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Protein

Large neutral amino acids transporter small subunit 1

Gene

Slc7a5

Organism
Mus musculus (Mouse)
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.3 Publications

Kineticsi

  1. KM=25 µM for 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_301178. Amino acid transport across the plasma membrane.
    REACT_323105. Basigin interactions.

    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
    L-type amino acid transporter 1
    Solute carrier family 7 member 5
    Gene namesi
    Name:Slc7a5
    Synonyms:Lat1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589 Componenti: Chromosome 8

    Organism-specific databases

    MGIiMGI:1298205. Slc7a5.

    Subcellular locationi

    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_0000054271Add
    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

    MaxQBiQ9Z127.
    PaxDbiQ9Z127.
    PRIDEiQ9Z127.

    PTM databases

    PhosphoSiteiQ9Z127.

    Expressioni

    Tissue specificityi

    Predominantly expressed in the microvessels in the brain parenchyma of the central nervous system. Also detected in the subfornical organ, the subcommissural organ, ventromedial nucleus of the hypothalamus, subgranular zone of the dentate gyrus in hippocampus, ependymal layer of the lateral ventricles, and the olfactory bulb. Very strong expression also seen in testis, ovary, and placenta with weaker expression in spleen, skin, brain, thymus, stomach, lung, heart, kidney, small intestine, uterus and skeletal muscle.4 Publications

    Developmental stagei

    Strong expression in the liver of 14 dpc embryo. In embryo of 18 dpc expressed strongly in brain, moderate expression in spleen and brain and weak expression in liver.1 Publication

    Inductioni

    Expression induced by concanavilin-A stimulation.1 Publication

    Gene expression databases

    BgeeiQ9Z127.
    ExpressionAtlasiQ9Z127. baseline and differential.
    GenevisibleiQ9Z127. MM.

    Interactioni

    Subunit structurei

    Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc.1 Publication

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000041557.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9Z127.
    SMRiQ9Z127. Positions 59-395.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0531.
    GeneTreeiENSGT00760000119037.
    HOGENOMiHOG000098892.
    HOVERGENiHBG000476.
    InParanoidiQ9Z127.
    KOiK13780.
    OMAiRHRKPEL.
    OrthoDBiEOG73BVCR.
    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.

    Q9Z127-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAVAGAKRRA VATPAAAAAE EERQAREKML EARRGDGADP EGEGVTLQRN
    60 70 80 90 100
    ITLLNGVAII 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 GKDMGQGDAS NLQQKLSFEG 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 EGHLPSVLSM IHPQLLTPVP SLVFTCIMTL MYAFSRDIFS
    410 420 430 440 450
    IINFFSFFNW LCVALAIIGM MWLRFKKPEL ERPIKVNLAL PVFFILACLF
    460 470 480 490 500
    LIAVSFWKTP MECGIGFAII LSGLPVYFFG VWWKNKPKWI LQAIFSVTVL
    510
    CQKLMQVVPQ ET
    Length:512
    Mass (Da):55,872
    Last modified:July 27, 2011 - v2
    Checksum:i57045EC4DD9DE1A1
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti8 – 81R → M in BAA90556 (Ref. 2) Curated
    Sequence conflicti16 – 161A → T in BAA75520 (PubMed:9915839).Curated
    Sequence conflicti16 – 161A → T in BAA90556 (Ref. 2) Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB017189 mRNA. Translation: BAA75520.1.
    AB023409 mRNA. Translation: BAA90556.1.
    BC026131 mRNA. Translation: AAH26131.1.
    CCDSiCCDS22730.1.
    RefSeqiNP_035534.2. NM_011404.3.
    UniGeneiMm.27943.

    Genome annotation databases

    EnsembliENSMUST00000045557; ENSMUSP00000041557; ENSMUSG00000040010.
    GeneIDi20539.
    KEGGimmu:20539.
    UCSCiuc009nsc.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB017189 mRNA. Translation: BAA75520.1.
    AB023409 mRNA. Translation: BAA90556.1.
    BC026131 mRNA. Translation: AAH26131.1.
    CCDSiCCDS22730.1.
    RefSeqiNP_035534.2. NM_011404.3.
    UniGeneiMm.27943.

    3D structure databases

    ProteinModelPortaliQ9Z127.
    SMRiQ9Z127. Positions 59-395.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000041557.

    PTM databases

    PhosphoSiteiQ9Z127.

    Proteomic databases

    MaxQBiQ9Z127.
    PaxDbiQ9Z127.
    PRIDEiQ9Z127.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000045557; ENSMUSP00000041557; ENSMUSG00000040010.
    GeneIDi20539.
    KEGGimmu:20539.
    UCSCiuc009nsc.2. mouse.

    Organism-specific databases

    CTDi8140.
    MGIiMGI:1298205. Slc7a5.

    Phylogenomic databases

    eggNOGiCOG0531.
    GeneTreeiENSGT00760000119037.
    HOGENOMiHOG000098892.
    HOVERGENiHBG000476.
    InParanoidiQ9Z127.
    KOiK13780.
    OMAiRHRKPEL.
    OrthoDBiEOG73BVCR.
    TreeFamiTF313355.

    Enzyme and pathway databases

    ReactomeiREACT_301178. Amino acid transport across the plasma membrane.
    REACT_323105. Basigin interactions.

    Miscellaneous databases

    ChiTaRSiSlc7a5. mouse.
    NextBioi298819.
    PROiQ9Z127.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ9Z127.
    ExpressionAtlasiQ9Z127. baseline and differential.
    GenevisibleiQ9Z127. MM.

    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

    « Hide 'large scale' publications
    1. "4F2 (CD98) heavy chain is associated covalently with an amino acid transporter and controls intracellular trafficking and membrane topology of 4F2 heterodimer."
      Nakamura E., Sato M., Yang H., Miyagawa F., Harasaki M., Tomita K., Matsuoka S., Noma A., Iwai K., Minato N.
      J. Biol. Chem. 274:3009-3016(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION, INHIBITION.
      Strain: BALB/c.
    2. "Localization of expression of system L neutral amino acid transporter LAT1 in brain."
      Kanai Y., Watanabe M., Endou H.
      Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: ICR.
    3. "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].
      Strain: FVB/N.
      Tissue: Salivary gland.
    4. "LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine."
      Rossier G., Meier C., Bauch C., Summa V., Sordat B., Verrey F., Kuehn L.C.
      J. Biol. Chem. 274:34948-34954(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    5. Cited for: FUNCTION, TISSUE SPECIFICITY.
    6. "Distribution of the 4F2 light chain, LAT1, in the mouse brain."
      Kageyama T., Imura T., Matsuo A., Minato N., Shimohama S.
      NeuroReport 11:3663-3666(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiLAT1_MOUSE
    AccessioniPrimary (citable) accession number: Q9Z127
    Secondary accession number(s): Q8R0X8, Q9JMI4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 24, 2001
    Last sequence update: July 27, 2011
    Last modified: June 24, 2015
    This is version 122 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Leucine uptake was inhibited by ileum, valine histidine and phenylalanine as well as by 2-amino-bicyclo-(2,2,1)-heptane-2-carboxylate (BCH) (a specific inhibitor of system L transport).

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. 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.