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Protein

Sodium-coupled monocarboxylate transporter 1

Gene

SLC5A8

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

Functioni

Acts as an electrogenic sodium (Na+) and chloride (Cl-)-dependent sodium-coupled solute transporter, including transport of monocarboxylates (short-chain fatty acids including L-lactate, D-lactate, pyruvate, acetate, propionate, valerate and butyrate), lactate, mocarboxylate drugs (nicotinate, benzoate, salicylate and 5-aminosalicylate) and ketone bodies (beta-D-hydroxybutyrate, acetoacetate and alpha-ketoisocaproate), with a Na+:substrate stoichiometry of between 4:1 and 2:1. Catalyzes passive carrier mediated diffusion of iodide. Mediates iodide transport from the thyrocyte into the colloid lumen through the apical membrane. May be responsible for the absorption of D-lactate and monocarboxylate drugs from the intestinal tract. Acts as a tumor suppressor, suppressing colony formation in colon cancer, prostate cancer and glioma cell lines. May play a critical role in the entry of L-lactate and ketone bodies into neurons by a process driven by an electrochemical Na+ gradient and hence contribute to the maintenance of the energy status and function of neurons.11 Publications

Miscellaneous

Increase of iodide influx inhibited by addition of perchlorate (NaClO4), a competitive inhibitor of iodide uptake catalyzed by sodium iodide symporter (NIS). Cotransport of monocarboxylates and nicotinate strongly inhibited by probenecid, nonsteroid anti-inflammatory drugs (ibuprofen, fenoprofen, ketprofen, naproxen) in a Na+-dependent manner or by prolonged exposure to external concentrations of monocarboxylates.

Kineticsi

  1. KM=1442 µM for beta-D-hydroxybutyate1 Publication
  2. KM=2327 µM for beta-L-hydroxybutyate1 Publication
  3. KM=1088 µM for D-lactate1 Publication
  4. KM=184 µM for L-lactate1 Publication
  5. KM=387 µM for pyruvate1 Publication
  6. KM=213 µM for acetoacetate1 Publication
  7. KM=209 µM for alpha-ketoisocaproate1 Publication

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Biological processApoptosis, Ion transport, Sodium transport, Symport, Transport
    LigandSodium

    Enzyme and pathway databases

    ReactomeiR-HSA-197264 Nicotinamide salvaging
    R-HSA-428643 Organic anion transporters
    SIGNORiQ8N695

    Protein family/group databases

    TCDBi2.A.21.5.3 the solute:sodium symporter (sss) family

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sodium-coupled monocarboxylate transporter 1
    Alternative name(s):
    Apical iodide transporter
    Electrogenic sodium monocarboxylate cotransporter
    Sodium iodide-related cotransporter
    Solute carrier family 5 member 8
    Gene namesi
    Name:SLC5A8Imported
    Synonyms:AITImported, SMCT2 Publications, SMCT11 Publication
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 12

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000256870.2
    HGNCiHGNC:19119 SLC5A8
    MIMi608044 gene
    neXtProtiNX_Q8N695

