)5 Publications
  19. KM=153 µM for alpha-methyltyrosine (in T24 human bladder carcinoma cells)5 Publications
  20. KM=216 µM for alpha-methyldopa (in T24 human bladder carcinoma cells)5 Publications
  21. KM=191 µM for gabapentin (in T24 human bladder carcinoma cells)5 Publications
  22. KM=7.3 µM for triiodothyronine (in T24 human bladder carcinoma cells)5 Publications
  23. KM=162 µM for thyroxine (in T24 human bladder carcinoma cells)5 Publications
  24. KM=75.3 µM for melphanan (in T24 human bladder carcinoma cells)5 Publications
  25. KM=156 µM for BCH (in T24 human bladder carcinoma cells)5 Publications

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionDevelopmental protein
    Biological processAmino-acid transport, Differentiation, Neurogenesis, Transport

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000103257-MONOMER
    ReactomeiR-HSA-210991 Basigin interactions
    R-HSA-352230 Amino acid transport across the plasma membrane
    R-HSA-71240 Tryptophan catabolism
    SABIO-RKiQ01650

    Protein family/group databases

    TCDBi2.A.3.8.25 the amino acid-polyamine-organocation (apc) family

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Large neutral amino acids transporter small subunit 1
    Alternative name(s):
    4F2 light chain
    Short name:
    4F2 LC
    Short name:
    4F2LC
    CD98 light chain
    Integral membrane protein E16
    L-type amino acid transporter 1
    Short name:
    hLAT1
    Solute carrier family 7 member 5
    y+ system cationic amino acid transporter
    Gene namesi
    Name:SLC7A5
    Synonyms:CD98LC, LAT1, MPE16
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 16

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000103257.8
    HGNCiHGNC:11063 SLC7A5
    MIMi600182 gene
    neXtProtiNX_Q01650

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Transmembranei50 – 70HelicalSequence analysisAdd BLAST21
    Transmembranei84 – 104HelicalSequence analysisAdd BLAST21
    Transmembranei120 – 140HelicalSequence analysisAdd BLAST21
    Transmembranei146 – 166HelicalSequence analysisAdd BLAST21
    Transmembranei170 – 190HelicalSequence analysisAdd BLAST21
    Transmembranei199 – 219HelicalSequence analysisAdd BLAST21
    Transmembranei243 – 263HelicalSequence analysisAdd BLAST21
    Transmembranei274 – 294HelicalSequence analysisAdd BLAST21
    Transmembranei319 – 339HelicalSequence analysisAdd BLAST21
    Transmembranei396 – 416HelicalSequence analysisAdd BLAST21
    Transmembranei431 – 451HelicalSequence analysisAdd BLAST21
    Transmembranei458 – 478HelicalSequence analysisAdd BLAST21

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi8140
    OpenTargetsiENSG00000103257
    PharmGKBiPA35923

    Chemistry databases

    ChEMBLiCHEMBL4459
    DrugBankiDB01746 D-Leucine
    DB02556 D-Phenylalanine
    DB00509 Dextrothyroxine
    DB01235 Levodopa
    DB00451 Levothyroxine
    DB00279 Liothyronine
    DB01042 Melphalan
    DB02750 S-(Methylmercury)-L-Cysteine

    Polymorphism and mutation databases

    BioMutaiSLC7A5
    DMDMi12643412

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000542701 – 507Large neutral amino acids transporter small subunit 1Add BLAST507

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Cross-linki19Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
    Cross-linki30Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
    Modified residuei31PhosphoserineCombined sources1
    Modified residuei35PhosphoserineCombined sources1
    Modified residuei45PhosphothreonineCombined sources1
    Glycosylationi49N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi230N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi340N-linked (GlcNAc...) asparagineSequence analysis1

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    EPDiQ01650
    MaxQBiQ01650
    PaxDbiQ01650
    PeptideAtlasiQ01650
    PRIDEiQ01650
    ProteomicsDBi57978
    TopDownProteomicsiQ01650

    PTM databases

    iPTMnetiQ01650
    PhosphoSitePlusiQ01650
    SwissPalmiQ01650

    Expressioni

    Tissue specificityi

    Expressed abundantly in adult lung, liver, brain, skeletal muscle, placenta, bone marrow, testis, resting lymphocytes and monocytes, and in fetal liver. Weaker expression in thymus, cornea, retina, peripheral leukocytes, spleen, kidney, colon and lymph node. During gestation, expression in the placenta was significantly stronger at full-term than at the mid-trimester stage. Also expressed in all human tumor cell lines tested and in the astrocytic process of primary astrocytic gliomas. Expressed in retinal endothelial cells and in the intestinal epithelial cell line Caco-2.9 Publications

    Inductioni

    Expression induced in quiescent peripheral blood lymphocytes after treatment with phorbol myristate acetate (PMA) and phytohemagglutinin (PHA). Expression and the uptake of leucine is stimulated in mononuclear, cytotrophoblast-like choriocarcinoma cells by combined treatment with PMA and calcium ionophore.2 Publications

    Gene expression databases

    BgeeiENSG00000103257
    CleanExiHS_SLC7A5
    ExpressionAtlasiQ01650 baseline and differential
    GenevisibleiQ01650 HS

