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Protein

Large neutral amino acids transporter small subunit 1

Gene

Slc7a5

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. 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. 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.2 Publications

Kineticsi

  1. KM=14.1 µM for L-leucine1 Publication

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Developmental protein

    Keywords - Biological processi

    Amino-acid transport, Differentiation, Neurogenesis, Transport

    Enzyme and pathway databases

    ReactomeiREACT_311758. Amino acid transport across the plasma membrane.
    REACT_336327. Basigin interactions.
    SABIO-RKQ63016.

    Protein family/group databases

    TCDBi2.A.3.8.1. 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
    Integral membrane protein E16
    Short name:
    Protein TA1
    L-type amino acid transporter 1
    Solute carrier family 7 member 5
    Gene namesi
    Name:Slc7a5
    Synonyms:Mpe16, Ta1
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494 Componenti: Chromosome 19

    Organism-specific databases

    RGDi620639. Slc7a5.

    Subcellular locationi

    • Cytoplasmcytosol By similarity
    • Apical cell membrane; Multi-pass membrane protein

    • Note: Located to the plasma membrane by SLC3A2/4F2hc. Expressed in both luminal and abluminal membranes of brain capillary endothelial cells. Expressed along the retinal capillaries in the ganglion cell and inner plexiform layers. Localized to the apical membrane of placental syncytiophoblastic cells (By similarity).By similarity

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei51 – 7121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei85 – 10521HelicalSequence AnalysisAdd
    BLAST
    Transmembranei121 – 14121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei147 – 16721HelicalSequence AnalysisAdd
    BLAST
    Transmembranei174 – 19421HelicalSequence AnalysisAdd
    BLAST
    Transmembranei200 – 22021HelicalSequence AnalysisAdd
    BLAST
    Transmembranei248 – 26821HelicalSequence AnalysisAdd
    BLAST
    Transmembranei279 – 29921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei324 – 34421HelicalSequence AnalysisAdd
    BLAST
    Transmembranei398 – 41821HelicalSequence AnalysisAdd
    BLAST
    Transmembranei436 – 45621HelicalSequence AnalysisAdd
    BLAST
    Transmembranei463 – 48321HelicalSequence AnalysisAdd
    BLAST

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 512512Large neutral amino acids transporter small subunit 1PRO_0000054272Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei46 – 461PhosphothreonineBy similarity
    Glycosylationi50 – 501N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi345 – 3451N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiQ63016.
    PRIDEiQ63016.

    Expressioni

    Tissue specificityi

    Expressed in hepatoma but not in normal liver. Also expressed in placenta, testis, brain, ovary, spleen, mammary gland, and uterus. In brain expressed on capillary endothelia in cerebral cortex. Expressed in jejunum mucosa and the epithelial cells of the jejunum, ileum and colon. Also expressed in the intestinal epithelial cell line IEC-6. Expressed in the brain, retina, inner blood-retinal barrier of retina, retinal vascular endothelial cells, and in the retinal capillary endothelial cell line TR-iBRB2.5 Publications

    Inductioni

    Expression induced in normal hepatic cells cultured in arginine-depleted medium.1 Publication

    Gene expression databases

    GenevisibleiQ63016. RN.

    Interactioni

    Subunit structurei

    Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc.

    Protein-protein interaction databases

    BioGridi248432. 1 interaction.
    IntActiQ63016. 1 interaction.
    STRINGi10116.ENSRNOP00000025784.

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0531.
    GeneTreeiENSGT00760000119037.
    HOGENOMiHOG000098892.
    HOVERGENiHBG000476.
    InParanoidiQ63016.
    KOiK13780.
    OMAiRHRKPEL.
    OrthoDBiEOG73BVCR.
    PhylomeDBiQ63016.
    TreeFamiTF313355.

    Family and domain databases

    InterProiIPR002293. AA/rel_permease1.
    IPR004760. L_AA_transporter.
    [Graphical view]
    PANTHERiPTHR11785. PTHR11785. 1 hit.
    PfamiPF13520. AA_permease_2. 1 hit.
    [Graphical view]
    PIRSFiPIRSF006060. AA_transporter. 1 hit.
    TIGRFAMsiTIGR00911. 2A0308. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Q63016-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAVAGAKRRA VAAPATTAAE EERQAREKML EARRGDGADP EGEGVTLQRN
    60 70 80 90 100
    ITLINGVAII VGTIIGSGIF VTPTGVLKEA GSPGLSLVVW AVCGVFSIVG
    110 120 130 140 150
    ALCYAELGTT ISKSGGDYAY MLEVYGSLPA FLKLWIELLI IRPSSQYIVA
    160 170 180 190 200
    LVFATYLLKP VFPTCPVPEE AAKLVACLCV LLLTAVNCYS VKAATRVQDA
    210 220 230 240 250
    FAAAKLLALA LIILLGFIQM GKDIGQGDAS NLHQKLSFEG TNLDVGNIVL
    260 270 280 290 300
    ALYSGLFAYG GWNYLNFVTE EMINPYRNLP LAIIISLPIV TLVYVLTNLA
    310 320 330 340 350
    YFTTLSTNQM LTSEAVAVDF GNYHLGVMSW IIPVFVGLSC FGSVNGSLFT
    360 370 380 390 400
    SSRLFFVGSR EGHLPSILSM IHPQLLTPVP SLVFTCVMTL MYAFSRDIFS
    410 420 430 440 450
    IINFFSFFNW LCVALAIIGM MWLRFKKPEL ERPIKVNLAL PVFFILACLF
    460 470 480 490 500
    LIAVSFWKTP LECGIGFAII LSGLPVYFFG VWWKNKPKWI LQVIFSVTVL
    510
    CQKLMQVVPQ ET
    Length:512
    Mass (Da):55,903
    Last modified:January 24, 2001 - v2
    Checksum:iB487CE0B58D73A02
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB015432 mRNA. Translation: BAA33035.1.
    U00995 mRNA. Translation: AAA74411.1.
    RefSeqiNP_059049.1. NM_017353.1.
    UniGeneiRn.32261.