    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
    Topological domaini1 – 9ExtracellularSequence analysis9
    Transmembranei10 – 30HelicalSequence analysisAdd BLAST21
    Topological domaini31 – 51CytoplasmicSequence analysisAdd BLAST21
    Transmembranei52 – 72HelicalSequence analysisAdd BLAST21
    Topological domaini73 – 83ExtracellularSequence analysisAdd BLAST11
    Transmembranei84 – 104HelicalSequence analysisAdd BLAST21
    Topological domaini105 – 132CytoplasmicSequence analysisAdd BLAST28
    Transmembranei133 – 153HelicalSequence analysisAdd BLAST21
    Topological domaini154 – 161ExtracellularSequence analysis8
    Transmembranei162 – 182HelicalSequence analysisAdd BLAST21
    Topological domaini183 – 189CytoplasmicSequence analysis7
    Transmembranei190 – 210HelicalSequence analysisAdd BLAST21
    Topological domaini211 – 239ExtracellularSequence analysisAdd BLAST29
    Transmembranei240 – 260HelicalSequence analysisAdd BLAST21
    Topological domaini261 – 279CytoplasmicSequence analysisAdd BLAST19
    Transmembranei280 – 300HelicalSequence analysisAdd BLAST21
    Topological domaini301 – 336ExtracellularSequence analysisAdd BLAST36
    Transmembranei337 – 359HelicalSequence analysisAdd BLAST23
    Topological domaini360 – 389CytoplasmicSequence analysisAdd BLAST30
    Transmembranei390 – 410HelicalSequence analysisAdd BLAST21
    Topological domaini411 – 415ExtracellularSequence analysis5
    Transmembranei416 – 436HelicalSequence analysisAdd BLAST21
    Topological domaini437 – 439CytoplasmicSequence analysis3
    Transmembranei440 – 460HelicalSequence analysisAdd BLAST21
    Topological domaini461 – 518ExtracellularSequence analysisAdd BLAST58
    Transmembranei519 – 539HelicalSequence analysisAdd BLAST21
    Topological domaini540 – 610CytoplasmicSequence analysisAdd BLAST71

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Keywords - Diseasei

    Tumor suppressor

    Organism-specific databases

    DisGeNETi160728
    OpenTargetsiENSG00000256870
    PharmGKBiPA134989874

    Chemistry databases

    DrugBankiDB01762 Acetoacetic Acid
    DB08872 gabapentin enacarbil
    DB00627 Niacin
    GuidetoPHARMACOLOGYi922

    Polymorphism and mutation databases

    BioMutaiSLC5A8
    DMDMi296452898

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00003344991 – 610Sodium-coupled monocarboxylate transporter 1Add BLAST610

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Glycosylationi485N-linked (GlcNAc...) asparagineSequence analysis1

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    PaxDbiQ8N695
    PeptideAtlasiQ8N695
    PRIDEiQ8N695
    ProteomicsDBi72147

    PTM databases

    iPTMnetiQ8N695
    PhosphoSitePlusiQ8N695

    Expressioni

    Tissue specificityi

    Expressed in normal thyroid, localized at the apical pole of thyroid cells facing the colloid lumen, but expression profoundly decreased in thyroid carcinomas. Expressed in normal colon but absent in colon aberrant crypt foci and colon cancers. Present in normal kidney cortex, brain, prostate, gastric mucosa and breast tissue but was significantly down-regulated in primary gliomas, gastric cancer, prostate tumors and breast tumors.10 Publications

    Inductioni

    Down-regulated in some primary cancers; due to aberrant methylation in primary colon cancers, astrocytomas and oligodendrogliomas as well as in cancers of the colon, prostate and gastric regions, and glial cell lines. Expression reactivated on treatment with a demethylating drug, 5-azacytidine.4 Publications

    Gene expression databases

    BgeeiENSG00000256870
    CleanExiHS_SLC5A8
    GenevisibleiQ8N695 HS

    Interactioni

    Protein-protein interaction databases

    BioGridi127763, 27 interactors
    IntActiQ8N695, 1 interactor
    STRINGi9606.ENSP00000445340

    Structurei

    3D structure databases

    ProteinModelPortaliQ8N695
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Compositional biasi569 – 572Poly-LysSequence analysis4

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG2349 Eukaryota
    COG0591 LUCA
    GeneTreeiENSGT00760000118955
    HOGENOMiHOG000261662
    HOVERGENiHBG057280
    InParanoidiQ8N695
    KOiK14388
    OMAiFSHTMAM
    OrthoDBiEOG091G07OC
    PhylomeDBiQ8N695
    TreeFamiTF316728

    Family and domain databases

    Gene3Di1.20.1730.10, 1 hit
    InterProiView protein in InterPro
    IPR038377 Na/Glc_symporter_sf
    IPR001734 Na/solute_symporter
    PfamiView protein in Pfam
    PF00474 SSF, 1 hit
    TIGRFAMsiTIGR00813 sss, 1 hit
    PROSITEiView protein in PROSITE
    PS50283 NA_SOLUT_SYMP_3, 1 hit

    Sequencei

    Sequence statusi: Complete.

