SC5A8_MOUSE
ID SC5A8_MOUSE Reviewed; 611 AA.
AC Q8BYF6; Q8VD01;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Sodium-coupled monocarboxylate transporter 1;
DE AltName: Full=Electrogenic sodium monocarboxylate cotransporter;
DE AltName: Full=Solute carrier family 5 member 8;
GN Name=Slc5a8 {ECO:0000312|MGI:MGI:2384916};
GN Synonyms=Smct {ECO:0000303|PubMed:15651982},
GN Smct1 {ECO:0000250|UniProtKB:Q8N695};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAS49159.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, STOICHIOMETRY, STIMULATION,
RP INHIBITION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAS49159.1};
RC TISSUE=Kidney {ECO:0000312|EMBL:AAS49159.1};
RX PubMed=15322102; DOI=10.1074/jbc.m405365200;
RA Gopal E., Fei Y.-J., Sugawara M., Miyauchi S., Zhuang L., Martin P.,
RA Smith S.B., Prasad P.D., Ganapathy V.;
RT "Expression of slc5a8 in kidney and its role in Na(+)-coupled transport of
RT lactate.";
RL J. Biol. Chem. 279:44522-44532(2004).
RN [2] {ECO:0000312|EMBL:BAC30480.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC30480.1};
RC TISSUE=Thymus {ECO:0000312|EMBL:BAC30480.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3] {ECO:0000312|EMBL:AAH17691.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N {ECO:0000312|EMBL:AAH17691.1};
RC TISSUE=Kidney {ECO:0000312|EMBL:AAH17691.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4] {ECO:0000305}
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15651982; DOI=10.1042/bj20041916;
RA Gopal E., Fei Y.J., Miyauchi S., Zhuang L., Prasad P.D., Ganapathy V.;
RT "Sodium-coupled and electrogenic transport of B-complex vitamin nicotinic
RT acid by slc5a8, a member of the Na/glucose co-transporter gene family.";
RL Biochem. J. 388:309-316(2005).
RN [5] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15867356; DOI=10.1158/0008-5472.can-05-0048;
RA Hong C., Maunakea A., Jun P., Bollen A.W., Hodgson J.G., Goldenberg D.D.,
RA Weiss W.A., Costello J.F.;
RT "Shared epigenetic mechanisms in human and mouse gliomas inactivate
RT expression of the growth suppressor SLC5A8.";
RL Cancer Res. 65:3617-3623(2005).
RN [6] {ECO:0000305}
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17099289; DOI=10.2220/biomedres.27.243;
RA Iwanaga T., Takebe K., Kato I., Karaki S., Kuwahara A.;
RT "Cellular expression of monocarboxylate transporters (MCT) in the digestive
RT tract of the mouse, rat, and humans, with special reference to slc5a8.";
RL Biomed. Res. 27:243-254(2006).
RN [7] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16805814; DOI=10.1111/j.1471-4159.2006.03878.x;
RA Martin P.M., Gopal E., Ananth S., Zhuang L., Itagaki S., Prasad B.M.,
RA Smith S.B., Prasad P.D., Ganapathy V.;
RT "Identity of SMCT1 (SLC5A8) as a neuron-specific Na+-coupled transporter
RT for active uptake of L-lactate and ketone bodies in the brain.";
RL J. Neurochem. 98:279-288(2006).
RN [8] {ECO:0000305}
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17245649; DOI=10.1007/s11095-006-9176-1;
RA Gopal E., Miyauchi S., Martin P.M., Ananth S., Roon P., Smith S.B.,
RA Ganapathy V.;
RT "Transport of nicotinate and structurally related compounds by human SMCT1
RT (SLC5A8) and its relevance to drug transport in the mammalian intestinal
RT tract.";
RL Pharm. Res. 24:575-584(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Acts as an electrogenic sodium (Na(+)) and chloride (Cl-)-
CC dependent sodium-coupled solute transporter, including transport of
CC monocarboxylates (short-chain fatty acids including L-lactate, D-
CC lactate, pyruvate, acetate, propionate, valerate and butyrate),
CC lactate, mocarboxylate drugs (nicotinate, benzoate, salicylate and 5-
CC aminosalicylate) and ketone bodies (beta-D-hydroxybutyrate,
CC acetoacetate and alpha-ketoisocaproate), with a Na(+):substrate
CC stoichiometry of between 4:1 and 2:1. Catalyzes passive carrier
CC mediated diffusion of iodide. Mediates iodide transport from the
CC thyrocyte into the colloid lumen through the apical membrane. May be
CC responsible for the absorption of D-lactate and monocarboxylate drugs
CC from the intestinal tract. May play a critical role in the entry of L-
CC lactate and ketone bodies into neurons by a process driven by an
CC electrochemical Na(+) gradient and hence contribute to the maintenance
CC of the energy status and function of neurons.
