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Q8BYF6 (SC5A8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 86. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium-coupled monocarboxylate transporter 1
Alternative name(s):
Electrogenic sodium monocarboxylate cotransporter
Solute carrier family 5 member 8
Gene names
Name:Slc5a8
Synonyms:Smct, Smct1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length611 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.4 Ref.5 Ref.7

Subcellular location

Membrane; Multi-pass membrane protein. Apical cell membrane; Multi-pass membrane protein. Note: Restricted to the apical cell membrane of enterocytes. Ref.6 Ref.8

Tissue specificity

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. Ref.1 Ref.5 Ref.6 Ref.7 Ref.8

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. Ref.1

Sequence similarities

Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family. [View classification]

Biophysicochemical properties

Kinetic parameters:

KM=296 µM for nicotinate Ref.4

Sequence caution

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

Ontologies

Keywords
   Biological processApoptosis
Ion transport
Sodium transport
Symport
Transport
   Cellular componentCell membrane
Membrane
   DiseaseTumor suppressor
   DomainTransmembrane
Transmembrane helix
   LigandSodium
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

sodium ion transport

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentapical plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionsymporter activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 611611Sodium-coupled monocarboxylate transporter 1
PRO_0000334500

Regions

Topological domain1 – 99Extracellular Potential
Transmembrane10 – 3021Helical; Potential
Topological domain31 – 5121Cytoplasmic Potential
Transmembrane52 – 7221Helical; Potential
Topological domain73 – 8614Extracellular Potential
Transmembrane87 – 10721Helical; Potential
Topological domain108 – 13225Cytoplasmic Potential
Transmembrane133 – 15321Helical; Potential
Topological domain154 – 1618Extracellular Potential
Transmembrane162 – 18221Helical; Potential
Topological domain183 – 1842Cytoplasmic Potential
Transmembrane185 – 20521Helical; Potential
Topological domain206 – 23934Extracellular Potential
Transmembrane240 – 26021Helical; Potential
Topological domain261 – 27919Cytoplasmic Potential
Transmembrane280 – 30021Helical; Potential
Topological domain301 – 33636Extracellular Potential
Transmembrane337 – 35923Helical; Potential
Topological domain360 – 38930Cytoplasmic Potential
Transmembrane390 – 41021Helical; Potential
Topological domain411 – 4155Extracellular Potential
Transmembrane416 – 43621Helical; Potential
Topological domain437 – 4393Cytoplasmic Potential
Transmembrane440 – 46021Helical; Potential
Topological domain461 – 51858Extracellular Potential
Transmembrane519 – 53921Helical; Potential
Topological domain540 – 61172Cytoplasmic Potential

Amino acid modifications

Glycosylation4851N-linked (GlcNAc...) Potential

Experimental info

Sequence conflict5871T → N in AAH17691. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q8BYF6 [UniParc].

Last modified March 1, 2003. Version 1.
Checksum: 406A49B543EA1D96

FASTA61166,766
        10         20         30         40         50         60 
MDASRDIGSF VVWDYVVFAG MLLISAAIGI YYAFAGGGQQ TSKDFLMGGR SMSAVPVALS 

        70         80         90        100        110        120 
LTASFMSAVT VLGTPAEVYR FGAIFSIFVI TYFFVVVISA EVFLPVFYRL GITSTYEYLE 

       130        140        150        160        170        180 
LRFNRCIRLC GTILFIVQTI LYTGIVIYAP ALALNQVTGF DLWGAVVATG VVCTFYCTLG 

       190        200        210        220        230        240 
GLKAVVWTDV FQVGIMVAGF ASVIIQASIT QHGINKILSD AFNGGRLNFW NFDPNPLQRH 

       250        260        270        280        290        300 
TFWTIVIGGT FTWTTIYGVN QSQVQRYISC KSRLHAKLSL YVNLVGLWVI LTCSIFCGLA 

       310        320        330        340        350        360 
LYSRYRECDP WTSKKVSAID QLMPYLVLDI LKNYPGVPGL FVACAYSGTL STVSSSINAL 

       370        380        390        400        410        420 
AAVTVEDLIK PRFKSLSEKS LSWISQGMSV LYGALCIGMA ALASLMGALL QAALSIFGMV 

       430        440        450        460        470        480 
GGPLLGLFSL GILVPFANSI GALTGLLAGF AISLWVGIGA QLYPPLPERT LPLPLETYGC 

       490        500        510        520        530        540 
NITHNGSDWM STTEMPFSTS AFQIHNAERT PLMDNWYSLS YLYFSTIGTL TTLFVGILIS 

       550        560        570        580        590        600 
LSTGGRKQNL DPRFLLTKQD FLSNFDVFKK RNHVLNYKLH PVEVGGTDNP AFNHVELNFT 

       610 
DHSGKINGTR L

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AY484428 mRNA. Translation: AAS49159.1.
AK039927 mRNA. Translation: BAC30480.1.
BC017691 mRNA. Translation: AAH17691.1. Different initiation.
IPIIPI00227082.
RefSeqNP_663398.2. NM_145423.2.
UniGeneMm.77381.

3D structure databases

ProteinModelPortalQ8BYF6.
SMRQ8BYF6. Positions 57-456.
ModBaseSearch...

Protein-protein interaction databases

STRING10090.ENSMUSP00000020255.

PTM databases

PhosphoSiteQ8BYF6.

Proteomic databases

PaxDbQ8BYF6.
PRIDEQ8BYF6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000020255; ENSMUSP00000020255; ENSMUSG00000020062.
GeneID216225.
KEGGmmu:216225.
UCSCuc007grz.1. mouse.

Organism-specific databases

CTD160728.
MGIMGI:2384916. Slc5a8.

Phylogenomic databases

eggNOGCOG0591.
GeneTreeENSGT00550000074437.
HOGENOMHOG000261662.
HOVERGENHBG057280.
InParanoidQ8BYF6.
KOK14388.
OMAWISQGMS.
OrthoDBEOG44TP7T.

Gene expression databases

ArrayExpressQ8BYF6.
BgeeQ8BYF6.
GenevestigatorQ8BYF6.

Family and domain databases

InterProIPR001734. Na/solute_symporter.
IPR019900. Na/solute_symporter_subgr.
[Graphical view]
PANTHERPTHR11819. PTHR11819. 1 hit.
PfamPF00474. SSF. 1 hit.
[Graphical view]
TIGRFAMsTIGR00813. sss. 1 hit.
PROSITEPS00456. NA_SOLUT_SYMP_1. False negative.
PS00457. NA_SOLUT_SYMP_2. False negative.
PS50283. NA_SOLUT_SYMP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio375078.
SOURCESearch...

Entry information

Entry nameSC5A8_MOUSE
AccessionPrimary (citable) accession number: Q8BYF6
Secondary accession number(s): Q8VD01
Entry history
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: March 1, 2003
Last modified: May 1, 2013
This is version 86 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

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