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Q8BYF6

- SC5A8_MOUSE

UniProt

Q8BYF6 - SC5A8_MOUSE

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Protein

Sodium-coupled monocarboxylate transporter 1

Gene
Slc5a8, Smct, Smct1
Organism
Mus musculus (Mouse)
Status
Reviewed - 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

  1. symporter activity Source: UniProtKB-KW

GO - Biological processi

  1. apoptotic process Source: UniProtKB-KW
  2. sodium ion transport Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Apoptosis, Ion transport, Sodium transport, Symport, Transport

Keywords - Ligandi

Sodium

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:Slc5a8
Synonyms:Smct, Smct1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 10

Organism-specific databases

MGIiMGI:2384916. Slc5a8.

Subcellular locationi

Membrane; Multi-pass membrane protein. Apical cell membrane; Multi-pass membrane protein
Note: Restricted to the apical cell membrane of enterocytes.2 Publications

Topology

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

GO - Cellular componenti

  1. apical plasma membrane Source: UniProtKB-SubCell
  2. integral component of membrane Source: UniProtKB-KW
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...) Reviewed prediction

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.
GenevestigatoriQ8BYF6.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000020255.

Structurei

3D structure databases

ProteinModelPortaliQ8BYF6.
SMRiQ8BYF6. Positions 57-456.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0591.
GeneTreeiENSGT00550000074437.
HOGENOMiHOG000261662.
HOVERGENiHBG057280.
InParanoidiQ8BYF6.
KOiK14388.
OMAiWISQGMS.
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

MDASRDIGSF VVWDYVVFAG MLLISAAIGI YYAFAGGGQQ TSKDFLMGGR    50
SMSAVPVALS LTASFMSAVT VLGTPAEVYR FGAIFSIFVI TYFFVVVISA 100
EVFLPVFYRL GITSTYEYLE LRFNRCIRLC GTILFIVQTI LYTGIVIYAP 150
ALALNQVTGF DLWGAVVATG VVCTFYCTLG GLKAVVWTDV FQVGIMVAGF 200
ASVIIQASIT QHGINKILSD AFNGGRLNFW NFDPNPLQRH TFWTIVIGGT 250
FTWTTIYGVN QSQVQRYISC KSRLHAKLSL YVNLVGLWVI LTCSIFCGLA 300
LYSRYRECDP WTSKKVSAID QLMPYLVLDI LKNYPGVPGL FVACAYSGTL 350
STVSSSINAL AAVTVEDLIK PRFKSLSEKS LSWISQGMSV LYGALCIGMA 400
ALASLMGALL QAALSIFGMV GGPLLGLFSL GILVPFANSI GALTGLLAGF 450
AISLWVGIGA QLYPPLPERT LPLPLETYGC NITHNGSDWM STTEMPFSTS 500
AFQIHNAERT PLMDNWYSLS YLYFSTIGTL TTLFVGILIS LSTGGRKQNL 550
DPRFLLTKQD FLSNFDVFKK RNHVLNYKLH PVEVGGTDNP AFNHVELNFT 600
DHSGKINGTR L 611
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.

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti587 – 5871T → N in AAH17691. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
AY484428 mRNA. Translation: AAS49159.1 .
AK039927 mRNA. Translation: BAC30480.1 .
BC017691 mRNA. Translation: AAH17691.1 . Different initiation.
CCDSi CCDS36026.1.
RefSeqi NP_663398.2. NM_145423.2.
UniGenei Mm.77381.

3D structure databases

ProteinModelPortali Q8BYF6.
SMRi Q8BYF6. Positions 57-456.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10090.ENSMUSP00000020255.

PTM databases

PhosphoSitei Q8BYF6.

Proteomic databases

MaxQBi Q8BYF6.
PaxDbi Q8BYF6.
PRIDEi Q8BYF6.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000020255 ; ENSMUSP00000020255 ; ENSMUSG00000020062 .
GeneIDi 216225.
KEGGi mmu:216225.
UCSCi uc007grz.1. mouse.

Organism-specific databases

CTDi 160728.
MGIi MGI:2384916. Slc5a8.

Phylogenomic databases

eggNOGi COG0591.
GeneTreei ENSGT00550000074437.
HOGENOMi HOG000261662.
HOVERGENi HBG057280.
InParanoidi Q8BYF6.
KOi K14388.
OMAi WISQGMS.
OrthoDBi EOG70PBX7.
PhylomeDBi Q8BYF6.
TreeFami TF316728.

Miscellaneous databases

NextBioi 375078.
PROi Q8BYF6.
SOURCEi Search...

Gene expression databases

Bgeei Q8BYF6.
Genevestigatori Q8BYF6.

Family and domain databases

InterProi IPR001734. Na/solute_symporter.
IPR019900. Na/solute_symporter_subgr.
[Graphical view ]
PANTHERi PTHR11819. PTHR11819. 1 hit.
Pfami PF00474. SSF. 1 hit.
[Graphical view ]
TIGRFAMsi TIGR00813. sss. 1 hit.
PROSITEi PS50283. NA_SOLUT_SYMP_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

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/6.
    Tissue: Kidney.
  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/6J.
    Tissue: Thymus.
  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/N.
    Tissue: Kidney.
  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 9, 2014
This is version 96 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

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