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Protein

Large neutral amino acids transporter small subunit 2

Gene

Slc7a8

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 small and large neutral amino acids such as alanine, serine, threonine, cysteine, phenylalanine, tyrosine, leucine, arginine and tryptophan, when associated with SLC3A2/4F2hc. Acts as an amino acid exchanger. Has higher affinity for L-phenylalanine than LAT1 but lower affinity for glutamine and serine. L-alanine is transported at physiological concentrations. Plays a role in basolateral (re)absorption of neutral amino acids. 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. Plays an essential role in the reabsorption of neutral amino acids from the epithelial cells to the bloodstream in the kidney.1 Publication

Kineticsi

  1. KM=119 µM for L-leucine1 Publication
  2. KM=265 µM for glycine1 Publication
  3. KM=187 µM for L-alanine1 Publication
  4. KM=116 µM for L-serine1 Publication
  5. KM=68.6 µM for L-threonine1 Publication
  6. KM=109 µM for L-cysteine1 Publication
  7. KM=80.7 µM for L-asparginine1 Publication
  8. KM=151 µM for L-glutamine1 Publication
  9. KM=96.7 µM for L-isoleucine1 Publication
  10. KM=124 µM for L-valine1 Publication
  11. KM=204 µM for L-methionine1 Publication
  12. KM=45 µM for L-phenylalanine1 Publication
  13. KM=35.9 µM for L-tyrosine1 Publication
  14. KM=57.6 µM for L-tryptophan1 Publication
  15. KM=181 µM for L-histidine1 Publication

    pH dependencei

    Optimum pH is 6.25.1 Publication

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Biological processi

    Amino-acid transport, Transport

    Enzyme and pathway databases

    ReactomeiREACT_311758. Amino acid transport across the plasma membrane.
    REACT_336327. Basigin interactions.
    SABIO-RKQ9WVR6.

    Protein family/group databases

    TCDBi2.A.3.8.6. the amino acid-polyamine-organocation (apc) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Large neutral amino acids transporter small subunit 2
    Alternative name(s):
    L-type amino acid transporter 2
    Solute carrier family 7 member 8
    Gene namesi
    Name:Slc7a8
    Synonyms:Lat2, Lat4
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494 Componenti: Chromosome 15

    Organism-specific databases

    RGDi619904. Slc7a8.

    Subcellular locationi

    • Cytoplasm By similarity
    • Basolateral cell membrane 1 Publication; Multi-pass membrane protein 1 Publication

    • Note: Localized to the cytoplasm when expressed alone (By similarity). When coexpressed with SLC3A2/4F2hc, is localized to the plasma membrane. Colocalized with SLC3A2/4F2hc at the basolateral membrane of kidney cortex proximal tubules and small intestine epithelia of the villi (By similarity).By similarity

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei41 – 6121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei73 – 9321HelicalSequence AnalysisAdd
    BLAST
    Transmembranei114 – 13421HelicalSequence AnalysisAdd
    BLAST
    Transmembranei156 – 17621HelicalSequence AnalysisAdd
    BLAST
    Transmembranei190 – 21021HelicalSequence AnalysisAdd
    BLAST
    Transmembranei232 – 25221HelicalSequence AnalysisAdd
    BLAST
    Transmembranei269 – 28921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei311 – 33121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei363 – 38321HelicalSequence AnalysisAdd
    BLAST
    Transmembranei389 – 40921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei423 – 44321HelicalSequence AnalysisAdd
    BLAST
    Transmembranei448 – 46821HelicalSequence 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 – 533533Large neutral amino acids transporter small subunit 2PRO_0000054275Add
    BLAST

    Keywords - PTMi

    Disulfide bond

    Proteomic databases

    PaxDbiQ9WVR6.
    PRIDEiQ9WVR6.

    Expressioni

    Tissue specificityi

    Expression is seen in jejunum mucosa and the epithelial cells of the jejunum, ileum and colon, as well as in kidney, placenta, brain, testis and skeletal muscle. Expressed in retina, inner blood-retinal barrier of retina, retinal vascular endothelial cells. Also expressed in the intestinal epithelial cell line IEC-6 and in the retinal capillary endothelial cell line TR-iBRB2.3 Publications

    Gene expression databases

    GenevestigatoriQ9WVR6.

    Interactioni

    Subunit structurei

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

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000019618.

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0531.
    GeneTreeiENSGT00760000119037.
    HOGENOMiHOG000098892.
    HOVERGENiHBG000476.
    InParanoidiQ9WVR6.
    KOiK13781.
    OMAiEVYGEFW.
    OrthoDBiEOG73BVCR.
    PhylomeDBiQ9WVR6.
    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.

