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Protein

Sodium-coupled monocarboxylate transporter 1

Gene

Slc5a8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 4 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. 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.4 Publications

Kineticsi

  1. KM=296 µM for nicotinate1 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

    ReactomeiREACT_280974. Organic anion transporters.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sodium-coupled monocarboxylate transporter 1
    Alternative name(s):
    Electrogenic sodium monocarboxylate cotransporter
    Solute carrier family 5 member 8
    Gene namesi
    Name:Slc5a8Imported
    Synonyms:Smct1 Publication, Smct1By similarity
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589 Componenti: Chromosome 10

    Organism-specific databases

    MGIiMGI:2384916. Slc5a8.

    Subcellular locationi

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 99ExtracellularSequence Analysis
    Transmembranei10 – 3021HelicalSequence AnalysisAdd
    BLAST
    Topological domaini31 – 5121CytoplasmicSequence AnalysisAdd
    BLAST
    Transmembranei52 – 7221HelicalSequence AnalysisAdd
    BLAST
    Topological domaini73 – 8614ExtracellularSequence AnalysisAdd
    BLAST
    Transmembranei87 – 10721HelicalSequence AnalysisAdd
    BLAST
    Topological domaini108 – 13225CytoplasmicSequence AnalysisAdd
    BLAST
    Transmembranei133 – 15321HelicalSequence AnalysisAdd
    BLAST
    Topological domaini154 – 1618ExtracellularSequence Analysis
    Transmembranei162 – 18221HelicalSequence AnalysisAdd
    BLAST
    Topological domaini183 – 1842CytoplasmicSequence Analysis
    Transmembranei185 – 20521HelicalSequence AnalysisAdd
    BLAST
    Topological domaini206 – 23934ExtracellularSequence AnalysisAdd
    BLAST
    Transmembranei240 – 26021HelicalSequence AnalysisAdd
    BLAST
    Topological domaini261 – 27919CytoplasmicSequence AnalysisAdd
    BLAST
    Transmembranei280 – 30021HelicalSequence AnalysisAdd
    BLAST
    Topological domaini301 – 33636ExtracellularSequence AnalysisAdd
    BLAST
    Transmembranei337 – 35923HelicalSequence AnalysisAdd
    BLAST
    Topological domaini360 – 38930CytoplasmicSequence AnalysisAdd
    BLAST
    Transmembranei390 – 41021HelicalSequence AnalysisAdd
    BLAST
    Topological domaini411 – 4155ExtracellularSequence Analysis
    Transmembranei416 – 43621HelicalSequence AnalysisAdd
    BLAST
    Topological domaini437 – 4393CytoplasmicSequence Analysis
    Transmembranei440 – 46021HelicalSequence AnalysisAdd
    BLAST
    Topological domaini461 – 51858ExtracellularSequence AnalysisAdd
    BLAST
    Transmembranei519 – 53921HelicalSequence AnalysisAdd
    BLAST
    Topological domaini540 – 61172CytoplasmicSequence AnalysisAdd
    BLAST

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Keywords - Diseasei

    Tumor suppressor

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 611611Sodium-coupled monocarboxylate transporter 1PRO_0000334500Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi485 – 4851N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    MaxQBiQ8BYF6.
    PaxDbiQ8BYF6.
    PRIDEiQ8BYF6.

    PTM databases

    PhosphoSiteiQ8BYF6.

    Expressioni

    Tissue specificityi

    Expressed in brain, colon, kidney and in the ileum and jejunum of small intestine. In the kidney, expression occurred in the proximal tubule and the loop of Henle, being restricted to tubular epithelial cells in both the cortex and the medulla. In the colon, predominantly expressed in the distal half of the large bowel and in the most terminal ileum. Localized selectively in the luminal surface of crypts in the large intestine and to the brush border in the middle parts of crypts in the cecum. In the brain, expression was seen throughout, exclusively in neurons, including the cortex, hippocampus, cerebellum and pituitary gland (at protein level). Expression is reduced in oligodendrogliomas.5 Publications

    Gene expression databases

    BgeeiQ8BYF6.
    ExpressionAtlasiQ8BYF6. baseline and differential.
    GenevisibleiQ8BYF6. MM.

