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Protein

Large neutral amino acids transporter small subunit 2

Gene

SLC7A8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.8 Publications

Miscellaneous

L-leucine transport activity inhibited by small zwitterionic amino acids (i.e. glycine, alanine, serine, threonine asparagine, glutamine, methionine, leucine, isoleucine, valine, phenylalanine, tyrosine, tryptophan, histidine and cysteine) and by glutamine and asparagine. Methionine uptake was inhibited by the L-system substrates L-leucine, 2-amino-bicyclo-(2,2,1)-heptane-2-carboxylate (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.

Kineticsi

  1. KM=221 µM for L-leucine4 Publications
  2. KM=64 µM for MeHg-L-cysteine4 Publications
  3. KM=161 µM for methionine4 Publications
  4. KM=978 µM for L-alanine4 Publications
  5. KM=89.35 µM for L-phenylalanine4 Publications
  6. KM=57.3 µM for L-tryptophan4 Publications
  7. KM=48.8 µM for L-tyrosine4 Publications

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Biological processAmino-acid transport, Transport

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000092068-MONOMER
    ReactomeiR-HSA-210991 Basigin interactions
    R-HSA-352230 Amino acid transport across the plasma membrane
    SABIO-RKiQ9UHI5

    Protein family/group databases

    TCDBi2.A.3.8.20 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
    Short name:
    hLAT2
    Solute carrier family 7 member 8
    Gene namesi
    Name:SLC7A8
    Synonyms:LAT2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 14

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000092068.18
    HGNCiHGNC:11066 SLC7A8
    MIMi604235 gene
    neXtProtiNX_Q9UHI5

    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
    Transmembranei40 – 60HelicalSequence analysisAdd BLAST21
    Transmembranei72 – 92HelicalSequence analysisAdd BLAST21
    Transmembranei113 – 133HelicalSequence analysisAdd BLAST21
    Transmembranei155 – 175HelicalSequence analysisAdd BLAST21
    Transmembranei189 – 209HelicalSequence analysisAdd BLAST21
    Transmembranei231 – 251HelicalSequence analysisAdd BLAST21
    Transmembranei268 – 288HelicalSequence analysisAdd BLAST21
    Transmembranei310 – 330HelicalSequence analysisAdd BLAST21
    Transmembranei362 – 382HelicalSequence analysisAdd BLAST21
    Transmembranei388 – 408HelicalSequence analysisAdd BLAST21
    Transmembranei424 – 444HelicalSequence analysisAdd BLAST21
    Transmembranei447 – 467HelicalSequence analysisAdd BLAST21

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi23428
    OpenTargetsiENSG00000092068
    PharmGKBiPA35926

    Chemistry databases

    DrugBankiDB00160 L-Alanine
    DB00130 L-Glutamine
    DB00120 L-Phenylalanine
    DB01235 Levodopa
    DB02750 S-(Methylmercury)-L-Cysteine

    Polymorphism and mutation databases

    BioMutaiSLC7A8
    DMDMi12643348

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000542731 – 535Large neutral amino acids transporter small subunit 2Add BLAST535

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei29PhosphoserineBy similarity1

    Keywords - PTMi

    Disulfide bond, Phosphoprotein

    Proteomic databases

    EPDiQ9UHI5
    PaxDbiQ9UHI5
    PeptideAtlasiQ9UHI5
    PRIDEiQ9UHI5
    ProteomicsDBi84356

    PTM databases

    iPTMnetiQ9UHI5
    PhosphoSitePlusiQ9UHI5
    SwissPalmiQ9UHI5

    Expressioni

    Tissue specificityi

    Strongest expression is observed in kidney and moderate expression in placenta and brain, followed by liver, prostate, testis, ovary, lymph node, thymus, spleen, skeletal muscle and heart. Also expressed in fetal liver as well as in the retinal pigment epithelial cell line ARPE-19 and the intestinal epithelial cell line Caco-2.4 Publications

    Inductioni

    Activity in polarized intestinal cells is regulated by the association between SLC3A2/4F2 (in the SLC3A2/4F2-LAT2 heterodimer) and ICAM1.1 Publication