CC {ECO:0000269|PubMed:15322102, ECO:0000269|PubMed:15651982,
CC ECO:0000269|PubMed:15867356, ECO:0000269|PubMed:16805814}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=296 uM for nicotinate {ECO:0000269|PubMed:15651982};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:17099289,
CC ECO:0000269|PubMed:17245649}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:17099289, ECO:0000269|PubMed:17245649}. Apical cell
CC membrane; Multi-pass membrane protein {ECO:0000269|PubMed:17099289,
CC ECO:0000269|PubMed:17245649}. Note=Restricted to the apical cell
CC membrane of enterocytes. {ECO:0000269|PubMed:17099289,
CC ECO:0000269|PubMed:17245649}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, colon, kidney and in the ileum
CC and jejunum of small intestine. In the kidney, expression occurred in
CC the proximal tubule and the loop of Henle, being restricted to tubular
CC epithelial cells in both the cortex and the medulla. In the colon,
CC predominantly expressed in the distal half of the large bowel and in
CC the most terminal ileum. Localized selectively in the luminal surface
CC of crypts in the large intestine and to the brush border in the middle
CC parts of crypts in the cecum. In the brain, expression was seen
CC throughout, exclusively in neurons, including the cortex, hippocampus,
CC cerebellum and pituitary gland (at protein level). Expression is
CC reduced in oligodendrogliomas. {ECO:0000269|PubMed:15322102,
CC ECO:0000269|PubMed:15867356, ECO:0000269|PubMed:16805814,
CC ECO:0000269|PubMed:17099289, ECO:0000269|PubMed:17245649}.
CC -!- MISCELLANEOUS: Transport of D-lactate and pyruvate stimulated by alpha-
CC cyano-4-hydroxycinnamic acid, but inhibited by the short-chain fatty
CC acids acetate, propionate and butyrate. {ECO:0000269|PubMed:15322102}.
CC -!- SIMILARITY: Belongs to the sodium:solute symporter (SSF) (TC 2.A.21)
CC family. {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH17691.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY484428; AAS49159.1; -; mRNA.
DR EMBL; AK039927; BAC30480.1; -; mRNA.
DR EMBL; BC017691; AAH17691.1; ALT_INIT; mRNA.
DR CCDS; CCDS36026.1; -.
DR RefSeq; NP_663398.2; NM_145423.2.
DR AlphaFoldDB; Q8BYF6; -.
DR SMR; Q8BYF6; -.
DR STRING; 10090.ENSMUSP00000020255; -.
DR GlyGen; Q8BYF6; 1 site.
DR iPTMnet; Q8BYF6; -.
DR PhosphoSitePlus; Q8BYF6; -.
DR jPOST; Q8BYF6; -.
DR MaxQB; Q8BYF6; -.
DR PaxDb; Q8BYF6; -.
DR PRIDE; Q8BYF6; -.
DR ProteomicsDB; 255469; -.
DR Antibodypedia; 51376; 182 antibodies from 24 providers.
DR DNASU; 216225; -.
DR Ensembl; ENSMUST00000020255; ENSMUSP00000020255; ENSMUSG00000020062.
DR GeneID; 216225; -.
DR KEGG; mmu:216225; -.
DR UCSC; uc007grz.1; mouse.
DR CTD; 160728; -.
DR MGI; MGI:2384916; Slc5a8.
DR VEuPathDB; HostDB:ENSMUSG00000020062; -.
DR eggNOG; KOG2349; Eukaryota.
DR GeneTree; ENSGT00940000155166; -.
DR HOGENOM; CLU_018808_11_1_1; -.
DR InParanoid; Q8BYF6; -.
DR OMA; ILSYKSH; -.
DR OrthoDB; 1180002at2759; -.
DR PhylomeDB; Q8BYF6; -.
DR TreeFam; TF316728; -.
DR Reactome; R-MMU-197264; Nicotinamide salvaging.