    Interactioni

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000020255.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8BYF6.
    SMRiQ8BYF6. Positions 57-456.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0591.
    GeneTreeiENSGT00760000118955.
    HOGENOMiHOG000261662.
    HOVERGENiHBG057280.
    InParanoidiQ8BYF6.
    KOiK14388.
    OMAiTCSVLCG.
    OrthoDBiEOG70PBX7.
    PhylomeDBiQ8BYF6.
    TreeFamiTF316728.

    Family and domain databases

    InterProiIPR001734. Na/solute_symporter.
    IPR019900. Na/solute_symporter_subgr.
    [Graphical view]
    PANTHERiPTHR11819. PTHR11819. 1 hit.
    PfamiPF00474. SSF. 1 hit.
    [Graphical view]
    TIGRFAMsiTIGR00813. sss. 1 hit.
    PROSITEiPS50283. NA_SOLUT_SYMP_3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q8BYF6-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MDASRDIGSF VVWDYVVFAG MLLISAAIGI YYAFAGGGQQ TSKDFLMGGR
    60 70 80 90 100
    SMSAVPVALS LTASFMSAVT VLGTPAEVYR FGAIFSIFVI TYFFVVVISA
    110 120 130 140 150
    EVFLPVFYRL GITSTYEYLE LRFNRCIRLC GTILFIVQTI LYTGIVIYAP
    160 170 180 190 200
    ALALNQVTGF DLWGAVVATG VVCTFYCTLG GLKAVVWTDV FQVGIMVAGF
    210 220 230 240 250
    ASVIIQASIT QHGINKILSD AFNGGRLNFW NFDPNPLQRH TFWTIVIGGT
    260 270 280 290 300
    FTWTTIYGVN QSQVQRYISC KSRLHAKLSL YVNLVGLWVI LTCSIFCGLA
    310 320 330 340 350
    LYSRYRECDP WTSKKVSAID QLMPYLVLDI LKNYPGVPGL FVACAYSGTL
    360 370 380 390 400
    STVSSSINAL AAVTVEDLIK PRFKSLSEKS LSWISQGMSV LYGALCIGMA
    410 420 430 440 450
    ALASLMGALL QAALSIFGMV GGPLLGLFSL GILVPFANSI GALTGLLAGF
    460 470 480 490 500
    AISLWVGIGA QLYPPLPERT LPLPLETYGC NITHNGSDWM STTEMPFSTS
    510 520 530 540 550
    AFQIHNAERT PLMDNWYSLS YLYFSTIGTL TTLFVGILIS LSTGGRKQNL
    560 570 580 590 600
    DPRFLLTKQD FLSNFDVFKK RNHVLNYKLH PVEVGGTDNP AFNHVELNFT
    610
    DHSGKINGTR L
    Length:611
    Mass (Da):66,766
    Last modified:March 1, 2003 - v1
    Checksum:i406A49B543EA1D96
    GO

    Sequence cautioni

    The sequence AAH17691.1 differs from that shown. Reason: Erroneous initiation. Curated

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti587 – 5871T → N in AAH17691 (PubMed:15489334).Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY484428 mRNA. Translation: AAS49159.1.
    AK039927 mRNA. Translation: BAC30480.1.
    BC017691 mRNA. Translation: AAH17691.1. Different initiation.
    CCDSiCCDS36026.1.
    RefSeqiNP_663398.2. NM_145423.2.
    UniGeneiMm.77381.

    Genome annotation databases

    EnsembliENSMUST00000020255; ENSMUSP00000020255; ENSMUSG00000020062.
    GeneIDi216225.
    KEGGimmu:216225.
    UCSCiuc007grz.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY484428 mRNA. Translation: AAS49159.1.
    AK039927 mRNA. Translation: BAC30480.1.
    BC017691 mRNA. Translation: AAH17691.1. Different initiation.
    CCDSiCCDS36026.1.
    RefSeqiNP_663398.2. NM_145423.2.
    UniGeneiMm.77381.

    3D structure databases

    ProteinModelPortaliQ8BYF6.
    SMRiQ8BYF6. Positions 57-456.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000020255.

    PTM databases

    PhosphoSiteiQ8BYF6.

