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Protein

Sodium-coupled monocarboxylate transporter 1

Gene

SLC5A8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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

    Complete GO annotation...

    Keywords - Biological processi

    Apoptosis, Ion transport, Sodium transport, Symport, Transport

    Keywords - Ligandi

    Sodium

    Enzyme and pathway databases

    BioCyciZFISH:ENSG00000139357-MONOMER.
    ReactomeiR-HSA-428643. Organic anion transporters.

    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

    HGNCiHGNC:19119. SLC5A8.

    Subcellular locationi

    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

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Keywords - Diseasei

    Tumor suppressor

    Organism-specific databases

    DisGeNETi160728.
    OpenTargetsiENSG00000256870.
    ENSG00000262217.
    PharmGKBiPA134989874.

    Chemistry databases

    DrugBankiDB08872. 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...)Sequence analysis1

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    PaxDbiQ8N695.
    PeptideAtlasiQ8N695.
    PRIDEiQ8N695.

    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. 21 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.
    OMAiDILQDFP.
    OrthoDBiEOG091G07OC.
    PhylomeDBiQ8N695.
    TreeFamiTF316728.

    Family and domain databases

    InterProiIPR001734. Na/solute_symporter.
    [Graphical view]
    PANTHERiPTHR11819. PTHR11819. 2 hits.
    PfamiPF00474. SSF. 1 hit.
    [Graphical view]
    TIGRFAMsiTIGR00813. sss. 1 hit.
    PROSITEiPS50283. NA_SOLUT_SYMP_3. 1 hit.
    [Graphical view]

    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 → I.2 PublicationsCorresponds to variant rs1709189dbSNPEnsembl.1
    Natural variantiVAR_057337251F → V.1 PublicationCorresponds to variant rs11834933dbSNPEnsembl.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

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    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.

    3D structure databases

    ProteinModelPortaliQ8N695.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi127763. 21 interactors.
    IntActiQ8N695. 1 interactor.
    STRINGi9606.ENSP00000445340.

    Chemistry databases

    DrugBankiDB08872. gabapentin enacarbil.
    DB00627. Niacin.
    GuidetoPHARMACOLOGYi922.

    Protein family/group databases

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

    PTM databases

    iPTMnetiQ8N695.
    PhosphoSitePlusiQ8N695.

    Polymorphism and mutation databases

    BioMutaiSLC5A8.
    DMDMi296452898.

    Proteomic databases

    PaxDbiQ8N695.
    PeptideAtlasiQ8N695.
    PRIDEiQ8N695.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

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

    Organism-specific databases

    CTDi160728.
    DisGeNETi160728.
    GeneCardsiSLC5A8.
    H-InvDBHIX0036731.
    HGNCiHGNC:19119. SLC5A8.
    MIMi608044. gene.
    neXtProtiNX_Q8N695.
    OpenTargetsiENSG00000256870.
    ENSG00000262217.
    PharmGKBiPA134989874.
    GenAtlasiSearch...

    Phylogenomic databases

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

    Enzyme and pathway databases

    BioCyciZFISH:ENSG00000139357-MONOMER.
    ReactomeiR-HSA-428643. Organic anion transporters.

    Miscellaneous databases

    GeneWikiiSLC5A8.
    GenomeRNAii160728.
    PROiQ8N695.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000256870.
    CleanExiHS_SLC5A8.
    GenevisibleiQ8N695. HS.

    Family and domain databases

    InterProiIPR001734. Na/solute_symporter.
    [Graphical view]
    PANTHERiPTHR11819. PTHR11819. 2 hits.
    PfamiPF00474. SSF. 1 hit.
    [Graphical view]
    TIGRFAMsiTIGR00813. sss. 1 hit.
    PROSITEiPS50283. NA_SOLUT_SYMP_3. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiSC5A8_HUMAN
    AccessioniPrimary (citable) accession number: Q8N695
    Secondary accession number(s): Q2TB99, Q7Z2H9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 20, 2008
    Last sequence update: May 18, 2010
    Last modified: November 2, 2016
    This is version 105 of the entry and version 2 of the sequence. [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

    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.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    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 one 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.