    Gene expression databases

    BgeeiENSG00000092068 Expressed in 228 organ(s), highest expression level in cortex of kidney
    CleanExiHS_LAT2
    HS_SLC7A8
    ExpressionAtlasiQ9UHI5 baseline and differential
    GenevisibleiQ9UHI5 HS

    Organism-specific databases

    HPAiCAB046015
    HPA051950
    HPA060672

    Interactioni

    Subunit structurei

    Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc.6 Publications

    Protein-protein interaction databases

    BioGridi116996, 1 interactor
    CORUMiQ9UHI5
    IntActiQ9UHI5, 22 interactors
    STRINGi9606.ENSP00000320378

    Structurei

    3D structure databases

    ProteinModelPortaliQ9UHI5
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG1287 Eukaryota
    COG0531 LUCA
    GeneTreeiENSGT00760000119037
    HOGENOMiHOG000098892
    HOVERGENiHBG000476
    InParanoidiQ9UHI5
    KOiK13781
    OMAiANAFEPF
    OrthoDBiEOG091G07EM
    PhylomeDBiQ9UHI5
    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

    Sequences (4+)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 4 described isoforms and 6 potential isoforms that are computationally mapped.iShow all

    Isoform 1 (identifier: Q9UHI5-1) [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
    MEEGARHRNN TEKKHPGGGE SDASPEAGSG GGGVALKKEI GLVSACGIIV
    60 70 80 90 100
    GNIIGSGIFV SPKGVLENAG SVGLALIVWI VTGFITVVGA LCYAELGVTI
    110 120 130 140 150
    PKSGGDYSYV KDIFGGLAGF LRLWIAVLVI YPTNQAVIAL TFSNYVLQPL
    160 170 180 190 200
    FPTCFPPESG LRLLAAICLL LLTWVNCSSV RWATRVQDIF TAGKLLALAL
    210 220 230 240 250
    IIIMGIVQIC KGEYFWLEPK NAFENFQEPD IGLVALAFLQ GSFAYGGWNF
    260 270 280 290 300
    LNYVTEELVD PYKNLPRAIF ISIPLVTFVY VFANVAYVTA MSPQELLASN
    310 320 330 340 350
    AVAVTFGEKL LGVMAWIMPI SVALSTFGGV NGSLFTSSRL FFAGAREGHL
    360 370 380 390 400
    PSVLAMIHVK RCTPIPALLF TCISTLLMLV TSDMYTLINY VGFINYLFYG
    410 420 430 440 450
    VTVAGQIVLR WKKPDIPRPI KINLLFPIIY LLFWAFLLVF SLWSEPVVCG
    460 470 480 490 500
    IGLAIMLTGV PVYFLGVYWQ HKPKCFSDFI ELLTLVSQKM CVVVYPEVER
    510 520 530
    GSGTEEANED MEEQQQPMYQ PTPTKDKDVA GQPQP
    Length:535
    Mass (Da):58,382
    Last modified:May 1, 2000 - v1
    Checksum:iAC129146353F1E47
    GO
    Isoform 2 (identifier: Q9UHI5-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-203: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:332
    Mass (Da):37,184
    Checksum:iE6DD8F71252E064D
    GO
    Isoform 3 (identifier: Q9UHI5-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-263: MEEGARHRNN...VTEELVDPYK → MGQLFQCAVG...HHGDCTDMQR

    Note: No experimental confirmation available.
    Show »
    Length:311
    Mass (Da):34,602
    Checksum:i4CF5A20AD230155C
    GO
    Isoform 4 (identifier: Q9UHI5-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-169: MEEGARHRNN...GLRLLAAICL → MGQYGQELSW...LEGVPRFLKR

    Note: No experimental confirmation available.
    Show »
    Length:430
    Mass (Da):48,283
    Checksum:i4F7293A07EBFE696
    GO