DR Reactome; R-MMU-428643; Organic anion transporters.
DR BioGRID-ORCS; 216225; 5 hits in 73 CRISPR screens.
DR ChiTaRS; Slc5a8; mouse.
DR PRO; PR:Q8BYF6; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q8BYF6; protein.
DR Bgee; ENSMUSG00000020062; Expressed in left colon and 58 other tissues.
DR Genevisible; Q8BYF6; MM.
DR GO; GO:0016324; C:apical plasma membrane; TAS:MGI.
DR GO; GO:0031526; C:brush border membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0015129; F:lactate transmembrane transporter activity; IDA:MGI.
DR GO; GO:0140161; F:monocarboxylate:sodium symporter activity; IDA:MGI.
DR GO; GO:0005343; F:organic acid:sodium symporter activity; IDA:MGI.
DR GO; GO:0015552; F:propionate transmembrane transporter activity; IDA:MGI.
DR GO; GO:0015636; F:short-chain fatty acid transmembrane transporter activity; IDA:MGI.
DR GO; GO:0015293; F:symporter activity; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0015718; P:monocarboxylic acid transport; IDA:MGI.
DR GO; GO:0015730; P:propanoate transport; IDA:MGI.
DR GO; GO:0015913; P:short-chain fatty acid import; IDA:MGI.
DR GO; GO:0006814; P:sodium ion transport; IBA:GO_Central.
DR CDD; cd11519; SLC5sbd_SMCT1; 1.
DR Gene3D; 1.20.1730.10; -; 1.
DR InterPro; IPR038377; Na/Glc_symporter_sf.
DR InterPro; IPR001734; Na/solute_symporter.
DR InterPro; IPR041992; SLC5sbd_SMCT1.
DR Pfam; PF00474; SSF; 1.
DR TIGRFAMs; TIGR00813; sss; 1.
DR PROSITE; PS50283; NA_SOLUT_SYMP_3; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Cell membrane; Glycoprotein; Ion transport; Membrane;
KW Reference proteome; Sodium; Sodium transport; Symport; Transmembrane;
KW Transmembrane helix; Transport; Tumor suppressor.
FT CHAIN 1..611
FT /note="Sodium-coupled monocarboxylate transporter 1"
FT /id="PRO_0000334500"
FT TOPO_DOM 1..9
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 31..51
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 52..72
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 73..86
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 87..107
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 108..132
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 133..153
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 154..161
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 162..182
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 183..184
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 185..205
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 206..239
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 240..260
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 261..279
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 280..300
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 301..336
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 337..359
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 360..389
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 390..410
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 411..415
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 416..436
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 437..439
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 440..460
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 461..518
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 519..539
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 540..611
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 485
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 587
FT /note="T -> N (in Ref. 3; AAH17691)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 611 AA; 66766 MW; 406A49B543EA1D96 CRC64;
MDASRDIGSF VVWDYVVFAG MLLISAAIGI YYAFAGGGQQ TSKDFLMGGR SMSAVPVALS
LTASFMSAVT VLGTPAEVYR FGAIFSIFVI TYFFVVVISA EVFLPVFYRL GITSTYEYLE
LRFNRCIRLC GTILFIVQTI LYTGIVIYAP ALALNQVTGF DLWGAVVATG VVCTFYCTLG
GLKAVVWTDV FQVGIMVAGF ASVIIQASIT QHGINKILSD AFNGGRLNFW NFDPNPLQRH
TFWTIVIGGT FTWTTIYGVN QSQVQRYISC KSRLHAKLSL YVNLVGLWVI LTCSIFCGLA
LYSRYRECDP WTSKKVSAID QLMPYLVLDI LKNYPGVPGL FVACAYSGTL STVSSSINAL
AAVTVEDLIK PRFKSLSEKS LSWISQGMSV LYGALCIGMA ALASLMGALL QAALSIFGMV
GGPLLGLFSL GILVPFANSI GALTGLLAGF AISLWVGIGA QLYPPLPERT LPLPLETYGC
NITHNGSDWM STTEMPFSTS AFQIHNAERT PLMDNWYSLS YLYFSTIGTL TTLFVGILIS
LSTGGRKQNL DPRFLLTKQD FLSNFDVFKK RNHVLNYKLH PVEVGGTDNP AFNHVELNFT
DHSGKINGTR L