    Q9WVR6-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MEKGTRQRNN TAKNHPDRGS DTSPEAEASS GGGGVALKKE IGLVSACGII
    60 70 80 90 100
    VGNIIGSGIF VSPKGVLENA GSVGLALIVW IVTGVITAVG ALCYAELGVT
    110 120 130 140 150
    IPKSGGDYSY VKDIFGGLAG FLRLWIAVLV IYPTNQAVIA LTFSNYVLQP
    160 170 180 190 200
    LFPTCFPPES GLRLLAAICL LLLTWVNCSS VRWATRVQDI FTAGKLLALA
    210 220 230 240 250
    LIIIMGVVQI CKGEFFWLEP KNAFENFQEP DIGLVALAFL QGSFAYGGWN
    260 270 280 290 300
    FLNYVTEELV DPYKNLPRAI FISIPLVTFV YVFANIAYVT AMSPQELLAS
    310 320 330 340 350
    NAVAVTFGEK LLGVMAWIMP ISVALSTFGG VNGSLFTSSR LFFAGAREGH
    360 370 380 390 400
    LPSVLAMIHV KRCTPIPALL FTCLSTLLML VTSDMYTLIN YVGFINYLFY
    410 420 430 440 450
    GVTVAGQIVL RWKKPDIPRP IKISLLFPII YLLFWAFLLI FSLWSEPVVC
    460 470 480 490 500
    GIGLAIMLTG VPVYFLGVYW QHKPKCFNDF IESLTLVSQK MCVVVYPQEG
    510 520 530
    DSGTEETIDD VEEQHKPIFQ PTPVKDPDSE EQP
    Length:533
    Mass (Da):58,190
    Last modified:November 1, 1999 - v1
    Checksum:i99479DB60DA69DF0
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB024400 mRNA. Translation: BAA82517.1.
    RefSeqiNP_445894.1. NM_053442.1.
    UniGeneiRn.82734.

    Genome annotation databases

    EnsembliENSRNOT00000019618; ENSRNOP00000019618; ENSRNOG00000014311.
    GeneIDi84551.
    KEGGirno:84551.
    UCSCiRGD:619904. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB024400 mRNA. Translation: BAA82517.1.
    RefSeqiNP_445894.1. NM_053442.1.
    UniGeneiRn.82734.

    3D structure databases

    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000019618.

    Protein family/group databases

    TCDBi2.A.3.8.6. the amino acid-polyamine-organocation (apc) family.

    Proteomic databases

    PaxDbiQ9WVR6.
    PRIDEiQ9WVR6.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSRNOT00000019618; ENSRNOP00000019618; ENSRNOG00000014311.
    GeneIDi84551.
    KEGGirno:84551.
    UCSCiRGD:619904. rat.

    Organism-specific databases

    CTDi23428.
    RGDi619904. Slc7a8.

    Phylogenomic databases

    eggNOGiCOG0531.
    GeneTreeiENSGT00760000119037.
    HOGENOMiHOG000098892.
    HOVERGENiHBG000476.
    InParanoidiQ9WVR6.
    KOiK13781.
    OMAiEVYGEFW.
    OrthoDBiEOG73BVCR.
    PhylomeDBiQ9WVR6.
    TreeFamiTF313355.

    Enzyme and pathway databases

    ReactomeiREACT_311758. Amino acid transport across the plasma membrane.
    REACT_336327. Basigin interactions.
    SABIO-RKQ9WVR6.

    Miscellaneous databases

    NextBioi617101.
    PROiQ9WVR6.

    Gene expression databases

    GenevestigatoriQ9WVR6.

    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. "Identification and functional characterization of a Na+-independent neutral amino acid transporter with broad substrate selectivity."
      Segawa H., Fukasawa Y., Miyamoto K., Takeda E., Endou H., Kanai Y.
      J. Biol. Chem. 274:19745-19751(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, TISSUE SPECIFICITY, INHIBITION.
      Tissue: Small intestine.
    2. "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.
    3. "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: TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiLAT2_RAT
    AccessioniPrimary (citable) accession number: Q9WVR6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 24, 2001
    Last sequence update: November 1, 1999
    Last modified: May 27, 2015
    This is version 107 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Leucine transport activity is inhibited by 2-amino-bicyclo-(2,2,1)-heptane-2-carboxylate (BCH), glycine, L-isomers of the neutral amino acids and histidine.

    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.