    Computationally mapped potential isoform sequencesi

    There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    H0Y2X7H0Y2X7_HUMAN
    Large neutral amino acids transport...
    SLC7A8
    230Annotation score:
    E9PLV9E9PLV9_HUMAN
    Large neutral amino acids transport...
    SLC7A8
    289Annotation score:
    A0A087WWF3A0A087WWF3_HUMAN
    Large neutral amino acids transport...
    SLC7A8
    210Annotation score:
    E9PQT4E9PQT4_HUMAN
    Large neutral amino acids transport...
    SLC7A8
    94Annotation score:
    E9PIC3E9PIC3_HUMAN
    Large neutral amino acids transport...
    SLC7A8
    78Annotation score:
    E9PS92E9PS92_HUMAN
    Large neutral amino acids transport...
    SLC7A8
    49Annotation score:

    Sequence cautioni

    The sequence CAD62616 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti225N → D in CAB40137 (PubMed:10080183).Curated1
    Sequence conflicti401V → G in CAB40137 (PubMed:10080183).Curated1
    Sequence conflicti503G → R in AAF05696 (PubMed:10391915).Curated1
    Sequence conflicti503G → R in AAF05697 (PubMed:10391915).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0469451 – 263MEEGA…VDPYK → MGQLFQCAVGHPGSRHLHSW EAPGLGPDYHHGDCTDMQR in isoform 3. 1 PublicationAdd BLAST263
    Alternative sequenceiVSP_0469461 – 203Missing in isoform 2. 1 PublicationAdd BLAST203
    Alternative sequenceiVSP_0469471 – 169MEEGA…AAICL → MGQYGQELSWKCLVKAVCLQ EHSQPSQLLCTLLLCWCVLG RERPFRKAQSTSSPLEGVPR FLKR in isoform 4. 1 PublicationAdd BLAST169

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF135828 mRNA Translation: AAF05695.1
    AF135829 mRNA Translation: AAF05696.1
    AF135830 mRNA Translation: AAF05697.1
    AF171669 mRNA Translation: AAF20381.1
    Y18483 mRNA Translation: CAB40137.1
    AB037669 mRNA Translation: BAB21519.1
    BX248288 mRNA Translation: CAD62616.1 Different initiation.
    AK296702 mRNA Translation: BAG59296.1
    AK300384 mRNA Translation: BAG62118.1
    AK313465 mRNA Translation: BAG36251.1
    AL117258 Genomic DNA No translation available.
    CH471078 Genomic DNA Translation: EAW66181.1
    CH471078 Genomic DNA Translation: EAW66182.1
    BC052250 mRNA Translation: AAH52250.1
    CCDSiCCDS41924.1 [Q9UHI5-2]
    CCDS58304.1 [Q9UHI5-3]
    CCDS58305.1 [Q9UHI5-4]
    CCDS9590.1 [Q9UHI5-1]
    RefSeqiNP_001253965.1, NM_001267036.1 [Q9UHI5-4]
    NP_001253966.1, NM_001267037.1 [Q9UHI5-3]
    NP_036376.2, NM_012244.3 [Q9UHI5-1]
    NP_877392.1, NM_182728.2 [Q9UHI5-2]
    UniGeneiHs.596643

    Genome annotation databases

    EnsembliENST00000316902; ENSP00000320378; ENSG00000092068 [Q9UHI5-1]
    ENST00000422941; ENSP00000416398; ENSG00000092068 [Q9UHI5-3]
    ENST00000453702; ENSP00000391577; ENSG00000092068 [Q9UHI5-2]
    ENST00000529705; ENSP00000434345; ENSG00000092068 [Q9UHI5-4]
    GeneIDi23428
    KEGGihsa:23428
    UCSCiuc001wix.5 human [Q9UHI5-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Entry informationi

    Entry nameiLAT2_HUMAN
    AccessioniPrimary (citable) accession number: Q9UHI5
    Secondary accession number(s): B2R8Q4
    , B4DKT4, B4DTV6, D3DS46, F2Z2J4, Q86U05, Q9UKQ6, Q9UKQ7, Q9UKQ8, Q9Y445
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 24, 2001
    Last sequence update: May 1, 2000
    Last modified: September 12, 2018
    This is version 165 of the entry and version 1 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, Reference proteome
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    Main funding by: National Institutes of Health

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