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Q8BYF6

- SC5A8_MOUSE

UniProt

Q8BYF6 - SC5A8_MOUSE

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Protein

Sodium-coupled monocarboxylate transporter 1

Gene

Slc5a8

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

Enzyme and pathway databases

ReactomeiREACT_251149. 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: Chromosome 10

Organism-specific databases

MGIiMGI:2384916. Slc5a8.

Subcellular locationi

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

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

  1. extracellular vesicular exosome Source: Ensembl
  2. integral component of membrane Source: UniProtKB-KW
  3. plasma 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...)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.
GenevestigatoriQ8BYF6.

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.
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

        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.
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 ENSGT00760000118955.
HOGENOMi HOG000261662.
HOVERGENi HBG057280.
InParanoidi Q8BYF6.
KOi K14388.
OMAi WISQGMS.
OrthoDBi EOG70PBX7.
PhylomeDBi Q8BYF6.
TreeFami TF316728.

Enzyme and pathway databases

Reactomei REACT_251149. Organic anion transporters.

Miscellaneous databases

NextBioi 375078.
PROi Q8BYF6.
SOURCEi Search...

Gene expression databases

Bgeei Q8BYF6.
ExpressionAtlasi Q8BYF6. baseline and differential.
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/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: November 26, 2014
This is version 99 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