    Q8N695-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MDTPRGIGTF VVWDYVVFAG MLVISAAIGI YYAFAGGGQQ TSKDFLMGGR
    60 70 80 90 100
    RMTAVPVALS LTASFMSAVT VLGTPSEVYR FGAIFSIFAF TYFFVVVISA
    110 120 130 140 150
    EVFLPVFYKL GITSTYEYLE LRFNKCVRLC GTVLFIVQTI LYTGIVIYAP
    160 170 180 190 200
    ALALNQVTGF DLWGAVVATG VVCTFYCTLG GLKAVIWTDV FQVGIMVAGF
    210 220 230 240 250
    ASVIIQAVVM QGGISTILND AYDGGRLNFW NFNPNPLQRH TFWTIIIGGT
    260 270 280 290 300
    FTWTSIYGVN QSQVQRYISC KSRFQAKLSL YINLVGLWAI LTCSVFCGLA
    310 320 330 340 350
    LYSRYHDCDP WTAKKVSAPD QLMPYLVLDI LQDYPGLPGL FVACAYSGTL
    360 370 380 390 400
    STVSSSINAL AAVTVEDLIK PYFRSLSERS LSWISQGMSV VYGALCIGMA
    410 420 430 440 450
    ALASLMGALL QAALSVFGMV GGPLMGLFAL GILVPFANSI GALVGLMAGF
    460 470 480 490 500
    AISLWVGIGA QIYPPLPERT LPLHLDIQGC NSTYNETNLM TTTEMPFTTS
    510 520 530 540 550
    VFQIYNVQRT PLMDNWYSLS YLYFSTVGTL VTLLVGILVS LSTGGRKQNL
    560 570 580 590 600
    DPRYILTKED FLSNFDIFKK KKHVLSYKSH PVEDGGTDNP AFNHIELNSD
    610
    QSGKSNGTRL
    Length:610
    Mass (Da):66,578
    Last modified:May 18, 2010 - v2
    Checksum:i47FF410B895DB692
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti490M → I in AAL88746 (PubMed:12107270).Curated1
    Sequence conflicti490M → I in AAP46193 (PubMed:12829793).Curated1
    Sequence conflicti490M → I in AAP46194 (PubMed:12829793).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_057336193V → I2 PublicationsCorresponds to variant dbSNP:rs1709189Ensembl.1
    Natural variantiVAR_057337251F → V1 PublicationCorresponds to variant dbSNP:rs11834933Ensembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY081220 mRNA Translation: AAL88746.1
    AF536216 mRNA Translation: AAP46193.1
    AF536217 Genomic DNA Translation: AAP46194.1
    AC079953 Genomic DNA No translation available.
    CH471054 Genomic DNA Translation: EAW97649.1
    BC110492 mRNA Translation: AAI10493.1
    CCDSiCCDS9080.1
    RefSeqiNP_666018.3, NM_145913.3
    UniGeneiHs.444536

    Genome annotation databases

    EnsembliENST00000536262; ENSP00000445340; ENSG00000256870
    ENST00000572861; ENSP00000461697; ENSG00000262217
    GeneIDi160728
    KEGGihsa:160728
    UCSCiuc001thz.5 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiSC5A8_HUMAN
    AccessioniPrimary (citable) accession number: Q8N695
    Secondary accession number(s): Q2TB99, Q7Z2H9
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 20, 2008
    Last sequence update: May 18, 2010
    Last modified: June 20, 2018
    This is version 116 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, Reference proteome

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