    Genome annotation databases

    EnsembliENSRNOT00000025784; ENSRNOP00000025784; ENSRNOG00000018824.
    GeneIDi50719.
    KEGGirno:50719.
    UCSCiRGD:620639. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB015432 mRNA. Translation: BAA33035.1.
    U00995 mRNA. Translation: AAA74411.1.
    RefSeqiNP_059049.1. NM_017353.1.
    UniGeneiRn.32261.

    3D structure databases

    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi248432. 1 interaction.
    IntActiQ63016. 1 interaction.
    STRINGi10116.ENSRNOP00000025784.

    Chemistry

    BindingDBiQ63016.
    ChEMBLiCHEMBL4149.

    Protein family/group databases

    TCDBi2.A.3.8.1. the amino acid-polyamine-organocation (apc) family.

    Proteomic databases

    PaxDbiQ63016.
    PRIDEiQ63016.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSRNOT00000025784; ENSRNOP00000025784; ENSRNOG00000018824.
    GeneIDi50719.
    KEGGirno:50719.
    UCSCiRGD:620639. rat.

    Organism-specific databases

    CTDi8140.
    RGDi620639. Slc7a5.

    Phylogenomic databases

    eggNOGiCOG0531.
    GeneTreeiENSGT00760000119037.
    HOGENOMiHOG000098892.
    HOVERGENiHBG000476.
    InParanoidiQ63016.
    KOiK13780.
    OMAiRHRKPEL.
    OrthoDBiEOG73BVCR.
    PhylomeDBiQ63016.
    TreeFamiTF313355.

    Enzyme and pathway databases

    ReactomeiREACT_311758. Amino acid transport across the plasma membrane.
    REACT_336327. Basigin interactions.
    SABIO-RKQ63016.

    Miscellaneous databases

    NextBioi610578.
    PROiQ63016.

    Gene expression databases

    GenevisibleiQ63016. RN.

    Family and domain databases

    InterProiIPR002293. AA/rel_permease1.
    IPR004760. L_AA_transporter.
    [Graphical view]
    PANTHERiPTHR11785. PTHR11785. 1 hit.
    PfamiPF13520. AA_permease_2. 1 hit.
    [Graphical view]
    PIRSFiPIRSF006060. AA_transporter. 1 hit.
    TIGRFAMsiTIGR00911. 2A0308. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    1. "Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98)."
      Kanai Y., Segawa H., Miyamoto K., Uchino H., Takeda E., Endou H.
      J. Biol. Chem. 273:23629-23632(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "TA1, a highly conserved oncofetal complementary DNA from rat hepatoma, encodes an integral membrane protein associated with liver development, carcinogenesis, and cell activation."
      Sang J., Lim Y.P., Panzica M., Finch P., Thompson N.L.
      Cancer Res. 55:1152-1159(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 272-512, TISSUE SPECIFICITY.
      Tissue: Hepatoma.
    3. "Expression of a system L neutral amino acid transporter at the blood-brain barrier."
      Matsuo H., Tsukada S., Nakata T., Chairoungdua A., Kim D.K., Cha S.H., Inatomi J., Yorifuji H., Fukuda J., Endou H., Kanai Y.
      NeuroReport 11:3507-3511(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    4. Cited for: FUNCTION, TISSUE SPECIFICITY, INDUCTION.
    5. "Expression of LAT1 and LAT2 amino acid transporters in human and rat intestinal epithelial cells."
      Fraga S., Pinho M.J., Soares-da-Silva P.
      Amino Acids 29:229-233(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    6. "L-type amino acid transporter 1-mediated L-leucine transport at the inner blood-retinal barrier."
      Tomi M., Mori M., Tachikawa M., Katayama K., Terasaki T., Hosoya K.
      Invest. Ophthalmol. Vis. Sci. 46:2522-2530(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INHIBITION.

    Entry informationi

    Entry nameiLAT1_RAT
    AccessioniPrimary (citable) accession number: Q63016
    Secondary accession number(s): Q9QWL4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: January 24, 2001
    Last modified: June 24, 2015
    This is version 119 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    L-leucine uptake by TR-iBRB2 cells was inhibited by L-leucine, L-phenylalanine, L-methionine, L-isoleucine, L-valine, L-tyrosine, L-tryptophan, D-leucine, D-phenylalanine, D-methionine and by 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) (a specific inhibitor of system L transport).

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    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 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.