    Proteomic databases

    MaxQBiQ8BYF6.
    PaxDbiQ8BYF6.
    PRIDEiQ8BYF6.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000020255; ENSMUSP00000020255; ENSMUSG00000020062.
    GeneIDi216225.
    KEGGimmu:216225.
    UCSCiuc007grz.1. mouse.

    Organism-specific databases

    CTDi160728.
    MGIiMGI:2384916. Slc5a8.

    Phylogenomic databases

    eggNOGiCOG0591.
    GeneTreeiENSGT00760000118955.
    HOGENOMiHOG000261662.
    HOVERGENiHBG057280.
    InParanoidiQ8BYF6.
    KOiK14388.
    OMAiTCSVLCG.
    OrthoDBiEOG70PBX7.
    PhylomeDBiQ8BYF6.
    TreeFamiTF316728.

    Enzyme and pathway databases

    ReactomeiREACT_280974. Organic anion transporters.

    Miscellaneous databases

    NextBioi375078.
    PROiQ8BYF6.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ8BYF6.
    ExpressionAtlasiQ8BYF6. baseline and differential.
    GenevisibleiQ8BYF6. MM.

    Family and domain databases

    InterProiIPR001734. Na/solute_symporter.
    IPR019900. Na/solute_symporter_subgr.
    [Graphical view]
    PANTHERiPTHR11819. PTHR11819. 1 hit.
    PfamiPF00474. SSF. 1 hit.
    [Graphical view]
    TIGRFAMsiTIGR00813. sss. 1 hit.
    PROSITEiPS50283. NA_SOLUT_SYMP_3. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Expression of slc5a8 in kidney and its role in Na(+)-coupled transport of lactate."
      Gopal E., Fei Y.-J., Sugawara M., Miyauchi S., Zhuang L., Martin P., Smith S.B., Prasad P.D., Ganapathy V.
      J. Biol. Chem. 279:44522-44532(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, STOICHIOMETRY, STIMULATION, INHIBITION, TISSUE SPECIFICITY.
      Strain: C57BL/6Imported.
      Tissue: KidneyImported.
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6JImported.
      Tissue: ThymusImported.
    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/NImported.
      Tissue: KidneyImported.
    4. "Sodium-coupled and electrogenic transport of B-complex vitamin nicotinic acid by slc5a8, a member of the Na/glucose co-transporter gene family."
      Gopal E., Fei Y.J., Miyauchi S., Zhuang L., Prasad P.D., Ganapathy V.
      Biochem. J. 388:309-316(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
    5. "Shared epigenetic mechanisms in human and mouse gliomas inactivate expression of the growth suppressor SLC5A8."
      Hong C., Maunakea A., Jun P., Bollen A.W., Hodgson J.G., Goldenberg D.D., Weiss W.A., Costello J.F.
      Cancer Res. 65:3617-3623(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY.
    6. "Cellular expression of monocarboxylate transporters (MCT) in the digestive tract of the mouse, rat, and humans, with special reference to slc5a8."
      Iwanaga T., Takebe K., Kato I., Karaki S., Kuwahara A.
      Biomed. Res. 27:243-254(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    7. "Identity of SMCT1 (SLC5A8) as a neuron-specific Na+-coupled transporter for active uptake of L-lactate and ketone bodies in the brain."
      Martin P.M., Gopal E., Ananth S., Zhuang L., Itagaki S., Prasad B.M., Smith S.B., Prasad P.D., Ganapathy V.
      J. Neurochem. 98:279-288(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY.
    8. "Transport of nicotinate and structurally related compounds by human SMCT1 (SLC5A8) and its relevance to drug transport in the mammalian intestinal tract."
      Gopal E., Miyauchi S., Martin P.M., Ananth S., Roon P., Smith S.B., Ganapathy V.
      Pharm. Res. 24:575-584(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiSC5A8_MOUSE
    AccessioniPrimary (citable) accession number: Q8BYF6
    Secondary accession number(s): Q8VD01
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 20, 2008
    Last sequence update: March 1, 2003
    Last modified: July 22, 2015
    This is version 105 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Transport of D-lactate and pyruvate stimulated by alpha-cyano-4-hydroxycinnamic acid, but inhibited by the short-chain fatty acids acetate, propionate and butyrate.1 Publication

    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.