    Organism-specific databases

    HPAiHPA052673
    HPA056077

    Interactioni

    Subunit structurei

    Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc (PubMed:10049700, PubMed:11311135, PubMed:11389679, PubMed:11557028, PubMed:11564694, PubMed:12225859, PubMed:15769744, PubMed:9751058). Interacts with LAPTM4B; recruits SLC3A2 and SLC7A5 to lysosomes to promote leucine uptake into these organelles and is required for mTORC1 activation (PubMed:25998567).9 Publications

    Protein-protein interaction databases

    BioGridi113801, 19 interactors
    IntActiQ01650, 25 interactors
    MINTiQ01650
    STRINGi9606.ENSP00000261622

    Structurei

    3D structure databases

    ProteinModelPortaliQ01650
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG1287 Eukaryota
    COG0531 LUCA
    GeneTreeiENSGT00760000119037
    HOGENOMiHOG000098892
    HOVERGENiHBG000476
    InParanoidiQ01650
    KOiK13780
    OMAiHKAFGIH
    OrthoDBiEOG091G07EM
    PhylomeDBiQ01650
    TreeFamiTF313355

    Family and domain databases

    InterProiView protein in InterPro
    IPR002293 AA/rel_permease1
    IPR004760 L_AA_transporter
    PfamiView protein in Pfam
    PF13520 AA_permease_2, 1 hit
    PIRSFiPIRSF006060 AA_transporter, 1 hit
    TIGRFAMsiTIGR00911 2A0308, 1 hit

    Sequencei

    Sequence statusi: Complete.

    Q01650-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAGAGPKRRA LAAPAAEEKE EAREKMLAAK SADGSAPAGE GEGVTLQRNI
    60 70 80 90 100
    TLLNGVAIIV GTIIGSGIFV TPTGVLKEAG SPGLALVVWA ACGVFSIVGA
    110 120 130 140 150
    LCYAELGTTI SKSGGDYAYM LEVYGSLPAF LKLWIELLII RPSSQYIVAL
    160 170 180 190 200
    VFATYLLKPL FPTCPVPEEA AKLVACLCVL LLTAVNCYSV KAATRVQDAF
    210 220 230 240 250
    AAAKLLALAL IILLGFVQIG KGDVSNLDPN FSFEGTKLDV GNIVLALYSG
    260 270 280 290 300
    LFAYGGWNYL NFVTEEMINP YRNLPLAIII SLPIVTLVYV LTNLAYFTTL
    310 320 330 340 350
    STEQMLSSEA VAVDFGNYHL GVMSWIIPVF VGLSCFGSVN GSLFTSSRLF
    360 370 380 390 400
    FVGSREGHLP SILSMIHPQL LTPVPSLVFT CVMTLLYAFS KDIFSVINFF
    410 420 430 440 450
    SFFNWLCVAL AIIGMIWLRH RKPELERPIK VNLALPVFFI LACLFLIAVS
    460 470 480 490 500
    FWKTPVECGI GFTIILSGLP VYFFGVWWKN KPKWLLQGIF STTVLCQKLM

    QVVPQET
    Length:507
    Mass (Da):55,010
    Last modified:January 24, 2001 - v2
    Checksum:i767F3C60B62C0F02
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti15A → V in BAA75746 (Ref. 5) Curated1
    Sequence conflicti29 – 31AKS → SKR in BAA75746 (Ref. 5) Curated3
    Sequence conflicti35S → A in BAA75746 (Ref. 5) Curated1
    Sequence conflicti62T → A in BAA75746 (Ref. 5) Curated1
    Sequence conflicti88V → M in BAA75746 (Ref. 5) Curated1
    Sequence conflicti154T → A in BAA75746 (Ref. 5) Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_070119223D → V1 PublicationCorresponds to variant dbSNP:rs17853937Ensembl.1
    Natural variantiVAR_048157230N → K1 PublicationCorresponds to variant dbSNP:rs1060250Ensembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF077866 mRNA Translation: AAC61479.1
    AF104032 mRNA Translation: AAD20464.1
    AB018542 mRNA Translation: BAA33851.1
    AB018009 mRNA Translation: BAA84648.1
    AB017908 mRNA Translation: BAA75746.1
    BC039692 mRNA Translation: AAH39692.1
    BC042600 mRNA Translation: AAH42600.1
    M80244 mRNA Translation: AAA35780.1
    CCDSiCCDS10964.1
    PIRiJG0165
    RefSeqiNP_003477.4, NM_003486.6
    UniGeneiHs.513797

    Genome annotation databases

    EnsembliENST00000261622; ENSP00000261622; ENSG00000103257
    GeneIDi8140
    KEGGihsa:8140
    UCSCiuc002fkm.4 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiLAT1_HUMAN
    AccessioniPrimary (citable) accession number: Q01650
    Secondary accession number(s): Q8IV97
    , Q9UBN8, Q9UP15, Q9UQC0
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: January 24, 2001
    Last modified: June 20, 2018
    This is version 187 of the entry and version 2 of the sequence. See 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, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 16
      Human chromosome 16: 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

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